Trial Outcomes & Findings for Effects of PTH Replacement on Bone in Hypoparathyroidism (NCT NCT00395538)

NCT ID: NCT00395538

Last Updated: 2019-08-28

Results Overview

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, so the 2-, and 4-year biopsies were collapsed into one biopsy year group. Cn.BV/TV is one of 8 primary endpoints measured from the bone biopsy. The changes in Cn.BV/TV outcome between two time-points are being reported. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 46 participants
• Primary outcome timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies
• Results posted on: 2019-08-28

Participant Flow

Individuals with hypoparathyroidism were enrolled at the NIH clinical center, beginning in October 2006. The protocol was redesigned and amended in February 2010. Some of the previously enrolled participants were re-enrolled in the new study. New participants were also enrolled on the new study through October 2014.

All participants were put on conventional care therapy for 2-6 months prior to HPTH therapy. Previously enrolled participants had their baseline bone biopsy prior to the study's conventional care period. Newly enrolled participants had their baseline bone biopsy performed at the started of HPTH therapy.

Participant milestones

Measure	Cohort 1: Received HPTH on Original Protocol Treated with HPTH therapy on original protocol	Cohort 2: Received Conventional Care on Original Protocol Treated with conventional care (CC) throughout original protocol	Cohort 3: Newly Enrolled No Prior Participation New participants in revised protocol
Overall Study STARTED	8	15	23
Overall Study Signed Consent to the New Protocol	7	5	23
Overall Study Received HPTH on New Protocol	7	5	19
Overall Study Randomized to Bone Biopsy Year 1	0	1	5
Overall Study Randomized to Bone Biopsy Year 2	0	2	6
Overall Study Randomized to Bone Biospy Year 4	0	2	8
Overall Study Completed Bone Biopsy Year 1	0	1	4
Overall Study Completed Bone Biopsy Year 2	0	2	3
Overall Study Completed Bone Biopsy Year 4	0	1	1
Overall Study COMPLETED	5	2	0
Overall Study NOT COMPLETED	3	13	23

Reasons for withdrawal

Measure	Cohort 1: Received HPTH on Original Protocol Treated with HPTH therapy on original protocol	Cohort 2: Received Conventional Care on Original Protocol Treated with conventional care (CC) throughout original protocol	Cohort 3: Newly Enrolled No Prior Participation New participants in revised protocol
Overall Study Did not re-consent to revised protocol	1	10	0
Overall Study FDA partial hold on PTH	0	0	11
Overall Study Failed screening	0	0	4
Overall Study Switch to Natpara	0	0	3
Overall Study Adverse Event	1	0	2
Overall Study DXA or QCT z-score or t-score<-2	0	2	0
Overall Study Non-compliance with study protocol	0	1	0
Overall Study PTH resistance	0	0	1
Overall Study Pregnancy	1	0	0
Overall Study Partial recovery of parathyroid function	0	0	1
Overall Study Participant elected to discontinue	0	0	1

Baseline Characteristics

Baseline height was missing for some participants.

Baseline characteristics by cohort

Measure	Cohort 1 (HPTH on Old Study) and Received HPTH on New Study n=7 Participants Cohort 1 was treated with HPTH therapy on original protocol. Cohort 1 participants who consented to the new protocol and were treated with HPTH on the new protocol were followed for safety outcomes only. The Safety population of Cohort 1 consisted of 7 participants.	Cohort 2 (CC on Old Study) and Treated With HPTH on New Study n=5 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 2 participants who received at least one dose of HPTH on the new protocol were included in safety population. Cohort 2 safety population includes 5 participants.	Cohort 3 (Newly Enrolled) and Treated With HPTH on New Study n=19 Participants Cohort 3 consists of new participants (i.e. not previously enrolled) that consented to the revised protocol. The Cohort 3 safety population includes 19 subjects who received any HPTH on the new study.	Total n=31 Participants Total of all reporting groups
Age, Customized Age · < 20 years	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=19 Participants	2 Participants n=31 Participants
Age, Customized Age · 20-29 years	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=19 Participants	2 Participants n=31 Participants
Age, Customized Age · 30-39 years	1 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=19 Participants	8 Participants n=31 Participants
Age, Customized Age · 40-49 years	3 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=19 Participants	13 Participants n=31 Participants
Age, Customized Age · 50-59 years	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=19 Participants	6 Participants n=31 Participants
Sex: Female, Male Female	6 Participants n=7 Participants	3 Participants n=5 Participants	16 Participants n=19 Participants	25 Participants n=31 Participants
Sex: Female, Male Male	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=19 Participants	6 Participants n=31 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=19 Participants	0 Participants n=31 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=7 Participants	5 Participants n=5 Participants	19 Participants n=19 Participants	31 Participants n=31 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=19 Participants	0 Participants n=31 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=19 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Asian	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=19 Participants	1 Participants n=31 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=19 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Black or African American	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=19 Participants	0 Participants n=31 Participants
Race (NIH/OMB) White	7 Participants n=7 Participants	5 Participants n=5 Participants	18 Participants n=19 Participants	30 Participants n=31 Participants
Race (NIH/OMB) More than one race	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=19 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=19 Participants	0 Participants n=31 Participants
Weight	72.2 kg STANDARD_DEVIATION 14.39 • n=7 Participants	74.9 kg STANDARD_DEVIATION 21.92 • n=5 Participants	82.6 kg STANDARD_DEVIATION 19.01 • n=19 Participants	79.0 kg STANDARD_DEVIATION 18.56 • n=31 Participants
Height	160.8 cm STANDARD_DEVIATION 6.93 • n=3 Participants • Baseline height was missing for some participants.	—	171.1 cm STANDARD_DEVIATION 9.67 • n=7 Participants • Baseline height was missing for some participants.	168.0 cm STANDARD_DEVIATION 9.89 • n=10 Participants • Baseline height was missing for some participants.
BMI	29.71 kg/m^2 STANDARD_DEVIATION 2.232 • n=3 Participants • Since some participants had missing height measures, the BMI could not be calculated for these participants.	—	29.14 kg/m^2 STANDARD_DEVIATION 6.310 • n=7 Participants • Since some participants had missing height measures, the BMI could not be calculated for these participants.	29.31 kg/m^2 STANDARD_DEVIATION 5.266 • n=10 Participants • Since some participants had missing height measures, the BMI could not be calculated for these participants.

PRIMARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, so the 2-, and 4-year biopsies were collapsed into one biopsy year group. Cn.BV/TV is one of 8 primary endpoints measured from the bone biopsy. The changes in Cn.BV/TV outcome between two time-points are being reported. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=12 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Bone Biopsy Cancellous Bone Volume (Cn.BV/TV) Biopsy Year 1 - Baseline	3.05 z-score Standard Error 1.095
Change in Bone Biopsy Cancellous Bone Volume (Cn.BV/TV) Biopsy Years 2 and 4 (combined) - Baseline	3.69 z-score Standard Error 0.940
Change in Bone Biopsy Cancellous Bone Volume (Cn.BV/TV) Biopsy Years 2 and 4 (combined) - Year 1	0.64 z-score Standard Error 1.379

PRIMARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, so the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ct.Po.N is a bone biopsy measure that assess the amount of holes in the cortical bone within a predetermined area of cortical bone. The changes in Cn.BV/TV outcome between two time-points are being reported. Cortical bone with a higher number of holes may be at greater risk of fracture. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=11 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Total Number of Cortical Pores Per mm^2 (Ct.Po.N) Biopsy Year 1 - Baseline	1.12 cortical pores/mm^2 Standard Error 1.214
Change in Total Number of Cortical Pores Per mm^2 (Ct.Po.N) Biopsy Years 2 and 4 (combined) - Baseline	1.86 cortical pores/mm^2 Standard Error 1.149
Change in Total Number of Cortical Pores Per mm^2 (Ct.Po.N) Biopsy Years 2 and 4 (combined) - Year 1	0.74 cortical pores/mm^2 Standard Error 1.175

PRIMARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Cn.BFR/BS, measured from the bone biopsy, is the cancellous bone formation rate per unit of bone surface where cancellous refers to the spongy structure of the bone. The changes in Cn.BFR/BS between two time-points are being reported. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=12 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Cancellous Bone Formation Rate Per Unit of Bone Surface (Cn.BFR/BS) Biopsy Year 1 - Baseline	4.25 z-score Standard Error 1.420
Change in Cancellous Bone Formation Rate Per Unit of Bone Surface (Cn.BFR/BS) Biopsy Years 2 and 4 (combined) - Baseline	5.75 z-score Standard Error 1.251
Change in Cancellous Bone Formation Rate Per Unit of Bone Surface (Cn.BFR/BS) Biopsy Years 2 and 4 (combined) - Year 1	1.50 z-score Standard Error 1.647

PRIMARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Following their baseline bone biopsy, 5, 5, and 2 participants were randomized to receive their second bone biopsy at years 1, 2, and 4 after the start of HPTH therapy, respectively. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced in size due to withdrawal and the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Cn.MS/BS is measured from the bone biopsy. This measure demonstrates the percentage of the cancellous bone surface that is actively forming bone. The region of interest is the predefined area of total bone that is being measured. The changes in Cn.MS/BS between two time-points are being reported.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=12 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Cancellous Mineralizing Surface (Bone Surface Based)(Cn.MS/BS) Biopsy Year 1 - Baseline	14.63 percentage of predefined area of bone Standard Error 3.996
Change in Cancellous Mineralizing Surface (Bone Surface Based)(Cn.MS/BS) Biopsy Years 2 and 4 (combined) - Baseline	21.47 percentage of predefined area of bone Standard Error 3.489
Change in Cancellous Mineralizing Surface (Bone Surface Based)(Cn.MS/BS) Biopsy Years 2 and 4 (combined) - Year 1	6.85 percentage of predefined area of bone Standard Error 4.774

PRIMARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. However, because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ec.BFR/BS is measured from the bone biopsy. This measures the rate of new bone formation per day on the inner cortical (endocortical) surface in a predefined region of cortical bone. The changes in Ec.BFR/BS between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=11 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Endocortical Bone Formation Rate Per Unit of Bone Surface (Ec.BFR/BS) Biopsy Year 1 - Baseline	0.12 um^2/um/d Standard Error 0.063
Change in Endocortical Bone Formation Rate Per Unit of Bone Surface (Ec.BFR/BS) Biopsy Years 2 and 4 (combined) - Baseline	0.22 um^2/um/d Standard Error 0.055
Change in Endocortical Bone Formation Rate Per Unit of Bone Surface (Ec.BFR/BS) Biopsy Years 2 and 4 (combined) - Year 1	0.10 um^2/um/d Standard Error 0.072

PRIMARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants who completed both their baseline and randomized 1, 2, or 4 year bone biopsies. This will only include participants from cohorts 2 and 3.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ec.MS/BS is measured from the bone biopsy. This measure demonstrates the percentage of the endocortical bone surface that is actively forming bone. The region of interest is the predefined area of total bone that is being measured. The changes in Ec.MS/BS between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=11 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Endocortical Mineralizing Surface (Bone Surface Based) (Ec.MS/BS) Biopsy Year 1 - Baseline	18.39 percentage of regional interest Standard Error 7.748
Change in Endocortical Mineralizing Surface (Bone Surface Based) (Ec.MS/BS) Biopsy Years 2 and 4 (combined) - Baseline	30.94 percentage of regional interest Standard Error 6.757
Change in Endocortical Mineralizing Surface (Bone Surface Based) (Ec.MS/BS) Biopsy Years 2 and 4 (combined) - Year 1	12.55 percentage of regional interest Standard Error 8.944

PRIMARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. However, because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ic.BFR/BS is measured from the bone biopsy. This measures the rate of new bone formation between the two cortical surfaces (intracortical) in a predefined region of cortical bone. The changes in Ic.BFR/BS between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=11 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Intracortical Bone Formation Rate Per Unit of Bone Surface (Ic.BFR/BS) Biopsy Year 1 - Baseline	0.18 um^2/um/d Standard Error 0.045
Change in Intracortical Bone Formation Rate Per Unit of Bone Surface (Ic.BFR/BS) Biopsy Years 2 and 4 (combined) - Baseline	0.10 um^2/um/d Standard Error 0.040
Change in Intracortical Bone Formation Rate Per Unit of Bone Surface (Ic.BFR/BS) Biopsy Years 2 and 4 (combined) - Year 1	-0.07 um^2/um/d Standard Error 0.052

PRIMARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ic.MS/BS is measured from the bone biopsy. This measure demonstrates the percentage of the intracortical bone surface that is actively forming bone. The region of interest is the predefined area of total bone that is being measured. The changes in Ic.MS/BS between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=11 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Intracortical Mineralizing Surface (Bone Surface Based) (Ic.MS/BS) Biopsy Year 1 - Baseline	24.75 percentage of regional interest Standard Error 6.000
Change in Intracortical Mineralizing Surface (Bone Surface Based) (Ic.MS/BS) Biopsy Years 2 and 4 (combined) - Baseline	14.36 percentage of regional interest Standard Error 5.208
Change in Intracortical Mineralizing Surface (Bone Surface Based) (Ic.MS/BS) Biopsy Years 2 and 4 (combined) - Year 1	-10.4 percentage of regional interest Standard Error 6.999

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Tb.Th is measured from the bone biopsy. Tb.Th is the mean thickness of trabeculae, assessed using direct 3D methods. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes. The changes in Tb.Th between two time-points are being reported.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=12 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Trabecular Thickness (Tb.Th) Biopsy Year 1 - Baseline	-0.28 z-score Standard Error 0.779
Change in Trabecular Thickness (Tb.Th) Biopsy Years 2 and 4 (combined) - Baseline	0.05 z-score Standard Error 0.675
Change in Trabecular Thickness (Tb.Th) Biopsy Years 2 and 4 (combined) - Year 1	0.33 z-score Standard Error 0.950

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Tb.N is measured from the bone biopsy. Tb.N is the measure of the average number of trabeculae per unit length. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes. The changes in Tb.N between two time-points are being reported.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=12 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Trabecular Number (Tb.N) Biopsy Year 1 - Baseline	3.62 z-score Standard Error 1.382
Change in Trabecular Number (Tb.N) Biopsy Years 2 and 4 (combined) - Baseline	3.30 z-score Standard Error 1.221
Change in Trabecular Number (Tb.N) Biopsy Years 2 and 4 (combined) - Year 1	-0.32 z-score Standard Error 1.586

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Tb.Sp is measured from the bone biopsy. Tb.Sp is the mean distance between trabeculae, assessed using direct 3D methods. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes. The changes in Tb.Sp between two time-points are being reported.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=12 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Trabecular Separation (Tb.Sp) Biopsy Year 1 - Baseline	-2.28 z-score Standard Error 0.803
Change in Trabecular Separation (Tb.Sp) Biopsy Years 2 and 4 (combined) - Baseline	-1.76 z-score Standard Error 0.693
Change in Trabecular Separation (Tb.Sp) Biopsy Years 2 and 4 (combined) - Year 1	0.52 z-score Standard Error 0.997

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ct.Th, measured from the bone biopsy, is the average thickness of the inner and outer cortices. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes. The changes in Ct.Th between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=11 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Average Thickness of Inner and Outer Cortices (Ct.Th) Biopsy Year 1 - Baseline	2.02 z-score Standard Error 0.916
Change in Average Thickness of Inner and Outer Cortices (Ct.Th) Biopsy Years 2 and 4 (combined) - Baseline	0.78 z-score Standard Error 0.771
Change in Average Thickness of Inner and Outer Cortices (Ct.Th) Biopsy Years 2 and 4 (combined) - Year 1	-1.25 z-score Standard Error 1.092

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ct.AR is measured from the bone biopsy. This measure defines the area of the outer cortex and inner cortex within a predefined section of cortical bone. The changes in Ct.Ar between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=11 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Total Area of Inner and Outer Cortices (Ct.Ar) Biopsy Year 1 - Baseline	6.56 percentage of region of interest Standard Error 6.905
Total Area of Inner and Outer Cortices (Ct.Ar) Biopsy Years 2 and 4 (combined) - Baseline	1.93 percentage of region of interest Standard Error 6.128
Total Area of Inner and Outer Cortices (Ct.Ar) Biopsy Years 2 and 4 (combined) - Year 1	-4.64 percentage of region of interest Standard Error 8.006

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants who completed both their baseline and randomized 1, 2, or 4 year bone biopsies. This will only include participants from cohorts 2 and 3.

Following their baseline bone biopsy, 5, 5, and 2 participants were randomized to receive their second bone biopsy at years 1, 2, and 4 after the start of HPTH therapy, respectively. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced in size due to withdrawal and the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ct.Po.Ar is measured from the bone biopsy. This measure defines the area of the cortical bone with holes within a predefined section of cortical bone. The changes in Tb.Sp between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=11 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Total Area of Cortical Porosity (Ct.Po.Ar) Biopsy Year 1 - Baseline	3.41 percentage of region of interest Standard Error 2.337
Change in Total Area of Cortical Porosity (Ct.Po.Ar) Biopsy Years 2 and 4 (combined) - Baseline	0.26 percentage of region of interest Standard Error 1.911
Change in Total Area of Cortical Porosity (Ct.Po.Ar) Biopsy Years 2 and 4 (combined) - Year 1	-3.15 percentage of region of interest Standard Error 2.837

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Cn.O.Th measured from the bone biopsy. This measures the thickness of the unmineralized bone (osteoid) in a predefined region of cancellous bone. The changes in Cn.O.Th between two time-points are being reported.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=12 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Cancellous Osteoid Thickness (Cn.O.Th) Biopsy Year 1 - Baseline	1.99 um Standard Error 0.553
Change in Cancellous Osteoid Thickness (Cn.O.Th) Biopsy Years 2 and 4 (combined) - Baseline	2.29 um Standard Error 0.472
Change in Cancellous Osteoid Thickness (Cn.O.Th) Biopsy Years 2 and 4 (combined) - Year 1	0.30 um Standard Error 0.704

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Cn.MAR is measured from the bone biopsy. This measures the rate mineral is being laid down per day in a predefined region of the cancellous bone. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes. The changes in Cn.MAR between two time-points are being reported.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=12 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Cancellous Bone Mineral Apposition Rate (Cn.MAR) Biopsy Year 1 - Baseline	3.21 z-score Standard Error 1.002
Change in Cancellous Bone Mineral Apposition Rate (Cn.MAR) Biopsy Years 2 and 4 (combined) - Baseline	3.07 z-score Standard Error 0.885
Change in Cancellous Bone Mineral Apposition Rate (Cn.MAR) Biopsy Years 2 and 4 (combined) - Year 1	-0.14 z-score Standard Error 1.151

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Cn.OS/BS is measured from the bone biopsy. This measure demonstrates the percentage of the cancellous bone surface that contains unmineralized bone (osteoid). The region of interest is the predefined area of total bone that is being measured. The changes in Cn.OS/BS between two time-points are being reported.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=12 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Cancellous Osteoid Surface / Bone Surface (Cn.OS/BS) Biopsy Year 1 - Baseline	12.70 percentage of region of interest Standard Error 3.407
Change in Cancellous Osteoid Surface / Bone Surface (Cn.OS/BS) Biopsy Years 2 and 4 (combined) - Baseline	24.34 percentage of region of interest Standard Error 2.971
Change in Cancellous Osteoid Surface / Bone Surface (Cn.OS/BS) Biopsy Years 2 and 4 (combined) - Year 1	11.64 percentage of region of interest Standard Error 4.084

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Cn.ES/BS is measured from the bone biopsy. This measure demonstrates the percentage of the cancellous bone surface that contains unmineralized bone (osteoid). The region of interest is the predefined area of total bone that is being measured. The changes in Cn.ES/BS between two time-points are being reported.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=12 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Cancellous Eroded Surface / Bone Surface (Cn.ES/BS) Biopsy Year 1 - Baseline	6.55 percentage of region of interest Standard Error 1.648
Change in Cancellous Eroded Surface / Bone Surface (Cn.ES/BS) Biopsy Years 2 and 4 (combined) - Baseline	10.30 percentage of region of interest Standard Error 1.543
Change in Cancellous Eroded Surface / Bone Surface (Cn.ES/BS) Biopsy Years 2 and 4 (combined) - Year 1	3.75 percentage of region of interest Standard Error 1.415

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Cn.AjAR is measured from the bone biopsy. Cn.AjAR represents the Cn.MAR averaged over the entire osteoid surface.The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes. The changes in Cn.AjAR between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=11 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Cancellous Adjusted Apposition Rate (Cn.AjAR) Biopsy Year 1 - Baseline	3.10 z-score Standard Error 0.824
Change in Cancellous Adjusted Apposition Rate (Cn.AjAR) Biopsy Years 2 and 4 (combined) - Baseline	1.89 z-score Standard Error 0.722
Change in Cancellous Adjusted Apposition Rate (Cn.AjAR) Biopsy Years 2 and 4 (combined) - Year 1	-1.21 z-score Standard Error 0.972

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ec.O.Th is measured from the bone biopsy. This measures the thickness of the unmineralized bone (osteoid) on the inner side of the cortex(endocortical). The changes in Cn.AjAR between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=11 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Endocortical Osteoid Thickness (Ec.O.Th) Biopsy Year 1 - Baseline	2.15 um Standard Error 0.628
Change in Endocortical Osteoid Thickness (Ec.O.Th) Biopsy Years 2 and 4 (combined) - Baseline	1.84 um Standard Error 0.552
Change in Endocortical Osteoid Thickness (Ec.O.Th) Biopsy Years 2 and 4 (combined) - Year 1	-0.31 um Standard Error 0.718

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose.Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ec.MAR is measured from the bone biopsy. This measures the rate mineral is being laid down per day on the inner cortical (endocortical) surface in a predefined region of cortical bone. The changes in Ec.MAR between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=11 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Endocortical Bone Mineral Apposition Rate (Ec.MAR) Biopsy Year 1 - Baseline	0.41 um/d Standard Error 0.115
Change in Endocortical Bone Mineral Apposition Rate (Ec.MAR) Biopsy Years 2 and 4 (combined) - Baseline	0.46 um/d Standard Error 0.104
Change in Endocortical Bone Mineral Apposition Rate (Ec.MAR) Biopsy Years 2 and 4 (combined) - Year 1	0.05 um/d Standard Error 0.126

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ec.OS/BS is measured from the bone biopsy. This measures the rate mineral is being laid down per day on the inner cortical (endocortical) surface in a predefined region of cortical bone. The changes in Ec.OS/BS between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=11 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Endocortical Osteoid Surface / Bone Surface (Ec.OS/BS) Biopsy Year 1 - Baseline	13.43 percentage of region of interest Standard Error 5.606
Change in Endocortical Osteoid Surface / Bone Surface (Ec.OS/BS) Biopsy Years 2 and 4 (combined) - Baseline	24.56 percentage of region of interest Standard Error 4.872
Change in Endocortical Osteoid Surface / Bone Surface (Ec.OS/BS) Biopsy Years 2 and 4 (combined) - Year 1	11.13 percentage of region of interest Standard Error 6.491

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4- year biopsies were collapsed into one biopsy year group. Ec.ES/BS is measured from the bone biopsy. This measure demonstrates the percentage of the endocortical bone surface that is resorbed (eroded). The region of interest is the predefined area of total bone that is being measured. The changes in Ec.ES/BS between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=11 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Endocortical Eroded Surface / Bone Surface (Ec.ES/BS) Biopsy Year 1 - Baseline	5.95 percentage of region of interest Standard Error 3.270
Change in Endocortical Eroded Surface / Bone Surface (Ec.ES/BS) Biopsy Years 2 and 4 (combined) - Baseline	9.29 percentage of region of interest Standard Error 3.063
Change in Endocortical Eroded Surface / Bone Surface (Ec.ES/BS) Biopsy Years 2 and 4 (combined) - Year 1	3.34 percentage of region of interest Standard Error 3.288

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ec.AjAR is measured from the bone biopsy. Ec.AjAR represents the endocortical mineral apposition rate (Ec.MAR) averaged over the entire osteoid surface. This is another histomorphometric way to evaluate the rate at which bone is laid down on the inner cortical surface per day. The changes in Ec.AjAR between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=8 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Endocortical Adjusted Apposition Rate (Ec.AjAR) Biopsy Year 1 - Baseline	0.50 um/d Standard Error 0.109
Change in Endocortical Adjusted Apposition Rate (Ec.AjAR) Biopsy Years 2 and 4 (combined) - Baseline	0.49 um/d Standard Error 0.088
Change in Endocortical Adjusted Apposition Rate (Ec.AjAR) Biopsy Years 2 and 4 (combined) - Year 1	-0.00 um/d Standard Error 0.135

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ic.O.Th is one of 21 secondary endpoints measured from the bone biopsy. This measures the thickness of the unmineralized bone (osteoid) within the middle of the cortex (intracortical). The changes in Ic.O.Th between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=11 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Intracortical Osteoid Thickness (Ic.O.Th) Biopsy Year 1 - Baseline	2.39 um Standard Error 0.687
Change in Intracortical Osteoid Thickness (Ic.O.Th) Biopsy Years 2 and 4 (combined) - Baseline	1.48 um Standard Error 0.564
Change in Intracortical Osteoid Thickness (Ic.O.Th) Biopsy Years 2 and 4 (combined) - Year 1	-0.91 um Standard Error 0.833

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ic.MAR is measured from the bone biopsy. This measures the rate mineral is being laid down per day within the middle of the cortex (intracortical) surface in a predefined region of cortical bone. The changes in Ic.MAR between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=11 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Intracortical Bone Mineral Apposition Rate (Ic.MAR) Biopsy Year 1 - Baseline	0.23 um/d Standard Error 0.174
Change in Intracortical Bone Mineral Apposition Rate (Ic.MAR) Biopsy Years 2 and 4 (combined) - Baseline	0.12 um/d Standard Error 0.161
Change in Intracortical Bone Mineral Apposition Rate (Ic.MAR) Biopsy Years 2 and 4 (combined) - Year 1	-0.12 um/d Standard Error 0.185

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ic.OS/BS measured from the bone biopsy. This measure demonstrates the percentage of the intracortical bone surface that is not mineralized (osteoid). The region of interest is the predefined area of total bone that is being measured. The changes in OS/BS between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=11 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Intracortical Osteoid Surface / Bone Surface (Ic.OS/BS) Biopsy Year 1 - Baseline	18.39 percentage of region of interest Standard Error 4.284
Change in Intracortical Osteoid Surface / Bone Surface (Ic.OS/BS) Biopsy Years 2 and 4 (combined) - Baseline	13.17 percentage of region of interest Standard Error 3.540
Change in Intracortical Osteoid Surface / Bone Surface (Ic.OS/BS) Years 2 and 4 (combined) - Year 1 Biopsy	-5.22 percentage of region of interest Standard Error 5.181

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ic.ES/BS is measured from the bone biopsy. This measure demonstrates the percentage of bone surface within the middle of the cortex that is resorbed (eroded). The region of interest is the predefined area of total bone that is being measured. The changes in Ic.ES/BS between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=11 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Intracortical Eroded Surface / Bone Surface (Ic.ES/BS) Biopsy Year 1 - Baseline	6.79 percentage of region of interest Standard Error 1.840
Change in Intracortical Eroded Surface / Bone Surface (Ic.ES/BS) Biopsy Years 2 and 4 (combined) - Baseline	7.40 percentage of region of interest Standard Error 1.500
Change in Intracortical Eroded Surface / Bone Surface (Ic.ES/BS) Biopsy Years 2 and 4 (combined) - Year 1	0.61 percentage of region of interest Standard Error 2.239

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ic.AjAR is one of 21 secondary endpoints measured from the bone biopsy. Ic.AjAR represents the intracortical mineral apposition rate (Ic.MAR) averaged over the the entire osteoid surface. This is another histomorphometric way to evaluate the rate at which bone is laid down within the middle of the cortex per day. The changes in Ic.AjAR between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline values)

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=10 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Intracortical Adjusted Apposition Rate (Ic.AjAR) Biopsy Year 1 - Baseline	0.16 um/d Standard Error 0.349
Change in Intracortical Adjusted Apposition Rate (Ic.AjAR) Biopsy Years 2 and 4 (combined) - Baseline	-0.18 um/d Standard Error 0.318
Change in Intracortical Adjusted Apposition Rate (Ic.AjAR) Biopsy Years 2 and 4 (combined) - Year 1	-0.34 um/d Standard Error 0.345

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. The Cortex 1 Spectral Calcium Mean is a measure of mean bone calcium content of the bone cortex 1 based on the mineralization density distribution (BMDD) from the back-scattered electron imaging scan of the bone biopsies. The changes in Ic.MAR between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=11 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Cortex 1 Spectral Calcium Mean From the Back-Scattered Electron Imaging of Bone-Biopsies Year 1 - Baseline Biopsy	-0.98 Percentage of the region of interest Standard Error 0.357
Change in Cortex 1 Spectral Calcium Mean From the Back-Scattered Electron Imaging of Bone-Biopsies Years 2 and 4 (combined) - Baseline Biopsy	-1.15 Percentage of the region of interest Standard Error 0.633
Change in Cortex 1 Spectral Calcium Mean From the Back-Scattered Electron Imaging of Bone-Biopsies Years 2 and 4 (combined) - Year 1 Biopsy	-0.16 Percentage of the region of interest Standard Error 0.525

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. The Cortex 1 Spectral Calcium Peak is a measure of the most frequent calcium content of the bone cortex 1 based on the bone mineralization density distribution (BMDD) from the back-scattered electron imaging scan of the bone biopsies. The changes in Ic.MAR between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=11 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Cortex 1 Spectral Calcium Peak From the Back-Scattered Electron Imaging of Bone-Biopsies Year 1 Biopsy - Baseline Biopsy	-0.47 Percentage of the region of interest Standard Error 0.365
Change in Cortex 1 Spectral Calcium Peak From the Back-Scattered Electron Imaging of Bone-Biopsies Years 2 and 4 (combined) - Baseline Biopsy	-0.96 Percentage of the region of interest Standard Error 0.673
Change in Cortex 1 Spectral Calcium Peak From the Back-Scattered Electron Imaging of Bone-Biopsies Years 2 and 4 (combined) - Year 1 Biopsy	-0.49 Percentage of the region of interest Standard Error 0.588

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. The Cortex 1 Spectral Calcium Low is a measure of the area of low bone cortex 1 mineralization based on the mineralization density distribution (BMDD) from the back-scattered electron imaging scan of the bone biopsies. The changes in Ic.MAR between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=11 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Cortex 1 Spectral Calcium Width From the Back-Scattered Electron Imaging of Bone-Biopsies Year 1 - Baseline Biopsy	1.24 Percentage of the region of interest Standard Error 0.343
Change in Cortex 1 Spectral Calcium Width From the Back-Scattered Electron Imaging of Bone-Biopsies Years 2 and 4 (combined) - Baseline Biopsy	1.13 Percentage of the region of interest Standard Error 0.302
Change in Cortex 1 Spectral Calcium Width From the Back-Scattered Electron Imaging of Bone-Biopsies Years 2 and 4 (combined) - Year 1 Biopsy	-0.11 Percentage of the region of interest Standard Error 0.415

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. The Cortex 1 Spectral Calcium Low is a measure of the area of low bone cortex 1 mineralization based on the mineralization density distribution (BMDD) from the back-scattered electron imaging scan of the bone biopsies. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=11 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Cortex 1 Spectral Calcium Low From the Back-Scattered Electron Imaging of Bone-Biopsies Year 1 - Baseline Biopsy	4.95 Percentage of the region of interest Standard Error 2.172
Change in Cortex 1 Spectral Calcium Low From the Back-Scattered Electron Imaging of Bone-Biopsies Years 2 and 4 (combined) - Baseline Biopsy	7.51 Percentage of the region of interest Standard Error 3.245
Change in Cortex 1 Spectral Calcium Low From the Back-Scattered Electron Imaging of Bone-Biopsies Years 2 and 4 (combined) - Year 1 Biopsy	2.55 Percentage of the region of interest Standard Error 4.088

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. The Cortex 1 Spectral Calcium High is a measure of the area of high bone cortex 1 mineralization based on the mineralization density distribution (BMDD) from the back-scattered electron imaging scan of the bone biopsies. The changes in Ic.MAR between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=11 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Change in Cortex 1 Spectral Calcium High From the Back-Scattered Electron Imaging of Bone-Biopsies Year 1 - Baseline Biopsy	-0.40 Percentage of the region of interest Standard Error 4.052
Change in Cortex 1 Spectral Calcium High From the Back-Scattered Electron Imaging of Bone-Biopsies Years 2 and 4 (combined) - Baseline Biopsy	-3.54 Percentage of the region of interest Standard Error 3.592
Change in Cortex 1 Spectral Calcium High From the Back-Scattered Electron Imaging of Bone-Biopsies Years 2 and 4 (combined) - Year 1 Biopsy	-3.14 Percentage of the region of interest Standard Error 4.049

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD measures were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit The 1/3 Radius BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Raw 1/3 Radius Bone Mineralization Density (BMD) Assessed by DXA. Raw BMD at Baseline	0.746 g/cm^2 Standard Error 0.0138
Raw 1/3 Radius Bone Mineralization Density (BMD) Assessed by DXA. Raw BMD at 6 months	0.741 g/cm^2 Standard Error 0.0149
Raw 1/3 Radius Bone Mineralization Density (BMD) Assessed by DXA. Raw BMD at last HPTH visit	0.731 g/cm^2 Standard Error 0.0258
Raw 1/3 Radius Bone Mineralization Density (BMD) Assessed by DXA. Raw BMD at Follow-up	0.716 g/cm^2 Standard Error 0.0181

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit. The AP Spine BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Raw AP Spine Bone Mineralization Density (BMD) Assessed by DXA Raw BMD at Baseline	1.175 g/cm^2 Standard Error 0.0253
Raw AP Spine Bone Mineralization Density (BMD) Assessed by DXA Raw BMD at 6 months	1.139 g/cm^2 Standard Error 0.0228
Raw AP Spine Bone Mineralization Density (BMD) Assessed by DXA Raw BMD at last HPTH visit	1.178 g/cm^2 Standard Error 0.0427
Raw AP Spine Bone Mineralization Density (BMD) Assessed by DXA Raw BMD at Follow-up	1.250 g/cm^2 Standard Error 0.0362

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD measures were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit. The Femoral BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Raw Femoral Neck Bone Mineralization Density (BMD) Assessed by DXA Raw BMD at Baseline	0.909 g/cm^2 Standard Error 0.0234
Raw Femoral Neck Bone Mineralization Density (BMD) Assessed by DXA Raw BMD at 6 months	0.881 g/cm^2 Standard Error 0.0233
Raw Femoral Neck Bone Mineralization Density (BMD) Assessed by DXA Raw BMD at last HPTH visit	0.935 g/cm^2 Standard Error 0.0328
Raw Femoral Neck Bone Mineralization Density (BMD) Assessed by DXA Raw BMD at Follow-up	0.925 g/cm^2 Standard Error 0.0339

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit. The Lateral Spine BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA .

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Raw Lateral Spine Bone Mineralization Density (BMD) Assessed by DXA Raw BMD at Baseline	0.916 g/cm^2 Standard Error 0.0179
Raw Lateral Spine Bone Mineralization Density (BMD) Assessed by DXA Raw BMD at 6 months	0.918 g/cm^2 Standard Error 0.0215
Raw Lateral Spine Bone Mineralization Density (BMD) Assessed by DXA Raw BMD at last HPTH visit	1.032 g/cm^2 Standard Error 0.0404
Raw Lateral Spine Bone Mineralization Density (BMD) Assessed by DXA Raw BMD at Follow-up	1.094 g/cm^2 Standard Error 0.0676

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD measures were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit. The Total Hip BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Raw Total Hip Bone Mineralization Density (BMD) Assessed by DXA Raw BMD at Baseline	1.043 g/cm^2 Standard Error 0.0246
Raw Total Hip Bone Mineralization Density (BMD) Assessed by DXA Raw BMD at 6 months	1.010 g/cm^2 Standard Error 0.0238
Raw Total Hip Bone Mineralization Density (BMD) Assessed by DXA Raw BMD at last HPTH visit	1.043 g/cm^2 Standard Error 0.0301
Raw Total Hip Bone Mineralization Density (BMD) Assessed by DXA Raw BMD at Follow-up	1.045 g/cm^2 Standard Error 0.0279

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD measures were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit. The Whole Body BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Raw Whole Body Bone Mineralization Density (BMD) Assessed by DXA Raw BMD at Baseline	1.248 g/cm^2 Standard Error 0.0162
Raw Whole Body Bone Mineralization Density (BMD) Assessed by DXA Raw BMD at 6 months	1.230 g/cm^2 Standard Error 0.0198
Raw Whole Body Bone Mineralization Density (BMD) Assessed by DXA Raw BMD at last HPTH visit	1.193 g/cm^2 Standard Error 0.0213
Raw Whole Body Bone Mineralization Density (BMD) Assessed by DXA Raw BMD at Follow-up	1.228 g/cm^2 Standard Error 0.0241

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Perceived interference is measured using seven separate items that assess the degree to which fatigue in the past week was judged to interfere with general level of activity, ability to bathe and dress, normal work activity, ability to concentrate, relations with others, enjoyment of life, and mood. The interference ratings were summed to yield a total interference score ranging from 0 (no perceived interference due to fatigue) to 70 (maximum possible perceived interference due to fatigue).

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Perceived Interference (PI) of the Fatigue Symptom Inventory (FSI) Baseline visit	18.9 score on a scale Standard Error 3.40
Perceived Interference (PI) of the Fatigue Symptom Inventory (FSI) Six-month visit after start of HPTH	15.3 score on a scale Standard Error 3.20
Perceived Interference (PI) of the Fatigue Symptom Inventory (FSI) Last visit on HPTH prior to weaning	15.6 score on a scale Standard Error 3.74
Perceived Interference (PI) of the Fatigue Symptom Inventory (FSI) Post-HPTH follow-up visit	19.3 score on a scale Standard Error 4.45

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Severity is measured using four separate items of the FSI questionnaire that assesses how the participant felt on their most, least, and average fatigue days in the past week as well as current fatigue. Participants score their level of fatigue for each item on an 11-point scale (0=not at all fatigued, 10=as fatigued as I could be). An average is taken of sum of these 4 scores. The average severity score can range from 0 to 10. A higher average severity score indicates that the participant is experiencing more severe fatigue.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Average Severity Score of the Fatigue Symptom Inventory (FSI) Baseline visit	4.16 score on a scale Standard Error 0.398
Average Severity Score of the Fatigue Symptom Inventory (FSI) Six-month visit after start of HPTH	3.53 score on a scale Standard Error 0.356
Average Severity Score of the Fatigue Symptom Inventory (FSI) Last visit on HPTH prior to weaning	3.63 score on a scale Standard Error 0.427
Average Severity Score of the Fatigue Symptom Inventory (FSI) Post-HPTH follow-up visit	4.03 score on a scale Standard Error 0.638

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Severity is measured using four separate items of the FSI questionnaire that assesses how the participant felt on their most, least, and average fatigue days in the past week as well as current fatigue. Participants score their level of fatigue for each item on an 11-point scale (0=not at all fatigued, 10=as fatigued as I could be). The composite severity score reflects the sum of these 4 scores. The composite severity scores can range from 0 to 40. A higher composite severity scores indicates that the participant is experiencing more severe fatigue.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Composite Severity Score of the Fatigue Symptom Inventory (FSI) Baseline visit	15.4 Composite score from the FSI Standard Error 1.56
Composite Severity Score of the Fatigue Symptom Inventory (FSI) Six-month visit after start of HPTH	14.1 Composite score from the FSI Standard Error 1.43
Composite Severity Score of the Fatigue Symptom Inventory (FSI) Last visit on HPTH prior to weaning	14.6 Composite score from the FSI Standard Error 1.69
Composite Severity Score of the Fatigue Symptom Inventory (FSI) Post-HPTH follow-up visit	16.1 Composite score from the FSI Standard Error 2.55

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The total distance a participant was able to walk during a 6-minute walk

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Total Distance Walked During a 6-minute Walk Baseline visit	606.3 Distance in meters Standard Error 19.50
Total Distance Walked During a 6-minute Walk Six-month visit after start of HPTH	608.0 Distance in meters Standard Error 18.83
Total Distance Walked During a 6-minute Walk Last visit on HPTH prior to weaning	567.2 Distance in meters Standard Error 23.16
Total Distance Walked During a 6-minute Walk Post-HPTH follow-up visit	604.5 Distance in meters Standard Error 26.67

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The Bodily Pain (BP) domain scores are derived from the SF36 Health Survey taken by the participant. The SF-36 is a validated questionnaire assessing 4 physical domains: physical function, physical role limitations, bodily pain, and general health, and 4 mental domains: vitality, emotional role limitations, social function and mental health. From the 36 questions asked, a scoring tool derives SF36 domain scores for each of the eight domains. These domain scores are scaled to range from 0 to 100 with a population mean of 50 and a standard deviation of 10. Lower scores indicate more disability; and, higher scores indicate less disability. The BP domain scores indicate to what extent a participant's bodily pain hinders their performance of daily activities.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
SF36 Bodily Pain Domain Baseline visit	48.97 score on a scale Standard Error 1.749
SF36 Bodily Pain Domain Six-month visit after start of HPTH	49.53 score on a scale Standard Error 1.705
SF36 Bodily Pain Domain Last visit on HPTH prior to weaning	47.52 score on a scale Standard Error 1.628
SF36 Bodily Pain Domain Post-HPTH follow-up visit	47.02 score on a scale Standard Error 2.709

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Emotional Role Limitations (RE) Domain scores are derived from the SF36 Health Survey taken by the participant. The SF-36 is a validated questionnaire assessing 4 physical domains: physical function, physical role limitations, bodily pain, and general health, and 4 mental domains: vitality, emotional role limitations, social function and mental health. From the 36 questions asked, a scoring tool derives SF36 domain scores for each of the eight domains. These domain scores are scaled to range from 0 to 100 with a population mean of 50 and a standard deviation of 10. Lower scores indicate more disability; and, higher scores indicate less disability. The RE Domain score assesses the extent to which the emotional condition of the participant, e.g. feeling depressed or anxious, limits his/her daily functioning and ability to perform roles, such as in cutting down on the amount of time spent on work or other activities and accomplishing less than he/she would like to.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
SF36 Emotional Role Limitations Domain Baseline visit	48.27 score on a scale Standard Error 2.310
SF36 Emotional Role Limitations Domain Six-month visit after start of HPTH	51.34 score on a scale Standard Error 1.852
SF36 Emotional Role Limitations Domain Last visit on HPTH prior to weaning	51.02 score on a scale Standard Error 1.539
SF36 Emotional Role Limitations Domain Post-HPTH follow-up visit	47.24 score on a scale Standard Error 3.040

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

General Health (GH) Domain scores are derived from the SF36 Health Survey taken by the participant. The SF-36 is a validated questionnaire assessing 4 physical domains: physical function, physical role limitations, bodily pain, and general health, and 4 mental domains: vitality, emotional role limitations, social function and mental health. From the 36 questions asked, a scoring tool derives SF36 domain scores for each of the eight domains. These domain scores are scaled to range from 0 to 100 with a population mean of 50 and a standard deviation of 10. Lower scores indicate more disability; and, higher scores indicate less disability. The GH domain score assesses a participant's perception of their general health in terms of concepts such as excellent, very good, good, fair or poor, getting ill easier than other people, and just as healthy as anyone he/she knows.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
SF36 General Health Domain Baseline visit	43.80 score on a scale Standard Error 1.907
SF36 General Health Domain Six-month visit after start of HPTH	48.11 score on a scale Standard Error 1.801
SF36 General Health Domain Last visit on HPTH prior to weaning	45.25 score on a scale Standard Error 1.976
SF36 General Health Domain Post-HPTH follow-up visit	42.45 score on a scale Standard Error 2.578

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Mental Health (MH) Domain scores are derived from the SF36 Health Survey taken by the participant. The SF-36 is a validated questionnaire assessing 4 physical domains: physical function, physical role limitations, bodily pain, and general health, and 4 mental domains: vitality, emotional role limitations, social function and mental health. From the 36 questions asked, a scoring tool derives SF36 domain scores for each of the eight domains. These domain scores are scaled to range from 0 to 100 with a population mean of 50 and a standard deviation of 10. Lower scores indicate more disability; and, higher scores indicate less disability. The MH domain assesses the extent to which the participant is, among other things, feeling full of pep, is happy, is feeling calm and peaceful, is very nervous, or is feeling worn out and tired.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
SF36 Mental Health Domain Baseline visit	47.07 score on a scale Standard Error 2.120
SF36 Mental Health Domain Six-month visit after start of HPTH	49.51 score on a scale Standard Error 1.736
SF36 Mental Health Domain Last visit on HPTH prior to weaning	49.30 score on a scale Standard Error 2.029
SF36 Mental Health Domain Post-HPTH follow-up visit	47.04 score on a scale Standard Error 2.793

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Physical Function (PF) Domain scores are derived from the SF36 Health Survey taken by the participant. The SF-36 is a validated questionnaire assessing 4 physical domains: physical function, physical role limitations, bodily pain, and general health, and 4 mental domains: vitality, emotional role limitations, social function and mental health. From the 36 questions asked, a scoring tool derives SF36 domain scores for each of the eight domains. These domain scores are scaled to range from 0 to 100 with a population mean of 50 and a standard deviation of 10. Lower scores indicate more disability; and, higher scores indicate less disability. The PF domain assesses the extent to which the participant's perceptions of his/her ability to perform vigorous and moderate physical activities are influenced by his/her physical condition.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
SF36 Physical Function Domain Baseline visit	49.14 score on a scale Standard Error 1.479
SF36 Physical Function Domain Six-month visit after start of HPTH	51.07 score on a scale Standard Error 1.265
SF36 Physical Function Domain Last visit on HPTH prior to weaning	48.97 score on a scale Standard Error 1.807
SF36 Physical Function Domain Post-HPTH follow-up visit	47.91 score on a scale Standard Error 2.333

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Physical Role Limitations (RP) Domain scores are derived from the SF36 Health Survey taken by the participant. The SF-36 is a validated questionnaire assessing 4 physical domains: physical function, physical role limitations, bodily pain, and general health, and 4 mental domains: vitality, emotional role limitations, social function and mental health. From the 36 questions asked, a scoring tool derives SF36 domain scores for each of the eight domains. These domain scores are scaled to range from 0 to 100 with a population mean of 50 and a standard deviation of 10. Lower scores indicate more disability; and, higher scores indicate less disability. The RP Domain assesses the extent to which a participant's' performance of his/her roles in daily activities is impeded by his/her physical state of health.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
SF36 Physical Role Limitations Domain Baseline visit	44.10 score on a scale Standard Error 2.085
SF36 Physical Role Limitations Domain Six-month visit after start of HPTH	45.73 score on a scale Standard Error 2.206
SF36 Physical Role Limitations Domain Last visit on HPTH prior to weaning	48.49 score on a scale Standard Error 1.699
SF36 Physical Role Limitations Domain Post-HPTH follow-up visit	45.56 score on a scale Standard Error 2.938

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Social Function (SF) Domain scores are derived from the SF36 Health Survey taken by the participant. The SF-36 is a validated questionnaire assessing 4 physical components: physical function, physical role limitations, bodily pain, and general health, and 4 mental components: vitality, emotional role limitations, social function and mental health. From the 36 questions asked, a scoring tool is used to calculate each of the eight domain scores. The scoring tool transforms the score into a 0-100 scale on the assumption that each question carries equal weight. SF36 domain scores are scaled to have a population mean of 50 and a standard deviation of 10. The SF Domain assesses the level of a participant's social activities and interaction with significant others such as family members, friends, neighbours and other social relations. Lower scores indicate more disability; higher scores indicate less disability with respect to social function.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
SF36 Social Function Domain Baseline visit	46.40 score on a scale Standard Error 2.562
SF36 Social Function Domain Six-month visit after start of HPTH	48.67 score on a scale Standard Error 2.178
SF36 Social Function Domain Last visit on HPTH prior to weaning	49.12 score on a scale Standard Error 2.048
SF36 Social Function Domain Post-HPTH follow-up visit	42.00 score on a scale Standard Error 2.782

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Vitality (VT) Domain scores are derived from the SF36 Health Survey taken by the participant. SF36 domain scores are scaled to have a population mean of 50 and a standard deviation of 10. Higher scores reflect a better quality of life.The SF-36 is a validated questionnaire assessing 4 physical components: physical function, physical role limitations, bodily pain, and general health, and 4 mental components: vitality, emotional role limitations, social function and mental health. From the 36 questions asked, a scoring tool is used to calculate the eight domain scores. The scoring tool transforms the score into a 0-100 scale on the assumption that each question carries equal weight. SF36 domain scores are scaled to have a population mean of 50 and a standard deviation of 10. Lower scores indicate more disability; and, higher scores indicate less disability. The VT Domain assesses the participant's experience of feeling energetic and full of pep, or worn out and tired.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
SF36 Vitality Domain Baseline visit	43.37 score on a scale Standard Error 2.347
SF36 Vitality Domain Six-month visit after start of HPTH	46.89 score on a scale Standard Error 2.090
SF36 Vitality Domain Last visit on HPTH prior to weaning	48.45 score on a scale Standard Error 2.284
SF36 Vitality Domain Post-HPTH follow-up visit	44.98 score on a scale Standard Error 2.457

SECONDARY outcome

Timeframe: Baseline, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Serum Alkaline Phosphatase concentration

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Serum Alkaline Phosphatase Baseline visit	9.92 ug/L Standard Error 1.017
Serum Alkaline Phosphatase Last visit on HPTH prior to weaning	33.34 ug/L Standard Error 5.148
Serum Alkaline Phosphatase Post-HPTH follow-up visit	12.69 ug/L Standard Error 3.254

SECONDARY outcome

Timeframe: Baseline, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Serum Calcium concentration

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Serum Calcium Baseline visit	2.02 Mmol/L Standard Error 0.035
Serum Calcium Last visit on HPTH prior to weaning	2.06 Mmol/L Standard Error 0.028
Serum Calcium Post-HPTH follow-up visit	2.02 Mmol/L Standard Error 0.041

SECONDARY outcome

Timeframe: Baseline, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Serum Osteocalcin concentration

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Serum Osteocalcin Baseline visit	14.86 ng/mL Standard Error 0.877
Serum Osteocalcin Last visit on HPTH prior to weaning	164.6 ng/mL Standard Error 28.390
Serum Osteocalcin Post-HPTH follow-up visit	49.15 ng/mL Standard Error 22.412

SECONDARY outcome

Timeframe: Baseline, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Serum Phosphorus concentration

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Serum Phosphorus Baseline visit	4.74 mg/dL Standard Error 0.118
Serum Phosphorus Last visit on HPTH prior to weaning	4.62 mg/dL Standard Error 0.108
Serum Phosphorus Post-HPTH follow-up visit	4.59 mg/dL Standard Error 0.145

SECONDARY outcome

Timeframe: Baseline, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Urine was collected over 24 hours and the total NTX Telopeptide measured

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
24 Hour Urine NTX Telopeptide Baseline visit	21.35 nmol Bone Collagen Equiv/mmol Creatinine Standard Error 6.117
24 Hour Urine NTX Telopeptide Last visit on HPTH prior to weaning	305.1 nmol Bone Collagen Equiv/mmol Creatinine Standard Error 60.885
24 Hour Urine NTX Telopeptide Post-HPTH follow-up visit	29.89 nmol Bone Collagen Equiv/mmol Creatinine Standard Error 14.758

SECONDARY outcome

Timeframe: Baseline, 12-Month Visit, 24-Month Visit, 36-Month Visit, 48-Month Visit, and 60-Month Visit

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Participants had ultrasound and CT imaging of the kidney were performed yearly. The rates of new, stable, and progressing nephrocalcinosis and nephrolithiasis (NCNL) were recorded.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Number of Participants With Nephrolithiasis/Nephrocalcinosis No detectable NCNL at any time during study	5 Participants
Number of Participants With Nephrolithiasis/Nephrocalcinosis Baseline NCNL that remains stable on HPTH therapy	7 Participants
Number of Participants With Nephrolithiasis/Nephrocalcinosis New/progressing NCNL on HPTH therapy	10 Participants
Number of Participants With Nephrolithiasis/Nephrocalcinosis NCNL that resolved on HPTH therapy	2 Participants

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

The 8 primary bone biopsy measures were to be adjusted HPTH dose by fitting the primary bone biopsy model with both linear and quadratic dose covariates added to the model. However, the study was terminated early resulting in only 5, 5, and 2 participants having their biopsies at 1, 2, and 4 years respectively. To add additional linear and quadratic dose covariates to the statistical model with an already small sample sizes would highly risk over-parameterizing the model. Thus no new analysis was performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

As a sensitivity analysis, the 8 primary bone biopsy measures were to be adjusted for female menopausal status, by fitting the primary bone biopsy model with a menopausal status covariate added to the model. However, the study was terminated early resulting in only 5, 5, and 2 participants having their biopsies at 1, 2, and 4 years respectively. Furthermore, 3 males would need to be removed from the model leaving 4, 3, 2 participants with bone biopsies with an additional degree of freedom consumed for the menopausal status covariate. Thus, the planned mixed models analysis was not performed since with such small samples sizes random fluctuations in the data could give misleading erroneous results.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD measures were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit The 1/3 Radius BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Z-score of 1/3 Radius Bone Mineralization Density (BMD) Assessed by DXA. Z-score BMD at Baseline	0.89 z-score Standard Error 0.197
Z-score of 1/3 Radius Bone Mineralization Density (BMD) Assessed by DXA. Z-score BMD at 6 months	0.82 z-score Standard Error 0.190
Z-score of 1/3 Radius Bone Mineralization Density (BMD) Assessed by DXA. Z-score BMD at last HPTH visit	0.26 z-score Standard Error 0.273
Z-score of 1/3 Radius Bone Mineralization Density (BMD) Assessed by DXA. Z-score BMD at Follow-up	0.50 z-score Standard Error 0.276

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH, and post-HPTH follow-up visits

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit. The AP Spine BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Z-score of AP Spine Bone Mineralization Density (BMD) Assessed by DXA Z-score BMD at Baseline	1.46 z-score Standard Error 0.221
Z-score of AP Spine Bone Mineralization Density (BMD) Assessed by DXA Z-score BMD at 6 months	1.15 z-score Standard Error 0.207
Z-score of AP Spine Bone Mineralization Density (BMD) Assessed by DXA Z-score BMD at last HPTH visit	1.24 z-score Standard Error 0.279
Z-score of AP Spine Bone Mineralization Density (BMD) Assessed by DXA Z-score BMD at Follow-up	2.30 z-score Standard Error 0.306

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH, and post-HPTH follow-up visits

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD measures were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit. The Femoral BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Z-score of Femoral Neck Bone Mineralization Density (BMD) Assessed by DXA Z-score BMD at Baseline	0.85 z-score Standard Error 0.192
Z-score of Femoral Neck Bone Mineralization Density (BMD) Assessed by DXA Z-score BMD at 6 months	0.59 z-score Standard Error 0.186
Z-score of Femoral Neck Bone Mineralization Density (BMD) Assessed by DXA Z-score BMD at last HPTH visit	0.99 z-score Standard Error 0.229
Z-score of Femoral Neck Bone Mineralization Density (BMD) Assessed by DXA Z-score BMD at Follow-up	1.10 z-score Standard Error 0.249

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH, and post-HPTH follow-up visits

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit. The Lateral Spine BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA . The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Z-score of Lateral Spine Bone Mineralization Density (BMD) Assessed by DXA Z-score BMD at Baseline	2.16 z-score Standard Error 0.215
Z-score of Lateral Spine Bone Mineralization Density (BMD) Assessed by DXA Z-score BMD at 6 months	2.22 z-score Standard Error 0.223
Z-score of Lateral Spine Bone Mineralization Density (BMD) Assessed by DXA Z-score BMD at last HPTH visit	3.87 z-score Standard Error 0.483
Z-score of Lateral Spine Bone Mineralization Density (BMD) Assessed by DXA Z-score BMD at Follow-up	4.72 z-score Standard Error 0.737

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH, and post-HPTH follow-up visits

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD measures were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit. The Total Hip BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Z-score of Total Hip Bone Mineralization Density (BMD) Assessed by DXA Z-score BMD at Baseline	0.85 z-score Standard Error 0.161
Z-score of Total Hip Bone Mineralization Density (BMD) Assessed by DXA Z-score BMD at 6 months	0.66 z-score Standard Error 0.165
Z-score of Total Hip Bone Mineralization Density (BMD) Assessed by DXA Z-score BMD at last HPTH visit	0.89 z-score Standard Error 0.212
Z-score of Total Hip Bone Mineralization Density (BMD) Assessed by DXA Z-score BMD at Follow-up	1.01 z-score Standard Error 0.172

SECONDARY outcome

Timeframe: Baseline, 6-months after start of HPTH, last visit on HPTH, and post-HPTH follow-up visits

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD measures were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit. The Whole Body BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes.

Outcome measures

Measure	Cohorts 2 (CC on Old Study) and 3 (Newly Enrolled) Combined n=24 Participants Cohort 2 consists of participants previously treated with conventional care (CC) throughout the original protocol. Cohort 3 consisted of all new participants. Efficacy outcomes were only analyzed for Cohorts 2 and 3. (Cohort 1 consisted of previously enrolled participants who were on HPTH therapy on the original protocol and continued on HPTH on the new study as a separate group. These participants were not randomized to a bone biopsy year, nor did they have additional biopsies performed. Cohort 1 participants were followed for safety outcomes only.)
Z-score of Whole Body Bone Mineralization Density (BMD) Assessed by DXA Z-score BMD at Baseline	1.59 z-score Standard Error 0.193
Z-score of Whole Body Bone Mineralization Density (BMD) Assessed by DXA Z-score BMD at 6 months	1.32 z-score Standard Error 0.180
Z-score of Whole Body Bone Mineralization Density (BMD) Assessed by DXA Z-score BMD at last HPTH visit	0.66 z-score Standard Error 0.172
Z-score of Whole Body Bone Mineralization Density (BMD) Assessed by DXA Z-score BMD at Follow-up	1.12 z-score Standard Error 0.173

Adverse Events

All Cohorts, Treated With HPTH on the New Study

Serious events: 8 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Measure	All Cohorts, Treated With HPTH on the New Study n=31 participants at risk Participants from Cohorts 1, 2, and 3, who were treated with HPTH on the new study.
Nervous system disorders Headache	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Nervous system disorders Hypocalcaemic seizure	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Nervous system disorders Sciatica	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Nervous system disorders Syncope	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Gastrointestinal disorders Colitis	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Gastrointestinal disorders Diarrhoea	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Gastrointestinal disorders Gastritis	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Infections and infestations Appendicitis perforated	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Infections and infestations Gastroenteritis	9.7% 3/31 • Number of events 3 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Infections and infestations Pneumonia	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Injury, poisoning and procedural complications Alcohol poisoning	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Injury, poisoning and procedural complications Medication error	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Metabolism and nutrition disorders Hypercalcaemia	6.5% 2/31 • Number of events 2 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Metabolism and nutrition disorders Hypocalcaemia	12.9% 4/31 • Number of events 7 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.

Other adverse events

Measure	All Cohorts, Treated With HPTH on the New Study n=31 participants at risk Participants from Cohorts 1, 2, and 3, who were treated with HPTH on the new study.
Blood and lymphatic system disorders Anaemia	9.7% 3/31 • Number of events 3 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Blood and lymphatic system disorders Iron deficiency anaemia	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Blood and lymphatic system disorders Lymphadenopathy	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Blood and lymphatic system disorders Neutropenia	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Cardiac disorders Palpitations	6.5% 2/31 • Number of events 2 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Cardiac disorders Supraventricular tachycardia	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Cardiac disorders Tachycardia	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Ear and labyrinth disorders Middle ear effusion	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Ear and labyrinth disorders Vertigo	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Eye disorders Vision blurred	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Gastrointestinal disorders Abdominal pain	9.7% 3/31 • Number of events 3 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Gastrointestinal disorders Coeliac disease	6.5% 2/31 • Number of events 2 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Gastrointestinal disorders Constipation	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Gastrointestinal disorders Diarrhoea	16.1% 5/31 • Number of events 7 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Gastrointestinal disorders Dry mouth	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Gastrointestinal disorders Gastrooesophageal reflux disease	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Gastrointestinal disorders Gingival disorder	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Gastrointestinal disorders Haemorrhoids	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Gastrointestinal disorders Melaena	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Gastrointestinal disorders Nausea	16.1% 5/31 • Number of events 7 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Gastrointestinal disorders Toothache	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Gastrointestinal disorders Vomiting	12.9% 4/31 • Number of events 10 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
General disorders Chest pain	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
General disorders Chronic fatigue syndrome	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
General disorders Fatigue	12.9% 4/31 • Number of events 4 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
General disorders Injection site dryness	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
General disorders Injection site erythema	6.5% 2/31 • Number of events 2 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
General disorders Non-cardiac chest pain	6.5% 2/31 • Number of events 2 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
General disorders Pain	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
General disorders Pyrexia	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Hepatobiliary disorders Hepatic cyst	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Immune system disorders Hypersensitivity	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Infections and infestations Bronchitis	9.7% 3/31 • Number of events 4 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Infections and infestations Ear infection	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Infections and infestations Gastroenteritis	9.7% 3/31 • Number of events 3 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Infections and infestations Herpes zoster	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Infections and infestations Paronychia	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Infections and infestations Pharyngitis	6.5% 2/31 • Number of events 2 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Infections and infestations Pneumonia	9.7% 3/31 • Number of events 3 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Infections and infestations Sinusitis	22.6% 7/31 • Number of events 8 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Infections and infestations Tooth infection	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Infections and infestations Upper respiratory tract infection	9.7% 3/31 • Number of events 4 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Infections and infestations Urinary tract infection	12.9% 4/31 • Number of events 6 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Infections and infestations Viral infection	9.7% 3/31 • Number of events 3 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Infections and infestations Wound infection	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Injury, poisoning and procedural complications Bone contusion	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Injury, poisoning and procedural complications Contrast media reaction	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Injury, poisoning and procedural complications Contusion	12.9% 4/31 • Number of events 4 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Injury, poisoning and procedural complications Epicondylitis	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Injury, poisoning and procedural complications Fibula fracture	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Injury, poisoning and procedural complications Forearm fracture	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Injury, poisoning and procedural complications Incision site pruritus	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Injury, poisoning and procedural complications Injury	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Injury, poisoning and procedural complications Joint injury	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Injury, poisoning and procedural complications Ligament sprain	9.7% 3/31 • Number of events 3 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Injury, poisoning and procedural complications Post procedural complication	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Injury, poisoning and procedural complications Post procedural haematoma	6.5% 2/31 • Number of events 2 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Injury, poisoning and procedural complications Procedural pain	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Injury, poisoning and procedural complications Stress fracture	6.5% 2/31 • Number of events 3 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Injury, poisoning and procedural complications Upper limb fracture	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Investigations Blood creatine phosphokinase increased	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Investigations Bone density decreased	6.5% 2/31 • Number of events 2 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Investigations Cardiac murmur	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Investigations Haemoglobin decreased	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Investigations Lipase increased	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Investigations Transaminases increased	6.5% 2/31 • Number of events 2 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Investigations Weight decreased	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Metabolism and nutrition disorders Gout	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Metabolism and nutrition disorders Hypercalcaemia	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Metabolism and nutrition disorders Hyperuricaemia	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Metabolism and nutrition disorders Hypocalcaemia	12.9% 4/31 • Number of events 8 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Metabolism and nutrition disorders Hypokalaemia	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Metabolism and nutrition disorders Vitamin D deficiency	9.7% 3/31 • Number of events 3 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Musculoskeletal and connective tissue disorders Arthralgia	9.7% 3/31 • Number of events 3 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Musculoskeletal and connective tissue disorders Arthritis	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Musculoskeletal and connective tissue disorders Back pain	16.1% 5/31 • Number of events 5 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Musculoskeletal and connective tissue disorders Bone pain	12.9% 4/31 • Number of events 5 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Musculoskeletal and connective tissue disorders Bursitis	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Musculoskeletal and connective tissue disorders Chondrocalcinosis pyrophosphate	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Musculoskeletal and connective tissue disorders Groin pain	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Musculoskeletal and connective tissue disorders Muscular weakness	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Musculoskeletal and connective tissue disorders Musculoskeletal deformity	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Musculoskeletal and connective tissue disorders Musculoskeletal disorder	6.5% 2/31 • Number of events 2 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.5% 2/31 • Number of events 4 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Musculoskeletal and connective tissue disorders Pain in extremity	22.6% 7/31 • Number of events 10 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Musculoskeletal and connective tissue disorders Patellofemoral pain syndrome	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Musculoskeletal and connective tissue disorders Temporomandibular joint syndrome	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Musculoskeletal and connective tissue disorders Tendonitis	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adrenal neoplasm	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm of skin	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma of liver	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocytic naevus	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	6.5% 2/31 • Number of events 2 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Nervous system disorders Convulsion	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Nervous system disorders Dizziness	9.7% 3/31 • Number of events 4 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Nervous system disorders Headache	12.9% 4/31 • Number of events 4 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Nervous system disorders Hyperreflexia	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Nervous system disorders Hypoaesthesia	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Nervous system disorders Paraesthesia	6.5% 2/31 • Number of events 2 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Nervous system disorders Thoracic outlet syndrome	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Psychiatric disorders Anxiety	6.5% 2/31 • Number of events 2 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Psychiatric disorders Depression	6.5% 2/31 • Number of events 2 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Psychiatric disorders Insomnia	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Psychiatric disorders Mood altered	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Renal and urinary disorders Flank pain	6.5% 2/31 • Number of events 2 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Renal and urinary disorders Hypocitraturia	48.4% 15/31 • Number of events 16 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Renal and urinary disorders Micturition urgency	9.7% 3/31 • Number of events 3 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Renal and urinary disorders Nephrocalcinosis	19.4% 6/31 • Number of events 6 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Renal and urinary disorders Nephrolithiasis	45.2% 14/31 • Number of events 14 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Renal and urinary disorders Pollakiuria	9.7% 3/31 • Number of events 3 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Renal and urinary disorders Renal cyst	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Renal and urinary disorders Ureteric obstruction	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Renal and urinary disorders Urinary hesitation	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Renal and urinary disorders Urinary retention	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Reproductive system and breast disorders Breast cyst	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Reproductive system and breast disorders Menstruation irregular	6.5% 2/31 • Number of events 2 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Reproductive system and breast disorders Ovarian cyst	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Respiratory, thoracic and mediastinal disorders Cough	9.7% 3/31 • Number of events 3 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Skin and subcutaneous tissue disorders Acne	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Skin and subcutaneous tissue disorders Dermal cyst	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Skin and subcutaneous tissue disorders Hyperhidrosis	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Skin and subcutaneous tissue disorders Neurodermatitis	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Skin and subcutaneous tissue disorders Photosensitivity reaction	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Skin and subcutaneous tissue disorders Pruritus allergic	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Skin and subcutaneous tissue disorders Rash	6.5% 2/31 • Number of events 2 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Vascular disorders Flushing	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Vascular disorders Hypertension	6.5% 2/31 • Number of events 4 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Vascular disorders Varicose vein	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.
Vascular disorders Venous insufficiency	3.2% 1/31 • Number of events 1 • From time of the start of HPTH therapy through the date of last dose of HPTH (i.e., the end of the weaning period off HPTH). The last dose occurred up to 64 months after the start of HPTH therapy. Treatment emergent adverse events are those events that begin on or after the first dose of HPTH through the date last dose of HPTH.

Additional Information

Robert James

Rho, Inc

Phone: (919) 595-6468

Email: robert_james@rhoworld.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place