Trial Outcomes & Findings for Effects of Teriparatide or Denosumab on Bone in Postmenopausal Women With Osteoporosis (NCT NCT01753856)

Last Updated: 2015-10-08

Results Overview

MS /BS is a measure of the proportion of BS on which new mineralized bone is deposited at the time of DEM or TET labeling, and calculated as the sum of the total extent of double label (DL) plus half the extent of single label (SL) divided by BS. At baseline (18 days prior to randomization / study drug administration), DEM was administered (3 days on, 12 days off, 3 days on). 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered (same dosing schedule as DEM). Both DEM and TET temporarily bind to new bone and fluoresce under UV light. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or no label (NL) suggested varying degrees of suppression of bone formation.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

69 participants

Primary outcome timeframe

Baseline, 3 months post first dose of study drug

Results posted on

2015-10-08

Participant Flow

Tetracycline (TET) and demeclocycline (DEM) temporarily bind to new bone and are detected as different colors under ultraviolet light in bone biopsy samples. In this study, participants were administered DEM prior to randomization (baseline) and again with TET 22 days prior to bone biopsy obtained 3 months post first dose of study drug.

Participant milestones

Participant milestones
Measure	Teriparatide Teriparatide: 20-microgram (µg) subcutaneous (SC) injection once daily for 6 months. DEM: 150-milligram (mg) tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 milligrams per day (mg/day) administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 International Units per day (IU/day) administered orally for 6 months.	Denosumab Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Overall Study STARTED	33	36
Overall Study Received at Least 1 Dose of Study Drug	33	36
Overall Study Completed 3-Month Bone Biopsy	31	35
Overall Study COMPLETED	30	34
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Teriparatide Teriparatide: 20-microgram (µg) subcutaneous (SC) injection once daily for 6 months. DEM: 150-milligram (mg) tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 milligrams per day (mg/day) administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 International Units per day (IU/day) administered orally for 6 months.	Denosumab Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Overall Study Adverse Event	1	0
Overall Study Withdrawal by Subject	0	2
Overall Study Sponsor Decision	2	0

Baseline Characteristics

Effects of Teriparatide or Denosumab on Bone in Postmenopausal Women With Osteoporosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Teriparatide n=33 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=36 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Total n=69 Participants Total of all reporting groups
Age, Continuous	61.58 years STANDARD_DEVIATION 5.84 • n=5 Participants	65.17 years STANDARD_DEVIATION 8.32 • n=7 Participants	63.45 years STANDARD_DEVIATION 7.42 • n=5 Participants
Sex: Female, Male Female	33 Participants n=5 Participants	36 Participants n=7 Participants	69 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	31 Participants n=5 Participants	32 Participants n=7 Participants	63 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	31 Participants n=5 Participants	31 Participants n=7 Participants	62 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	21 participants n=5 Participants	27 participants n=7 Participants	48 participants n=5 Participants
Region of Enrollment Canada	12 participants n=5 Participants	9 participants n=7 Participants	21 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 3 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with MS/BS measurements in the CC of the iliac crest.

Outcome measures

Outcome measures
Measure	Teriparatide n=31 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=35 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Change From Baseline to 3 Months in Mineralizing Surface (MS) /Bone Surface (BS) in the Cancellous Compartment (CC) of the Iliac Crest Bone Biopsies	12.43 percentage of BS Interval 7.81 to 18.97	-2.51 percentage of BS Interval -5.08 to -1.22

SECONDARY outcome

Timeframe: 3 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with an assessment of the number of samples with specified labels in the various compartments of the iliac crest.

Outcome measures

Outcome measures
Measure	Teriparatide n=31 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=35 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Number of Samples With Single or Double Tetracycline Labels, SL and DL, or No Tetracycline Labels in the CC, Endocortical Compartment (EC), Intracortical Compartment (IC) and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies DL and SL, in CC (n=31, 35)	31 Samples	24 Samples
Number of Samples With Single or Double Tetracycline Labels, SL and DL, or No Tetracycline Labels in the CC, Endocortical Compartment (EC), Intracortical Compartment (IC) and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies SL Only, in CC (n=31, 35)	0 Samples	9 Samples
Number of Samples With Single or Double Tetracycline Labels, SL and DL, or No Tetracycline Labels in the CC, Endocortical Compartment (EC), Intracortical Compartment (IC) and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies No Label, in CC (n=31, 35)	0 Samples	2 Samples
Number of Samples With Single or Double Tetracycline Labels, SL and DL, or No Tetracycline Labels in the CC, Endocortical Compartment (EC), Intracortical Compartment (IC) and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies SL Only, in PC (n=30, 35)	19 Samples	4 Samples
Number of Samples With Single or Double Tetracycline Labels, SL and DL, or No Tetracycline Labels in the CC, Endocortical Compartment (EC), Intracortical Compartment (IC) and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies DL Only, in CC (n=31, 35)	0 Samples	0 Samples
Number of Samples With Single or Double Tetracycline Labels, SL and DL, or No Tetracycline Labels in the CC, Endocortical Compartment (EC), Intracortical Compartment (IC) and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies DL and SL, in EC (n=30, 35)	30 Samples	25 Samples
Number of Samples With Single or Double Tetracycline Labels, SL and DL, or No Tetracycline Labels in the CC, Endocortical Compartment (EC), Intracortical Compartment (IC) and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies DL Only, in EC (n=30, 35)	0 Samples	0 Samples
Number of Samples With Single or Double Tetracycline Labels, SL and DL, or No Tetracycline Labels in the CC, Endocortical Compartment (EC), Intracortical Compartment (IC) and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies SL Only, in EC (n=30, 35)	0 Samples	6 Samples
Number of Samples With Single or Double Tetracycline Labels, SL and DL, or No Tetracycline Labels in the CC, Endocortical Compartment (EC), Intracortical Compartment (IC) and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies No Label, in EC (n=30, 35)	0 Samples	4 Samples
Number of Samples With Single or Double Tetracycline Labels, SL and DL, or No Tetracycline Labels in the CC, Endocortical Compartment (EC), Intracortical Compartment (IC) and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies DL and SL, in IC (n=30, 35)	30 Samples	24 Samples
Number of Samples With Single or Double Tetracycline Labels, SL and DL, or No Tetracycline Labels in the CC, Endocortical Compartment (EC), Intracortical Compartment (IC) and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies DL Only, in IC (n=30, 35)	0 Samples	0 Samples
Number of Samples With Single or Double Tetracycline Labels, SL and DL, or No Tetracycline Labels in the CC, Endocortical Compartment (EC), Intracortical Compartment (IC) and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies SL Only, in IC (n=30, 35)	0 Samples	10 Samples
Number of Samples With Single or Double Tetracycline Labels, SL and DL, or No Tetracycline Labels in the CC, Endocortical Compartment (EC), Intracortical Compartment (IC) and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies No Label, in IC (n=30, 35)	0 Samples	1 Samples
Number of Samples With Single or Double Tetracycline Labels, SL and DL, or No Tetracycline Labels in the CC, Endocortical Compartment (EC), Intracortical Compartment (IC) and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies DL and SL, in PC (n=30, 35)	10 Samples	1 Samples
Number of Samples With Single or Double Tetracycline Labels, SL and DL, or No Tetracycline Labels in the CC, Endocortical Compartment (EC), Intracortical Compartment (IC) and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies DL Only, in PC (n=30, 35)	0 Samples	0 Samples
Number of Samples With Single or Double Tetracycline Labels, SL and DL, or No Tetracycline Labels in the CC, Endocortical Compartment (EC), Intracortical Compartment (IC) and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies No Label, in PC (n=30, 35)	1 Samples	30 Samples

SECONDARY outcome

Timeframe: Baseline, 3 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with MS/BS measurements in the specified compartments of the iliac crest.

MS /BS is a measure of the proportion of BS on which new mineralized bone is deposited at the time of DEM or TET labeling and is calculated as the sum of the total extent of DL plus half the extent of SL divided by BS. At baseline (18 days prior to randomization / study drug administration), DEM was administered (3 days on, 12 days off, 3 days on). 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered (same dosing schedule as DEM). Both DEM and TET temporarily bind to new bone and fluoresce under UV light. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or NL suggested varying degrees of suppression of bone formation.

Outcome measures

Outcome measures
Measure	Teriparatide n=30 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=35 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Change From Baseline to 3 Months in MS/BS in the Endocortical Compartment (EC), Intracortical Compartment (IC), and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies EC	26.12 percentage of BS Interval 13.76 to 47.63	-2.97 percentage of BS Interval -5.39 to 0.08
Change From Baseline to 3 Months in MS/BS in the Endocortical Compartment (EC), Intracortical Compartment (IC), and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies IC	9.39 percentage of BS Interval 4.46 to 19.31	-6.70 percentage of BS Interval -12.8 to -3.87
Change From Baseline to 3 Months in MS/BS in the Endocortical Compartment (EC), Intracortical Compartment (IC), and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies PC	2.40 percentage of BS Interval 0.81 to 7.85	-0.39 percentage of BS Interval -1.75 to 0.0

SECONDARY outcome

Timeframe: 3 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with MS/BS measurements in the specified compartments of the iliac crest.

Outcome measures

Outcome measures
Measure	Teriparatide n=31 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=35 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
MS/BS in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies 3 Months Post First Dose of Study Drug EC (n=30, 35)	39.50 percentage of BS Interval 23.92 to 60.39	5.42 percentage of BS Interval 2.63 to 10.15
MS/BS in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies 3 Months Post First Dose of Study Drug CC (n=31, 35)	18.73 percentage of BS Interval 11.13 to 26.64	0.96 percentage of BS Interval 0.44 to 1.93
MS/BS in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies 3 Months Post First Dose of Study Drug IC (n=30, 35)	21.69 percentage of BS Interval 15.61 to 30.17	3.05 percentage of BS Interval 2.03 to 7.38
MS/BS in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies 3 Months Post First Dose of Study Drug PC (n=30, 35)	4.69 percentage of BS Interval 1.24 to 8.98	0.00 percentage of BS Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: 3 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with the classification of TET DLs as remodeling-based or modeling-based formation in the specified compartments of the iliac crest.

In this study, post-treatment DLs in the CC, EC, and PC were classified as remodeling-based or modeling-based bone formations which was determined by whether the underlying reversal line was scalloped or smooth and by the collagen fiber orientation. Percentage = (remodeling-based formation units or modeling-based formation units/ total bone formation units) \* 100.

Outcome measures

Outcome measures
Measure	Teriparatide n=31 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=32 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Percentage of Bone With Remodeling-Based and Modeling-Based Formations in the CC, EC and PC of the Iliac Crest Bone Biopsies Remodeling-Based Bone Formation in CC (n=31, 32)	89.02 percentage of the total formation unit Interval 86.52 to 92.86	90.83 percentage of the total formation unit Interval 70.71 to 100.0
Percentage of Bone With Remodeling-Based and Modeling-Based Formations in the CC, EC and PC of the Iliac Crest Bone Biopsies Modeling-Based Bone Formation in CC (n=31, 32)	10.98 percentage of the total formation unit Interval 7.14 to 13.48	9.17 percentage of the total formation unit Interval 0.0 to 29.29
Percentage of Bone With Remodeling-Based and Modeling-Based Formations in the CC, EC and PC of the Iliac Crest Bone Biopsies Remodeling-Based Bone Formation in EC (n=30, 29)	83.33 percentage of the total formation unit Interval 65.0 to 90.0	100.00 percentage of the total formation unit Interval 80.0 to 100.0
Percentage of Bone With Remodeling-Based and Modeling-Based Formations in the CC, EC and PC of the Iliac Crest Bone Biopsies Modeling-Based Bone Formation in EC (n=30, 29)	16.67 percentage of the total formation unit Interval 10.0 to 35.0	0.00 percentage of the total formation unit Interval 0.0 to 20.0
Percentage of Bone With Remodeling-Based and Modeling-Based Formations in the CC, EC and PC of the Iliac Crest Bone Biopsies Remodeling-Based Bone Formation in PC (n=29, 5)	0.00 percentage of the total formation unit Interval 0.0 to 11.11	0.00 percentage of the total formation unit Interval 0.0 to 0.0
Percentage of Bone With Remodeling-Based and Modeling-Based Formations in the CC, EC and PC of the Iliac Crest Bone Biopsies Modeling-Based Bone Formation in PC (n=29, 5)	100.0 percentage of the total formation unit Interval 88.89 to 100.0	100.00 percentage of the total formation unit Interval 100.0 to 100.0

SECONDARY outcome

Timeframe: 3 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with the classification of TET DLs as remodeling- or modeling-based formation in the specified compartments of the iliac crest.

The percentage of mineralizing surface where post-treatment DLs in the CC, EC, and PC were classified as remodeling-based or modeling based bone formation based on collagen fiber orientation and whether the underlying reversal line was scalloped or smooth. Percentage = percentage remodeling- or modeling-based formation units \* MS/BS

Outcome measures

Outcome measures
Measure	Teriparatide n=31 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=35 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Percentage of Mineralizing Surface With Remodeling-Based Formation and Modeling-Based Formation in the CC, EC and PC of the Iliac Crest Bone Biopsies Remodeling-Based Bone Formation in CC (n=31, 35)	16.67 percentage of the total formation unit Interval 0.0 to 100.0	0.87 percentage of the total formation unit Interval 0.0 to 100.0
Percentage of Mineralizing Surface With Remodeling-Based Formation and Modeling-Based Formation in the CC, EC and PC of the Iliac Crest Bone Biopsies Modeling-Based Bone Formation in CC (n=31, 35)	2.06 percentage of the total formation unit Interval 0.0 to 100.0	0.09 percentage of the total formation unit Interval 0.0 to 100.0
Percentage of Mineralizing Surface With Remodeling-Based Formation and Modeling-Based Formation in the CC, EC and PC of the Iliac Crest Bone Biopsies Remodeling-Based Bone Formation in EC (n=30, 35)	32.92 percentage of the total formation unit Interval 0.0 to 100.0	5.42 percentage of the total formation unit Interval 0.0 to 100.0
Percentage of Mineralizing Surface With Remodeling-Based Formation and Modeling-Based Formation in the CC, EC and PC of the Iliac Crest Bone Biopsies Modeling-Based Bone Formation in EC (n=30, 35)	6.58 percentage of the total formation unit Interval 0.0 to 100.0	0.00 percentage of the total formation unit Interval 0.0 to 100.0
Percentage of Mineralizing Surface With Remodeling-Based Formation and Modeling-Based Formation in the CC, EC and PC of the Iliac Crest Bone Biopsies Remodeling-Based Bone Formation in PC (n=30, 35)	0.00 percentage of the total formation unit Interval 0.0 to 100.0	0.00 percentage of the total formation unit Interval 0.0 to 100.0
Percentage of Mineralizing Surface With Remodeling-Based Formation and Modeling-Based Formation in the CC, EC and PC of the Iliac Crest Bone Biopsies Modeling-Based Bone Formation in PC (n=30, 35)	4.69 percentage of the total formation unit Interval 0.0 to 100.0	0.00 percentage of the total formation unit Interval 0.0 to 100.0

SECONDARY outcome

Timeframe: 3 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy evaluated for overfilled remodeling sites in the specified compartments of the iliac crest.

The percentage of overfilled remodeling sites in the CC, EC, and PC were defined as the percentage of observed remodeling units in which the second DL (TET) extended beyond the limits of the scalloped reversal line and into the adjacent, previously unresorbed surface of the bone. Percentage = (overfilled remodeling bone formation unit / total bone formation unit) \* 100.

Outcome measures

Outcome measures
Measure	Teriparatide n=31 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=32 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Percentage of Overfilled Remodeling Sites in the CC, EC and PC of the Iliac Crest Bone Biopsies CC (n=31, 32)	17.74 percentage of overfilled remodeling site Interval 10.94 to 23.85	0.00 percentage of overfilled remodeling site Interval 0.0 to 14.29
Percentage of Overfilled Remodeling Sites in the CC, EC and PC of the Iliac Crest Bone Biopsies EC (n=30, 29)	21.98 percentage of overfilled remodeling site Interval 11.11 to 33.33	0.00 percentage of overfilled remodeling site Interval 0.0 to 14.29
Percentage of Overfilled Remodeling Sites in the CC, EC and PC of the Iliac Crest Bone Biopsies PC (n=29, 5)	0.00 percentage of overfilled remodeling site Interval 0.0 to 0.0	0.00 percentage of overfilled remodeling site Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Baseline, 3 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with label lengths measured in the specified compartments of the iliac crest.

BMUs are local groups of osteoblasts and osteoclasts that act in concert to complete a single remodeling cycle. The label length is a measure of the extent of the mineralization front within each BMU in the CC, EC, IC and PC. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation, and a SL or NL suggested suppression of bone formation.

Outcome measures

Outcome measures
Measure	Teriparatide n=30 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=25 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Change From Baseline to 3 Months in Label Length Within Each Basic Multicellular Unit (BMU) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies CC (n=30, 24)	0.19 millimeters (mm) Interval 0.13 to 0.22	0.05 millimeters (mm) Interval 0.0 to 0.12
Change From Baseline to 3 Months in Label Length Within Each Basic Multicellular Unit (BMU) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies EC (n=28, 25)	0.25 millimeters (mm) Interval 0.08 to 0.31	0.03 millimeters (mm) Interval -0.04 to 0.18
Change From Baseline to 3 Months in Label Length Within Each Basic Multicellular Unit (BMU) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies IC (n=30, 24)	0.18 millimeters (mm) Interval 0.16 to 0.25	0.02 millimeters (mm) Interval -0.07 to 0.11
Change From Baseline to 3 Months in Label Length Within Each Basic Multicellular Unit (BMU) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies PC (n=4, 1)	0.12 millimeters (mm) Interval -0.02 to 0.6	0.10 millimeters (mm) Interval 0.1 to 0.1

SECONDARY outcome

Timeframe: Baseline, 3 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with an evaluation of MAR in the CC, EC, IC and PC of the iliac crest.

MAR is a measure of the linear rate of production of mineralized bone matrix by osteoblasts and is measured by the mean distance between 2 consecutive labels divided by the time interval. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation, and a SL or NL suggested suppression of bone formation. SL cases were imputed to a value of 0.3 micrometers per day (µm/day) or counted as missing. NL cases were reported as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=31 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=34 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Change From Baseline to 3 Months in Mineral Apposition Rate (MAR) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies DL Only, in CC (n=30, 24)	0.00 mcm/day Interval -0.02 to 0.04	-0.04 mcm/day Interval -0.11 to 0.01
Change From Baseline to 3 Months in Mineral Apposition Rate (MAR) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies DL and Imputed SL, in CC (n=31, 33)	0.01 mcm/day Interval -0.02 to 0.06	-0.06 mcm/day Interval -0.15 to 0.0
Change From Baseline to 3 Months in Mineral Apposition Rate (MAR) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies DL Only, in EC (n=28, 25)	0.03 mcm/day Interval -0.03 to 0.08	-0.07 mcm/day Interval -0.12 to 0.01
Change From Baseline to 3 Months in Mineral Apposition Rate (MAR) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies DL and Imputed SL, in EC (n=29, 31)	0.03 mcm/day Interval -0.03 to 0.08	-0.09 mcm/day Interval -0.16 to 0.0
Change From Baseline to 3 Months in Mineral Apposition Rate (MAR) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies DL Only, in IC (n=30, 24)	0.20 mcm/day Interval 0.09 to 0.34	-0.18 mcm/day Interval -0.28 to -0.1
Change From Baseline to 3 Months in Mineral Apposition Rate (MAR) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies DL and Imputed SL, in IC (n=30, 34)	0.20 mcm/day Interval 0.09 to 0.34	-0.22 mcm/day Interval -0.33 to -0.12
Change From Baseline to 3 Months in Mineral Apposition Rate (MAR) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies DL Only, in PC (n=4, 1)	0.05 mcm/day Interval -0.14 to 0.11	-0.04 mcm/day Interval -0.04 to -0.04
Change From Baseline to 3 Months in Mineral Apposition Rate (MAR) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies DL and Imputed SL, in PC (n=19, 4)	0.00 mcm/day Interval -0.03 to 0.08	-0.04 mcm/day Interval -0.07 to -0.02

SECONDARY outcome

Timeframe: Baseline, 3 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with BFR/BS assessments in the specified compartments of the iliac crest.

BFR/BS is the volume of mineralized bone formed per unit surface of bone per unit of time \[mm cubed per mm squared per year (mm³/mm²/year)\]. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicates active bone formation, a SL or NL suggests suppression of bone formation. BFR = MAR \* (MS/BS). SL cases were imputed to a value of 0.3 mcm/day or counted as missing. NL cases were assigned a value of zero.

Outcome measures

Outcome measures
Measure	Teriparatide n=31 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=35 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Change From Baseline to 3 Months in Bone Formation Rate/Bone Surface (BFR/BS ) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies DL Only, in CC (n=30, 26)	0.0280 mm³/mm²/year Interval 0.0173 to 0.0426	-0.0056 mm³/mm²/year Interval -0.0093 to -0.0021
Change From Baseline to 3 Months in Bone Formation Rate/Bone Surface (BFR/BS ) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies DL and Imputed SL, in CC (n=31, 35)	0.0275 mm³/mm²/year Interval 0.0143 to 0.0426	-0.0055 mm³/mm²/year Interval -0.0094 to -0.0021
Change From Baseline to 3 Months in Bone Formation Rate/Bone Surface (BFR/BS ) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies DL Only, in EC (n=29, 28)	0.0509 mm³/mm²/year Interval 0.03 to 0.1105	-0.0069 mm³/mm²/year Interval -0.0118 to 0.0002
Change From Baseline to 3 Months in Bone Formation Rate/Bone Surface (BFR/BS ) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies DL and Imputed SL, in EC (n=30, 35)	0.0501 mm³/mm²/year Interval 0.03 to 0.1105	-0.0069 mm³/mm²/year Interval -0.0123 to -0.0016
Change From Baseline to 3 Months in Bone Formation Rate/Bone Surface (BFR/BS ) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies DL Only, in IC (n=30, 25)	0.0455 mm³/mm²/year Interval 0.0208 to 0.0654	-0.0184 mm³/mm²/year Interval -0.029 to -0.0103
Change From Baseline to 3 Months in Bone Formation Rate/Bone Surface (BFR/BS ) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies DL and Imputed SL, in IC (n=30, 35)	0.0455 mm³/mm²/year Interval 0.0208 to 0.0654	-0.0184 mm³/mm²/year Interval -0.029 to -0.0103
Change From Baseline to 3 Months in Bone Formation Rate/Bone Surface (BFR/BS ) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies DL Only, in PC (n=6, 16)	0.0231 mm³/mm²/year Interval 0.0058 to 0.0369	0.0000 mm³/mm²/year Interval -0.0019 to 0.0
Change From Baseline to 3 Months in Bone Formation Rate/Bone Surface (BFR/BS ) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies DL and Imputed SL, in PC (n=30, 35)	0.0015 mm³/mm²/year Interval 0.0008 to 0.0101	-0.0005 mm³/mm²/year Interval -0.0019 to 0.0

SECONDARY outcome

Timeframe: 3 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with label surface measured in the specified compartments of the iliac crest.

At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or NL suggested suppression of bone formation. Percentage = (Single or double TET labels / BS) \*100.

Outcome measures

Outcome measures
Measure	Teriparatide n=31 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=35 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Percentage of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS or dLS/BS) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies sLS/BS, in CC (n=31, 35)	15.44 percentage of TET label Interval 10.16 to 18.53	1.28 percentage of TET label Interval 0.66 to 2.62
Percentage of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS or dLS/BS) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies dLS/BS, in CC (n=31, 35)	10.44 percentage of TET label Interval 6.0 to 15.41	0.22 percentage of TET label Interval 0.0 to 0.79
Percentage of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS or dLS/BS) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies sLS/BS, in EC (n=30, 35)	24.24 percentage of TET label Interval 14.65 to 30.32	7.18 percentage of TET label Interval 4.13 to 10.58
Percentage of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS or dLS/BS) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies dLS/BS, in EC (n=30, 35)	28.84 percentage of TET label Interval 12.83 to 43.96	1.68 percentage of TET label Interval 0.0 to 5.08
Percentage of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS or dLS/BS) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies sLS/BS, in IC (n=30, 35)	15.28 percentage of TET label Interval 11.17 to 17.26	4.66 percentage of TET label Interval 2.54 to 9.57
Percentage of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS or dLS/BS) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies dLS/BS, in IC (n=30, 35)	14.96 percentage of TET label Interval 10.55 to 19.69	0.83 percentage of TET label Interval 0.0 to 1.87
Percentage of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS or dLS/BS) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies sLS/BS, in PC (n=30, 35)	9.37 percentage of TET label Interval 2.47 to 13.92	0.00 percentage of TET label Interval 0.0 to 0.0
Percentage of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS or dLS/BS) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies dLS/BS, in PC (n=30, 35)	0.00 percentage of TET label Interval 0.0 to 0.62	0.00 percentage of TET label Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Baseline, 1, 3, and 6 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and had serum PTH assessed at baseline and the specified time points.

PTH regulates calcium and phosphate metabolism in bone and kidney, and is typically measured in serum using the intact PTH assay. Percentage = (PTH value at specified time points - PTH value at baseline) / PTH value at baseline \* 100.

Outcome measures

Outcome measures
Measure	Teriparatide n=28 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=34 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Percentage Change From Baseline to 1, 3, and 6 Months in Intact Parathyroid Hormone (PTH) 1 month (n=28, 34)	-26.89 percentage change in PTH Interval -52.28 to -12.81	72.24 percentage change in PTH Interval 29.87 to 119.53
Percentage Change From Baseline to 1, 3, and 6 Months in Intact Parathyroid Hormone (PTH) 3 months (n=18, 28)	-32.16 percentage change in PTH Interval -38.8 to -10.17	46.68 percentage change in PTH Interval 0.21 to 78.87
Percentage Change From Baseline to 1, 3, and 6 Months in Intact Parathyroid Hormone (PTH) 6 months (n=27, 33)	-40.18 percentage change in PTH Interval -63.29 to -10.14	30.40 percentage change in PTH Interval 0.0 to 60.57

SECONDARY outcome

Timeframe: Baseline, 1, 3, and 6 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and had serum P1NP measurements at baseline and the specified time points.

P1NP is a marker of bone turnover and is a measure of bone formation. Percentage = (P1NP value at specified time points - P1NP value at baseline) / P1NP value at baseline \* 100.

Outcome measures

Outcome measures
Measure	Teriparatide n=33 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=34 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Percentage Change From Baseline to 1, 3, and 6 Months in Serum Procollagen Type I N-terminal Propeptide (P1NP) 1 month (n=33, 34)	134.38 percentage change in P1NP Interval 93.77 to 194.96	-11.56 percentage change in P1NP Interval -26.87 to -0.73
Percentage Change From Baseline to 1, 3, and 6 Months in Serum Procollagen Type I N-terminal Propeptide (P1NP) 3 months (n=22, 29)	213.15 percentage change in P1NP Interval 104.94 to 325.78	-66.64 percentage change in P1NP Interval -73.46 to -59.26
Percentage Change From Baseline to 1, 3, and 6 Months in Serum Procollagen Type I N-terminal Propeptide (P1NP) 6 months (n=31, 32)	284.22 percentage change in P1NP Interval 180.86 to 536.92	-68.24 percentage change in P1NP Interval -75.31 to -55.31

SECONDARY outcome

Timeframe: Baseline, 1, 3, and 6 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and had serum osteocalcin measured at baseline and the specified time points.

Osteocalcin is a marker of bone turnover and a measure of osteoblast function. Percentage = (osteocalcin value at specified time points - osteocalcin value at baseline) / (osteocalcin value at baseline) \* 100.

Outcome measures

Outcome measures
Measure	Teriparatide n=31 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=33 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Percentage Change From Baseline to 1, 3, and 6 Months in Serum Osteocalcin 1 month (n=31, 33)	90.53 percentage change in osteocalcin Interval 61.19 to 127.56	-6.56 percentage change in osteocalcin Interval -16.83 to 7.34
Percentage Change From Baseline to 1, 3, and 6 Months in Serum Osteocalcin 3 months (n=20, 29)	123.66 percentage change in osteocalcin Interval 83.2 to 174.59	-45.70 percentage change in osteocalcin Interval -52.2 to -38.6
Percentage Change From Baseline to 1, 3, and 6 Months in Serum Osteocalcin 6 months (n=29, 31)	187.29 percentage change in osteocalcin Interval 131.24 to 290.3	-50.53 percentage change in osteocalcin Interval -59.89 to -37.15

SECONDARY outcome

Timeframe: Baseline, 1, 3, and 6 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and serum CTX measured at baseline and the specified time points.

CTX is a marker of bone turnover and is a measure of bone resorption. Percentage = (CTX value at specified time points - CTX value at baseline) / (CTX value at baseline) \* 100.

Outcome measures

Outcome measures
Measure	Teriparatide n=31 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=33 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Percentage Change From Baseline to 1, 3, and 6 Months in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) 1 month (n=31, 33)	6.09 percentage change in CTX Interval -21.35 to 43.75	-90.70 percentage change in CTX Interval -92.11 to -87.5
Percentage Change From Baseline to 1, 3, and 6 Months in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) 3 months (n=21, 29)	73.04 percentage change in CTX Interval 33.33 to 140.0	-90.77 percentage change in CTX Interval -92.59 to -85.92
Percentage Change From Baseline to 1, 3, and 6 Months in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) 6 months (n=29, 33)	89.13 percentage change in CTX Interval 50.0 to 220.29	-82.50 percentage change in CTX Interval -86.96 to -60.0

SECONDARY outcome

Timeframe: 3 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with Ac.f assessments in the CC, EC and IC of the iliac crest.

Ac.f is the probability of new remodeling cycles initiated on the BS per year. Ac.f = (BFR/BS) / wall thickness. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. NL cases were assigned a value of zero.

Outcome measures

Outcome measures
Measure	Teriparatide n=31 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=35 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Activation Frequency (Ac.f) in the CC, EC and IC of the Iliac Crest DL Only, in CC (n=31, 26)	1.41 new cycles per year Interval 0.88 to 2.02	0.10 new cycles per year Interval 0.04 to 0.2
Activation Frequency (Ac.f) in the CC, EC and IC of the Iliac Crest DL and Imputed SL, in CC (n=31, 35)	1.41 new cycles per year Interval 0.88 to 2.02	0.06 new cycles per year Interval 0.02 to 0.14
Activation Frequency (Ac.f) in the CC, EC and IC of the Iliac Crest DL Only, in EC (n=30, 29)	2.77 new cycles per year Interval 1.48 to 4.31	0.35 new cycles per year Interval 0.19 to 0.62
Activation Frequency (Ac.f) in the CC, EC and IC of the Iliac Crest DL and Imputed SL, in EC (n=30, 35)	2.77 new cycles per year Interval 1.48 to 4.31	0.34 new cycles per year Interval 0.09 to 0.59
Activation Frequency (Ac.f) in the CC, EC and IC of the Iliac Crest DL Only, in IC (n=30, 25)	1.88 new cycles per year Interval 1.13 to 2.48	0.17 new cycles per year Interval 0.11 to 0.36
Activation Frequency (Ac.f) in the CC, EC and IC of the Iliac Crest DL and Imputed SL, in IC (n=30, 35)	1.88 new cycles per year Interval 1.13 to 2.48	0.12 new cycles per year Interval 0.06 to 0.27

SECONDARY outcome

Timeframe: 3 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with Aj.AR assessments in the CC, EC and IC of the iliac crest.

Aj.AR is MAR averaged over the entire osteoid surface and in a steady state is an estimate of the mean rate of matrix apposition. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or NL suggested suppression of bone formation. BFR = MAR \* (MS/BS). SL cases were imputed to a value of 0.3 µm/day or counted as missing. NL cases were counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=31 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=33 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Adjusted Apposition Rate (Aj.AR) in the CC, EC and IC of the Iliac Crest DL Only, in CC (n=31, 24)	0.58 µm/day Interval 0.46 to 0.67	0.21 µm/day Interval 0.09 to 0.48
Adjusted Apposition Rate (Aj.AR) in the CC, EC and IC of the Iliac Crest DL and Imputed SL, in CC (n=31, 33)	0.58 µm/day Interval 0.46 to 0.67	0.14 µm/day Interval 0.08 to 0.33
Adjusted Apposition Rate (Aj.AR) in the CC, EC and IC of the Iliac Crest DL Only, in EC (n=30, 25)	0.76 µm/day Interval 0.56 to 0.88	0.65 µm/day Interval 0.41 to 0.82
Adjusted Apposition Rate (Aj.AR) in the CC, EC and IC of the Iliac Crest DL and Imputed SL, in EC (n=30, 30)	0.76 µm/day Interval 0.56 to 0.88	0.58 µm/day Interval 0.22 to 0.81
Adjusted Apposition Rate (Aj.AR) in the CC, EC and IC of the Iliac Crest DL Only, in IC (n=30, 24)	1.03 µm/day Interval 0.88 to 1.18	0.58 µm/day Interval 0.26 to 0.83
Adjusted Apposition Rate (Aj.AR) in the CC, EC and IC of the Iliac Crest DL and Imputed SL, in IC (n=30, 33)	1.03 µm/day Interval 0.88 to 1.18	0.35 µm/day Interval 0.19 to 0.73

SECONDARY outcome

Timeframe: 3 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with an assessment of OV/BV in the CC of the iliac crest.

OV is the percentage of a given volume of bone tissue that consists of new unmineralized bone matrix (osteoid). Percentage = (OV/BV) \*100.

Outcome measures

Outcome measures
Measure	Teriparatide n=31 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=35 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the CC of the Iliac Crest	2.58 percentage of BV Interval 1.67 to 3.51	0.39 percentage of BV Interval 0.17 to 0.65

SECONDARY outcome

Timeframe: 3 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with the assessment of OS/BS in the CC, EC and IC of the iliac crest.

OS is the percentage of the entire trabecular BS that is covered by osteoid. Percentage = (OS / BS) \*100.

Outcome measures

Outcome measures
Measure	Teriparatide n=31 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=35 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the CC, EC and IC of the Iliac Crest CC (n=31, 35)	20.51 percentage of BS Interval 12.5 to 24.13	3.46 percentage of BS Interval 2.05 to 5.4
Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the CC, EC and IC of the Iliac Crest EC (n=30, 35)	30.85 percentage of BS Interval 21.47 to 48.02	6.95 percentage of BS Interval 2.82 to 10.88
Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the CC, EC and IC of the Iliac Crest IC (n=30, 35)	17.81 percentage of BS Interval 11.89 to 22.5	4.34 percentage of BS Interval 2.07 to 6.17

SECONDARY outcome

Timeframe: 3 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with an O.Th assessment in the CC, EC and IC of the iliac crest.

O.Th is a measure of the average thickness of osteoid seams.

Outcome measures

Outcome measures
Measure	Teriparatide n=31 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=35 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Osteoid Thickness (O.Th) in the CC, EC and IC of the Iliac Crest CC (n= 31, 35)	6.12 micrometers (mcm) Interval 5.52 to 6.71	3.78 micrometers (mcm) Interval 3.49 to 4.18
Osteoid Thickness (O.Th) in the CC, EC and IC of the Iliac Crest EC (n= 30, 35)	6.99 micrometers (mcm) Interval 5.61 to 7.99	4.33 micrometers (mcm) Interval 3.49 to 4.78
Osteoid Thickness (O.Th) in the CC, EC and IC of the Iliac Crest IC (n= 30, 35)	7.08 micrometers (mcm) Interval 6.15 to 7.92	4.68 micrometers (mcm) Interval 3.68 to 5.13

SECONDARY outcome

Timeframe: 3 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with a W. Th assessment in the CC, EC and IC of the iliac crest.

W.Th is the distance from the cement line to the marrow space of completed trabecular bone packets.

Outcome measures

Outcome measures
Measure	Teriparatide n=31 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=35 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Wall Thickness (W.Th) in the CC, EC and IC of the Iliac Crest CC (n=31, 35)	26.29 µm Interval 25.58 to 27.84	24.03 µm Interval 22.79 to 25.23
Wall Thickness (W.Th) in the CC, EC and IC of the Iliac Crest EC (n=30, 35)	31.88 µm Interval 29.75 to 32.99	30.08 µm Interval 27.61 to 32.03
Wall Thickness (W.Th) in the CC, EC and IC of the Iliac Crest IC (n=30, 35)	38.25 µm Interval 33.87 to 39.84	37.80 µm Interval 34.61 to 40.15

SECONDARY outcome

Timeframe: 3 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with ES/BS assessed in the CC, EC and IC of the iliac crest.

ES/BS is the fraction of the entire trabecular surface occupied by resorption bays, including both those with and without osteoclasts. It is an indicator of bone resorption. Percentage = (ES/BS) \*100.

Outcome measures

Outcome measures
Measure	Teriparatide n=31 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=35 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Percentage of Eroded Surface/Bone Surface (ES/BS) in the CC, EC and IC of the Iliac Crest CC (n=31, 35)	3.73 percentage of BS Interval 2.95 to 6.05	1.52 percentage of BS Interval 0.92 to 2.87
Percentage of Eroded Surface/Bone Surface (ES/BS) in the CC, EC and IC of the Iliac Crest EC (n=30, 35)	3.79 percentage of BS Interval 2.79 to 6.25	1.65 percentage of BS Interval 0.78 to 2.47
Percentage of Eroded Surface/Bone Surface (ES/BS) in the CC, EC and IC of the Iliac Crest IC (n=30, 35)	11.19 percentage of BS Interval 7.37 to 13.71	1.27 percentage of BS Interval 0.9 to 3.82

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months post first dose of study drug

Population: Randomized participants who received at least 1 dose of study drug and had an evaluable 3-month bone biopsy with an assessment of DL length in the various compartments of the iliac crest.

The length of TET DLs is a measure of the extent of bone formation in each compartment within individual remodeling units and is measured in mm. At baseline (18 days prior to randomization / study drug administration), DEM was administered. 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation.

Outcome measures

Outcome measures
Measure	Teriparatide n=31 Participants Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=25 Participants Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Average Length of DLs in the CC, EC, IC and PC of the Iliac Crest DL, in CC (n=31, 24)	0.40 mm Standard Deviation 0.08	0.31 mm Standard Deviation 0.10
Average Length of DLs in the CC, EC, IC and PC of the Iliac Crest DL, in EC (n=30, 25)	0.48 mm Standard Deviation 0.15	0.35 mm Standard Deviation 0.20
Average Length of DLs in the CC, EC, IC and PC of the Iliac Crest DL, in IC (n=30, 24)	0.43 mm Standard Deviation 0.11	0.27 mm Standard Deviation 0.12
Average Length of DLs in the CC, EC, IC and PC of the Iliac Crest DL, in PC (n=10, 1)	0.38 mm Standard Deviation 0.41	0.32 mm Standard Deviation NA n=1

Adverse Events

Teriparatide

Serious events: 2 serious events

Other events: 27 other events

Deaths: 0 deaths

Denosumab

Serious events: 2 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Teriparatide n=33 participants at risk Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=36 participants at risk Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
General disorders Chest pain	3.0% 1/33 • Number of events 1	0.00% 0/36
Infections and infestations Appendicitis	0.00% 0/33	2.8% 1/36 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	3.0% 1/33 • Number of events 1	0.00% 0/36
Vascular disorders Deep vein thrombosis	0.00% 0/33	2.8% 1/36 • Number of events 1

Other adverse events

Other adverse events
Measure	Teriparatide n=33 participants at risk Teriparatide: 20-µg SC injection once daily for 6 months. DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.	Denosumab n=36 participants at risk Denosumab: A single 60-mg SC injection. DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization: * Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours. * Days 4 through 15: DEM was not administered. TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure: * Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours. * Days 4 through 15: TET was not administered. Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months. Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.
Blood and lymphatic system disorders Lymph node pain	3.0% 1/33 • Number of events 1	0.00% 0/36
Eye disorders Dry eye	3.0% 1/33 • Number of events 1	0.00% 0/36
Gastrointestinal disorders Abdominal discomfort	3.0% 1/33 • Number of events 1	0.00% 0/36
Gastrointestinal disorders Abdominal pain	3.0% 1/33 • Number of events 1	0.00% 0/36
Gastrointestinal disorders Abdominal pain lower	3.0% 1/33 • Number of events 1	0.00% 0/36
Gastrointestinal disorders Constipation	3.0% 1/33 • Number of events 1	11.1% 4/36 • Number of events 4
Gastrointestinal disorders Diarrhoea	3.0% 1/33 • Number of events 1	2.8% 1/36 • Number of events 1
Gastrointestinal disorders Gastrooesophageal reflux disease	3.0% 1/33 • Number of events 1	0.00% 0/36
Gastrointestinal disorders Nausea	12.1% 4/33 • Number of events 4	0.00% 0/36
General disorders Fatigue	12.1% 4/33 • Number of events 5	2.8% 1/36 • Number of events 1
General disorders Injection site erythema	3.0% 1/33 • Number of events 1	0.00% 0/36
General disorders Local swelling	6.1% 2/33 • Number of events 2	0.00% 0/36
General disorders Thirst	3.0% 1/33 • Number of events 1	0.00% 0/36
Infections and infestations Bronchitis	9.1% 3/33 • Number of events 3	2.8% 1/36 • Number of events 1
Infections and infestations Ear infection	3.0% 1/33 • Number of events 1	0.00% 0/36
Infections and infestations Gastroenteritis	3.0% 1/33 • Number of events 1	0.00% 0/36
Infections and infestations Nasopharyngitis	3.0% 1/33 • Number of events 1	5.6% 2/36 • Number of events 2
Injury, poisoning and procedural complications Contusion	30.3% 10/33 • Number of events 10	11.1% 4/36 • Number of events 4
Injury, poisoning and procedural complications Fall	3.0% 1/33 • Number of events 1	0.00% 0/36
Injury, poisoning and procedural complications Post procedural discomfort	3.0% 1/33 • Number of events 1	11.1% 4/36 • Number of events 4
Metabolism and nutrition disorders Hypokalaemia	6.1% 2/33 • Number of events 2	2.8% 1/36 • Number of events 1
Musculoskeletal and connective tissue disorders Arthralgia	15.2% 5/33 • Number of events 6	2.8% 1/36 • Number of events 1
Musculoskeletal and connective tissue disorders Bone pain	3.0% 1/33 • Number of events 1	0.00% 0/36
Musculoskeletal and connective tissue disorders Foot deformity	3.0% 1/33 • Number of events 1	0.00% 0/36
Musculoskeletal and connective tissue disorders Groin pain	3.0% 1/33 • Number of events 1	2.8% 1/36 • Number of events 1
Musculoskeletal and connective tissue disorders Joint stiffness	3.0% 1/33 • Number of events 1	0.00% 0/36
Musculoskeletal and connective tissue disorders Joint swelling	3.0% 1/33 • Number of events 1	0.00% 0/36
Musculoskeletal and connective tissue disorders Muscular weakness	3.0% 1/33 • Number of events 1	0.00% 0/36
Musculoskeletal and connective tissue disorders Pain in extremity	9.1% 3/33 • Number of events 5	2.8% 1/36 • Number of events 1
Musculoskeletal and connective tissue disorders Sensation of heaviness	3.0% 1/33 • Number of events 1	0.00% 0/36
Musculoskeletal and connective tissue disorders Tendon disorder	3.0% 1/33 • Number of events 1	0.00% 0/36
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	3.0% 1/33 • Number of events 1	0.00% 0/36
Nervous system disorders Dizziness	3.0% 1/33 • Number of events 2	0.00% 0/36
Nervous system disorders Dysgeusia	6.1% 2/33 • Number of events 2	0.00% 0/36
Nervous system disorders Headache	12.1% 4/33 • Number of events 6	0.00% 0/36
Nervous system disorders Loss of consciousness	3.0% 1/33 • Number of events 1	0.00% 0/36
Nervous system disorders Tremor	3.0% 1/33 • Number of events 1	2.8% 1/36 • Number of events 1
Renal and urinary disorders Bladder spasm	3.0% 1/33 • Number of events 1	0.00% 0/36
Renal and urinary disorders Nephrolithiasis	3.0% 1/33 • Number of events 1	0.00% 0/36
Renal and urinary disorders Urine abnormality	6.1% 2/33 • Number of events 2	0.00% 0/36
Reproductive system and breast disorders Vaginal discharge	3.0% 1/33 • Number of events 1	0.00% 0/36
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	3.0% 1/33 • Number of events 1	0.00% 0/36
Respiratory, thoracic and mediastinal disorders Cough	9.1% 3/33 • Number of events 3	2.8% 1/36 • Number of events 1
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.0% 1/33 • Number of events 1	0.00% 0/36
Respiratory, thoracic and mediastinal disorders Sneezing	3.0% 1/33 • Number of events 1	0.00% 0/36
Skin and subcutaneous tissue disorders Alopecia	3.0% 1/33 • Number of events 1	0.00% 0/36
Skin and subcutaneous tissue disorders Hyperhidrosis	3.0% 1/33 • Number of events 1	0.00% 0/36
Skin and subcutaneous tissue disorders Onychoclasis	3.0% 1/33 • Number of events 1	0.00% 0/36
Skin and subcutaneous tissue disorders Pruritus	3.0% 1/33 • Number of events 2	2.8% 1/36 • Number of events 1
Skin and subcutaneous tissue disorders Rash	6.1% 2/33 • Number of events 2	5.6% 2/36 • Number of events 2
Skin and subcutaneous tissue disorders Skin induration	3.0% 1/33 • Number of events 1	2.8% 1/36 • Number of events 1
Skin and subcutaneous tissue disorders Swelling face	3.0% 1/33 • Number of events 1	0.00% 0/36
Skin and subcutaneous tissue disorders Urticaria	3.0% 1/33 • Number of events 1	0.00% 0/36
Vascular disorders Haematoma	3.0% 1/33 • Number of events 1	0.00% 0/36
Vascular disorders Hypotension	3.0% 1/33 • Number of events 1	0.00% 0/36
Vascular disorders Spider vein	3.0% 1/33 • Number of events 1	0.00% 0/36

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60