Trial Outcomes & Findings for Effects of Teriparatide or Zoledronic Acid Treatment on Bone in Postmenopausal Osteoporotic Women (NCT NCT00927186)

Results Overview

MS/BS in CC is a measure of the proportion of BS on which new mineralized bone is deposited at the time of tetracycline (T) labeling and is calculated as sum of total extent of double label (DL) plus half the extent of single label (SL) divided by BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in the biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under a microscope. DL indicates active bone formation, SL or no label (NL) suggests suppression of bone formation.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

69 participants

Primary outcome timeframe

6 months

Results posted on

2013-04-04

Participant Flow

This was a Phase 4, multicenter, randomized, stratified, double-blind, active comparator-controlled study with the primary endpoint at 6 months. Following the bone biopsy visit at 6 months, the study became open label for an additional 6 months. All participants who complete 12 months of treatment are eligible for an additional 12-month extension.

Participant milestones

Participant milestones
Measure	Teriparatide 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
12 Months Primary Study STARTED	34	35
12 Months Primary Study Completed 6 Months Double Blind Phase	28	31
12 Months Primary Study COMPLETED	27	31
12 Months Primary Study NOT COMPLETED	7	4
12 - 24 Months Extension Treatment STARTED	10	11
12 - 24 Months Extension Treatment COMPLETED	10	11
12 - 24 Months Extension Treatment NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Teriparatide 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
12 Months Primary Study Adverse Event	5	2
12 Months Primary Study Lost to Follow-up	1	0
12 Months Primary Study Protocol Violation	0	1
12 Months Primary Study Withdrawal by Subject	1	1

Baseline Characteristics

Effects of Teriparatide or Zoledronic Acid Treatment on Bone in Postmenopausal Osteoporotic Women

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Teriparatide n=34 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=35 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Total n=69 Participants Total of all reporting groups
Age Continuous	65.49 years STANDARD_DEVIATION 6.93 • n=5 Participants	64.20 years STANDARD_DEVIATION 5.96 • n=7 Participants	64.84 years STANDARD_DEVIATION 6.44 • n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants	35 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
Race/Ethnicity, Customized Black or African American	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized White	33 participants n=5 Participants	34 participants n=7 Participants	67 participants n=5 Participants
Region of Enrollment United States	21 participants n=5 Participants	25 participants n=7 Participants	46 participants n=5 Participants
Region of Enrollment Canada	13 participants n=5 Participants	10 participants n=7 Participants	23 participants n=5 Participants
Height	159.28 centimeters (cm) STANDARD_DEVIATION 5.92 • n=5 Participants	160.00 centimeters (cm) STANDARD_DEVIATION 7.38 • n=7 Participants	159.64 centimeters (cm) STANDARD_DEVIATION 6.66 • n=5 Participants
Weight	61.25 kilograms (kg) STANDARD_DEVIATION 9.21 • n=5 Participants	64.75 kilograms (kg) STANDARD_DEVIATION 11.66 • n=7 Participants	63.03 kilograms (kg) STANDARD_DEVIATION 10.60 • n=5 Participants
Pulse	67.41 beats per minute (bpm) STANDARD_DEVIATION 7.15 • n=5 Participants	70.60 beats per minute (bpm) STANDARD_DEVIATION 8.79 • n=7 Participants	69.03 beats per minute (bpm) STANDARD_DEVIATION 8.13 • n=5 Participants
Blood Pressure - Systolic	125.71 millimeters of mercury (mmHg) STANDARD_DEVIATION 16.19 • n=5 Participants	122.49 millimeters of mercury (mmHg) STANDARD_DEVIATION 16.25 • n=7 Participants	124.07 millimeters of mercury (mmHg) STANDARD_DEVIATION 16.18 • n=5 Participants
Blood Pressure - Diastolic	74.79 mmHg STANDARD_DEVIATION 8.24 • n=5 Participants	73.97 mmHg STANDARD_DEVIATION 10.15 • n=7 Participants	74.38 mmHg STANDARD_DEVIATION 9.20 • n=5 Participants
Alcohol Use Yes	21 participants n=5 Participants	17 participants n=7 Participants	38 participants n=5 Participants
Alcohol Use No	13 participants n=5 Participants	18 participants n=7 Participants	31 participants n=5 Participants
Tobacco Use Yes	5 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants
Tobacco Use No	29 participants n=5 Participants	30 participants n=7 Participants	59 participants n=5 Participants
Caffeine or Xanthine Use Yes	29 participants n=5 Participants	30 participants n=7 Participants	59 participants n=5 Participants
Caffeine or Xanthine Use No	5 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants
Previous Osteoporosis Therapy Yes	17 participants n=5 Participants	21 participants n=7 Participants	38 participants n=5 Participants
Previous Osteoporosis Therapy No	17 participants n=5 Participants	14 participants n=7 Participants	31 participants n=5 Participants
Fracture Status Yes	14 participants n=5 Participants	17 participants n=7 Participants	31 participants n=5 Participants
Fracture Status No	20 participants n=5 Participants	18 participants n=7 Participants	38 participants n=5 Participants
Lumbar Spine T-Score	-2.79 T-Score STANDARD_DEVIATION 0.83 • n=5 Participants	-2.93 T-Score STANDARD_DEVIATION 0.75 • n=7 Participants	-2.86 T-Score STANDARD_DEVIATION 0.79 • n=5 Participants
Femoral Neck T-Score	-2.25 T-Score STANDARD_DEVIATION 0.68 • n=5 Participants	-2.29 T-Score STANDARD_DEVIATION 0.74 • n=7 Participants	-2.27 T-Score STANDARD_DEVIATION 0.70 • n=5 Participants
Total Hip T-Score	-1.78 T-Score STANDARD_DEVIATION 0.78 • n=5 Participants	-1.88 T-Score STANDARD_DEVIATION 0.91 • n=7 Participants	-1.83 T-Score STANDARD_DEVIATION 0.84 • n=5 Participants
Serum Procollagen Type I N-Terminal Propeptide (PINP)	49.18 microgram/Liter (µg/L) STANDARD_DEVIATION 18.28 • n=5 Participants	52.88 microgram/Liter (µg/L) STANDARD_DEVIATION 19.43 • n=7 Participants	51.03 microgram/Liter (µg/L) STANDARD_DEVIATION 18.81 • n=5 Participants
Serum Carboxyterminal Cross-Linking Telopeptide of Collagen Type I (CTX)	0.43 nanogram/milliliter (ng/mL) STANDARD_DEVIATION 0.23 • n=5 Participants	0.42 nanogram/milliliter (ng/mL) STANDARD_DEVIATION 0.19 • n=7 Participants	0.43 nanogram/milliliter (ng/mL) STANDARD_DEVIATION 0.21 • n=5 Participants
Serum Osteocalcin	25.05 microgram/Liter (µg/L) STANDARD_DEVIATION 8.37 • n=5 Participants	24.92 microgram/Liter (µg/L) STANDARD_DEVIATION 8.53 • n=7 Participants	24.98 microgram/Liter (µg/L) STANDARD_DEVIATION 8.39 • n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.

MS/BS in CC is a measure of the proportion of BS on which new mineralized bone is deposited at the time of tetracycline (T) labeling and is calculated as sum of total extent of double label (DL) plus half the extent of single label (SL) divided by BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in the biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under a microscope. DL indicates active bone formation, SL or no label (NL) suggests suppression of bone formation.

Outcome measures

Outcome measures
Measure	Teriparatide n=28 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=30 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months	5.60 percentage of surface Inter-Quartile Range 10.20 • Interval 3.0 to 11.75	0.16 percentage of surface Inter-Quartile Range 2.62 • Interval 0.0 to 0.58

SECONDARY outcome

Timeframe: 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had MS/BS analysis of the CC at 24 months.

MS/BS in CC is a measure of the proportion of BS on which new mineralized bone is deposited at the time of tetracycline (T) labeling and is calculated as sum of total extent of double label (DL) plus half the extent of single label (SL) divided by BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in the biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under a microscope. DL indicates active bone formation, SL or no label (NL) suggests suppression of bone formation.

Outcome measures

Outcome measures
Measure	Teriparatide n=10 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=9 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months	3.00 percentage of surface Interval 1.49 to 4.58	0.07 percentage of surface Interval 0.0 to 0.42

SECONDARY outcome

Timeframe: 6 and 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had MS/BS analysis of the EC at 6 and 24 months.

MS/BS in EC is a measure of the proportion of BS on which new mineralized bone is deposited at the time of tetracycline (T) labeling and is calculated as sum of total extent of double label (DL) plus half the extent of single label (SL) divided by BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in the biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under a microscope. DL indicates active bone formation, SL or no label (NL) suggests suppression of bone formation.

Outcome measures

Outcome measures
Measure	Teriparatide n=23 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=29 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Mineralizing Surface/Bone Surface(MS/BS) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months 6 months (n=23, 29)	18.64 percentage of surface Interval 9.25 to 21.96	0.30 percentage of surface Interval 0.0 to 0.84
Mineralizing Surface/Bone Surface(MS/BS) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months 24 months (n=9, 8)	5.82 percentage of surface Interval 3.1 to 7.08	0.00 percentage of surface Interval 0.0 to 0.91

SECONDARY outcome

Timeframe: 6 months

Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.

Ac.f in CC represents the frequency of activation of new remodeling cycles on BS (bone formation rate \[BFR\]/BS divided by wall thickness) and is expressed in units of new cycles per unit of time. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 micrometer (µm)/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=28 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=30 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months DL and NL (n=28, 28)	0.37 new cycles/year Interval 0.17 to 0.82	0.01 new cycles/year Interval 0.0 to 0.04
Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months DL, Imputed SL (ISL) and NL (n=28, 30)	0.37 new cycles/year Interval 0.17 to 0.82	0.01 new cycles/year Interval 0.0 to 0.03

SECONDARY outcome

Timeframe: 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had Ac.f analysis of the CC at 24 months.

Ac.f in CC represents the frequency of activation of new remodeling cycles on the bone surface (BFR/BS divided by wall thickness) and is expressed in units of new cycles per unit of time. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=10 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=9 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months DL, Imputed SL (ISL) and NL (n=10, 9)	0.18 new cycles/year Interval 0.08 to 0.2	0.00 new cycles/year Interval 0.0 to 0.02
Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months DL and NL (n=9, 6)	0.19 new cycles/year Interval 0.1 to 0.2	0.00 new cycles/year Interval 0.0 to 0.02

SECONDARY outcome

Timeframe: 6 and 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had Ac.f analysis of the EC at 6 and 24 months.

Ac.f in EC represents the frequency of activation of new remodeling cycles on the bone surface (BFR/BS divided by wall thickness) and is expressed in units of new cycles per unit of time. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=23 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=29 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Activation Frequency (Ac.f) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL and NL at 6 Months (n=23, 20)	0.83 new cycles/year Interval 0.49 to 1.09	0.00 new cycles/year Interval 0.0 to 0.07
Activation Frequency (Ac.f) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL, Imputed SL (ISL) and NL at 6 Months (n=23, 29)	0.83 new cycles/year Interval 0.49 to 1.09	0.01 new cycles/year Interval 0.0 to 0.04
Activation Frequency (Ac.f) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL and NL at 24 Months (n=8, 7)	0.25 new cycles/year Interval 0.18 to 0.31	0.00 new cycles/year Interval 0.0 to 0.07
Activation Frequency (Ac.f) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL, ISL and NL at 24 Months (n=9, 8)	0.24 new cycles/year Interval 0.14 to 0.29	0.00 new cycles/year Interval 0.0 to 0.04

SECONDARY outcome

Timeframe: 6 months

Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.

BFR in CC is the volume of mineralized bone formed per unit surface bone per unit time (cubic millimeter/square millimeter/year \[mm³/mm²/year\]); calculated as mineral apposition rate (MAR) times MS/BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=28 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=30 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months DL and NL (n=28, 28)	0.0116 mm³/mm²/year Inter-Quartile Range 0.0666 • Interval 0.0051 to 0.0265	0.0002 mm³/mm²/year Inter-Quartile Range 0.0220 • Interval 0.0 to 0.001
Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months DL, ISL and NL (n=28, 30)	0.0116 mm³/mm²/year Interval 0.0051 to 0.0265	0.0002 mm³/mm²/year Interval 0.0 to 0.001

SECONDARY outcome

Timeframe: 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had BFR analysis of the CC at 24 months.

BFR in CC is the volume of mineralized bone formed per unit surface bone per unit time (mm³/mm²/year); calculated as MAR times MS/BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=10 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=9 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months DL and NL (n=9, 6)	0.0057 mm³/mm²/year Interval 0.0033 to 0.0061	0.0000 mm³/mm²/year Interval 0.0 to 0.0005
Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months DL, Imputed SL (ISL) and NL (n=10, 9)	0.0057 mm³/mm²/year Interval 0.0022 to 0.0061	0.0001 mm³/mm²/year Interval 0.0 to 0.0005

SECONDARY outcome

Timeframe: 6 and 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had BFR analysis of EC at 6 and 24 months.

BFR in EC is the volume of mineralized bone formed per unit surface bone per unit time (mm³/mm²/year); calculated as MAR times MS/BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=23 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=29 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Bone Formation Rate (BFR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL and NL at 6 Months (n=23, 20)	0.0307 mm³/mm²/year Interval 0.0182 to 0.0411	0.0000 mm³/mm²/year Interval 0.0 to 0.0022
Bone Formation Rate (BFR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL, Imputed SL (ISL) and NL at 6 Months (n=23, 29)	0.0307 mm³/mm²/year Interval 0.0182 to 0.0411	0.0003 mm³/mm²/year Interval 0.0 to 0.0014
Bone Formation Rate (BFR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL and NL at 24 Months (n=8, 7)	0.0093 mm³/mm²/year Interval 0.0064 to 0.0109	0.0000 mm³/mm²/year Interval 0.0 to 0.0027
Bone Formation Rate (BFR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL, ISL and NL at 24 Months (n=9, 8)	0.0090 mm³/mm²/year Interval 0.0049 to 0.01	0.0000 mm³/mm²/year Interval 0.0 to 0.0016

SECONDARY outcome

Timeframe: 6 months

Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.

MAR in CC is a measure of the linear rate of production of mineralized bone matrix by osteoblasts and is measured by the mean distance between two consecutive T labels divided by the time interval. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=28 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=30 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months DL and NL (n=28, 28)	0.56 micrometer (µm)/day Inter-Quartile Range 0.10 • Interval 0.48 to 0.62	0.35 micrometer (µm)/day Inter-Quartile Range 0.10 • Interval 0.0 to 0.51
Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months DL, ISL and NL (n=28, 30)	0.56 micrometer (µm)/day Interval 0.48 to 0.62	0.33 micrometer (µm)/day Interval 0.0 to 0.51

SECONDARY outcome

Timeframe: 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had MAR analysis of the CC at 24 months.

MAR in CC is a measure of the linear rate of production of mineralized bone matrix by osteoblasts and is measured by the mean distance between two consecutive labels divided by the time interval. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=10 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=9 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months DL and NL (n=9, 6)	0.44 micrometer (µm)/day Interval 0.4 to 0.52	0.00 micrometer (µm)/day Interval 0.0 to 0.34
Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months DL, Imputed SL (ISL) and NL (n=10, 9)	0.43 micrometer (µm)/day Interval 0.37 to 0.52	0.30 micrometer (µm)/day Interval 0.0 to 0.3

SECONDARY outcome

Timeframe: 6 and 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had MAR analysis of the EC at 6 and 24 months.

MAR in EC is a measure of the linear rate of production of mineralized bone matrix by osteoblasts and is measured by the mean distance between two consecutive labels divided by the time interval. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=23 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=29 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Mineral Apposition Rate (MAR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL and NL at 6 Months (n=23, 20)	0.50 micrometer (µm/day) Interval 0.43 to 0.56	0.00 micrometer (µm/day) Interval 0.0 to 0.41
Mineral Apposition Rate (MAR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL, Imputed SL (ISL) and NL at 6 Months (n=23, 29)	0.50 micrometer (µm/day) Interval 0.43 to 0.56	0.30 micrometer (µm/day) Interval 0.0 to 0.3
Mineral Apposition Rate (MAR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL and NL at 24 Months (n=8, 7)	0.43 micrometer (µm/day) Interval 0.38 to 0.5	0.00 micrometer (µm/day) Interval 0.0 to 0.44
Mineral Apposition Rate (MAR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL, ISL and NL at 24 Months (n=9, 8)	0.42 micrometer (µm/day) Interval 0.37 to 0.45	0.00 micrometer (µm/day) Interval 0.0 to 0.37

SECONDARY outcome

Timeframe: 6 months

Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.

Aj.AR in CC is MAR averaged over the entire osteoid surface and in a steady state is an estimate of the mean rate of matrix apposition. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=28 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=30 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months DL and NL (n=28, 28)	0.34 µm/day Inter-Quartile Range 0.22 • Interval 0.15 to 0.51	0.02 µm/day Inter-Quartile Range 0.17 • Interval 0.0 to 0.06
Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months DL, ISL and NL (n=28, 30)	0.34 µm/day Interval 0.15 to 0.51	0.02 µm/day Interval 0.0 to 0.07

SECONDARY outcome

Timeframe: 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had Aj.AR analysis of the CC at 24 months.

Aj.AR in CC is MAR averaged over the entire osteoid surface and in a steady state is an estimate of the mean rate of matrix apposition. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=10 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=9 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months DL and NL (n=9, 6)	0.13 micrometer (µm)/day Interval 0.07 to 0.32	0.00 micrometer (µm)/day Interval 0.0 to 0.13
Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months DL, Imputed SL (ISL) and NL (n=10, 9)	0.12 micrometer (µm)/day Interval 0.07 to 0.32	0.02 micrometer (µm)/day Interval 0.0 to 0.03

SECONDARY outcome

Timeframe: 6 and 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had Aj.AR analysis of the EC at 6 and 24 months.

Aj.AR in EC is MAR averaged over the entire osteoid surface and in a steady state is an estimate of the mean rate of matrix apposition. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=23 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=29 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Adjusted Apposition Rate (Aj.AR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL and NL at 6 Months (n=23, 20)	0.41 micrometer (µm)/day Interval 0.34 to 0.57	0.00 micrometer (µm)/day Interval 0.0 to 0.05
Adjusted Apposition Rate (Aj.AR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL, Imputed SL (ISL) and NL at 6 Months (n=23, 29)	0.41 micrometer (µm)/day Interval 0.34 to 0.57	0.03 micrometer (µm)/day Interval 0.0 to 0.16
Adjusted Apposition Rate (Aj.AR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL and NL at 24 Months (n=8, 7)	0.35 micrometer (µm)/day Interval 0.25 to 0.45	0.00 micrometer (µm)/day Interval 0.0 to 0.12
Adjusted Apposition Rate (Aj.AR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL, ISL and NL at 24 Months (n=9, 8)	0.32 micrometer (µm)/day Interval 0.19 to 0.45	0.00 micrometer (µm)/day Interval 0.0 to 0.11

SECONDARY outcome

Timeframe: 6 months

Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.

Mlt in CC is the period between deposition and subsequent mineralization of osteoid. Mlt is calculated as Osteoid Thickness (O.Th) divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=28 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=30 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months DL and NL (n=28, 16)	13.63 day Interval 11.22 to 29.22	75.72 day Interval 26.84 to 193.78
Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months DL, ISL and NL (n=28, 18)	13.63 day Interval 11.22 to 29.22	75.72 day Interval 24.99 to 215.85

SECONDARY outcome

Timeframe: 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had Mlt analysis of the CC at 24 months.

Mlt in CC is the period between deposition and subsequent mineralization of osteoid. Mlt is calculated as O.Th divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=10 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=5 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months DL and NL (n=9, 2)	38.84 day Interval 22.81 to 57.02	45.67 day Interval 37.7 to 53.65
Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months DL, Imputed SL (ISL) and NL (n=10, 5)	45.33 day Interval 22.81 to 81.83	128.37 day Interval 53.65 to 169.31

SECONDARY outcome

Timeframe: 6 and 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had Mlt analysis of the EC at 6 and 24 months.

Mlt in EC is the period between deposition and subsequent mineralization of osteoid. Mlt is calculated as O.Th divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=23 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=15 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Mineralization Lag Time (Mlt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL and NL at 6 Months (n=23, 6)	12.63 day Interval 9.03 to 17.46	26.97 day Interval 24.61 to 72.03
Mineralization Lag Time (Mlt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL, Imputed SL (ISL) and NL at 6 Months (n=23, 15)	12.63 day Interval 9.03 to 17.46	26.70 day Interval 19.84 to 47.31
Mineralization Lag Time (Mlt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL and NL at 24 Months (n=8, 2)	15.67 day Interval 10.56 to 22.99	42.86 day Interval 23.5 to 62.23
Mineralization Lag Time (Mlt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL, ISL and NL at 24 Months (n=9, 3)	17.04 day Interval 11.97 to 23.37	29.03 day Interval 23.5 to 62.23

SECONDARY outcome

Timeframe: 6 months

Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.

Omt in CC is the period between the onset of deposition and onset of mineralization of a given amount of osteoid. Omt is calculated as O.Th divided by MAR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=28 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=30 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months DL and NL (n=28, 16)	9.99 day Interval 8.39 to 10.74	9.05 day Interval 7.83 to 10.76
Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months DL, ISL and NL (n=28, 18)	9.99 day Interval 8.39 to 10.74	9.05 day Interval 7.97 to 10.8

SECONDARY outcome

Timeframe: 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had Omt analysis of the CC at 24 months.

Omt in CC is the period between the onset of deposition and onset of mineralization of a given amount of osteoid. Omt is calculated as O.Th divided by MAR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=10 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=5 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months DL and NL (n=9, 2)	13.42 day Interval 11.62 to 13.72	17.38 day Interval 13.92 to 20.84
Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months DL, Imputed SL (ISL) and NL (n=10, 5)	13.52 day Interval 11.62 to 13.81	13.92 day Interval 13.26 to 18.98

SECONDARY outcome

Timeframe: 6 and 24 Months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had Omt analysis of the EC at 6 and 24 months.

Omt in EC is the period between the onset of deposition and onset of mineralization of a given amount of osteoid. Omt is calculated as O.Th divided by MAR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=23 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=15 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Osteoid Maturation Time (Omt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL and NL at 6 Months (n=23, 6)	10.57 day Interval 9.67 to 11.06	11.27 day Interval 9.62 to 12.8
Osteoid Maturation Time (Omt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL, Imputed SL (ISL) and NL at 6 Months (n=23, 15)	10.57 day Interval 9.67 to 11.06	11.34 day Interval 9.92 to 16.34
Osteoid Maturation Time (Omt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL and NL at 24 Months (n=8, 2)	12.30 day Interval 9.86 to 16.61	14.94 day Interval 12.12 to 17.76
Osteoid Maturation Time (Omt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL, ISL and NL at 24 Months (n=9, 3)	13.03 day Interval 10.64 to 16.18	12.12 day Interval 9.54 to 17.76

SECONDARY outcome

Timeframe: 6 months

Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.

Tt.FP in CC is a measure of bone formation and is calculated as wall thickness divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=28 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=30 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months DL and NL (n=28, 16)	0.24 year Interval 0.16 to 0.5	1.46 year Interval 0.44 to 3.1
Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months DL, ISL and NL (n=28, 18)	0.24 year Interval 0.16 to 0.5	1.46 year Interval 0.44 to 3.49

SECONDARY outcome

Timeframe: 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had Tt.FP analysis of the CC at 24 months.

Tt.FP in CC is a measure of bone formation and is calculated as wall thickness divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=10 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=5 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months DL and NL (n=9, 2)	0.60 year Interval 0.31 to 1.12	0.51 year Interval 0.39 to 0.63
Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months DL, Imputed SL (ISL) and NL (n=10, 5)	0.68 year Interval 0.31 to 1.15	2.62 year Interval 0.63 to 2.82

SECONDARY outcome

Timeframe: 6 and 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had Tt.FP analysis of the EC at 6 and 24 months.

Tt.FP in EC is a measure of bone formation and is calculated as wall thickness divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=23 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=15 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Total Formation Period (Tt.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL and NL at 6 Months (n=23, 6)	0.24 year Interval 0.17 to 0.3	0.43 year Interval 0.3 to 1.62
Total Formation Period (Tt.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL, Imputed SL (ISL) and NL at 6 Months (n=23, 15)	0.24 year Interval 0.17 to 0.3	0.54 year Interval 0.32 to 1.37
Total Formation Period (Tt.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL and NL at 24 Months (n=8, 2)	0.27 year Interval 0.22 to 0.43	0.62 year Interval 0.38 to 0.86
Total Formation Period (Tt.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL, ISL and NL at 24 Months (n=9, 3)	0.31 year Interval 0.22 to 0.5	0.86 year Interval 0.38 to 0.89

SECONDARY outcome

Timeframe: 6 months

Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.

a. FP in CC is the mean time required to rebuild a new bone structural unit, calculated as wall thickness divided by MAR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=28 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=30 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months DL and NL (n=28, 16)	0.15 year Interval 0.14 to 0.17	0.16 year Interval 0.15 to 0.19
Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months DL, ISL and NL (n=28, 18)	0.15 year Interval 0.14 to 0.17	0.16 year Interval 0.15 to 0.21

SECONDARY outcome

Timeframe: 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had a.FP analysis of the CC at 24 months.

a. FP in CC is the mean time required to rebuild a new bone structural unit, calculated as wall thickness divided by MAR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=10 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=5 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months DL and NL (n=9, 2)	0.19 year Interval 0.17 to 0.22	0.19 year Interval 0.14 to 0.25
Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months DL, Imputed SL (ISL) and NL (n=10, 5)	0.19 year Interval 0.17 to 0.22	0.25 year Interval 0.24 to 0.27

SECONDARY outcome

Timeframe: 6 and 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had a.FP analysis of the EC at 6 and 24 months.

a. FP in EC is the mean time required to rebuild a new bone structural unit, calculated as wall thickness divided by MAR. Participants were given T for two 3 day-periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing.

Outcome measures

Outcome measures
Measure	Teriparatide n=23 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=15 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Active Formation Period (a.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL and NL at 6 Months (n=23, 6)	0.20 year Interval 0.17 to 0.22	0.20 year Interval 0.16 to 0.25
Active Formation Period (a.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL, Imputed SL (ISL) and NL at 6 Months (n=23, 15)	0.20 year Interval 0.17 to 0.22	0.28 year Interval 0.21 to 0.32
Active Formation Period (a.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL and NL at 24 Months (n=8, 2)	0.23 year Interval 0.21 to 0.26	0.22 year Interval 0.2 to 0.25
Active Formation Period (a.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months DL, ISL and NL at 24 Months (n=9, 3)	0.24 year Interval 0.21 to 0.27	0.25 year Interval 0.2 to 0.29

SECONDARY outcome

Timeframe: 6 months

Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.

The percent of single or double tetracycline labels per bone surface (sLS/BS, dLS/BS) in the cancellous compartment. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.

Outcome measures

Outcome measures
Measure	Teriparatide n=28 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=30 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months sLS/BS	3.19 percentage of tetracycline labels Inter-Quartile Range 2.85 • Interval 1.58 to 4.86	0.02 percentage of tetracycline labels Inter-Quartile Range 1.70 • Interval 0.0 to 0.38
Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months dLS/BS	4.13 percentage of tetracycline labels Inter-Quartile Range 8.90 • Interval 2.14 to 8.88	0.07 percentage of tetracycline labels Inter-Quartile Range 1.78 • Interval 0.0 to 0.3

SECONDARY outcome

Timeframe: 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had sLS/BS and dLS/BS analysis of the cancellous compartment at 24 months.

The percent of single or double tetracycline labels per bone surface (sLS/BS, dLS/BS) in the cancellous compartment. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.

Outcome measures

Outcome measures
Measure	Teriparatide n=10 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=9 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months sLS/BS	2.25 percentage of tetracycline labels Interval 1.27 to 2.9	0.15 percentage of tetracycline labels Interval 0.0 to 0.42
Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months dLS/BS	1.69 percentage of tetracycline labels Interval 0.41 to 3.69	0.00 percentage of tetracycline labels Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: 6 and 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had sLS/BS and dLS/BS analysis of the endocortical compartment at 6 and 24 months.

The percent of single or double tetracycline labels per bone surface (sLS/BS, dLS/BS) in the endocortical compartment. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.

Outcome measures

Outcome measures
Measure	Teriparatide n=23 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=29 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months sLS/BS at 24 months (n=9, 8)	3.75 percentage of tetracycline labels Interval 3.16 to 5.69	0.00 percentage of tetracycline labels Interval 0.0 to 1.12
Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months sLS/BS at 6 months (n=23, 29)	5.56 percentage of tetracycline labels Interval 3.42 to 8.06	0.25 percentage of tetracycline labels Interval 0.0 to 1.42
Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months dLS/BS at 6 months (n=23, 29)	13.46 percentage of tetracycline labels Interval 6.04 to 18.68	0.00 percentage of tetracycline labels Interval 0.0 to 0.0
Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months dLS/BS at 24 months (n=9, 8)	2.77 percentage of tetracycline labels Interval 0.95 to 2.98	0.00 percentage of tetracycline labels Interval 0.0 to 0.35

SECONDARY outcome

Timeframe: 6 months

Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.

Number of samples with single or double tetracycline labels, both single and double labels, or no labels in the cancellous compartment were compared between teriparatide and zoledronic acid treated participants. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.

Outcome measures

Outcome measures
Measure	Teriparatide n=28 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=30 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months No Label	0 samples	12 samples
Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months Single Label Only	0 samples	2 samples
Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months Double Label Only	0 samples	3 samples
Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months Single and Double Label	28 samples	13 samples

SECONDARY outcome

Timeframe: 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy of the cancellous compartment at 24 months.

Number of samples with single or double tetracycline labels, both single and double labels, or no labels in the cancellous compartment were compared between teriparatide and zoledronic acid treated participants. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.

Outcome measures

Outcome measures
Measure	Teriparatide n=10 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=9 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months No Label	0 samples	4 samples
Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months Single Label Only	1 samples	3 samples
Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months Double Label Only	0 samples	0 samples
Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months Single and Double Label	9 samples	2 samples

SECONDARY outcome

Timeframe: 6 and 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy of the endocortical compartment at 6 and 24 months.

Number of samples with single or double tetracycline labels, both single and double labels, or no labels in the endocortical compartment were compared between teriparatide and zoledronic acid treated participants. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.

Outcome measures

Outcome measures
Measure	Teriparatide n=23 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=29 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months No Label at 24 months (n=9, 8)	0 samples	5 samples
Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months No Label at 6 months (n=23, 29)	0 samples	14 samples
Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months Single Label Only at 6 months (n=23, 29)	0 samples	9 samples
Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months Double Label Only at 6 months (n=23, 29)	0 samples	0 samples
Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months Single and Double Label at 6 months (n=23, 29)	23 samples	6 samples
Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months Single Label Only at 24 months (n=9, 8)	1 samples	1 samples
Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months Double Label Only at 24 months (n=9, 8)	0 samples	0 samples
Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months Single and Double Label at 24 months (n=9, 8)	8 samples	2 samples

SECONDARY outcome

Timeframe: 6 months

Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.

The length of tetracycline double labels is a measure of the extent of bone formation in the cancellous compartment within individual remodeling units and is measured in millimeters (mm). Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.

Outcome measures

Outcome measures
Measure	Teriparatide n=28 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=16 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months	0.35 millimeter (mm) Inter-Quartile Range 0.08 • Interval 0.28 to 0.38	0.24 millimeter (mm) Inter-Quartile Range 0.08 • Interval 0.19 to 0.3

SECONDARY outcome

Timeframe: 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had length of tetracycline double labels analysis of the cancellous compartment at 24 months.

The length of tetracycline double labels is a measure of the extent of bone formation in the cancellous compartment within individual remodeling units and is measured in millimeters (mm). Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.

Outcome measures

Outcome measures
Measure	Teriparatide n=9 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=2 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months	0.23 millimeter (mm) Interval 0.22 to 0.29	0.29 millimeter (mm) Interval 0.19 to 0.38

SECONDARY outcome

Timeframe: 6 and 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had length of tetracycline double labels analysis of the endocortical compartment at 6 and 24 months.

The length of tetracycline double labels is a measure of the extent of bone formation in the endocortical compartment within individual remodeling units and is measured in millimeters (mm). Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation.

Outcome measures

Outcome measures
Measure	Teriparatide n=23 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=6 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Average Length of Tetracycline Double Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months 6 months (n=23, 6)	0.34 millimeter (mm) Interval 0.27 to 0.39	0.30 millimeter (mm) Interval 0.24 to 0.39
Average Length of Tetracycline Double Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months 24 months (n=8, 2)	0.27 millimeter (mm) Interval 0.24 to 0.43	0.30 millimeter (mm) Interval 0.24 to 0.36

SECONDARY outcome

Timeframe: 6 months

Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.

Osteoid volume (OV) in the cancellous compartment is the percent of a given volume of bone tissue that consists of unmineralized bone (osteoid).

Outcome measures

Outcome measures
Measure	Teriparatide n=28 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=30 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months	1.32 percentage of volume Inter-Quartile Range 1.47 • Interval 0.81 to 2.13	0.24 percentage of volume Inter-Quartile Range 0.76 • Interval 0.08 to 0.49

SECONDARY outcome

Timeframe: 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had OV/BV analysis of the CC at 24 months.

Osteoid volume (OV) in the cancellous compartment is the percent of a given volume of bone tissue that consists of unmineralized bone (osteoid).

Outcome measures

Outcome measures
Measure	Teriparatide n=10 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=9 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months	1.33 percentage of volume Interval 0.89 to 1.56	0.18 percentage of volume Interval 0.05 to 0.23

SECONDARY outcome

Timeframe: 6 months

Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.

Osteoid surface (OS) in the cancellous compartment is the fraction (%) of the entire trabecular bone surface that is covered by osteoid.

Outcome measures

Outcome measures
Measure	Teriparatide n=28 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=30 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months	11.34 percentage of surface Inter-Quartile Range 8.35 • Interval 6.58 to 16.52	2.51 percentage of surface Inter-Quartile Range 4.84 • Interval 1.27 to 4.58

SECONDARY outcome

Timeframe: 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had OS/BS analysis of the CC at 24 months.

Osteoid surface (OS) in the cancellous compartment is the fraction (%) of the entire trabecular bone surface that is covered by osteoid.

Outcome measures

Outcome measures
Measure	Teriparatide n=10 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=9 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months	11.19 percentage of surface Interval 7.23 to 13.14	1.26 percentage of surface Interval 0.72 to 2.89

SECONDARY outcome

Timeframe: 6 and 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had OS/BS analysis of the EC at 6 and 24 months.

Osteoid surface (OS) in the endocortical compartment is the fraction (%) of the entire trabecular bone surface that is covered by osteoid.

Outcome measures

Outcome measures
Measure	Teriparatide n=23 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=29 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months 6 months (n=23, 29)	16.33 percentage of surface Interval 13.57 to 24.34	1.87 percentage of surface Interval 1.08 to 3.99
Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months 24 months (n=9, 8)	7.48 percentage of surface Interval 6.39 to 10.1	1.55 percentage of surface Interval 1.19 to 3.47

SECONDARY outcome

Timeframe: 6 months

Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.

Osteoid thickness (OTh.) in the cancellous compartment is a measure of the average thickness of osteoid seams.

Outcome measures

Outcome measures
Measure	Teriparatide n=28 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=30 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Osteoid Thickness (OTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months	4.92 micrometer (µm) Inter-Quartile Range 1.38 • Interval 4.29 to 6.68	3.77 micrometer (µm) Inter-Quartile Range 1.10 • Interval 3.51 to 4.22

SECONDARY outcome

Timeframe: 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had OTh. analysis of the CC at 24 months.

Osteoid thickness (OTh.) in the cancellous compartment is a measure of the average thickness of osteoid seams.

Outcome measures

Outcome measures
Measure	Teriparatide n=10 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=9 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Osteoid Thickness (OTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months	5.71 micrometer (µm) Interval 4.68 to 6.15	3.98 micrometer (µm) Interval 3.48 to 5.69

SECONDARY outcome

Timeframe: 6 and 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had OTh. analysis of the EC at 6 and 24 months.

Osteoid thickness (OTh.) in the endocortical compartment is a measure of the average thickness of osteoid seams.

Outcome measures

Outcome measures
Measure	Teriparatide n=23 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=29 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Osteoid Thickness (OTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months 6 months (n=23, 29)	4.94 micrometer (µm) Interval 4.41 to 5.87	3.70 micrometer (µm) Interval 2.99 to 4.82
Osteoid Thickness (OTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months 24 months (n=9, 8)	5.23 micrometer (µm) Interval 4.22 to 7.24	3.53 micrometer (µm) Interval 3.21 to 5.07

SECONDARY outcome

Timeframe: 6 months

Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.

Wall thickness (WTh.) in the cancellous compartment is measured as the mean distance from the cement line to the marrow space of completed trabecular bone packets.

Outcome measures

Outcome measures
Measure	Teriparatide n=28 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=30 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Wall Thickness (WTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months	31.29 µm Inter-Quartile Range 3.25 • Interval 28.8 to 33.26	28.63 µm Inter-Quartile Range 2.59 • Interval 27.16 to 30.43

SECONDARY outcome

Timeframe: 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had WTh. analysis of the CC at 24 months.

Wall thickness (WTh.) in the cancellous compartment is measured as the mean distance from the cement line to the marrow space of completed trabecular bone packets.

Outcome measures

Outcome measures
Measure	Teriparatide n=10 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=9 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Wall Thickness (WTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months	31.37 micrometer (µm) Interval 28.29 to 32.34	29.26 micrometer (µm) Interval 27.04 to 29.66

SECONDARY outcome

Timeframe: 6 and 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had WTh. analysis of the EC at 6 and 24 months.

Wall thickness (WTh.) in the endocortical compartment is measured as the mean distance from the cement line to the marrow space of completed trabecular bone packets.

Outcome measures

Outcome measures
Measure	Teriparatide n=23 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=29 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Wall Thickness (WTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months 6 months (n=23, 29)	36.30 micrometer (µm) Interval 34.27 to 37.62	32.39 micrometer (µm) Interval 29.45 to 36.2
Wall Thickness (WTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months 24 months (n=9, 8)	34.00 micrometer (µm) Interval 33.59 to 36.92	32.45 micrometer (µm) Interval 31.43 to 36.44

SECONDARY outcome

Timeframe: 6 months

Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.

Eroded surface/bone surface (ES/BS) in the cancellous compartment 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.

Outcome measures

Outcome measures
Measure	Teriparatide n=28 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=30 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months	4.59 percentage of surface Interval 3.14 to 6.01	2.71 percentage of surface Interval 1.73 to 3.21

SECONDARY outcome

Timeframe: 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had ES/BS analysis of the CC at 24 months.

Eroded surface/bone surface (ES/BS) in the cancellous compartment 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.

Outcome measures

Outcome measures
Measure	Teriparatide n=10 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=9 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months	4.44 percentage of surface Interval 4.02 to 6.16	2.39 percentage of surface Interval 1.87 to 3.66

SECONDARY outcome

Timeframe: 6 and 24 months

Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had ES/BS analysis of the EC at 6 and 24 months.

Eroded surface/bone surface (ES/BS) in the endocortical compartment 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.

Outcome measures

Outcome measures
Measure	Teriparatide n=23 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=29 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Percentage of Eroded Surface/Bone Surface (ES/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months 6 months (n=23, 29)	4.06 percentage of surface Interval 1.92 to 6.32	1.87 percentage of surface Interval 1.54 to 3.33
Percentage of Eroded Surface/Bone Surface (ES/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months 24 months (n=9, 8)	3.43 percentage of surface Interval 2.1 to 4.72	1.88 percentage of surface Interval 1.55 to 2.27

SECONDARY outcome

Timeframe: Baseline, 1, 3, 6 months

Population: All randomized participants who received at least one dose of study drug with available biochemical marker of bone turnover data.

CTX is a measure of bone resorption.

Outcome measures

Outcome measures
Measure	Teriparatide n=34 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=35 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 1, 3 and 6 Endpoint Change at 1 month (n= 32, 31)	0.06 nanogram/milliliter (ng/mL) Inter-Quartile Range 0.20 • Interval -0.04 to 0.15	-0.37 nanogram/milliliter (ng/mL) Inter-Quartile Range 0.20 • Interval -0.46 to -0.29
Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 1, 3 and 6 Endpoint Change at 3 months (n= 32, 29)	0.26 nanogram/milliliter (ng/mL) Inter-Quartile Range 0.35 • Interval 0.06 to 0.51	-0.35 nanogram/milliliter (ng/mL) Inter-Quartile Range 0.19 • Interval -0.42 to -0.29
Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 1, 3 and 6 Endpoint Change at 6 months (n= 25, 28)	0.31 nanogram/milliliter (ng/mL) Inter-Quartile Range 0.48 • Interval 0.19 to 0.75	-0.32 nanogram/milliliter (ng/mL) Inter-Quartile Range 0.19 • Interval -0.42 to -0.23

SECONDARY outcome

Timeframe: Baseline, 12 months

Population: All participants who received at least one dose of study drug, had baseline and 12 months CTX measurement.

CTX is a measure of bone resorption.

Outcome measures

Outcome measures
Measure	Teriparatide n=26 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=28 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 12 Endpoint	0.42 nanogram/milliliter (ng/mL) Interval 0.22 to 0.66	-0.23 nanogram/milliliter (ng/mL) Interval -0.35 to -0.18

SECONDARY outcome

Timeframe: Baseline, 1, 3, 6 months

Population: All randomized participants who received at least one dose of study drug with available biochemical marker of bone turnover data.

PINP is a measure of bone formation.

Outcome measures

Outcome measures
Measure	Teriparatide n=34 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=35 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 1, 3 and 6 Endpoint Change at 1 month (n= 32, 31)	65.50 microgram/Liter (µg/L) Inter-Quartile Range 32.03 • Interval 35.5 to 82.0	-15.00 microgram/Liter (µg/L) Inter-Quartile Range 9.27 • Interval -21.0 to -11.0
Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 1, 3 and 6 Endpoint Change at 3 months (n= 32, 29)	66.00 microgram/Liter (µg/L) Inter-Quartile Range 68.65 • Interval 33.5 to 107.5	-39.00 microgram/Liter (µg/L) Inter-Quartile Range 14.58 • Interval -47.0 to -28.0
Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 1, 3 and 6 Endpoint Change at 6 months (n= 25, 28)	84.00 microgram/Liter (µg/L) Inter-Quartile Range 135.90 • Interval 63.0 to 155.0	-37.50 microgram/Liter (µg/L) Inter-Quartile Range 16.44 • Interval -48.5 to -26.5

SECONDARY outcome

Timeframe: Baseline, 12 months

Population: All participants who received at least one dose of study drug, had baseline and 12 months PINP measurement.

PINP is a measure of bone formation.

Outcome measures

Outcome measures
Measure	Teriparatide n=26 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=28 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 12 Endpoint	93.50 microgram/liter (µg/L) Interval 49.0 to 155.0	-33.00 microgram/liter (µg/L) Interval -38.0 to -21.5

SECONDARY outcome

Timeframe: Baseline, 1, 3, 6 months

Population: All randomized participants who received at least one dose of study drug with available biochemical marker of bone turnover data.

OC is a measure of osteoblast function.

Outcome measures

Outcome measures
Measure	Teriparatide n=34 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=35 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Change From Baseline in Serum Osteocalcin (OC) at Month 1, 3, and 6 Endpoint Change at 1 month (n= 32, 32)	22.35 µg/L Inter-Quartile Range 11.58 • Interval 17.89 to 29.01	-3.39 µg/L Inter-Quartile Range 2.82 • Interval -4.64 to -1.28
Change From Baseline in Serum Osteocalcin (OC) at Month 1, 3, and 6 Endpoint Change at 3 months (n=32, 30)	29.93 µg/L Inter-Quartile Range 19.02 • Interval 20.03 to 40.67	-12.30 µg/L Inter-Quartile Range 5.01 • Interval -13.39 to -8.08
Change From Baseline in Serum Osteocalcin (OC) at Month 1, 3, and 6 Endpoint Change at 6 months (n= 25, 29)	30.85 µg/L Inter-Quartile Range 33.21 • Interval 22.78 to 56.22	-14.06 µg/L Inter-Quartile Range 7.15 • Interval -15.97 to -11.08

SECONDARY outcome

Timeframe: Baseline, 12 months

Population: All participants who received at least one dose of study drug, had baseline and 12 months OC measurements.

OC is a measure of osteoblast function.

Outcome measures

Outcome measures
Measure	Teriparatide n=26 Participants 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=30 Participants 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Change From Baseline in Serum Osteocalcin (OC) at Month 12 Endpoint	32.98 microgram/liter (µg/L) Interval 15.14 to 45.56	-12.32 microgram/liter (µg/L) Interval -15.42 to -8.22

Adverse Events

Teriparatide

Serious events: 2 serious events

Other events: 31 other events

Deaths: 0 deaths

Zoledronic Acid

Serious events: 3 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Teriparatide n=34 participants at risk 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.	Zoledronic Acid n=35 participants at risk 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
General disorders Non-cardiac chest pain	2.9% 1/34 • Number of events 1 • 24 months Adverse events were updated to add the adverse events that occurred during the 12 month extension period to the adverse events that were previously reported from the initial 12 month period.	0.00% 0/35 • 24 months Adverse events were updated to add the adverse events that occurred during the 12 month extension period to the adverse events that were previously reported from the initial 12 month period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign salivary gland neoplasm	2.9% 1/34 • Number of events 1 • 24 months Adverse events were updated to add the adverse events that occurred during the 12 month extension period to the adverse events that were previously reported from the initial 12 month period.	0.00% 0/35 • 24 months Adverse events were updated to add the adverse events that occurred during the 12 month extension period to the adverse events that were previously reported from the initial 12 month period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma of liver	0.00% 0/34 • 24 months Adverse events were updated to add the adverse events that occurred during the 12 month extension period to the adverse events that were previously reported from the initial 12 month period.	2.9% 1/35 • Number of events 1 • 24 months Adverse events were updated to add the adverse events that occurred during the 12 month extension period to the adverse events that were previously reported from the initial 12 month period.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/34 • 24 months Adverse events were updated to add the adverse events that occurred during the 12 month extension period to the adverse events that were previously reported from the initial 12 month period.	2.9% 1/35 • Number of events 1 • 24 months Adverse events were updated to add the adverse events that occurred during the 12 month extension period to the adverse events that were previously reported from the initial 12 month period.
Vascular disorders Aneurysm	0.00% 0/34 • 24 months Adverse events were updated to add the adverse events that occurred during the 12 month extension period to the adverse events that were previously reported from the initial 12 month period.	2.9% 1/35 • Number of events 1 • 24 months Adverse events were updated to add the adverse events that occurred during the 12 month extension period to the adverse events that were previously reported from the initial 12 month period.

Other adverse events

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