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

Osteoporosis, Post-menopausal Clinical Trial

Official title:

Skeletal Histomorphometry in Patients on Teriparatide or Zoledronic Acid Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00927186
• Other study ID #: 13032
• Secondary ID: B3D-US-GHDL
• Status: Completed
• Phase: Phase 4
• First received: June 22, 2009
• Last updated: February 21, 2013
• Start date: July 2009
• Est. completion date: April 2012

Study information

• Verified date: February 2013
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate how teriparatide or zoledronic acid affects the bone of postmenopausal osteoporotic women after 6 months of treatment as determined by a bone biopsy sample taken from the iliac crest (upper part of the pelvis). After completing 12 months of treatment all participants are eligible to participate in an additional 12-month open label extension.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: April 2012
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 55 Years to 89 Years

Eligibility

Inclusion Criteria:

• Ambulatory, postmenopausal women with osteoporosis (no vaginal bleeding for at least 2 years prior to trial entry)

• Free of severe or chronically disabling conditions other than osteoporosis that will impair ability to complete the trial

• Bone mineral density (BMD) T-score of at least -2.5 at the femoral neck, total hip, or lumbar spine (L1-L4, with at least 2 evaluable vertebrae), with or without atraumatic fracture or,

• Bone mineral density (BMD) T-score of at least -1.5 at the femoral neck, or total hip, or lumbar spine (L1-L4, with at least 2 evaluable vertebrae), and either 1 or more atraumatic vertebral fracture(s) or an atraumatic nonvertebral fracture in the opinion of the investigator. Nonvertebral fracture sites allowed are wrist, hip, pelvis, ribs, humerus, clavicle, leg (femur, tibia, and fibula, excluding the ankle).

• Serum calcium, parathyroid hormone (PTH), alkaline phosphatase must be within normal reference range

Exclusion Criteria:

• Have an increased risk of osteosarcoma (bone tumor); this includes Paget's disease of bone, a previous bone tumor, or radiation involving the skeleton

• Are allergic or cannot tolerate teriparatide or zoledronic acid or any of their ingredients or components

• Are allergic to tetracycline

• Have a history of exposure to tetracycline therapy in the 3 months prior to trial entry

• Have participated in a prior PTH clinical trial or received prior treatment with teriparatide, PTH, or other related medications

• Have a vitamin D level below 10 nanogram/milliliter (ng/mL)

• Have a condition that could possibly put one at risk for an adverse event due to the bone biopsy procedure (e.g. bleeding disorder)

• Have undergone two previous iliac crest bone biopsies (one in each iliac crest)

• Have taken any intravenous (IV) osteoporosis medication

• Have taken other oral osteoporosis medications and have not been off of them for a specific period of time before trial entry

• Have a history of certain cancers in the 5 years prior to trial entry

• Have active liver disease

• Have significantly impaired kidney function

• Currently have active or suspected diseases that affect the bones, other than osteoporosis

• Have active or recent history of significant gastrointestinal (stomach or intestinal) disorders

• Have been treated with certain glucocorticoids for more than 30 days in the past 1 year prior to trial entry

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteoporosis
• Osteoporosis, Post-menopausal
• Osteoporosis, Postmenopausal

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Canada	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Calgary	Alberta
Canada	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sainte-Foy	Quebec
Canada	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Vancouver	British Columbia
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Albuquerque	New Mexico
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Atlanta	Georgia
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bethesda	Maryland
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Detroit	Michigan
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Gainesville	Georgia
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lakewood	Colorado
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Madison	Wisconsin
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Omaha	Nebraska
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	West Haverstraw	New York

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 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.	6 months	No
Secondary	Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies 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.	24 months	No
Secondary	Mineralizing Surface/Bone Surface(MS/BS) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies 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.	6 and 24 months	No
Secondary	Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months	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.	6 months	No
Secondary	Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies 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.	24 months	No
Secondary	Activation Frequency (Ac.f) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies 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.	6 and 24 months	No
Secondary	Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months	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.	6 months	No
Secondary	Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies 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.	24 months	No
Secondary	Bone Formation Rate (BFR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies 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.	6 and 24 months	No
Secondary	Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 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 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.	6 months	No
Secondary	Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies 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.	24 months	No
Secondary	Mineral Apposition Rate (MAR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies 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.	6 and 24 months	No
Secondary	Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 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.	6 months	No
Secondary	Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies 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.	24 months	No
Secondary	Adjusted Apposition Rate (Aj.AR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies 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.	6 and 24 months	No
Secondary	Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months	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.	6 months	No
Secondary	Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies 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.	24 months	No
Secondary	Mineralization Lag Time (Mlt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies 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.	6 and 24 months	No
Secondary	Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 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.	6 months	No
Secondary	Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies 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.	24 months	No
Secondary	Osteoid Maturation Time (Omt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies 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.	6 and 24 Months	No
Secondary	Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 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.	6 months	No
Secondary	Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies 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.	24 months	No
Secondary	Total Formation Period (Tt.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies 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.	6 and 24 months	No
Secondary	Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 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.	6 months	No
Secondary	Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies 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.	24 months	No
Secondary	Active Formation Period (a.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies 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.	6 and 24 months	No
Secondary	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	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.	6 months	No
Secondary	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	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.	24 months	No
Secondary	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	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.	6 and 24 months	No
Secondary	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	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.	6 months	No
Secondary	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	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.	24 months	No
Secondary	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	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.	6 and 24 months	No
Secondary	Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 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.	6 months	No
Secondary	Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies 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.	24 months	No
Secondary	Average Length of Tetracycline Double Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies 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.	6 and 24 months	No
Secondary	Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months	Osteoid volume (OV) in the cancellous compartment is the percent of a given volume of bone tissue that consists of unmineralized bone (osteoid).	6 months	No
Secondary	Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the Cancellous Compartment of Iliac Crest Bone Biopsies 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).	24 months	No
Secondary	Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months	Osteoid surface (OS) in the cancellous compartment is the fraction (%) of the entire trabecular bone surface that is covered by osteoid.	6 months	No
Secondary	Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months	Osteoid surface (OS) in the cancellous compartment is the fraction (%) of the entire trabecular bone surface that is covered by osteoid.	24 months	No
Secondary	Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies 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.	6 and 24 months	No
Secondary	Osteoid Thickness (OTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months	Osteoid thickness (OTh.) in the cancellous compartment is a measure of the average thickness of osteoid seams.	6 months	No
Secondary	Osteoid Thickness (OTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months	Osteoid thickness (OTh.) in the cancellous compartment is a measure of the average thickness of osteoid seams.	24 months	No
Secondary	Osteoid Thickness (OTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months	Osteoid thickness (OTh.) in the endocortical compartment is a measure of the average thickness of osteoid seams.	6 and 24 months	No
Secondary	Wall Thickness (WTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 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.	6 months	No
Secondary	Wall Thickness (WTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies 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.	24 months	No
Secondary	Wall Thickness (WTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies 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.	6 and 24 months	No
Secondary	Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 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.	6 months	No
Secondary	Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies 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.	24 months	No
Secondary	Percentage of Eroded Surface/Bone Surface (ES/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies 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.	6 and 24 months	No
Secondary	Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 1, 3 and 6 Endpoint	CTX is a measure of bone resorption.	Baseline, 1, 3, 6 months	No
Secondary	Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 12 Endpoint	CTX is a measure of bone resorption.	Baseline, 12 months	No
Secondary	Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 1, 3 and 6 Endpoint	PINP is a measure of bone formation.	Baseline, 1, 3, 6 months	No
Secondary	Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 12 Endpoint	PINP is a measure of bone formation.	Baseline, 12 months	No
Secondary	Change From Baseline in Serum Osteocalcin (OC) at Month 1, 3, and 6 Endpoint	OC is a measure of osteoblast function.	Baseline, 1, 3, 6 months	No
Secondary	Change From Baseline in Serum Osteocalcin (OC) at Month 12 Endpoint	OC is a measure of osteoblast function.	Baseline, 12 months	No