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

Primary Purpose

Osteoporosis, Post-menopausal

Status

Completed

Phase

Phase 4

Locations

International

Study Type

Interventional

Intervention

Teriparatide

Zoledronic Acid

About this trial

This is an interventional treatment trial for Osteoporosis, Post-menopausal focused on measuring osteoporosis, teriparatide, zoledronic acid, histomorphometry, bone biopsy, postmenopausal

Eligibility Criteria

55 Years - 89 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Teriparatide

Zoledronic Acid

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

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.

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.

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.

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.

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.

Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

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.

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.

Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

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.

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.

Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

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.

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.

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

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.

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.

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, 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.

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.

Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months

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.

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).

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months

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.

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.

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.

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.

Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 12 Endpoint

PINP is a measure of bone formation.

Change From Baseline in Serum Osteocalcin (OC) at Month 1, 3, and 6 Endpoint

OC is a measure of osteoblast function.

Change From Baseline in Serum Osteocalcin (OC) at Month 12 Endpoint

OC is a measure of osteoblast function.

Full Information

NCT ID

NCT00927186

First Posted

June 22, 2009

Last Updated

February 21, 2013

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT00927186

Brief Title

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

Official Title

Skeletal Histomorphometry in Patients on Teriparatide or Zoledronic Acid Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

February 2013

Overall Recruitment Status

Completed

Study Start Date

July 2009 (undefined)

Primary Completion Date

October 2010 (Actual)

Study Completion Date

April 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Osteoporosis, Post-menopausal

Keywords

osteoporosis, teriparatide, zoledronic acid, histomorphometry, bone biopsy, postmenopausal

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

69 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Teriparatide

Arm Type

Experimental

Arm Title

Zoledronic Acid

Arm Type

Active Comparator

Intervention Type

Drug

Intervention Name(s)

Teriparatide

Other Intervention Name(s)

LY333334, Forteo, Forsteo

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Zoledronic Acid

Intervention Description

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.

Primary Outcome Measure Information:

Title

Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months

Description

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

Description

Time Frame

24 months

Title

Mineralizing Surface/Bone Surface(MS/BS) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months

Description

Time Frame

6 and 24 months

Title

Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months

Description

Time Frame

6 months

Title

Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

Description

Time Frame

24 months

Title

Activation Frequency (Ac.f) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months

Description

Time Frame

6 and 24 months

Title

Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months

Description

Time Frame

6 months

Title

Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

Description

Time Frame

24 months

Title

Bone Formation Rate (BFR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months

Description

Time Frame

6 and 24 months

Title

Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months

Description

Time Frame

6 months

Title

Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

Description

Time Frame

24 months

Title

Mineral Apposition Rate (MAR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months

Description

Time Frame

6 and 24 months

Title

Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months

Description

Time Frame

6 months

Title

Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

Description

Time Frame

24 months

Title

Adjusted Apposition Rate (Aj.AR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months

Description

Time Frame

6 and 24 months

Title

Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months

Description

Time Frame

6 months

Title

Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

Description

Time Frame

24 months

Title

Mineralization Lag Time (Mlt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months

Description

Time Frame

6 and 24 months

Title

Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months

Description

Time Frame

6 months

Title

Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

Description

Time Frame

24 months

Title

Osteoid Maturation Time (Omt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months

Description

Time Frame

6 and 24 Months

Title

Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months

Description

Time Frame

6 months

Title

Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

Description

Time Frame

24 months

Title

Total Formation Period (Tt.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months

Description

Time Frame

6 and 24 months

Title

Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months

Description

Time Frame

6 months

Title

Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

Description

Time Frame

24 months

Title

Active Formation Period (a.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months

Description

Time Frame

6 and 24 months

Title

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

Description

Time Frame

6 months

Title

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

Description

Time Frame

24 months

Title

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

Description

Time Frame

6 and 24 months

Title

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

Description

Time Frame

6 months

Title

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

Description

Time Frame

24 months

Title

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

Description

Time Frame

6 and 24 months

Title

Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months

Description

Time Frame

6 months

Title

Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months

Description

Time Frame

24 months

Title

Average Length of Tetracycline Double Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months

Description

Time Frame

6 and 24 months

Title

Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months

Description

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

Time Frame

6 months

Title

Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months

Description

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

Time Frame

24 months

Title

Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months

Description

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

Time Frame

6 months

Title

Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months

Description

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

Time Frame

24 months

Title

Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months

Description

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

Time Frame

6 and 24 months

Title

Osteoid Thickness (OTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months

Description

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

Time Frame

6 months

Title

Osteoid Thickness (OTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months

Description

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

Time Frame

24 months

Title

Osteoid Thickness (OTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months

Description

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

Time Frame

6 and 24 months

Title

Wall Thickness (WTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months

Description

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.

Time Frame

6 months

Title

Wall Thickness (WTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months

Description

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.

Time Frame

24 months

Title

Wall Thickness (WTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months

Description

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.

Time Frame

6 and 24 months

Title

Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months

Description

Time Frame

6 months

Title

Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months

Description

Time Frame

24 months

Title

Percentage of Eroded Surface/Bone Surface (ES/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months

Description

Time Frame

6 and 24 months

Title

Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 1, 3 and 6 Endpoint

Description

CTX is a measure of bone resorption.

Time Frame

Baseline, 1, 3, 6 months

Title

Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 12 Endpoint

Description

CTX is a measure of bone resorption.

Time Frame

Baseline, 12 months

Title

Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 1, 3 and 6 Endpoint

Description

PINP is a measure of bone formation.

Time Frame

Baseline, 1, 3, 6 months

Title

Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 12 Endpoint

Description

PINP is a measure of bone formation.

Time Frame

Baseline, 12 months

Title

Change From Baseline in Serum Osteocalcin (OC) at Month 1, 3, and 6 Endpoint

Description

OC is a measure of osteoblast function.

Time Frame

Baseline, 1, 3, 6 months

Title

Change From Baseline in Serum Osteocalcin (OC) at Month 12 Endpoint

Description

OC is a measure of osteoblast function.

Time Frame

Baseline, 12 months

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

55 Years

Maximum Age & Unit of Time

89 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

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.

City

Lakewood

State/Province

Colorado

ZIP/Postal Code

80227

Country

United States

Facility Name

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30319

Country

United States

Facility Name

City

Gainesville

State/Province

Georgia

ZIP/Postal Code

30501

Country

United States

Facility Name

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20817

Country

United States

Facility Name

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48202

Country

United States

Facility Name

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68131

Country

United States

Facility Name

City

Albuquerque

State/Province

New Mexico

ZIP/Postal Code

87106

Country

United States

Facility Name

City

West Haverstraw

State/Province

New York

ZIP/Postal Code

10993

Country

United States

Facility Name

City

Madison

State/Province

Wisconsin

ZIP/Postal Code

53705

Country

United States

Facility Name

City

Calgary

State/Province

Alberta

ZIP/Postal Code

T2N 4Z6

Country

Canada

Facility Name

City

Vancouver

State/Province

British Columbia

ZIP/Postal Code

V6H 3X8

Country

Canada

Facility Name

City

Sainte-Foy

State/Province

Quebec

ZIP/Postal Code

G1V 3M7

Country

Canada

12. IPD Sharing Statement

Citations:

PubMed Identifier

26841258

Citation

Dempster DW, Zhou H, Recker RR, Brown JP, Bolognese MA, Recknor CP, Kendler DL, Lewiecki EM, Hanley DA, Rao SD, Miller PD, Woodson GC 3rd, Lindsay R, Binkley N, Alam J, Ruff VA, Gallagher ER, Taylor KA. A Longitudinal Study of Skeletal Histomorphometry at 6 and 24 Months Across Four Bone Envelopes in Postmenopausal Women With Osteoporosis Receiving Teriparatide or Zoledronic Acid in the SHOTZ Trial. J Bone Miner Res. 2016 Jul;31(7):1429-39. doi: 10.1002/jbmr.2804. Epub 2016 Mar 8.

Results Reference

derived

Learn more about this trial

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

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