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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00927186
First received: June 22, 2009
Last updated: February 21, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Osteoporosis, Post-menopausal
Drug: Teriparatide
Drug: Zoledronic Acid
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Skeletal Histomorphometry in Patients on Teriparatide or Zoledronic Acid Therapy

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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.

  • Mineralizing Surface/Bone Surface(MS/BS) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months [ Time Frame: 6 and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months [ Time Frame: 6 and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months [ Time Frame: 6 and 24 Months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months [ Time Frame: 6 and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months [ Time Frame: 6 and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months [ Time Frame: 6 and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months [ Time Frame: 6 and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months [ Time Frame: 6 and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months [ Time Frame: 6 and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 1, 3, 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 1, 3, 6 months ] [ Designated as safety issue: No ]
    PINP is a measure of bone formation.

  • Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 12 Endpoint [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: No ]
    PINP is a measure of bone formation.

  • Change From Baseline in Serum Osteocalcin (OC) at Month 1, 3, and 6 Endpoint [ Time Frame: Baseline, 1, 3, 6 months ] [ Designated as safety issue: No ]
    OC is a measure of osteoblast function.

  • Change From Baseline in Serum Osteocalcin (OC) at Month 12 Endpoint [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: No ]
    OC is a measure of osteoblast function.


Enrollment: 69
Study Start Date: July 2009
Study Completion Date: April 2012
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Teriparatide 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.

Other Names:
  • LY333334
  • Forteo
  • Forsteo
Active Comparator: Zoledronic Acid Drug: 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.


  Eligibility

Ages Eligible for Study:   55 Years to 89 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00927186

Locations
United States, Colorado
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, 80227
United States, Georgia
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, 30319
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, 30501
United States, Maryland
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, 20817
United States, Michigan
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, 48202
United States, Nebraska
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, 68131
United States, New Mexico
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, 87106
United States, New York
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, United States, 10993
United States, Wisconsin
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, 53705
Canada, Alberta
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, T2N 4Z6
Canada, British Columbia
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, Canada, V6H 3X8
Canada, Quebec
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, G1V 3M7
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00927186     History of Changes
Other Study ID Numbers: 13032, B3D-US-GHDL
Study First Received: June 22, 2009
Results First Received: October 7, 2011
Last Updated: February 21, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Eli Lilly and Company:
osteoporosis
teriparatide
zoledronic acid
histomorphometry
bone biopsy
postmenopausal

Additional relevant MeSH terms:
Osteoporosis
Osteoporosis, Postmenopausal
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Zoledronic acid
Teriparatide
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 26, 2014