Osteoporosis, Post-menopausal
Conditions
Keywords
osteoporosis, teriparatide, zoledronic acid, histomorphometry, bone biopsy, postmenopausal
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.
Interventions
DRUGTeriparatide
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.
DRUGZoledronic 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.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
55 Years to 89 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | 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
| Measure | Time frame | Description |
|---|---|---|
| Mineralizing Surface/Bone Surface(MS/BS) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
| Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | 6 months | Osteoid surface (OS) in the cancellous compartment is the fraction (%) of the entire trabecular bone surface that is covered by osteoid. |
| Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | 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. |
| Adjusted Apposition Rate (Aj.AR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | 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 | 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 | 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 | 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 | 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 | 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. |
| Osteoid Maturation Time (Omt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | 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 | 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 | 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. |
| Total Formation Period (Tt.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | 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 | 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 | 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. |
| Active Formation Period (a.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | 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 | 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 | 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. |
| 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 | 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 | 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 | 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. |
| Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | 24 months | Osteoid surface (OS) in the cancellous compartment is the fraction (%) of the entire trabecular bone surface that is covered by osteoid. |
| 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 | 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 | 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 | 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. |
| Average Length of Tetracycline Double Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 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 | 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 | 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 Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
| Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | 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. |
| Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 1, 3 and 6 Endpoint | Baseline, 1, 3, 6 months | 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 | Baseline, 12 months | 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 | Baseline, 1, 3, 6 months | PINP is a measure of bone formation. |
| Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 12 Endpoint | Baseline, 12 months | PINP is a measure of bone formation. |
| Change From Baseline in Serum Osteocalcin (OC) at Month 1, 3, and 6 Endpoint | Baseline, 1, 3, 6 months | OC is a measure of osteoblast function. |
| Change From Baseline in Serum Osteocalcin (OC) at Month 12 Endpoint | Baseline, 12 months | OC is a measure of osteoblast function. |
| Percentage of Eroded Surface/Bone Surface (ES/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 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. |
Countries
Canada, United States
Participant flow
Pre-assignment details
This was a Phase 4, multicenter, randomized, stratified, double-blind, active comparator-controlled study with the primary endpoint at 6 months. Following the bone biopsy visit at 6 months, the study became open label for an additional 6 months. All participants who complete 12 months of treatment are eligible for an additional 12-month extension.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 34 |
| 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. | 35 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 12 Months Primary Study | Adverse Event | 5 | 2 |
| 12 Months Primary Study | Lost to Follow-up | 1 | 0 |
| 12 Months Primary Study | Protocol Violation | 0 | 1 |
| 12 Months Primary Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Zoledronic Acid | Total | Teriparatide |
|---|---|---|---|
| Age Continuous | 64.20 years STANDARD_DEVIATION 5.96 | 64.84 years STANDARD_DEVIATION 6.44 | 65.49 years STANDARD_DEVIATION 6.93 |
| Alcohol Use No | 18 participants | 31 participants | 13 participants |
| Alcohol Use Yes | 17 participants | 38 participants | 21 participants |
| Blood Pressure - Diastolic | 73.97 mmHg STANDARD_DEVIATION 10.15 | 74.38 mmHg STANDARD_DEVIATION 9.2 | 74.79 mmHg STANDARD_DEVIATION 8.24 |
| Blood Pressure - Systolic | 122.49 millimeters of mercury (mmHg) STANDARD_DEVIATION 16.25 | 124.07 millimeters of mercury (mmHg) STANDARD_DEVIATION 16.18 | 125.71 millimeters of mercury (mmHg) STANDARD_DEVIATION 16.19 |
| Caffeine or Xanthine Use No | 5 participants | 10 participants | 5 participants |
| Caffeine or Xanthine Use Yes | 30 participants | 59 participants | 29 participants |
| Femoral Neck T-Score | -2.29 T-Score STANDARD_DEVIATION 0.74 | -2.27 T-Score STANDARD_DEVIATION 0.7 | -2.25 T-Score STANDARD_DEVIATION 0.68 |
| Fracture Status No | 18 participants | 38 participants | 20 participants |
| Fracture Status Yes | 17 participants | 31 participants | 14 participants |
| Height | 160.00 centimeters (cm) STANDARD_DEVIATION 7.38 | 159.64 centimeters (cm) STANDARD_DEVIATION 6.66 | 159.28 centimeters (cm) STANDARD_DEVIATION 5.92 |
| Lumbar Spine T-Score | -2.93 T-Score STANDARD_DEVIATION 0.75 | -2.86 T-Score STANDARD_DEVIATION 0.79 | -2.79 T-Score STANDARD_DEVIATION 0.83 |
| Previous Osteoporosis Therapy No | 14 participants | 31 participants | 17 participants |
| Previous Osteoporosis Therapy Yes | 21 participants | 38 participants | 17 participants |
| Pulse | 70.60 beats per minute (bpm) STANDARD_DEVIATION 8.79 | 69.03 beats per minute (bpm) STANDARD_DEVIATION 8.13 | 67.41 beats per minute (bpm) STANDARD_DEVIATION 7.15 |
| Race/Ethnicity, Customized Black or African American | 1 participants | 2 participants | 1 participants |
| Race/Ethnicity, Customized White | 34 participants | 67 participants | 33 participants |
| Region of Enrollment Canada | 10 participants | 23 participants | 13 participants |
| Region of Enrollment United States | 25 participants | 46 participants | 21 participants |
| Serum Carboxyterminal Cross-Linking Telopeptide of Collagen Type I (CTX) | 0.42 nanogram/milliliter (ng/mL) STANDARD_DEVIATION 0.19 | 0.43 nanogram/milliliter (ng/mL) STANDARD_DEVIATION 0.21 | 0.43 nanogram/milliliter (ng/mL) STANDARD_DEVIATION 0.23 |
| Serum Osteocalcin | 24.92 microgram/Liter (µg/L) STANDARD_DEVIATION 8.53 | 24.98 microgram/Liter (µg/L) STANDARD_DEVIATION 8.39 | 25.05 microgram/Liter (µg/L) STANDARD_DEVIATION 8.37 |
| Serum Procollagen Type I N-Terminal Propeptide (PINP) | 52.88 microgram/Liter (µg/L) STANDARD_DEVIATION 19.43 | 51.03 microgram/Liter (µg/L) STANDARD_DEVIATION 18.81 | 49.18 microgram/Liter (µg/L) STANDARD_DEVIATION 18.28 |
| Sex: Female, Male Female | 35 Participants | 69 Participants | 34 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Tobacco Use No | 30 participants | 59 participants | 29 participants |
| Tobacco Use Yes | 5 participants | 10 participants | 5 participants |
| Total Hip T-Score | -1.88 T-Score STANDARD_DEVIATION 0.91 | -1.83 T-Score STANDARD_DEVIATION 0.84 | -1.78 T-Score STANDARD_DEVIATION 0.78 |
| Weight | 64.75 kilograms (kg) STANDARD_DEVIATION 11.66 | 63.03 kilograms (kg) STANDARD_DEVIATION 10.6 | 61.25 kilograms (kg) STANDARD_DEVIATION 9.21 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 31 / 34 | 31 / 35 |
| serious Total, serious adverse events | 2 / 34 | 3 / 35 |
Outcome results
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.
Time frame: 6 months
Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Teriparatide | Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | 5.60 percentage of surface | Inter-Quartile Range 10.2 |
| Zoledronic Acid | Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | 0.16 percentage of surface | Inter-Quartile Range 2.62 |
p-value: <0.001Wilcoxon (Mann-Whitney)
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.
Time frame: 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had Ac.f analysis of the CC at 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL and NL (n=9, 6) | 0.19 new cycles/year |
| Teriparatide | Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL, Imputed SL (ISL) and NL (n=10, 9) | 0.18 new cycles/year |
| Zoledronic Acid | Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL and NL (n=9, 6) | 0.00 new cycles/year |
| Zoledronic Acid | Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL, Imputed SL (ISL) and NL (n=10, 9) | 0.00 new cycles/year |
p-value: 0.002Wilcoxon (Mann-Whitney)
p-value: 0.002Wilcoxon (Mann-Whitney)
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.
Time frame: 6 months
Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL and NL (n=28, 28) | 0.37 new cycles/year |
| Teriparatide | Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL, Imputed SL (ISL) and NL (n=28, 30) | 0.37 new cycles/year |
| Zoledronic Acid | Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL and NL (n=28, 28) | 0.01 new cycles/year |
| Zoledronic Acid | Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL, Imputed SL (ISL) and NL (n=28, 30) | 0.01 new cycles/year |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: <0.001Wilcoxon (Mann-Whitney)
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.
Time frame: 6 and 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had Ac.f analysis of the EC at 6 and 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Activation Frequency (Ac.f) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 6 Months (n=23, 20) | 0.83 new cycles/year |
| Teriparatide | Activation Frequency (Ac.f) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, Imputed SL (ISL) and NL at 6 Months (n=23, 29) | 0.83 new cycles/year |
| Teriparatide | Activation Frequency (Ac.f) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 24 Months (n=8, 7) | 0.25 new cycles/year |
| Teriparatide | Activation Frequency (Ac.f) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, ISL and NL at 24 Months (n=9, 8) | 0.24 new cycles/year |
| Zoledronic Acid | Activation Frequency (Ac.f) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, ISL and NL at 24 Months (n=9, 8) | 0.00 new cycles/year |
| Zoledronic Acid | Activation Frequency (Ac.f) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 6 Months (n=23, 20) | 0.00 new cycles/year |
| Zoledronic Acid | Activation Frequency (Ac.f) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 24 Months (n=8, 7) | 0.00 new cycles/year |
| Zoledronic Acid | Activation Frequency (Ac.f) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, Imputed SL (ISL) and NL at 6 Months (n=23, 29) | 0.01 new cycles/year |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: 0.002Wilcoxon (Mann-Whitney)
p-value: 0.002Wilcoxon (Mann-Whitney)
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.
Time frame: 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had a.FP analysis of the CC at 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL and NL (n=9, 2) | 0.19 year |
| Teriparatide | Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL, Imputed SL (ISL) and NL (n=10, 5) | 0.19 year |
| Zoledronic Acid | Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL and NL (n=9, 2) | 0.19 year |
| Zoledronic Acid | Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL, Imputed SL (ISL) and NL (n=10, 5) | 0.25 year |
p-value: 0.906Wilcoxon (Mann-Whitney)
p-value: 0.159Wilcoxon (Mann-Whitney)
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.
Time frame: 6 months
Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL and NL (n=28, 16) | 0.15 year |
| Teriparatide | Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL, ISL and NL (n=28, 18) | 0.15 year |
| Zoledronic Acid | Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL and NL (n=28, 16) | 0.16 year |
| Zoledronic Acid | Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL, ISL and NL (n=28, 18) | 0.16 year |
p-value: 0.154Wilcoxon (Mann-Whitney)
p-value: 0.052Wilcoxon (Mann-Whitney)
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.
Time frame: 6 and 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had a.FP analysis of the EC at 6 and 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Active Formation Period (a.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 6 Months (n=23, 6) | 0.20 year |
| Teriparatide | Active Formation Period (a.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, Imputed SL (ISL) and NL at 6 Months (n=23, 15) | 0.20 year |
| Teriparatide | Active Formation Period (a.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 24 Months (n=8, 2) | 0.23 year |
| Teriparatide | Active Formation Period (a.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, ISL and NL at 24 Months (n=9, 3) | 0.24 year |
| Zoledronic Acid | Active Formation Period (a.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, ISL and NL at 24 Months (n=9, 3) | 0.25 year |
| Zoledronic Acid | Active Formation Period (a.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 6 Months (n=23, 6) | 0.20 year |
| Zoledronic Acid | Active Formation Period (a.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 24 Months (n=8, 2) | 0.22 year |
| Zoledronic Acid | Active Formation Period (a.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, Imputed SL (ISL) and NL at 6 Months (n=23, 15) | 0.28 year |
p-value: 0.979Wilcoxon (Mann-Whitney)
p-value: 0.002Wilcoxon (Mann-Whitney)
p-value: 0.695Wilcoxon (Mann-Whitney)
p-value: 0.853Wilcoxon (Mann-Whitney)
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.
Time frame: 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had Aj.AR analysis of the CC at 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL and NL (n=9, 6) | 0.13 micrometer (µm)/day |
| Teriparatide | Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL, Imputed SL (ISL) and NL (n=10, 9) | 0.12 micrometer (µm)/day |
| Zoledronic Acid | Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL and NL (n=9, 6) | 0.00 micrometer (µm)/day |
| Zoledronic Acid | Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL, Imputed SL (ISL) and NL (n=10, 9) | 0.02 micrometer (µm)/day |
p-value: 0.05Wilcoxon (Mann-Whitney)
p-value: 0.016Wilcoxon (Mann-Whitney)
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.
Time frame: 6 months
Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL and NL (n=28, 28) | 0.34 µm/day | Inter-Quartile Range 0.22 |
| Teriparatide | Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL, ISL and NL (n=28, 30) | 0.34 µm/day | — |
| Zoledronic Acid | Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL and NL (n=28, 28) | 0.02 µm/day | Inter-Quartile Range 0.17 |
| Zoledronic Acid | Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL, ISL and NL (n=28, 30) | 0.02 µm/day | — |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: <0.001Wilcoxon (Mann-Whitney)
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.
Time frame: 6 and 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had Aj.AR analysis of the EC at 6 and 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Adjusted Apposition Rate (Aj.AR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 6 Months (n=23, 20) | 0.41 micrometer (µm)/day |
| Teriparatide | Adjusted Apposition Rate (Aj.AR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, Imputed SL (ISL) and NL at 6 Months (n=23, 29) | 0.41 micrometer (µm)/day |
| Teriparatide | Adjusted Apposition Rate (Aj.AR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 24 Months (n=8, 7) | 0.35 micrometer (µm)/day |
| Teriparatide | Adjusted Apposition Rate (Aj.AR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, ISL and NL at 24 Months (n=9, 8) | 0.32 micrometer (µm)/day |
| Zoledronic Acid | Adjusted Apposition Rate (Aj.AR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, ISL and NL at 24 Months (n=9, 8) | 0.00 micrometer (µm)/day |
| Zoledronic Acid | Adjusted Apposition Rate (Aj.AR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 6 Months (n=23, 20) | 0.00 micrometer (µm)/day |
| Zoledronic Acid | Adjusted Apposition Rate (Aj.AR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 24 Months (n=8, 7) | 0.00 micrometer (µm)/day |
| Zoledronic Acid | Adjusted Apposition Rate (Aj.AR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, Imputed SL (ISL) and NL at 6 Months (n=23, 29) | 0.03 micrometer (µm)/day |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: 0.003Wilcoxon (Mann-Whitney)
p-value: 0.003Wilcoxon (Mann-Whitney)
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.
Time frame: 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had length of tetracycline double labels analysis of the cancellous compartment at 24 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teriparatide | Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | 0.23 millimeter (mm) |
| Zoledronic Acid | Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | 0.29 millimeter (mm) |
p-value: 0.906Wilcoxon (Mann-Whitney)
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.
Time frame: 6 months
Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Teriparatide | Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | 0.35 millimeter (mm) | Inter-Quartile Range 0.08 |
| Zoledronic Acid | Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | 0.24 millimeter (mm) | Inter-Quartile Range 0.08 |
p-value: 0.002Wilcoxon (Mann-Whitney)
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.
Time frame: 6 and 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had length of tetracycline double labels analysis of the endocortical compartment at 6 and 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Average Length of Tetracycline Double Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 6 months (n=23, 6) | 0.34 millimeter (mm) |
| Teriparatide | Average Length of Tetracycline Double Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 24 months (n=8, 2) | 0.27 millimeter (mm) |
| Zoledronic Acid | Average Length of Tetracycline Double Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 6 months (n=23, 6) | 0.30 millimeter (mm) |
| Zoledronic Acid | Average Length of Tetracycline Double Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 24 months (n=8, 2) | 0.30 millimeter (mm) |
p-value: 0.536Wilcoxon (Mann-Whitney)
p-value: 0.896Wilcoxon (Mann-Whitney)
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.
Time frame: 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had BFR analysis of the CC at 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL and NL (n=9, 6) | 0.0057 mm³/mm²/year |
| Teriparatide | Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL, Imputed SL (ISL) and NL (n=10, 9) | 0.0057 mm³/mm²/year |
| Zoledronic Acid | Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL and NL (n=9, 6) | 0.0000 mm³/mm²/year |
| Zoledronic Acid | Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL, Imputed SL (ISL) and NL (n=10, 9) | 0.0001 mm³/mm²/year |
p-value: 0.002Wilcoxon (Mann-Whitney)
p-value: 0.002Wilcoxon (Mann-Whitney)
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.
Time frame: 6 months
Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL and NL (n=28, 28) | 0.0116 mm³/mm²/year | Inter-Quartile Range 0.0666 |
| Teriparatide | Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL, ISL and NL (n=28, 30) | 0.0116 mm³/mm²/year | — |
| Zoledronic Acid | Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL and NL (n=28, 28) | 0.0002 mm³/mm²/year | Inter-Quartile Range 0.022 |
| Zoledronic Acid | Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL, ISL and NL (n=28, 30) | 0.0002 mm³/mm²/year | — |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: <0.001Wilcoxon (Mann-Whitney)
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.
Time frame: 6 and 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had BFR analysis of EC at 6 and 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Bone Formation Rate (BFR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 6 Months (n=23, 20) | 0.0307 mm³/mm²/year |
| Teriparatide | Bone Formation Rate (BFR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, Imputed SL (ISL) and NL at 6 Months (n=23, 29) | 0.0307 mm³/mm²/year |
| Teriparatide | Bone Formation Rate (BFR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 24 Months (n=8, 7) | 0.0093 mm³/mm²/year |
| Teriparatide | Bone Formation Rate (BFR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, ISL and NL at 24 Months (n=9, 8) | 0.0090 mm³/mm²/year |
| Zoledronic Acid | Bone Formation Rate (BFR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, ISL and NL at 24 Months (n=9, 8) | 0.0000 mm³/mm²/year |
| Zoledronic Acid | Bone Formation Rate (BFR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 6 Months (n=23, 20) | 0.0000 mm³/mm²/year |
| Zoledronic Acid | Bone Formation Rate (BFR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 24 Months (n=8, 7) | 0.0000 mm³/mm²/year |
| Zoledronic Acid | Bone Formation Rate (BFR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, Imputed SL (ISL) and NL at 6 Months (n=23, 29) | 0.0003 mm³/mm²/year |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: 0.003Wilcoxon (Mann-Whitney)
p-value: 0.002Wilcoxon (Mann-Whitney)
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.
Time frame: Baseline, 12 months
Population: All participants who received at least one dose of study drug, had baseline and 12 months CTX measurement.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teriparatide | Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 12 Endpoint | 0.42 nanogram/milliliter (ng/mL) |
| Zoledronic Acid | Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 12 Endpoint | -0.23 nanogram/milliliter (ng/mL) |
p-value: <0.001t-test, 2 sided
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.
Time frame: Baseline, 1, 3, 6 months
Population: All randomized participants who received at least one dose of study drug with available biochemical marker of bone turnover data.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 1, 3 and 6 Endpoint | Change at 1 month (n= 32, 31) | 0.06 nanogram/milliliter (ng/mL) | Inter-Quartile Range 0.2 |
| Teriparatide | Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 1, 3 and 6 Endpoint | Change at 3 months (n= 32, 29) | 0.26 nanogram/milliliter (ng/mL) | Inter-Quartile Range 0.35 |
| Teriparatide | Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 1, 3 and 6 Endpoint | Change at 6 months (n= 25, 28) | 0.31 nanogram/milliliter (ng/mL) | Inter-Quartile Range 0.48 |
| Zoledronic Acid | Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 1, 3 and 6 Endpoint | Change at 1 month (n= 32, 31) | -0.37 nanogram/milliliter (ng/mL) | Inter-Quartile Range 0.2 |
| Zoledronic Acid | Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 1, 3 and 6 Endpoint | Change at 3 months (n= 32, 29) | -0.35 nanogram/milliliter (ng/mL) | Inter-Quartile Range 0.19 |
| Zoledronic Acid | Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 1, 3 and 6 Endpoint | Change at 6 months (n= 25, 28) | -0.32 nanogram/milliliter (ng/mL) | Inter-Quartile Range 0.19 |
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided
Secondary
Change From Baseline in Serum Osteocalcin (OC) at Month 12 Endpoint
OC is a measure of osteoblast function.
Time frame: Baseline, 12 months
Population: All participants who received at least one dose of study drug, had baseline and 12 months OC measurements.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teriparatide | Change From Baseline in Serum Osteocalcin (OC) at Month 12 Endpoint | 32.98 microgram/liter (µg/L) |
| Zoledronic Acid | Change From Baseline in Serum Osteocalcin (OC) at Month 12 Endpoint | -12.32 microgram/liter (µg/L) |
p-value: <0.001t-test, 2 sided
Secondary
Change From Baseline in Serum Osteocalcin (OC) at Month 1, 3, and 6 Endpoint
OC is a measure of osteoblast function.
Time frame: Baseline, 1, 3, 6 months
Population: All randomized participants who received at least one dose of study drug with available biochemical marker of bone turnover data.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | Change From Baseline in Serum Osteocalcin (OC) at Month 1, 3, and 6 Endpoint | Change at 1 month (n= 32, 32) | 22.35 µg/L | Inter-Quartile Range 11.58 |
| Teriparatide | Change From Baseline in Serum Osteocalcin (OC) at Month 1, 3, and 6 Endpoint | Change at 3 months (n=32, 30) | 29.93 µg/L | Inter-Quartile Range 19.02 |
| Teriparatide | Change From Baseline in Serum Osteocalcin (OC) at Month 1, 3, and 6 Endpoint | Change at 6 months (n= 25, 29) | 30.85 µg/L | Inter-Quartile Range 33.21 |
| Zoledronic Acid | Change From Baseline in Serum Osteocalcin (OC) at Month 1, 3, and 6 Endpoint | Change at 1 month (n= 32, 32) | -3.39 µg/L | Inter-Quartile Range 2.82 |
| Zoledronic Acid | Change From Baseline in Serum Osteocalcin (OC) at Month 1, 3, and 6 Endpoint | Change at 3 months (n=32, 30) | -12.30 µg/L | Inter-Quartile Range 5.01 |
| Zoledronic Acid | Change From Baseline in Serum Osteocalcin (OC) at Month 1, 3, and 6 Endpoint | Change at 6 months (n= 25, 29) | -14.06 µg/L | Inter-Quartile Range 7.15 |
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided
Secondary
Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 12 Endpoint
PINP is a measure of bone formation.
Time frame: Baseline, 12 months
Population: All participants who received at least one dose of study drug, had baseline and 12 months PINP measurement.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teriparatide | Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 12 Endpoint | 93.50 microgram/liter (µg/L) |
| Zoledronic Acid | Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 12 Endpoint | -33.00 microgram/liter (µg/L) |
p-value: <0.001t-test, 2 sided
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.
Time frame: Baseline, 1, 3, 6 months
Population: All randomized participants who received at least one dose of study drug with available biochemical marker of bone turnover data.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 1, 3 and 6 Endpoint | Change at 1 month (n= 32, 31) | 65.50 microgram/Liter (µg/L) | Inter-Quartile Range 32.03 |
| Teriparatide | Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 1, 3 and 6 Endpoint | Change at 3 months (n= 32, 29) | 66.00 microgram/Liter (µg/L) | Inter-Quartile Range 68.65 |
| Teriparatide | Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 1, 3 and 6 Endpoint | Change at 6 months (n= 25, 28) | 84.00 microgram/Liter (µg/L) | Inter-Quartile Range 135.9 |
| Zoledronic Acid | Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 1, 3 and 6 Endpoint | Change at 1 month (n= 32, 31) | -15.00 microgram/Liter (µg/L) | Inter-Quartile Range 9.27 |
| Zoledronic Acid | Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 1, 3 and 6 Endpoint | Change at 3 months (n= 32, 29) | -39.00 microgram/Liter (µg/L) | Inter-Quartile Range 14.58 |
| Zoledronic Acid | Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 1, 3 and 6 Endpoint | Change at 6 months (n= 25, 28) | -37.50 microgram/Liter (µg/L) | Inter-Quartile Range 16.44 |
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided
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.
Time frame: 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had MAR analysis of the CC at 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL and NL (n=9, 6) | 0.44 micrometer (µm)/day |
| Teriparatide | Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL, Imputed SL (ISL) and NL (n=10, 9) | 0.43 micrometer (µm)/day |
| Zoledronic Acid | Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL, Imputed SL (ISL) and NL (n=10, 9) | 0.30 micrometer (µm)/day |
| Zoledronic Acid | Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL and NL (n=9, 6) | 0.00 micrometer (µm)/day |
p-value: 0.02Wilcoxon (Mann-Whitney)
p-value: 0.005Wilcoxon (Mann-Whitney)
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.
Time frame: 6 months
Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL and NL (n=28, 28) | 0.56 micrometer (µm)/day | Inter-Quartile Range 0.1 |
| Teriparatide | Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL, ISL and NL (n=28, 30) | 0.56 micrometer (µm)/day | — |
| Zoledronic Acid | Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL and NL (n=28, 28) | 0.35 micrometer (µm)/day | Inter-Quartile Range 0.1 |
| Zoledronic Acid | Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL, ISL and NL (n=28, 30) | 0.33 micrometer (µm)/day | — |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: <0.001Wilcoxon (Mann-Whitney)
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.
Time frame: 6 and 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had MAR analysis of the EC at 6 and 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Mineral Apposition Rate (MAR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 6 Months (n=23, 20) | 0.50 micrometer (µm/day) |
| Teriparatide | Mineral Apposition Rate (MAR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, Imputed SL (ISL) and NL at 6 Months (n=23, 29) | 0.50 micrometer (µm/day) |
| Teriparatide | Mineral Apposition Rate (MAR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 24 Months (n=8, 7) | 0.43 micrometer (µm/day) |
| Teriparatide | Mineral Apposition Rate (MAR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, ISL and NL at 24 Months (n=9, 8) | 0.42 micrometer (µm/day) |
| Zoledronic Acid | Mineral Apposition Rate (MAR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, ISL and NL at 24 Months (n=9, 8) | 0.00 micrometer (µm/day) |
| Zoledronic Acid | Mineral Apposition Rate (MAR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 6 Months (n=23, 20) | 0.00 micrometer (µm/day) |
| Zoledronic Acid | Mineral Apposition Rate (MAR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 24 Months (n=8, 7) | 0.00 micrometer (µm/day) |
| Zoledronic Acid | Mineral Apposition Rate (MAR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, Imputed SL (ISL) and NL at 6 Months (n=23, 29) | 0.30 micrometer (µm/day) |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: 0.039Wilcoxon (Mann-Whitney)
p-value: 0.025Wilcoxon (Mann-Whitney)
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.
Time frame: 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had Mlt analysis of the CC at 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL and NL (n=9, 2) | 38.84 day |
| Teriparatide | Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL, Imputed SL (ISL) and NL (n=10, 5) | 45.33 day |
| Zoledronic Acid | Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL and NL (n=9, 2) | 45.67 day |
| Zoledronic Acid | Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL, Imputed SL (ISL) and NL (n=10, 5) | 128.37 day |
p-value: 0.906Wilcoxon (Mann-Whitney)
p-value: 0.159Wilcoxon (Mann-Whitney)
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.
Time frame: 6 months
Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL and NL (n=28, 16) | 13.63 day |
| Teriparatide | Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL, ISL and NL (n=28, 18) | 13.63 day |
| Zoledronic Acid | Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL and NL (n=28, 16) | 75.72 day |
| Zoledronic Acid | Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL, ISL and NL (n=28, 18) | 75.72 day |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: <0.001Wilcoxon (Mann-Whitney)
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.
Time frame: 6 and 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had Mlt analysis of the EC at 6 and 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Mineralization Lag Time (Mlt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 6 Months (n=23, 6) | 12.63 day |
| Teriparatide | Mineralization Lag Time (Mlt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, Imputed SL (ISL) and NL at 6 Months (n=23, 15) | 12.63 day |
| Teriparatide | Mineralization Lag Time (Mlt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 24 Months (n=8, 2) | 15.67 day |
| Teriparatide | Mineralization Lag Time (Mlt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, ISL and NL at 24 Months (n=9, 3) | 17.04 day |
| Zoledronic Acid | Mineralization Lag Time (Mlt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, ISL and NL at 24 Months (n=9, 3) | 29.03 day |
| Zoledronic Acid | Mineralization Lag Time (Mlt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 6 Months (n=23, 6) | 26.97 day |
| Zoledronic Acid | Mineralization Lag Time (Mlt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 24 Months (n=8, 2) | 42.86 day |
| Zoledronic Acid | Mineralization Lag Time (Mlt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, Imputed SL (ISL) and NL at 6 Months (n=23, 15) | 26.70 day |
p-value: 0.049Wilcoxon (Mann-Whitney)
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: 0.151Wilcoxon (Mann-Whitney)
p-value: 0.196Wilcoxon (Mann-Whitney)
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.
Time frame: 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had MS/BS analysis of the CC at 24 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teriparatide | Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | 3.00 percentage of surface |
| Zoledronic Acid | Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | 0.07 percentage of surface |
p-value: 0.002Wilcoxon (Mann-Whitney)
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.
Time frame: 6 and 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had MS/BS analysis of the EC at 6 and 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Mineralizing Surface/Bone Surface(MS/BS) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | 6 months (n=23, 29) | 18.64 percentage of surface |
| Teriparatide | Mineralizing Surface/Bone Surface(MS/BS) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | 24 months (n=9, 8) | 5.82 percentage of surface |
| Zoledronic Acid | Mineralizing Surface/Bone Surface(MS/BS) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | 6 months (n=23, 29) | 0.30 percentage of surface |
| Zoledronic Acid | Mineralizing Surface/Bone Surface(MS/BS) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | 24 months (n=9, 8) | 0.00 percentage of surface |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: 0.002Wilcoxon (Mann-Whitney)
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.
Time frame: 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy of the cancellous compartment at 24 months.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Teriparatide | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | No Label | 0 samples |
| Teriparatide | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | Single Label Only | 1 samples |
| Teriparatide | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | Double Label Only | 0 samples |
| Teriparatide | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | Single and Double Label | 9 samples |
| Zoledronic Acid | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | Single and Double Label | 2 samples |
| Zoledronic Acid | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | No Label | 4 samples |
| Zoledronic Acid | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | Double Label Only | 0 samples |
| Zoledronic Acid | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | Single Label Only | 3 samples |
p-value: 0.033Fisher Exact
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.
Time frame: 6 months
Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Teriparatide | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | No Label | 0 samples |
| Teriparatide | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | Single Label Only | 0 samples |
| Teriparatide | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | Double Label Only | 0 samples |
| Teriparatide | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | Single and Double Label | 28 samples |
| Zoledronic Acid | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | Single and Double Label | 13 samples |
| Zoledronic Acid | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | No Label | 12 samples |
| Zoledronic Acid | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | Double Label Only | 3 samples |
| Zoledronic Acid | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | Single Label Only | 2 samples |
p-value: <0.001Fisher Exact
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.
Time frame: 6 and 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy of the endocortical compartment at 6 and 24 months.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Teriparatide | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | No Label at 6 months (n=23, 29) | 0 samples |
| Teriparatide | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | Single Label Only at 6 months (n=23, 29) | 0 samples |
| Teriparatide | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | Double Label Only at 6 months (n=23, 29) | 0 samples |
| Teriparatide | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | Single and Double Label at 6 months (n=23, 29) | 23 samples |
| Teriparatide | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | No Label at 24 months (n=9, 8) | 0 samples |
| Teriparatide | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | Single Label Only at 24 months (n=9, 8) | 1 samples |
| Teriparatide | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | Double Label Only at 24 months (n=9, 8) | 0 samples |
| Teriparatide | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | Single and Double Label at 24 months (n=9, 8) | 8 samples |
| Zoledronic Acid | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | Single and Double Label at 24 months (n=9, 8) | 2 samples |
| Zoledronic Acid | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | No Label at 6 months (n=23, 29) | 14 samples |
| Zoledronic Acid | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | No Label at 24 months (n=9, 8) | 5 samples |
| Zoledronic Acid | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | Single Label Only at 6 months (n=23, 29) | 9 samples |
| Zoledronic Acid | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | Double Label Only at 24 months (n=9, 8) | 0 samples |
| Zoledronic Acid | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | Double Label Only at 6 months (n=23, 29) | 0 samples |
| Zoledronic Acid | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | Single Label Only at 24 months (n=9, 8) | 1 samples |
| Zoledronic Acid | Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | Single and Double Label at 6 months (n=23, 29) | 6 samples |
p-value: <0.001Fisher Exact
p-value: 0.009Fisher Exact
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.
Time frame: 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had Omt analysis of the CC at 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL and NL (n=9, 2) | 13.42 day |
| Teriparatide | Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL, Imputed SL (ISL) and NL (n=10, 5) | 13.52 day |
| Zoledronic Acid | Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL and NL (n=9, 2) | 17.38 day |
| Zoledronic Acid | Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL, Imputed SL (ISL) and NL (n=10, 5) | 13.92 day |
p-value: 0.077Wilcoxon (Mann-Whitney)
p-value: 0.358Wilcoxon (Mann-Whitney)
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.
Time frame: 6 months
Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL and NL (n=28, 16) | 9.99 day |
| Teriparatide | Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL, ISL and NL (n=28, 18) | 9.99 day |
| Zoledronic Acid | Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL and NL (n=28, 16) | 9.05 day |
| Zoledronic Acid | Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL, ISL and NL (n=28, 18) | 9.05 day |
p-value: 0.502Wilcoxon (Mann-Whitney)
p-value: 0.597Wilcoxon (Mann-Whitney)
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.
Time frame: 6 and 24 Months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had Omt analysis of the EC at 6 and 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Osteoid Maturation Time (Omt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 6 Months (n=23, 6) | 10.57 day |
| Teriparatide | Osteoid Maturation Time (Omt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 24 Months (n=8, 2) | 12.30 day |
| Teriparatide | Osteoid Maturation Time (Omt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, Imputed SL (ISL) and NL at 6 Months (n=23, 15) | 10.57 day |
| Teriparatide | Osteoid Maturation Time (Omt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, ISL and NL at 24 Months (n=9, 3) | 13.03 day |
| Zoledronic Acid | Osteoid Maturation Time (Omt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, Imputed SL (ISL) and NL at 6 Months (n=23, 15) | 11.34 day |
| Zoledronic Acid | Osteoid Maturation Time (Omt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 6 Months (n=23, 6) | 11.27 day |
| Zoledronic Acid | Osteoid Maturation Time (Omt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, ISL and NL at 24 Months (n=9, 3) | 12.12 day |
| Zoledronic Acid | Osteoid Maturation Time (Omt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 24 Months (n=8, 2) | 14.94 day |
p-value: 0.647Wilcoxon (Mann-Whitney)
p-value: 0.12Wilcoxon (Mann-Whitney)
p-value: 0.695Wilcoxon (Mann-Whitney)
p-value: 1Wilcoxon (Mann-Whitney)
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.
Time frame: 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had OTh. analysis of the CC at 24 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teriparatide | Osteoid Thickness (OTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | 5.71 micrometer (µm) |
| Zoledronic Acid | Osteoid Thickness (OTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | 3.98 micrometer (µm) |
p-value: 0.079Wilcoxon (Mann-Whitney)
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.
Time frame: 6 months
Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Teriparatide | Osteoid Thickness (OTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | 4.92 micrometer (µm) | Inter-Quartile Range 1.38 |
| Zoledronic Acid | Osteoid Thickness (OTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | 3.77 micrometer (µm) | Inter-Quartile Range 1.1 |
p-value: <0.001Wilcoxon (Mann-Whitney)
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.
Time frame: 6 and 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had OTh. analysis of the EC at 6 and 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Osteoid Thickness (OTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 6 months (n=23, 29) | 4.94 micrometer (µm) |
| Teriparatide | Osteoid Thickness (OTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 24 months (n=9, 8) | 5.23 micrometer (µm) |
| Zoledronic Acid | Osteoid Thickness (OTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 6 months (n=23, 29) | 3.70 micrometer (µm) |
| Zoledronic Acid | Osteoid Thickness (OTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 24 months (n=9, 8) | 3.53 micrometer (µm) |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: 0.039Wilcoxon (Mann-Whitney)
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.
Time frame: 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had ES/BS analysis of the CC at 24 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teriparatide | Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | 4.44 percentage of surface |
| Zoledronic Acid | Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | 2.39 percentage of surface |
p-value: 0.025Wilcoxon (Mann-Whitney)
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.
Time frame: 6 months
Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teriparatide | Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | 4.59 percentage of surface |
| Zoledronic Acid | Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | 2.71 percentage of surface |
p-value: <0.001Wilcoxon (Mann-Whitney)
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.
Time frame: 6 and 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had ES/BS analysis of the EC at 6 and 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Percentage of Eroded Surface/Bone Surface (ES/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 6 months (n=23, 29) | 4.06 percentage of surface |
| Teriparatide | Percentage of Eroded Surface/Bone Surface (ES/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 24 months (n=9, 8) | 3.43 percentage of surface |
| Zoledronic Acid | Percentage of Eroded Surface/Bone Surface (ES/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 6 months (n=23, 29) | 1.87 percentage of surface |
| Zoledronic Acid | Percentage of Eroded Surface/Bone Surface (ES/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 24 months (n=9, 8) | 1.88 percentage of surface |
p-value: 0.012Wilcoxon (Mann-Whitney)
p-value: 0.092Wilcoxon (Mann-Whitney)
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.
Time frame: 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had OS/BS analysis of the CC at 24 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teriparatide | Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | 11.19 percentage of surface |
| Zoledronic Acid | Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | 1.26 percentage of surface |
p-value: 0.008Wilcoxon (Mann-Whitney)
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.
Time frame: 6 months
Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Teriparatide | Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | 11.34 percentage of surface | Inter-Quartile Range 8.35 |
| Zoledronic Acid | Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | 2.51 percentage of surface | Inter-Quartile Range 4.84 |
p-value: <0.001Wilcoxon (Mann-Whitney)
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.
Time frame: 6 and 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had OS/BS analysis of the EC at 6 and 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 6 months (n=23, 29) | 16.33 percentage of surface |
| Teriparatide | Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 24 months (n=9, 8) | 7.48 percentage of surface |
| Zoledronic Acid | Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 6 months (n=23, 29) | 1.87 percentage of surface |
| Zoledronic Acid | Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 24 months (n=9, 8) | 1.55 percentage of surface |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: 0.006Wilcoxon (Mann-Whitney)
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).
Time frame: 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had OV/BV analysis of the CC at 24 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teriparatide | Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | 1.33 percentage of volume |
| Zoledronic Acid | Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | 0.18 percentage of volume |
p-value: 0.002Wilcoxon (Mann-Whitney)
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).
Time frame: 6 months
Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Teriparatide | Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | 1.32 percentage of volume | Inter-Quartile Range 1.47 |
| Zoledronic Acid | Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | 0.24 percentage of volume | Inter-Quartile Range 0.76 |
p-value: <0.001Wilcoxon (Mann-Whitney)
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.
Time frame: 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had sLS/BS and dLS/BS analysis of the cancellous compartment at 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | sLS/BS | 2.25 percentage of tetracycline labels |
| Teriparatide | Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | dLS/BS | 1.69 percentage of tetracycline labels |
| Zoledronic Acid | Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | sLS/BS | 0.15 percentage of tetracycline labels |
| Zoledronic Acid | Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | dLS/BS | 0.00 percentage of tetracycline labels |
p-value: 0.006Wilcoxon (Mann-Whitney)
p-value: 0.001Wilcoxon (Mann-Whitney)
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.
Time frame: 6 months
Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | sLS/BS | 3.19 percentage of tetracycline labels | Inter-Quartile Range 2.85 |
| Teriparatide | Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | dLS/BS | 4.13 percentage of tetracycline labels | Inter-Quartile Range 8.9 |
| Zoledronic Acid | Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | sLS/BS | 0.02 percentage of tetracycline labels | Inter-Quartile Range 1.7 |
| Zoledronic Acid | Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | dLS/BS | 0.07 percentage of tetracycline labels | Inter-Quartile Range 1.78 |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: <0.001Wilcoxon (Mann-Whitney)
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.
Time frame: 6 and 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had sLS/BS and dLS/BS analysis of the endocortical compartment at 6 and 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | sLS/BS at 6 months (n=23, 29) | 5.56 percentage of tetracycline labels |
| Teriparatide | Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | dLS/BS at 6 months (n=23, 29) | 13.46 percentage of tetracycline labels |
| Teriparatide | Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | sLS/BS at 24 months (n=9, 8) | 3.75 percentage of tetracycline labels |
| Teriparatide | Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | dLS/BS at 24 months (n=9, 8) | 2.77 percentage of tetracycline labels |
| Zoledronic Acid | Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | dLS/BS at 24 months (n=9, 8) | 0.00 percentage of tetracycline labels |
| Zoledronic Acid | Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | sLS/BS at 6 months (n=23, 29) | 0.25 percentage of tetracycline labels |
| Zoledronic Acid | Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | sLS/BS at 24 months (n=9, 8) | 0.00 percentage of tetracycline labels |
| Zoledronic Acid | Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | dLS/BS at 6 months (n=23, 29) | 0.00 percentage of tetracycline labels |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: 0.004Wilcoxon (Mann-Whitney)
p-value: 0.006Wilcoxon (Mann-Whitney)
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.
Time frame: 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had Tt.FP analysis of the CC at 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL and NL (n=9, 2) | 0.60 year |
| Teriparatide | Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL, Imputed SL (ISL) and NL (n=10, 5) | 0.68 year |
| Zoledronic Acid | Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL and NL (n=9, 2) | 0.51 year |
| Zoledronic Acid | Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months | DL, Imputed SL (ISL) and NL (n=10, 5) | 2.62 year |
p-value: 1Wilcoxon (Mann-Whitney)
p-value: 0.198Wilcoxon (Mann-Whitney)
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.
Time frame: 6 months
Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL and NL (n=28, 16) | 0.24 year |
| Teriparatide | Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL, ISL and NL (n=28, 18) | 0.24 year |
| Zoledronic Acid | Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL and NL (n=28, 16) | 1.46 year |
| Zoledronic Acid | Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months | DL, ISL and NL (n=28, 18) | 1.46 year |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: <0.001Wilcoxon (Mann-Whitney)
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.
Time frame: 6 and 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had Tt.FP analysis of the EC at 6 and 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Total Formation Period (Tt.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 6 Months (n=23, 6) | 0.24 year |
| Teriparatide | Total Formation Period (Tt.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, Imputed SL (ISL) and NL at 6 Months (n=23, 15) | 0.24 year |
| Teriparatide | Total Formation Period (Tt.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 24 Months (n=8, 2) | 0.27 year |
| Teriparatide | Total Formation Period (Tt.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, ISL and NL at 24 Months (n=9, 3) | 0.31 year |
| Zoledronic Acid | Total Formation Period (Tt.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, ISL and NL at 24 Months (n=9, 3) | 0.86 year |
| Zoledronic Acid | Total Formation Period (Tt.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 6 Months (n=23, 6) | 0.43 year |
| Zoledronic Acid | Total Formation Period (Tt.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL and NL at 24 Months (n=8, 2) | 0.62 year |
| Zoledronic Acid | Total Formation Period (Tt.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months | DL, Imputed SL (ISL) and NL at 6 Months (n=23, 15) | 0.54 year |
p-value: 0.022Wilcoxon (Mann-Whitney)
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: 0.151Wilcoxon (Mann-Whitney)
p-value: 0.139Wilcoxon (Mann-Whitney)
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.
Time frame: 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had WTh. analysis of the CC at 24 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teriparatide | Wall Thickness (WTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | 31.37 micrometer (µm) |
| Zoledronic Acid | Wall Thickness (WTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months | 29.26 micrometer (µm) |
p-value: 0.079Wilcoxon (Mann-Whitney)
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.
Time frame: 6 months
Population: All randomized participants who received at least one dose of study drug with an evaluable bone biopsy.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Teriparatide | Wall Thickness (WTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | 31.29 µm | Inter-Quartile Range 3.25 |
| Zoledronic Acid | Wall Thickness (WTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months | 28.63 µm | Inter-Quartile Range 2.59 |
p-value: 0.014Wilcoxon (Mann-Whitney)
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.
Time frame: 6 and 24 months
Population: All participants who received at least one dose of study drug with an evaluable bone biopsy and had WTh. analysis of the EC at 6 and 24 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teriparatide | Wall Thickness (WTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 6 months (n=23, 29) | 36.30 micrometer (µm) |
| Teriparatide | Wall Thickness (WTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 24 months (n=9, 8) | 34.00 micrometer (µm) |
| Zoledronic Acid | Wall Thickness (WTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 6 months (n=23, 29) | 32.39 micrometer (µm) |
| Zoledronic Acid | Wall Thickness (WTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months | 24 months (n=9, 8) | 32.45 micrometer (µm) |
p-value: 0.027Wilcoxon (Mann-Whitney)
p-value: 0.268Wilcoxon (Mann-Whitney)