Male Osteoporosis
Conditions
Keywords
Osteoporosis, males, vertebral fractures, clinical fractures, bone mineral density, bone biomarkers, zoledronic acid
Brief summary
This study will investigate if the drug zoledronic acid given once yearly is safe and has beneficial effects in treating osteoporosis by reducing bone loss and fractures in men with osteoporosis.
Interventions
DRUGZoledronic acid 5 mg iv
Zoledronic acid 5 mg iv given once a year.
DRUGPlacebo
Placebo intravenous (i.v.) once a year
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
• Osteoporosis as defined by very low bone mineral density in the hip and spine or low bone mineral density in the hip combined with presence of 1-3 mild or moderate fractures of the vertebrae
Exclusion criteria
* Low Vitamin D * Renal insufficiency * Previous treatment with certain anti-osteoporotic therapies (except after certain washout periods): calcitonin, bisphosphonates, parathyroid hormone (PTH), sodium fluoride, strontium ranelate, * Previous treatment with testosterone, anabolic steroids or growth hormone * Chronic use of systemic corticosteroids (oral or i.v.) within the last year * History of any cancer or metastases within the last 5 years * History of brittle bone disease, multiple myeloma, or Paget's disease, or any other metabolic bone disease, except osteoporosis * Bilateral hip replacements Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With at Least One New Morphometric Vertebral Fracture Over 24 Months | 24 Months | Vertebral fracture (VF) was assessed based on morphometry. QM(quantitative morphometry) incident VF(QM positive) is defined by at least 20% decrease in vertebral height of at least 4mm. If participant had QM positive at any vertebrae at any visit, x-rays from visits for participants were evaluated using Genant semi-quantitative method for VF assessment: Grade1 Mild VF is defined as 20-24% decrease in anterior, middle, and/or posterior vertebral height. Grade2 moderate VF is defined as 25-40% decrease in vertebral height. Grade3 Severe VF is defined as more than 40% decrease in vertebral height |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With at Least One New Moderate or Severe Morphometric Vertebral Fracture Over 12 Months | 12 months | Moderate or severe vertebral fracture (VF) was assessed based on morphometry. A QM (quantitative morphometry) incident VF(QM positive) was defined by at least a 20% decrease in any vertebral height (at least 4 mm). If a participant had a QM positive at any vertebrae at any visit,x-rays from all visits for participants were evaluated using Genant semi-quantitative (SQ) method for VF assessment. Grade 2 moderate VF was defined as a 25-40% reduction in any vertebral height.Grade 3 Severe: VF was defined as more than 40% reduction in any vertebral height. |
| Percentage of Participants With at Least One New Moderate or Severe Morphometric Vertebral Fracture Over 24 Months | 24 Months | Moderate or severe vertebral fracture (VF) was assessed based on morphometry. A QM (quantitative morphometry) incident VF(QM positive) was defined by at least a 20% decrease in any vertebral height (at least 4 mm). If a participant had a QM positive at any vertebrae at any visit,x-rays from all visits for participants were evaluated using Genant semi-quantitative (SQ) method for VF assessment. Grade 2 moderate VF was defined as a 25-40% reduction in any vertebral height.Grade 3 Severe: VF was defined as more than 40% reduction in any vertebral height. |
| Percentage of Participants With at Least One New or Worsening Morphometric Vertebral Fracture Over 12 Months | Baseline, 12 months | Worsening vertebral fracture (VF) was assessed based on morphometry. QM (quantitative morphometry) incident VF(QM positive) was defined by at least a 20% decrease in any vertebral height (at least 4 mm). If a participant had a QM positive at any vertebrae at any visit, x-rays from all visits for participants were evaluated using Genant semi-quantitative (SQ) method for VF assessment. A worsening fracture was defined as an SQ reading that was greater than the baseline SQ reading, which was at least 1 (prevalent fracture) |
| Percentage of Participants With at Least One New or Worsening Morphometric Vertebral Fracture Over 24 Months | Baseline, Month 24 | Worsening vertebral fracture (VF) was assessed based on morphometry. A QM (quantitative morphometry) incident VF(QM positive) was defined by at least a 20% decrease in any vertebral height (at least 4 mm). If a participant had a QM positive at any vertebrae at any visit,x-rays from all visits for participants were evaluated using Genant semi-quantitative (SQ) method for VF assessment. A worsening fracture was defined as an SQ reading that was greater than the baseline SQ reading, which was at least 1 (prevalent fracture) |
| Mean Change in Height From Baseline | from Baseline to 12 months and 24 months | Height was measured using a stadiometer. Two measurements were taken in millimeters (mm), and repeated if the two measurements differed by greater than 4 mm. The average of the two (or four) height measurements was used for analysis |
| Number of Participants With First Clinical Vertebral Fracture | 24 months | Clinical vertebral fracture is a painful vertebral fracture which came to clinical attention, e.g., with increased back pain, impairment of mobility or functional limitations. Subjects who did not experience a fracture event were censored at the end of study. End of study was defined as the last visit or date of death, whichever was earlier. |
| Percentage of Participants With at Least One New Morphometric Vertebral Fracture Over 12 Months | 12 Months | Vertebral fracture (VF) was assessed based on morphometry. QM(quantitative morphometry) incident VF(QM positive) is defined by at least 20% decrease in vertebral height of at least 4mm. If participant had QM positive at any vertebrae at any visit, x-rays from visits for participants were evaluated using Genant semi-quantitative method for VF assessment: Grade1 Mild VF is defined as 20-24% decrease in anterior, middle, and/or posterior vertebral height. Grade2 moderate VF is defined as 25-40% decrease in vertebral height. Grade3 Severe VF is defined as more than 40% decrease in vertebral height |
| Number of Participants With First Non-vertebral Fracture | 24 months | Non-vertebral fracture is any fracture which was not of the vertebrae. Subjects who did not experience a fracture event were censored at the end of study. End of study was defined as the last visit or date of death, whichever was earlier. |
| Percentage Change From Baseline in Lumbar Spine Bone Mass Density (BMD) | Month 6, Month 12, Month 24 | Dual energy x-ray absorptiometry (DXA) Least Square Means (LSM) were analyzed using an ANCOVA model with treatment and baseline value as explanatory variables. Percent change in BMD at lumbar spine at Months 6, 12, and 24 relative to baseline as measured by DXA in a subset of at least 100 evaluable subjects at selected sites. Percentage change from baseline = 100\*(endpoint - baseline) |
| Percentage Change From Baseline in Total Hip BMD (g/CM^2) | Month 6, Month 12, Month 24 | Dual energy x-ray absorptiometry (DXA) Least Square Means (LSM) were analyzed using an ANCOVA model with treatment and baseline value as explanatory variables. Percent change in total hip BMD at Months 6, 12, and 24 relative to baseline as measured by DXA in a subset of at least 100 evaluable subjects at selected sites. Percentage change from baseline = 100\*(endpoint - baseline) |
| Percentage Change From Baseline in Femoral Neck BMD (g/CM^2) | Month 6, Month 12, Month 24 | Dual energy x-ray absorptiometry (DXA) Least Square Means (LSM) were analyzed using an ANCOVA model with treatment and baseline value as explanatory variables. Percent change in total femoral neck BMD at Months 6, 12, and 24 relative to baseline as measured by DXA in a subset of at least 100 evaluable subjects at selected sites. Percentage change from baseline = 100\*(endpoint - baseline) |
| Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits | Baseline, Month 3, Month 6, Month 12, Month 15, month 18, Month 24 | — |
| Number of Participants With First Clinical Fracture | 24 months | Clinical fracture is painful fracture in any site which came to clinical attention, e.g., with increased pain, impaired mobility or functional limitations. Subjects who did not experience fracture were censored at end of study. End of study was defined as the earlier of last visit or date of death. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Czechia, Denmark, Finland, Germany, Hungary, Iceland, Italy, Norway, Poland, Portugal, Romania, Russia, Slovakia, South Africa, Spain, Sweden, Switzerland, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Zoledronic Acid 5 mg/100 ml administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year. | 588 |
| Placebo 100 ml Placebo administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year. | 611 |
| Total | 1,199 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 11 |
| Overall Study | Death | 15 | 18 |
| Overall Study | Lack of Efficacy | 0 | 4 |
| Overall Study | Lost to Follow-up | 4 | 12 |
| Overall Study | Protocol Violation | 3 | 4 |
| Overall Study | Withdrawal by Subject | 25 | 22 |
Baseline characteristics
| Characteristic | Zoledronic Acid | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 65.8 years STANDARD_DEVIATION 8.3 | 65.7 years STANDARD_DEVIATION 8.6 | 65.8 years STANDARD_DEVIATION 8.5 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 588 Participants | 611 Participants | 1199 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 399 / 588 | 256 / 611 |
| serious Total, serious adverse events | 149 / 588 | 154 / 611 |
Outcome results
Primary
Percentage of Participants With at Least One New Morphometric Vertebral Fracture Over 24 Months
Vertebral fracture (VF) was assessed based on morphometry. QM(quantitative morphometry) incident VF(QM positive) is defined by at least 20% decrease in vertebral height of at least 4mm. If participant had QM positive at any vertebrae at any visit, x-rays from visits for participants were evaluated using Genant semi-quantitative method for VF assessment: Grade1 Mild VF is defined as 20-24% decrease in anterior, middle, and/or posterior vertebral height. Grade2 moderate VF is defined as 25-40% decrease in vertebral height. Grade3 Severe VF is defined as more than 40% decrease in vertebral height
Time frame: 24 Months
Population: Modified Intent-to-treat (mITT) population included all randomized subjects who had a baseline and at least one post-baseline assessment of the primary efficacy variable. In this analysis, missing Month 24 fractures were imputed using LOCF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zoledronic Acid | Percentage of Participants With at Least One New Morphometric Vertebral Fracture Over 24 Months | 1.6 Percentage of Participants |
| Placebo | Percentage of Participants With at Least One New Morphometric Vertebral Fracture Over 24 Months | 4.9 Percentage of Participants |
Secondary
Mean Change in Height From Baseline
Height was measured using a stadiometer. Two measurements were taken in millimeters (mm), and repeated if the two measurements differed by greater than 4 mm. The average of the two (or four) height measurements was used for analysis
Time frame: from Baseline to 12 months and 24 months
Population: Modified Intent-to-treat (mITT) population included all randomized subjects who had a baseline and at least one post-baseline assessment of the primary efficacy variable. Patients with a baseline x-ray and a 12M x-ray are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zoledronic Acid | Mean Change in Height From Baseline | 12 months | -0.86 mm | Standard Error 0.333 |
| Zoledronic Acid | Mean Change in Height From Baseline | 24 months | -2.33 mm | Standard Error 0.389 |
| Placebo | Mean Change in Height From Baseline | 12 months | -2.50 mm | Standard Error 0.522 |
| Placebo | Mean Change in Height From Baseline | 24 months | -4.61 mm | Standard Error 0.61 |
Secondary
Number of Participants With First Clinical Fracture
Clinical fracture is painful fracture in any site which came to clinical attention, e.g., with increased pain, impaired mobility or functional limitations. Subjects who did not experience fracture were censored at end of study. End of study was defined as the earlier of last visit or date of death.
Time frame: 24 months
Population: The ITT (intent to treat) population consisted of all subjects as randomized.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Zoledronic Acid | Number of Participants With First Clinical Fracture | 6 Participants | 1.95 |
| Placebo | Number of Participants With First Clinical Fracture | 11 Participants | 3.09 |
Secondary
Number of Participants With First Clinical Vertebral Fracture
Clinical vertebral fracture is a painful vertebral fracture which came to clinical attention, e.g., with increased back pain, impairment of mobility or functional limitations. Subjects who did not experience a fracture event were censored at the end of study. End of study was defined as the last visit or date of death, whichever was earlier.
Time frame: 24 months
Population: The ITT (intent to treat) population consisted of all subjects as randomized.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Zoledronic Acid | Number of Participants With First Clinical Vertebral Fracture | 1 Participants | — |
| Placebo | Number of Participants With First Clinical Vertebral Fracture | 3 Participants | 1.63 |
Secondary
Number of Participants With First Non-vertebral Fracture
Non-vertebral fracture is any fracture which was not of the vertebrae. Subjects who did not experience a fracture event were censored at the end of study. End of study was defined as the last visit or date of death, whichever was earlier.
Time frame: 24 months
Population: The ITT (intent to treat) population consisted of all subjects as randomized.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Zoledronic Acid | Number of Participants With First Non-vertebral Fracture | 5 Participants | 1.88 |
| Placebo | Number of Participants With First Non-vertebral Fracture | 8 Participants | 2.83 |
Secondary
Percentage Change From Baseline in Femoral Neck BMD (g/CM^2)
Dual energy x-ray absorptiometry (DXA) Least Square Means (LSM) were analyzed using an ANCOVA model with treatment and baseline value as explanatory variables. Percent change in total femoral neck BMD at Months 6, 12, and 24 relative to baseline as measured by DXA in a subset of at least 100 evaluable subjects at selected sites. Percentage change from baseline = 100\*(endpoint - baseline)
Time frame: Month 6, Month 12, Month 24
Population: Intent-to-treat (ITT) population included all randomized subjects who had a baseline and at least one post-baseline assessment of the efficacy variable.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Zoledronic Acid | Percentage Change From Baseline in Femoral Neck BMD (g/CM^2) | Month 6 (n=60, n=63) | 2.21 Percent change in BMD | Standard Error 0.448 |
| Zoledronic Acid | Percentage Change From Baseline in Femoral Neck BMD (g/CM^2) | Month 12 (n=58, n=64) | 2.06 Percent change in BMD | Standard Error 0.465 |
| Zoledronic Acid | Percentage Change From Baseline in Femoral Neck BMD (g/CM^2) | Month 24 (n=56, n=63) | 3.39 Percent change in BMD | Standard Error 0.544 |
| Placebo | Percentage Change From Baseline in Femoral Neck BMD (g/CM^2) | Month 6 (n=60, n=63) | 0.58 Percent change in BMD | Standard Error 0.437 |
| Placebo | Percentage Change From Baseline in Femoral Neck BMD (g/CM^2) | Month 12 (n=58, n=64) | 0.59 Percent change in BMD | Standard Error 0.443 |
| Placebo | Percentage Change From Baseline in Femoral Neck BMD (g/CM^2) | Month 24 (n=56, n=63) | 0.09 Percent change in BMD | Standard Error 0.513 |
Secondary
Percentage Change From Baseline in Lumbar Spine Bone Mass Density (BMD)
Dual energy x-ray absorptiometry (DXA) Least Square Means (LSM) were analyzed using an ANCOVA model with treatment and baseline value as explanatory variables. Percent change in BMD at lumbar spine at Months 6, 12, and 24 relative to baseline as measured by DXA in a subset of at least 100 evaluable subjects at selected sites. Percentage change from baseline = 100\*(endpoint - baseline)
Time frame: Month 6, Month 12, Month 24
Population: Intent-to-treat (ITT) population included all randomized subjects who had a baseline and at least one post-baseline assessment of the efficacy variable.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Zoledronic Acid | Percentage Change From Baseline in Lumbar Spine Bone Mass Density (BMD) | Month 6 (n=61, n=61) | 4.87 Percent change in BMD | Standard Error 0.412 |
| Zoledronic Acid | Percentage Change From Baseline in Lumbar Spine Bone Mass Density (BMD) | Month 12 (n=60, n=62) | 5.51 Percent change in BMD | Standard Error 0.437 |
| Zoledronic Acid | Percentage Change From Baseline in Lumbar Spine Bone Mass Density (BMD) | Month 24 (n=58, n=61) | 7.73 Percent change in BMD | Standard Error 0.459 |
| Placebo | Percentage Change From Baseline in Lumbar Spine Bone Mass Density (BMD) | Month 6 (n=61, n=61) | 0.10 Percent change in BMD | Standard Error 0.412 |
| Placebo | Percentage Change From Baseline in Lumbar Spine Bone Mass Density (BMD) | Month 12 (n=60, n=62) | 0.84 Percent change in BMD | Standard Error 0.43 |
| Placebo | Percentage Change From Baseline in Lumbar Spine Bone Mass Density (BMD) | Month 24 (n=58, n=61) | 1.61 Percent change in BMD | Standard Error 0.448 |
Secondary
Percentage Change From Baseline in Total Hip BMD (g/CM^2)
Dual energy x-ray absorptiometry (DXA) Least Square Means (LSM) were analyzed using an ANCOVA model with treatment and baseline value as explanatory variables. Percent change in total hip BMD at Months 6, 12, and 24 relative to baseline as measured by DXA in a subset of at least 100 evaluable subjects at selected sites. Percentage change from baseline = 100\*(endpoint - baseline)
Time frame: Month 6, Month 12, Month 24
Population: Intent-to-treat (ITT) population included all randomized subjects who had a baseline and at least one post-baseline assessment of the efficacy variable.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Zoledronic Acid | Percentage Change From Baseline in Total Hip BMD (g/CM^2) | Month 6 (n=60, n=63) | 1.38 Percent change in BMD | Standard Error 0.294 |
| Zoledronic Acid | Percentage Change From Baseline in Total Hip BMD (g/CM^2) | Month 12 (n=58, n=64) | 1.66 Percent change in BMD | Standard Error 0.283 |
| Zoledronic Acid | Percentage Change From Baseline in Total Hip BMD (g/CM^2) | Month 24 (n=56, n=63) | 2.31 Percent change in BMD | Standard Error 0.346 |
| Placebo | Percentage Change From Baseline in Total Hip BMD (g/CM^2) | Month 6 (n=60, n=63) | -0.44 Percent change in BMD | Standard Error 0.287 |
| Placebo | Percentage Change From Baseline in Total Hip BMD (g/CM^2) | Month 12 (n=58, n=64) | 0.26 Percent change in BMD | Standard Error 0.269 |
| Placebo | Percentage Change From Baseline in Total Hip BMD (g/CM^2) | Month 24 (n=56, n=63) | 0.16 Percent change in BMD | Standard Error 0.326 |
Secondary
Percentage of Participants With at Least One New Moderate or Severe Morphometric Vertebral Fracture Over 12 Months
Moderate or severe vertebral fracture (VF) was assessed based on morphometry. A QM (quantitative morphometry) incident VF(QM positive) was defined by at least a 20% decrease in any vertebral height (at least 4 mm). If a participant had a QM positive at any vertebrae at any visit,x-rays from all visits for participants were evaluated using Genant semi-quantitative (SQ) method for VF assessment. Grade 2 moderate VF was defined as a 25-40% reduction in any vertebral height.Grade 3 Severe: VF was defined as more than 40% reduction in any vertebral height.
Time frame: 12 months
Population: Modified Intent-to-treat (mITT) population included all randomized subjects who had a baseline and at least one post-baseline assessment of the primary efficacy variable. Patients with a baseline x-ray and a 12M x-ray are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zoledronic Acid | Percentage of Participants With at Least One New Moderate or Severe Morphometric Vertebral Fracture Over 12 Months | 0.4 Percentage of participants |
| Placebo | Percentage of Participants With at Least One New Moderate or Severe Morphometric Vertebral Fracture Over 12 Months | 1.9 Percentage of participants |
Secondary
Percentage of Participants With at Least One New Moderate or Severe Morphometric Vertebral Fracture Over 24 Months
Moderate or severe vertebral fracture (VF) was assessed based on morphometry. A QM (quantitative morphometry) incident VF(QM positive) was defined by at least a 20% decrease in any vertebral height (at least 4 mm). If a participant had a QM positive at any vertebrae at any visit,x-rays from all visits for participants were evaluated using Genant semi-quantitative (SQ) method for VF assessment. Grade 2 moderate VF was defined as a 25-40% reduction in any vertebral height.Grade 3 Severe: VF was defined as more than 40% reduction in any vertebral height.
Time frame: 24 Months
Population: Modified Intent-to-treat (mITT) population included all randomized subjects who had a baseline and at least one post-baseline assessment of the primary efficacy variable. Patients with a baseline x-ray and a 12M x-ray are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zoledronic Acid | Percentage of Participants With at Least One New Moderate or Severe Morphometric Vertebral Fracture Over 24 Months | 1.1 Percentage of participants |
| Placebo | Percentage of Participants With at Least One New Moderate or Severe Morphometric Vertebral Fracture Over 24 Months | 3.0 Percentage of participants |
Secondary
Percentage of Participants With at Least One New Morphometric Vertebral Fracture Over 12 Months
Vertebral fracture (VF) was assessed based on morphometry. QM(quantitative morphometry) incident VF(QM positive) is defined by at least 20% decrease in vertebral height of at least 4mm. If participant had QM positive at any vertebrae at any visit, x-rays from visits for participants were evaluated using Genant semi-quantitative method for VF assessment: Grade1 Mild VF is defined as 20-24% decrease in anterior, middle, and/or posterior vertebral height. Grade2 moderate VF is defined as 25-40% decrease in vertebral height. Grade3 Severe VF is defined as more than 40% decrease in vertebral height
Time frame: 12 Months
Population: Modified Intent-to-treat (mITT) population included all randomized subjects who had a baseline and at least one post-baseline assessment of the primary efficacy variable. Patients with a baseline x-ray and a 12M x-ray are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zoledronic Acid | Percentage of Participants With at Least One New Morphometric Vertebral Fracture Over 12 Months | 0.9 Percentage of participants |
| Placebo | Percentage of Participants With at Least One New Morphometric Vertebral Fracture Over 12 Months | 2.8 Percentage of participants |
Secondary
Percentage of Participants With at Least One New or Worsening Morphometric Vertebral Fracture Over 12 Months
Worsening vertebral fracture (VF) was assessed based on morphometry. QM (quantitative morphometry) incident VF(QM positive) was defined by at least a 20% decrease in any vertebral height (at least 4 mm). If a participant had a QM positive at any vertebrae at any visit, x-rays from all visits for participants were evaluated using Genant semi-quantitative (SQ) method for VF assessment. A worsening fracture was defined as an SQ reading that was greater than the baseline SQ reading, which was at least 1 (prevalent fracture)
Time frame: Baseline, 12 months
Population: Modified Intent-to-treat (mITT) population included all randomized subjects who had a baseline and at least one post-baseline assessment of the primary efficacy variable. Patients with a baseline x-ray and a 12M x-ray are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zoledronic Acid | Percentage of Participants With at Least One New or Worsening Morphometric Vertebral Fracture Over 12 Months | 1.3 Percentage of Participants |
| Placebo | Percentage of Participants With at Least One New or Worsening Morphometric Vertebral Fracture Over 12 Months | 2.8 Percentage of Participants |
Secondary
Percentage of Participants With at Least One New or Worsening Morphometric Vertebral Fracture Over 24 Months
Worsening vertebral fracture (VF) was assessed based on morphometry. A QM (quantitative morphometry) incident VF(QM positive) was defined by at least a 20% decrease in any vertebral height (at least 4 mm). If a participant had a QM positive at any vertebrae at any visit,x-rays from all visits for participants were evaluated using Genant semi-quantitative (SQ) method for VF assessment. A worsening fracture was defined as an SQ reading that was greater than the baseline SQ reading, which was at least 1 (prevalent fracture)
Time frame: Baseline, Month 24
Population: Modified Intent-to-treat (mITT) population included all randomized subjects who had a baseline and at least one post-baseline assessment of the primary efficacy variable. In this analysis, missing Month 24 fractures were imputed using LOCF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zoledronic Acid | Percentage of Participants With at Least One New or Worsening Morphometric Vertebral Fracture Over 24 Months | 2.0 Percentage of Participants |
| Placebo | Percentage of Participants With at Least One New or Worsening Morphometric Vertebral Fracture Over 24 Months | 4.9 Percentage of Participants |
Secondary
Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits
Time frame: Baseline, Month 3, Month 6, Month 12, Month 15, month 18, Month 24
Population: The ITT, Intent to Treat population, includes all participants who received a single a dose of treatment and had data available for analysis. n = the number of subjects with evaluable measurements at visit, as determined by the efficacy window.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zoledronic Acid | Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits | Month 6 (n=62) (n=64) | 0.1384 ng/mL | Standard Error 0.00914 |
| Zoledronic Acid | Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits | Month 15 (n=55) (n=58) | 0.0996 ng/mL | Standard Error 0.0059 |
| Zoledronic Acid | Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits | Month 3 (n=63) (n=65) | 0.0990 ng/mL | Standard Error 0.008 |
| Zoledronic Acid | Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits | Month 18 (n=55) (n=60) | 0.1320 ng/mL | Standard Error 0.00661 |
| Zoledronic Acid | Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits | Month 12 (n=63) (n=64) | 0.1669 ng/mL | Standard Error 0.00925 |
| Zoledronic Acid | Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits | Month 24 (n=55) (n=62) | 0.1760 ng/mL | Standard Error 0.01248 |
| Zoledronic Acid | Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits | Baseline (n-64) (n=66) | 0.3646 ng/mL | Standard Error 0.02094 |
| Placebo | Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits | Month 24 (n=55) (n=62) | 0.4060 ng/mL | Standard Error 0.0264 |
| Placebo | Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits | Baseline (n-64) (n=66) | 0.3933 ng/mL | Standard Error 0.02955 |
| Placebo | Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits | Month 3 (n=63) (n=65) | 0.3647 ng/mL | Standard Error 0.02989 |
| Placebo | Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits | Month 6 (n=62) (n=64) | 0.3540 ng/mL | Standard Error 0.02576 |
| Placebo | Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits | Month 12 (n=63) (n=64) | 0.4042 ng/mL | Standard Error 0.03056 |
| Placebo | Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits | Month 15 (n=55) (n=58) | 0.3576 ng/mL | Standard Error 0.02519 |
| Placebo | Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits | Month 18 (n=55) (n=60) | 0.3954 ng/mL | Standard Error 0.03001 |