Postmenopausal Osteoporosis
Conditions
Keywords
Bone Loss, Vertebral fractures
Brief summary
The primary purpose of participation in this study is to answer whether teriparatide is superior to risedronate in reducing the occurrence of new vertebral fractures during 24 months of therapy.
Interventions
DRUGTeriparatide
Administered SC
DRUGRisedronate
Administered orally
DRUGPlacebo
Teriparatide arm placebo administered orally. Risedronate arm placebo administered SC.
DRUGCalcium
Administered orally
DRUGVitamin D
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Postmenopausal women with osteoporosis, as defined by low bone mineral density (BMD), i.e. anterior-posterior lumbar spine, total hip or femoral neck BMD ≥1.5 standard deviations below the average BMD for young, healthy, non-Hispanic, Caucasian women * A minimum of 2 moderate or 1 severe vertebral fragility fractures (confirmed by central reader) were required
Exclusion criteria
* Increased risk of osteosarcoma * History of unresolved skeletal diseases that affect bone metabolism * History of atypical subtrochanteric or diaphyseal femoral fractures * Abnormally high or low calcium levels * Abnormally high parathyroid hormone (PTH) levels * Severe vitamin D deficiency * Abnormal thyroid function not corrected by therapy * History of malignant neoplasms in the last 5 years * Active liver disease, clinical jaundice * Significant impairment of hepatic or renal function * History of nephro- or urolithiasis * Previous or planned kypho- or vertebroplasty * Active or risk for osteonecrosis of the jaw * Active or recent history of upper gastrointestinal disorders * Unable to stand or sit in the upright position for at least 30 minutes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With New Vertebral Fractures | Baseline through 24 Months | The incidence of new vertebral fractures was assessed by quantitative vertebral morphometry measurements (QM) with qualitative visual semiquantitative grading (SQ) confirmation. A new vertebral fracture was diagnosed in a vertebra that was non-fractured at the baseline radiological examination. It was defined as a loss of vertebral body height of at least 20% and 4 mm from the baseline radiograph by vertebral QM, based upon placement of six points by a trained, central reader. Any fractures identified by QM were confirmed using SQ: if the vertebral body also had an increase of one or more severity grade, it was considered an incident vertebral fracture. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Pooled Clinical Vertebral and Non-Vertebral Fragility Fractures | Baseline through 24 Months | A clinical vertebral fracture was defined as a new or worsening vertebral fracture, confirmed by radiography, that was associated with signs and symptoms highly suggestive of a vertebral fracture. All non-vertebral fractures that occurred and were diagnosed between visits required the confirmation by the site investigators after evaluating the original x-ray film(s), the radiology or surgical report. For clinical vertebral fractures, the final confirmation of the diagnosis required the centralized evaluation by a trained, independent reader. |
| Proportion of Participants With Non-Vertebral Fragility Fractures | Baseline through 24 Months | A non-vertebral fracture is a fracture at any of the following non-vertebral sites: clavicle, scapula, ribs, sternum, sacrum, coccyx, humerus, radius, ulna, carpus, pelvis, hip, femur, patella, tibia, fibula, ankle, calcaneus, tarsus, and metatarsal. Non-vertebral fractures were determined by direct questioning at each visit, and confirmed by the site investigators by x-ray, radiology or surgical report. Fractures resulting from a severe trauma such as a traffic collision, a beating, or having been struck by a falling or moving object were not considered fragility fractures but traumatic fractures. |
| Proportion of Participants With Major Non-Vertebral Fragility Fractures | Baseline through 24 Months | A major non-vertebral fracture is a fracture at any of the following non-vertebral sites hip, radius, humerus, ribs, pelvis, tibia and femur. Non-vertebral fractures were determined by direct questioning at each visit, and confirmed by the site investigators by x-ray, radiology or surgical report. Fractures resulting from a severe trauma such as a traffic collision, a beating, or having been struck by a falling or moving. |
| Proportion of Participants With New Moderate and/or Severe Vertebral Fractures | Baseline through 24 Months | Vertebrae were graded as moderate (SQ2), or severe (SQ3) fractures, based on \ 25 to 40% (moderate) or \ 40% or more (severe) decrease in anterior, central, or posterior vertebral height (T4 through L4). |
| Proportion of Participants With New Multiple (2 or More) Vertebral Fractures | Baseline through 24 Months | — |
| Proportion of Participants With Pooled New and Worsening Vertebral Fractures | Baseline through 24 Months | Worsening of a pre-existing fracture was considered if the decrease in vertebral height was at least one severity grade in the semi-quantitative assessment, confirmed by a trained central reader, where vertebrae were graded as normal (SQ0) or as with mild (SQ1), moderate (SQ2), or severe (SQ3) fractures, defined as \ 20 to 25% (mild), \ 25 to 40% (moderate) or \ 40% or more (severe) decrease in anterior, central, or posterior vertebral height (T4 to L4). |
| Change From Baseline to 24 Months Endpoint in Height | Baseline, 24 Months | — |
| Change From Baseline to 24 Months Endpoint in Back Pain Using an 11-point Numerical Pain Rating Scale | Baseline, 24 Months | Participants rated the worst back pain during the 24 hours preceding the visit at baseline and each post-baseline visit. An 11-point numerical back pain rating scale (rated from 0 = no back pain to 10 = worst possible back pain) was used. |
| Change From Baseline to 24 Months Endpoint in the European Quality of Life Questionnaire [EQ-5D-5L] (UK) | Baseline, 24 Months | The EQ-5D-5L is a generic, multidimensional, health-related, quality-of-life instrument completed on five dimensions to measure health-related quality of life. The profile allowed participants to rate their health state in five health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a five level scale (no problems, slight problems, moderate problems, severe problems, and unable to/extreme problems). The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.59 to 1.0. A higher score indicates better health state. |
| Change From Baseline to 24 Months Endpoint in the European Quality of Life Questionnaire [EQ-5D-5L] (US) | Baseline, 24 Months | The EQ-5D-5L is a generic, multidimensional, health-related, quality-of-life instrument completed on five dimensions to measure health-related quality of life. The profile allowed participants to rate their health state in five health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a five level scale (no problems, slight problems, moderate problems, severe problems, and unable to/extreme problems). The responses are used to derive the health state index scores using the United States (US) cross walk algorithm, with scores ranging from -0.11 to 1.0. A higher score indicates better health state. |
| Proportion of Participants With Pooled Fragility and Traumatic Non-Vertebral Fractures | Baseline through 24 Months | Traumatic fractures were considered if resulting from a severe trauma such as a traffic collision, a beating, or having been struck by a falling or moving object. |
Countries
Argentina, Austria, Belgium, Brazil, Canada, Czechia, France, Germany, Greece, Hungary, Italy, Poland, Puerto Rico, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Teriparatide Teriparatide 20 microgram administered by subcutaneous injection once daily for 24 months.
Placebo given orally once weekly for 24 months. | 680 |
| Risedronate Risedronate 35 milligram administered orally once weekly for 24 months.
Placebo given by SC injection once daily for 24 months. | 680 |
| Total | 1,360 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 56 | 48 |
| Overall Study | Caregiver Decision | 1 | 1 |
| Overall Study | Death | 14 | 6 |
| Overall Study | Lack of Efficacy | 1 | 1 |
| Overall Study | Lost to Follow-up | 7 | 5 |
| Overall Study | Physician Decision | 4 | 10 |
| Overall Study | Protocol Violation | 4 | 6 |
| Overall Study | Sponsor Decision | 2 | 2 |
| Overall Study | Withdrawal by Subject | 96 | 89 |
Baseline characteristics
| Characteristic | Risedronate | Total | Teriparatide |
|---|---|---|---|
| Age, Continuous | 71.6 years STANDARD_DEVIATION 8.58 | 72.1 years STANDARD_DEVIATION 8.68 | 72.6 years STANDARD_DEVIATION 8.77 |
| Bone Mineral Density (BMD) Femoral Neck | 0.667 Gram per square centimeter (g/cm2) STANDARD_DEVIATION 0.1129 | 0.664 Gram per square centimeter (g/cm2) STANDARD_DEVIATION 0.1107 | 0.662 Gram per square centimeter (g/cm2) STANDARD_DEVIATION 0.1085 |
| Bone Mineral Density (BMD) Lumbar Spine | 0.856 Gram per square centimeter (g/cm2) STANDARD_DEVIATION 0.1473 | 0.857 Gram per square centimeter (g/cm2) STANDARD_DEVIATION 0.1506 | 0.858 Gram per square centimeter (g/cm2) STANDARD_DEVIATION 0.1541 |
| Bone Mineral Density (BMD) Total Hip | 0.735 Gram per square centimeter (g/cm2) STANDARD_DEVIATION 0.1165 | 0.735 Gram per square centimeter (g/cm2) STANDARD_DEVIATION 0.1116 | 0.736 Gram per square centimeter (g/cm2) STANDARD_DEVIATION 0.1065 |
| Distribution of Stratification Factors Vertebral Fracture with Bisphosphonate Use | 79 Participants | 161 Participants | 82 Participants |
| Distribution of Stratification Factors Without Vertebral Fracture with Bisphosphonate Use | 189 Participants | 373 Participants | 184 Participants |
| Distribution of Stratification Factors Without Vertebral Fracture without Bisphosphonate | 247 Participants | 491 Participants | 244 Participants |
| Distribution of Stratification Factors With Vertebral Fracture without Bisphosphonate Use | 165 Participants | 335 Participants | 170 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 99 Participants | 203 Participants | 104 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 302 Participants | 612 Participants | 310 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 279 Participants | 545 Participants | 266 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 12 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 20 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 653 Participants | 1323 Participants | 670 Participants |
| Region of Enrollment Argentina | 78 Participants | 157 Participants | 79 Participants |
| Region of Enrollment Austria | 29 Participants | 53 Participants | 24 Participants |
| Region of Enrollment Belgium | 45 Participants | 88 Participants | 43 Participants |
| Region of Enrollment Brazil | 81 Participants | 144 Participants | 63 Participants |
| Region of Enrollment Canada | 33 Participants | 69 Participants | 36 Participants |
| Region of Enrollment Czech Republic | 68 Participants | 136 Participants | 68 Participants |
| Region of Enrollment France | 29 Participants | 55 Participants | 26 Participants |
| Region of Enrollment Germany | 30 Participants | 67 Participants | 37 Participants |
| Region of Enrollment Greece | 13 Participants | 40 Participants | 27 Participants |
| Region of Enrollment Hungary | 53 Participants | 121 Participants | 68 Participants |
| Region of Enrollment Italy | 36 Participants | 69 Participants | 33 Participants |
| Region of Enrollment Poland | 63 Participants | 118 Participants | 55 Participants |
| Region of Enrollment Spain | 55 Participants | 121 Participants | 66 Participants |
| Region of Enrollment United States | 67 Participants | 122 Participants | 55 Participants |
| Sex: Female, Male Female | 680 Participants | 1360 Participants | 680 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Vertebral Fracture Status 1 Fracture | 240 Participants | 471 Participants | 231 Participants |
| Vertebral Fracture Status 2 Fractures | 174 Participants | 352 Participants | 178 Participants |
| Vertebral Fracture Status 3 Fractures | 101 Participants | 205 Participants | 104 Participants |
| Vertebral Fracture Status 4 Fractures | 62 Participants | 122 Participants | 60 Participants |
| Vertebral Fracture Status 5 or More Fractures | 102 Participants | 208 Participants | 106 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 130 / 683 | 130 / 683 |
| serious Total, serious adverse events | 138 / 683 | 117 / 683 |
Outcome results
Primary
Proportion of Participants With New Vertebral Fractures
The incidence of new vertebral fractures was assessed by quantitative vertebral morphometry measurements (QM) with qualitative visual semiquantitative grading (SQ) confirmation. A new vertebral fracture was diagnosed in a vertebra that was non-fractured at the baseline radiological examination. It was defined as a loss of vertebral body height of at least 20% and 4 mm from the baseline radiograph by vertebral QM, based upon placement of six points by a trained, central reader. Any fractures identified by QM were confirmed using SQ: if the vertebral body also had an increase of one or more severity grade, it was considered an incident vertebral fracture.
Time frame: Baseline through 24 Months
Population: Full analysis set-modified: participants with baseline and at least one post-baseline spinal radiograph evaluable to assess the vertebral fracture status after 24 month of therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Teriparatide | Proportion of Participants With New Vertebral Fractures | 28 Participants (with at least one event) |
| Risedronate | Proportion of Participants With New Vertebral Fractures | 64 Participants (with at least one event) |
p-value: 0.00009495% CI: [0.256, 0.647]Cochran-Mantel-Haenszel
p-value: 0.00009495% CI: [0.29, 0.677]Cochran-Mantel-Haenszel
Secondary
Change From Baseline to 24 Months Endpoint in Back Pain Using an 11-point Numerical Pain Rating Scale
Participants rated the worst back pain during the 24 hours preceding the visit at baseline and each post-baseline visit. An 11-point numerical back pain rating scale (rated from 0 = no back pain to 10 = worst possible back pain) was used.
Time frame: Baseline, 24 Months
Population: Full analysis set: all participants who received at least one dose of study drug and had evaluable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | Change From Baseline to 24 Months Endpoint in Back Pain Using an 11-point Numerical Pain Rating Scale | Baseline | 4.5 units on a scale | Standard Deviation 2.9 |
| Teriparatide | Change From Baseline to 24 Months Endpoint in Back Pain Using an 11-point Numerical Pain Rating Scale | 24 Months | 3.4 units on a scale | Standard Deviation 2.95 |
| Risedronate | Change From Baseline to 24 Months Endpoint in Back Pain Using an 11-point Numerical Pain Rating Scale | Baseline | 4.5 units on a scale | Standard Deviation 2.91 |
| Risedronate | Change From Baseline to 24 Months Endpoint in Back Pain Using an 11-point Numerical Pain Rating Scale | 24 Months | 3.4 units on a scale | Standard Deviation 2.89 |
p-value: 0.58595% CI: [-0.42, 0.24]Mixed Models Analysis
Secondary
Change From Baseline to 24 Months Endpoint in Height
Time frame: Baseline, 24 Months
Population: Full analysis set: all participants who received at least one dose of study drug and had evaluable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | Change From Baseline to 24 Months Endpoint in Height | 24 Months | 154.3 Centimeter (cm) | Standard Deviation 7.05 |
| Teriparatide | Change From Baseline to 24 Months Endpoint in Height | Baseline | 154.7 Centimeter (cm) | Standard Deviation 7.15 |
| Risedronate | Change From Baseline to 24 Months Endpoint in Height | Baseline | 155.0 Centimeter (cm) | Standard Deviation 7.4 |
| Risedronate | Change From Baseline to 24 Months Endpoint in Height | 24 Months | 154.5 Centimeter (cm) | Standard Deviation 7.42 |
p-value: 0.09395% CI: [-0.28, 0.02]Mixed Models Analysis
Secondary
Change From Baseline to 24 Months Endpoint in the European Quality of Life Questionnaire [EQ-5D-5L] (UK)
The EQ-5D-5L is a generic, multidimensional, health-related, quality-of-life instrument completed on five dimensions to measure health-related quality of life. The profile allowed participants to rate their health state in five health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a five level scale (no problems, slight problems, moderate problems, severe problems, and unable to/extreme problems). The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.59 to 1.0. A higher score indicates better health state.
Time frame: Baseline, 24 Months
Population: Full analysis set: all participants who received at least one dose of study drug and had evaluable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | Change From Baseline to 24 Months Endpoint in the European Quality of Life Questionnaire [EQ-5D-5L] (UK) | Baseline | 0.59 units on a scale | Standard Deviation 0.243 |
| Teriparatide | Change From Baseline to 24 Months Endpoint in the European Quality of Life Questionnaire [EQ-5D-5L] (UK) | 24 Months | 0.65 units on a scale | Standard Deviation 0.249 |
| Risedronate | Change From Baseline to 24 Months Endpoint in the European Quality of Life Questionnaire [EQ-5D-5L] (UK) | Baseline | 0.62 units on a scale | Standard Deviation 0.228 |
| Risedronate | Change From Baseline to 24 Months Endpoint in the European Quality of Life Questionnaire [EQ-5D-5L] (UK) | 24 Months | 0.68 units on a scale | Standard Deviation 0.205 |
p-value: 0.75795% CI: [-0.03, 0.02]Mixed Models Analysis
Secondary
Change From Baseline to 24 Months Endpoint in the European Quality of Life Questionnaire [EQ-5D-5L] (US)
The EQ-5D-5L is a generic, multidimensional, health-related, quality-of-life instrument completed on five dimensions to measure health-related quality of life. The profile allowed participants to rate their health state in five health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a five level scale (no problems, slight problems, moderate problems, severe problems, and unable to/extreme problems). The responses are used to derive the health state index scores using the United States (US) cross walk algorithm, with scores ranging from -0.11 to 1.0. A higher score indicates better health state.
Time frame: Baseline, 24 Months
Population: Full analysis set: all participants who received at least one dose of study drug and had evaluable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | Change From Baseline to 24 Months Endpoint in the European Quality of Life Questionnaire [EQ-5D-5L] (US) | Baseline | 0.70 units on a scale | Standard Deviation 0.167 |
| Teriparatide | Change From Baseline to 24 Months Endpoint in the European Quality of Life Questionnaire [EQ-5D-5L] (US) | 24 Months | 0.74 units on a scale | Standard Deviation 0.176 |
| Risedronate | Change From Baseline to 24 Months Endpoint in the European Quality of Life Questionnaire [EQ-5D-5L] (US) | Baseline | 0.72 units on a scale | Standard Deviation 0.159 |
| Risedronate | Change From Baseline to 24 Months Endpoint in the European Quality of Life Questionnaire [EQ-5D-5L] (US) | 24 Months | 0.76 units on a scale | Standard Deviation 0.145 |
p-value: 0.69495% CI: [-0.02, 0.01]Mixed Models Analysis
Secondary
Proportion of Participants With Major Non-Vertebral Fragility Fractures
A major non-vertebral fracture is a fracture at any of the following non-vertebral sites hip, radius, humerus, ribs, pelvis, tibia and femur. Non-vertebral fractures were determined by direct questioning at each visit, and confirmed by the site investigators by x-ray, radiology or surgical report. Fractures resulting from a severe trauma such as a traffic collision, a beating, or having been struck by a falling or moving.
Time frame: Baseline through 24 Months
Population: Full analysis set: all participants who received at least one dose of study drug and had evaluable data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Teriparatide | Proportion of Participants With Major Non-Vertebral Fragility Fractures | 18 Participants (with at least one event) |
| Risedronate | Proportion of Participants With Major Non-Vertebral Fragility Fractures | 31 Participants (with at least one event) |
p-value: 0.06243295% CI: [0.318, 1.052]Stratified Log Rank
Secondary
Proportion of Participants With New Moderate and/or Severe Vertebral Fractures
Vertebrae were graded as moderate (SQ2), or severe (SQ3) fractures, based on \ 25 to 40% (moderate) or \ 40% or more (severe) decrease in anterior, central, or posterior vertebral height (T4 through L4).
Time frame: Baseline through 24 Months
Population: Full analysis set-modified: participants with baseline and at least one post-baseline spinal radiograph evaluable to assess the vertebral fracture status after 24 month of therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Teriparatide | Proportion of Participants With New Moderate and/or Severe Vertebral Fractures | 26 Participants (with at least one event) |
| Risedronate | Proportion of Participants With New Moderate and/or Severe Vertebral Fractures | 63 Participants (with at least one event) |
p-value: <0.00195% CI: [0.237, 0.614]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [0.27, 0.646]Cochran-Mantel-Haenszel
Secondary
Proportion of Participants With New Multiple (2 or More) Vertebral Fractures
Time frame: Baseline through 24 Months
Population: Full analysis set-modified: participants with baseline and at least one post-baseline spinal radiograph evaluable to assess the vertebral fracture status after 24 month of therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Teriparatide | Proportion of Participants With New Multiple (2 or More) Vertebral Fractures | 2 Participants (with at least one event) |
| Risedronate | Proportion of Participants With New Multiple (2 or More) Vertebral Fractures | 12 Participants (with at least one event) |
p-value: 0.00795% CI: [0.035, 0.728]Cochran-Mantel-Haenszel
p-value: 0.00795% CI: [0.036, 0.744]Cochran-Mantel-Haenszel
Secondary
Proportion of Participants With Non-Vertebral Fragility Fractures
A non-vertebral fracture is a fracture at any of the following non-vertebral sites: clavicle, scapula, ribs, sternum, sacrum, coccyx, humerus, radius, ulna, carpus, pelvis, hip, femur, patella, tibia, fibula, ankle, calcaneus, tarsus, and metatarsal. Non-vertebral fractures were determined by direct questioning at each visit, and confirmed by the site investigators by x-ray, radiology or surgical report. Fractures resulting from a severe trauma such as a traffic collision, a beating, or having been struck by a falling or moving object were not considered fragility fractures but traumatic fractures.
Time frame: Baseline through 24 Months
Population: Full analysis set: all participants who received at least one dose of study drug and had evaluable data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Teriparatide | Proportion of Participants With Non-Vertebral Fragility Fractures | 25 Participants (with at least one event) |
| Risedronate | Proportion of Participants With Non-Vertebral Fragility Fractures | 38 Participants (with at least one event) |
p-value: 0.09902395% CI: [0.39, 1.101]Stratified Log Rank
Secondary
Proportion of Participants With Pooled Clinical Vertebral and Non-Vertebral Fragility Fractures
A clinical vertebral fracture was defined as a new or worsening vertebral fracture, confirmed by radiography, that was associated with signs and symptoms highly suggestive of a vertebral fracture. All non-vertebral fractures that occurred and were diagnosed between visits required the confirmation by the site investigators after evaluating the original x-ray film(s), the radiology or surgical report. For clinical vertebral fractures, the final confirmation of the diagnosis required the centralized evaluation by a trained, independent reader.
Time frame: Baseline through 24 Months
Population: Full analysis set: all participants who received at least one dose of study drug and had evaluable data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Teriparatide | Proportion of Participants With Pooled Clinical Vertebral and Non-Vertebral Fragility Fractures | 30 Participants (with at least one event) |
| Risedronate | Proportion of Participants With Pooled Clinical Vertebral and Non-Vertebral Fragility Fractures | 61 Participants (with at least one event) |
p-value: 0.00086995% CI: [0.316, 0.739]Stratified Log Rank
Secondary
Proportion of Participants With Pooled Fragility and Traumatic Non-Vertebral Fractures
Traumatic fractures were considered if resulting from a severe trauma such as a traffic collision, a beating, or having been struck by a falling or moving object.
Time frame: Baseline through 24 Months
Population: Full analysis set: all participants who received at least one dose of study drug and had evaluable data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Teriparatide | Proportion of Participants With Pooled Fragility and Traumatic Non-Vertebral Fractures | 40 Participants (with at least one event) |
| Risedronate | Proportion of Participants With Pooled Fragility and Traumatic Non-Vertebral Fractures | 57 Participants (with at least one event) |
p-value: 0.07895% CI: [0.461, 1.05]Stratified Log Rank
Secondary
Proportion of Participants With Pooled New and Worsening Vertebral Fractures
Worsening of a pre-existing fracture was considered if the decrease in vertebral height was at least one severity grade in the semi-quantitative assessment, confirmed by a trained central reader, where vertebrae were graded as normal (SQ0) or as with mild (SQ1), moderate (SQ2), or severe (SQ3) fractures, defined as \ 20 to 25% (mild), \ 25 to 40% (moderate) or \ 40% or more (severe) decrease in anterior, central, or posterior vertebral height (T4 to L4).
Time frame: Baseline through 24 Months
Population: Full analysis set-modified: participants with baseline and at least one post-baseline spinal radiograph evaluable to assess the vertebral fracture status after 24 month of therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Teriparatide | Proportion of Participants With Pooled New and Worsening Vertebral Fractures | 31 Participants (with at least one event) |
| Risedronate | Proportion of Participants With Pooled New and Worsening Vertebral Fractures | 69 Participants (with at least one event) |
p-value: 0.00007595% CI: [0.269, 0.652]Cochran-Mantel-Haenszel
p-value: 0.00007595% CI: [0.305, 0.682]Cochran-Mantel-Haenszel