VERtebral Fracture Treatment Comparisons in Osteoporotic Women

Study Overview
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Brief Summary
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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.

Official Title
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Teriparatide and Risedronate in the Treatment of Patients With Severe Postmenopausal Osteoporosis: Comparative Effects on Vertebral Fractures

Conditions
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Postmenopausal Osteoporosis

Intervention / Treatment
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* Drug: Teriparatide
* Drug: Risedronate
* Drug: Placebo
* Drug: Calcium
* Drug: Vitamin D


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Teriparatide<br>Teriparatide 20 microgram (µg) administered by subcutaneous (SC) injection once daily for 24 months. Placebo given orally once weekly for 24 months. Elemental Calcium 500 to 1000 milligram per day and Vitamin D 400 to 800 International Units per day, both administered orally once daily while receiving treatment. | Drug: Teriparatide<br>* Administered SC<br>* Other names: Forsteo;Drug: Placebo<br>* Teriparatide arm placebo administered orally. Risedronate arm placebo administered SC.<br>Drug: Calcium<br>* Administered orally<br>Drug: Vitamin D<br>* Administered orally<br>|
| Active Comparator: Risedronate<br>Risedronate 35 milligram (mg) administered orally once weekly for 24 months. Placebo given by SC injection once daily for 24 months. Elemental Calcium 500 to 1000 milligram per day and Vitamin D 400 to 800 International Units per day, both administered orally once daily while receiving treatment. | Drug: Risedronate<br>* Administered orally<br>Drug: Placebo<br>* Teriparatide arm placebo administered orally. Risedronate arm placebo administered SC.<br>Drug: Calcium<br>* Administered orally<br>Drug: Vitamin D<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline through 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline through 24 Months | 
| 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. | Baseline through 24 Months | 
| 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. | Baseline through 24 Months | 
| 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. | Baseline through 24 Months | 
| 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). | Baseline through 24 Months | 
| Proportion of Participants With New Multiple (2 or More) Vertebral Fractures |  | Baseline through 24 Months | 
| 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. | Baseline through 24 Months | 
| 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 | 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. | Baseline, 24 Months | 
| 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. | Baseline, 24 Months | 
| 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. | Baseline, 24 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bone Loss, Vertebral fractures