Denosumab in Current Users of Bisphosphonates for Glucocorticoid-induced Osteoporosis

Study Overview
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Brief Summary
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The purpose of this study is to study the efficacy of denosumab, a new drug, in the treatment of osteoporosis in patients using bisphosphonates.

Detailed Description
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There are no data on the use of denosumab in steroid induced osteoporosis. Postmenopausal women with chronic use of Glucocorticoid (GCs) are at high-risk of osteoporotic fractures. Despite bisphosphonate treatment, a certain proportion of high-risk patients using chronic GCs either do not achieve a satisfactory gain in bone mineral density (BMD) or develop new fragility fractures. Thus, more potent osteoporosis treatment is necessary for this subgroup of patients. This prompts the current study which aims to examine the efficacy of denosumab in current users of oral bisphosphonates for Glucocorticoid-induced Osteoporosis (GIOP).

Official Title
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Denosumab in Current Users of Bisphosphonates for Glucocorticoid-induced Osteoporosis: a Randomized Controlled Trial

Conditions
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Osteoporosis

Intervention / Treatment
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* Drug: Denosumab
* Drug: bisphosphonates


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women or adult men (>18 years of age) with various medical diseases requiring long-term prednisolone treatment. Pre-menopausal women should have no plan for pregnancy within 2 years of study entry and agree to practice contraception during this 2-year period. A daily dose of prednisolone (or equivalent) of more than 2.5mg within 3 months of study entry. Having received oral bisphosphonate treatment for at least 2 years. Suboptimal response to bisphosphonate treatment, defined as either one of the following: (1) failure of lumbar spine, femoral neck or total hip BMD values to increase; (2) values of lumbar spine, femoral neck or total hip BMD remain osteoporotic, ie. T scores < -2.5 or Z scores < -2.0; or (3) development of new fragility vertebral or non-vertebral fractures despite at least 2 years' treatment with good compliance. Informed consent from patients. Exclusion Criteria: Patients with previous use of denosumab or teriparatide. Premenopausal women who plan for pregnancy within 2 years of study entry or who do not agree for contraception within this 2-year period. Patients with known bone disorders such as osteomalacia, renal osteodystrophy, and hyperparathyroidism. Patients with unexplained hypocalcemia. Patients with serum creatinine level of >=200umol/L.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Denosumab<br>denosumab | Drug: Denosumab<br>* 60mg subcutaneous injection 6 monthly for 2 doses<br>* Other names: Prolia;|
| Active Comparator: bisphosphonates<br>continuation of bisphosphonates | Drug: bisphosphonates<br>* continue present bisphosphonate treatment<br>* Other names: continuation of bisphosphonates in their usual dosages;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| bone mineral density (BMD) changes at the lumbar spine |  | baseline, 6 months and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BMD changes in the total hip and femoral neck |  | baseline, 6 months and 12 months | 
| bone turnover markers |  | baseline, 6 months and 12 months | 
| New vertebral fractures |  | 12 months | 
| adverse events |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RANKL, osteoporosis, denosumab, glucocorticoids