Effect of Raloxifene Plus Cholecalciferol and Cholecalciferol Alone on the Bone Mineral Density in Postmenopausal Women With Osteopenia

Study Overview
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Brief Summary
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Osteoporosis is a very strong predictor of fractures with low BMD, but more than half of osteoporotic fractures actually occur in the osteopenic patient group. Therefore, it is important to prevent fractures by actively evaluating fracture risk even in patients with osteopenia. Raloxifene is a second-generation SERM agent that inhibits bone resorption and is used for the prevention and treatment of postmenopausal osteoporosis. The clinical effect of raloxifene has already been demonstrated in the Multiple Outcomes of Raloxifene Evaluation (MORE) study, a large-scale RCT, to increase BMD and improve lipid profile. In this study, we aimed to evaluate the efficacy of Raloxifene plus cholecalciferol in postmenopausal women with osteopenia.

Detailed Description
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Backgroud : Osteoporosis is a powerful predictor of fractures with low BMD, but more than half of osteoporotic fractures occur in osteopenia. Therefore, it is important to start drug treatment after diagnosis of osteoporosis, but it is also important to prevent fractures by actively evaluating the risk of fractures in patients with osteopenia. Raloxifene is a selective oestrogen receptor modulator (SERM) that has beneficial effects on bone and lipid profile and has been approved by the FDA as a treatment to prevent osteoporosis. However, studies on the efficacy of Raloxifene plus cholecalciferol in osteopenia patients lack evidence. Aim : This study aimed to investigate the efficacy of raloxifene plus cholecalciferol in postmenopausal women with osteopenia. Methods : A prospective, single-center, randomized, opne label, parallel, intervention study in 112 patients investigating the difference in bone mineral density between raloxifene plus cholecalciferol group and cholecalciferol group. Study participants are randomly assigned using the R procedure in a 1:1 ratio at enrollment. Each participant takes raloxifene plus cholecalciferol or cholecalciferol for 48 weeks. All participants were tested for bone turnover markers, routine chemistry, and lipid profile at baseline and 6-month intervals. In addition, at baseline and 48 weeks, DXA, whole spine x-ray, quantitative CT, bioimpedance analysis, muscle function test (handgrip test, jump power), and EQ-5D test. Perspectives : More than half of osteoporotic fractures occur in patients with osteopenia. This study will confirm the effect of Raloxifene plus cholecalciferol on bone density and show changes in muscle function and lipid metabolism. Through this, early and active treatment can be suggested as a new guideline for preventing osteoporosis and osteoporotic fractures in postmenopausal women with osteopenia.

Official Title
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Effect of Raloxifene Plus Cholecalciferol and Cholecalciferol Alone on the Bone Mineral Density in Postmenopausal Women With Osteopenia: an 1-year Randomized Controlled Trial

Conditions
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Postemenopusal Women With Osteopenia

Intervention / Treatment
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* Drug: Raloxifene plus cholecalciferol
* Drug: Cholecalciferol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal women (defined as no menstruation for more than 48 weeks prior to screening and no other pathological or physiological causes. If in doubt, a serum follicle-stimulating hormone (FSH) test may be performed at screening) Osteopenia ( -2.5 SD< T-score≤ -1.0 SD in DXA) Exclusion Criteria: Secondary osteoporosis (Systemic glucocorticoid use, aromatase inhibitor, thyrotoxicosis, hypeparathyroidism, etc) Vitamin D deficiency at baseline (25-OH-vitD <10ng/mL) Active cancer treatment History of vascular thrombosis Bisphosphonate treatment within the last 12months Contraindication for Raloxifene according to the SPC

Ages Eligible for Study
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Minimum Age: 50 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Raloxifen plus cholecalciferol<br>Raloxifene 60mg + Cholecalciferol 800 IU | Drug: Raloxifene plus cholecalciferol<br>* Rabone D ( Raloxifene 60mg + Cholecalciferol 800 IU ) 1 Capsule once daily<br>* Other names: Rabone D;|
| Active Comparator: Cholecalciferol<br>Cholecalciferol 800 IU | Drug: Cholecalciferol<br>* D3 oral base drop, 4 drops once daily (800 IU)<br>* Other names: D3 base oral drop;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BMD lumbar spine | Change in lumbar spine BMD from baseline to 48 weeks after the Ralxifene plus cholecalciferol vs cholecalciferol | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BMD femoral neck an total hip | Change in femoral neck and total hip BMD from baseline to 48 weeks after the Ralxifene plus cholecalciferol vs cholecalciferol | 48 weeks | 
| Bone turnover marker | Changes in p-CTX and P1NP From Baseline to Six and twelve months after the Ralxifene plus cholecalciferol | 48 weeks | 
| Muscle function | Changes in muscle fucntion (Handgrip, jump power) From Baseline to Six and twelve months after the Ralxifene plus cholecalciferol | 48 weeks | 
| Lipid profile | Changes in lipid profile From Baseline to Six and twelve months after the Ralxifene plus cholecalciferol | 48 weeks | 
| Vertebral fracture | Morphometric Vertebral Fractures Assessed by whole spine x-ray | 48 weeks |