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

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

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.

Study Overview

• Status: Completed
• Conditions: Postemenopusal Women With Osteopenia
• Intervention / Treatment: Drug: Raloxifene plus cholecalciferol; Drug: Cholecalciferol

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Yonsei University Health system, Severance Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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)
2. Osteopenia ( -2.5 SD< T-score < -1.0 SD in DXA )

Exclusion Criteria:

1. Secondary osteoporosis (Systemic glucocorticoid use, aromatase inhibitor, thyrotoxicosis, hypeparathyroidism, etc)
2. Vitamin D deficiency at baseline (25-OH-vitD <10ng/mL)
3. Active cancer treatment
4. History of vascular thrombosis
5. Bisphosphonate treatment within the last 12months
6. Contraindication for Raloxifene according to the SPC

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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
Vertebral fracture	Morphometric Vertebral Fractures Assessed by whole spine x-ray	48 weeks
BMD femoral neck and 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 24 and 48 weeks after the Ralxifene plus cholecalciferol vs cholecalciferol	24 weeks, 48 weeks
Muscle function	Changes in muscle fucntion (Handgrip, jump power) From Baseline to 24 and 48 weeks after the Ralxifene plus cholecalciferol vs cholecalciferol	24 weeks, 48 weeks
Lipid profile	Changes in lipid profile From Baseline to 24 and 48 weeks after the Ralxifene plus cholecalciferol	24 weeks, 48 weeks
Quantitative CT	Change in quantitative CT from baseline to 48 weeks after the Ralxifene plus cholecalciferol vs cholecalciferol Morphometric Vertebral Fractures Assessed by whole spine x-ray Baseline to 48 weeks after the Ralxifene plus cholecalciferol vs cholecalciferol	48 weeks
Bioimpedance analysis	Changes in bioimpedance analysis From Baseline to 24 and 48 weeks after the Ralxifene plus cholecalciferol vs cholecalciferol	24 weeks, 48 weeks
EQ-5D test	Changes in EQ-5D test From Baseline to 24 and 48 weeks after the Ralxifene plus cholecalciferol vs cholecalciferol	24 weeks, 48 weeks

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Yumie Rhee, Department of Internal Medicine, Endocrine Research Institute, Yonsei University College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2020
• Primary Completion (Actual): July 14, 2022
• Study Completion (Actual): July 14, 2022

Study Registration Dates

• First Submitted: May 18, 2022
• First Submitted That Met QC Criteria: May 18, 2022
• First Posted (Actual): May 23, 2022

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Micronutrients; Hormone Antagonists; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Vitamin D; Cholecalciferol; Raloxifene Hydrochloride
• Other Study ID Numbers: 4-2020-0977

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No