Efficacy of vitamin D₃ supplementation in preventing fractures in elderly women: A meta-analysis

Abstract

Background:

The efficacy of vitamin D₃ in preventing fractures and falls has been explored in a number of clinical trials. However, recent evidence revealed new questions about the adequate doses of vitamin D₃ supplementation and its efficacy in fracture prevention independent of calcium supplements for various types of fractures.

Objective:

To conduct a meta-analysis to estimate the effectiveness of 800 IU daily vitamin D₃ supplementation for increasing bone mineral density (BMD) and preventing fractures in postmenopausal women.

Methods:

Medline and EMBASE were searched for controlled trials comparing the effectiveness of cholecalciferol (vitamin D₃) against placebo with or without background calcium supplementation in the treatment of postmenopausal women.

Results:

Eight controlled trials evaluating the effect of vitamin D₃ supplementation with or without calcium were assessed. Of 12 658 women included in a Bayesian meta-analysis, 6089 received vitamin D₃ (with or without calcium) and 6569 received placebo (with or without calcium). Compared to placebo, vitamin D₃ with calcium supplementation showed beneficial effects on the incidence of non-vertebral (odds ratio [OR] 0.77, 95% credibility limit [CL] 0.6–0.93) and hip (OR 0.70, 95% CL 0.53–0.90) fractures, while the effects on non-vertebral-non-hip fractures (OR 0.84, 95% CL 0.67–1.04) % point increase) were associated with more uncertainty. Vitamin D₃ supplementation showed a 70% probability of being a better treatment than placebo for the prevention of non-vertebral fractures, hip fractures, and non-vertebral, non-hip fractures. Compared to calcium supplementation, vitamin D₃ plus calcium reduced non-vertebral fractures (OR 0.68, 95% CL 0.43–1.01) and non-vertebral, non-hip fractures (OR 0.64, 95% CL 0.38–0.99), but did not reduce hip fractures (OR 1.03, 95% CL 0.39–2.25). Key limitations to this analysis include a small number of studies and heterogeneity in the study populations.

Conclusions:

This meta-analysis supports the use of vitamin D3 of 800 IU daily to reduce the incidence of osteoporotic non-vertebral, hip, and non-vertebral-non-hip fractures in elderly women. Vitamin D₃ with calcium appears to achieve benefits above those attained with calcium supplementation alone for non-vertebral and non-vertebral-non-hip fractures.

Key words::

• Bone
• Bone mineral density
• Fracture
• Osteoporosis
• Postmenopausal
• Women

Transparency

Declaration of funding

This study was supported by Merck & Co., Inc., which had a role in study design; data acquisition and interpretation; and the decision to publish the findings.

Declaration of financial/other relationships

T.F. and S.S. have disclosed that they are employees of and minor stockholders in Merck. G.JDB. have disclosed that he is a paid consultant to Merck. J.T.M. has disclosed that he is a paid research fellow with Merck.

Some peer reviewers receive honoraria from CMRO for their review work. The peer reviewers of this paper have disclosed that they have no relevant financial relationships.

Acknowledgments

Assistance in manuscript preparation was provided by Stephen W. Gutkin, Rete Biomedical Communications Corp., Wyckoff, NJ, USA.