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Need for Additional Calcium to Reduce the Risk of Hip Fracture with Vitamin D Supplementation: Evidence from a Comparative Metaanalysis of Randomized Controlled Trials

Leuven University Center for Metabolic Bone Diseases (S.B., D.V.), and Divisions of Geriatric Medicine (S.B.) and Endocrinology (R.B., D.V.), Katholieke Universiteit Leuven, B-3000 Leuven, Belgium; VU University Medical Center (P.L.), 1007 MB, Amsterdam, The Netherlands; Divisions of Aging and Rheumatology, Immunology, and Allergy (H.A.B.-F.), The Robert B. Brigham Arthritis and Musculoskeletal Diseases Clinical Research Center, Brigham and Women’s Hospital, Boston, Massachusetts 02115; and Department of Orthopaedics and Traumatology (P.H.), Vrije Universiteit Brussel, B-1090 Brussels, Belgium

Address all correspondence and requests for reprints to: S. Boonen, M.D., Ph.D., Leuven University Center for Metabolic Bone Diseases and Division of Geriatric Medicine, University Hospital Leuven, Herestraat 49, B-3000 Leuven, Belgium. E-mail: steven.boonen{at}uz.kuleuven.ac.be.

Purpose: The purpose of this study was to extend the metaanalysis of Bischoff-Ferrari et al., which found that 700–800 IU/d vitamin D reduced hip fracture risk in elderly individuals by 25%, by defining the need for additional calcium supplementation in individuals receiving vitamin D for the prevention of hip fractures.

Data Sources: MEDLINE and EMBASE.com (search terms: "vitamin D" and "hip fracture"), bibliographies of articles retrieved, and the authors’ reference files were used as data sources.

Study Selection: Selected studies were randomized controlled trials (RCTs) of oral vitamin D with or without calcium supplementation vs. placebo/no treatment in postmenopausal women and/or older men (50 yr) specifically reporting a risk of hip fracture.

Data Extraction: Independent extraction was performed by two authors using predefined criteria, including study quality indicators.

Data Synthesis: All pooled analyses are based on random-effects models. Based on four RCTs (9083 patients), the pooled relative risk (RR) of hip fracture for vitamin D alone was 1.10 [95% confidence intervals (CI) 0.89, 1.36]. No between-trial heterogeneity was observed. For the six RCTs (45,509 patients) of vitamin D with calcium supplementation, the pooled RR for hip fracture was 0.82 (95% CI 0.71, 0.94). There was no heterogeneity between trials. In an adjusted indirect comparison of the summary RRs from the two metaanalyses, the RR for hip fracture for vitamin D with calcium vs. vitamin D alone was 0.75 (95% CI 0.58, 0.96).

Conclusions: Our analyses, designed to extend the findings of Bischoff-Ferrari et al., suggest that oral vitamin D appears to reduce the risk of hip fractures only when calcium supplementation is added.

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