Need for additional calcium to reduce the risk of hip fracture with vitamin D supplementation: Evidence from a comparative metaanalysis of randomized controlled trials

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.