Vitamin D, Calcium, or Combined Supplementation for the Primary Prevention of Fractures in Community-Dwelling Adults
Authors: Leila C. Kahwati, Rachel Palmieri Weber, Huiling Pan, Margaret Gourlay, Erin LeBlanc, Manny Coker-Schwimmer, Meera Viswanathan
Journal: JAMA (2018)

<h3>Importance</h3> Osteoporotic fractures result in significant morbidity and mortality. <h3>Objective</h3> To update the evidence for benefits and harms of vitamin D, calcium, or combined supplementation for the primary prevention of fractures in community-dwelling adults to inform the US Preventive Services Task Force. <h3>Data Sources</h3> PubMed, EMBASE, Cochrane Library, and trial registries through March 21, 2017; references; and experts. Surveillance continued through February 28, 2018. <h3>Study Selection</h3> English-language randomized clinical trials (RCTs) or observational studies of supplementation with vitamin D, calcium, or both among adult populations; studies of populations that were institutionalized or had known vitamin D deficiency, osteoporosis, or prior fracture were excluded. <h3>Data Extraction and Synthesis</h3> Dual, independent review of titles/abstracts and full-text articles and study quality rating using predefined criteria. Random-effects meta-analysis used when at least 3 similar studies were available. <h3>Main Outcomes and Measures</h3> Incident fracture, mortality, kidney stones, cardiovascular events, and cancer. <h3>Results</h3> Eleven RCTs (N = 51 419) in adults 50 years and older conducted over 2 to 7 years were included. Compared with placebo, supplementation with vitamin D decreased total fracture incidence (1 RCT [n = 2686]; absolute risk difference [ARD], −2.26% [95% CI, −4.53% to 0.00%]) but had no significant association with hip fracture (3 RCTs [n = 5496]; pooled ARD, −0.01% [95% CI, −0.80% to 0.78%]). Supplementation using vitamin D with calcium had no effect on total fracture incidence (1 RCT [n = 36 282]; ARD, −0.35% [95% CI, −1.02% to 0.31%]) or hip fracture incidence (2 RCTs [n = 36 727]; ARD from the larger trial, −0.14% [95% CI, −0.34% to 0.07%]). The evidence for calcium alone was limited, with only 2 studies (n = 339 total) and very imprecise results. Supplementation with vitamin D alone or with calcium had no significant effect on all-cause mortality or incident cardiovascular disease; ARDs ranged from −1.93% to 1.79%, with CIs consistent with no significant differences. Supplementation using vitamin D with calcium was associated with an increased incidence of kidney stones (3 RCTs [n = 39 213]; pooled ARD, 0.33% [95% CI, 0.06% to 0.60%]), but supplementation with calcium alone was not associated with an increased risk (3 RCTs [n = 1259]; pooled ARD, 0.00% [95% CI, −0.87% to 0.87%]). Supplementation with vitamin D and calcium was not associated with an increase in cancer incidence (3 RCTs [n = 39 213]; pooled ARD, −1.48% [95% CI, −3.32% to 0.35%]). <h3>Conclusions and Relevance</h3> Vitamin D supplementation alone or with calcium was not associated with reduced fracture incidence among community-dwelling adults without known vitamin D deficiency, osteoporosis, or prior fracture. Vitamin D with calcium was associated with an increase in the incidence of kidney stones.