Review: Vitamin D with calcium reduces fractures in adults

What are the benefits and harms of vitamin D supplementation, with or without calcium, in adults?

Included studies compared oral vitamin D, with or without calcium, with placebo or no supplementation in healthy adults (< 20% had major chronic disease) or in ambulatory adults ≥ 65 years of age who did not have cancer (but may have had other diseases). Studies that included pregnant women only, measured vitamin D status only during pregnancy, compared vitamin D dosages without a control group that did not receive vitamin D, used synthetic vitamin D analogues, or had follow-up < 1 month were excluded. Outcomes were cancer, fracture, and adverse events.

MEDLINE and Cochrane Central Register of Controlled Trials (to Jul 2011) were searched for English-language, randomized, controlled trials (RCTs). Eligible articles from a broader search done in 2009 were also included. 63 RCTs met the selection criteria. 18 of these RCTs (n = 104 959, mean age 53 to 85 y, 24% to 100% women) reported cancer and fracture outcomes; vitamin D doses ranged from 300 IU/d to 1100 IU/d. Of the 18 RCTs, 4 were of good quality, 9 were of fair quality, and 5 were of poor quality. Mean follow-up ranged from 7 months to 7 years.

Meta-analyses were not done for the 3 trials (n = 40 147) that provided data for cancer outcomes. Of 4 comparisons, 1 (n = 734) found a reduction in cancer with vitamin D plus calcium compared with placebo; the results of the other 3 comparisons were not statistically significant. The findings for fracture are in the Table. 1 RCT found an increase in renal and urinary tract stones with vitamin D plus calcium (hazard ratio 1.2, 95% CI 1.0 to 1.3 for both outcomes), but there were too few data to assess other adverse events.

Oral vitamin D with—but not without—calcium reduces fracture risk in adults. Limited data are available to evaluate the effect of vitamin D on cancer or adverse events.