The authors reported that 19 RCTs were included for clinical outcome: three RCTs for cancer outcomes and 16 RCTs for fracture outcomes. Study quality was rated largely fair or good. Adjustment for confounders, loss to follow-up, unclear reporting of randomisation and allocation concealment were of concern in some studies. Follow-up ranged from seven months to seven years. It appeared that 35 studies were included for adverse events, but this was unclear.
Fracture outcomes (16 RCTs): Pooled analysis of combined Vitamin D and calcium supplementation versus placebo showed a statistically significant reduction in overall fracture risk (RR 0.88, 95% CI 0.79 to 0.99, I2=36%; 11 RCTs). This estimate was influenced by population setting, with a higher and statistically significant risk reduction in institutionalised elderly patients (RR 0.71, 95% CI 0.57 to 0.89, I2=0%; three RCTs) compared with patients who lived in the community.. There was no risk reduction in community-based women with a history of fracture (two RCTs). Pooled analysis showed no statistically significant effect on overall fracture risk in patients who received vitamin D supplementation versus placebo (five RCTs, I2=66%). Subgroup and meta-regression analyses did not reveal any influences on this finding.
Cancer outcomes (three RCTs): There were no statistically significant outcomes for cancer incidence or mortality in patients who received vitamin D supplementation versus placebo (two RCTs). Confidence intervals were wide in some cases, which suggested that clinically important effects in either direction could be possible. One trial (734 patients) assessed combined Vitamin D and calcium supplementation versus placebo and found significantly reductions in cancer incidence (RR 0.40, 95% CI 0.20 to 0.82) and mortality (RR 0.23, 95% CI 0.09 to 0.60). A second larger trial showed hazard ratios that ranged from 0.96 to 1.08 for cancer incidence, with narrow CIs for a range of cancer sites; none were statistically significant. .
Adverse events (apparently 35 RCTs): The authors reported that most studies did not supply sufficient information and were inadequately powered to detect adverse events. One RCT reported in detail (36,282 patients) in postmenopausal women who received vitamin D with or without calcium supplementation found a significantly increased risk for renal or urinary tract stones (HR 1.17, 1.02 to 1.34 for each outcome) compared with placebo.