Does vitamin D without calcium reduce fracture risk?
EVIDENCE-BASED ANSWER:
No. Supplemental vitamin D without calcium—in doses averaging as much as 800 IU per day—doesn’t reduce the risk of hip, vertebral, or nonvertebral fractures in postmenopausal women and older men (strength of recommendation [SOR]: A, large, high-quality meta-analysis of randomized or quasi-randomized placebo-controlled trials).
The vitamin D analogs alfacalcidol and calcitriol also don’t reduce hip or nonvertebral fractures (SOR: A, multiple randomized, controlled trials [RCTs]), although alfacalcidol (but not calcitriol) does reduce vertebral fractures by 43% (SOR: B, one RCT and one quasi-randomized trial with potential for bias)
Vitamin D supplementation, with or without calcium, doesn’t affect mortality. It does double the risk of mild hypercalcemia (about 2.7 mmol/L increase), raise the risk of renal calculi or mild renal insufficiency by 16%, and slightly increase (4%) gastrointestinal adverse effects (SOR: A, meta-analysis of RCTs or quasi-randomized trials).
Vitamin D analogs were given as alfacalcidol (1-alphahydroxyvitamin D3) 0.5 mcg twice daily or 1 mcg/d for 36 weeks to 2 years or calcitriol (1,25-dihydroxyvitamin D3) 0.25 to 1 mcg once or twice daily for one to 3 years. Researchers found a significant reduction in vertebral (but not nonvertebral or hip) fractures with alfacalcidol, but the finding occurred in a single trial that was assessed by the authors of the meta-analysis as subject to bias.
Supplementation doesn’t affect mortality, but does have some side effects
Patients taking vitamin D or an analog with or without calcium showed no difference in risk of death compared with patients taking placebo (29 trials, 71,032 patients; relative risk [RR]=0.97; 95% confidence interval [CI], 0.93-1.01).
Patients taking vitamin D or an analog were more likely than controls to have mild hypercalcemia, with an average increase of 2.7 mmol/L (21 trials, 17,124 patients; RR=2.28; 95% CI, 1.57-3.31). Patients taking calcitriol had the highest risk (4 trials, 988 patients; RR=4.41; 95% CI, 2.14-9.09).
Gastrointestinal adverse effects (4% increase) and renal calculi or mild renal insufficiency (16% increase) were more common with vitamin D and analogs than placebo (GI adverse effects: 15 trials, 47,761 patients; RR=1.04; 95% CI, 1.00-1.08; renal calculi or mild renal insufficiency: 11 trials, 46,548 patients; RR=1.16; 95% CI, 1.02-1.33).
RECOMMENDATIONS
There are no guidelines recommending vitamin D supplementation without calcium to prevent fracture.
