A Cochrane review [Abstract] 1 included 45 randomised or quasi-randomised studies comparing vitamin D or an analogue, alone or with calcium, against placebo, no intervention, or calcium, reporting fracture outcomes, in older people, with a total of over 50 000.
Vitamin D with calcium marginally reduced hip fractures (RR 0.84, 95% CI 0.73 to 0.96; 8 trials, n=46 658). Although subgroup analysis by residential status showed a significant reduction in hip fractures in people in institutional care, the difference between this and the community-dwelling subgroup was not significant (P = 0.15).
A systematic review 3 included 17 trials with a total of 52 625 subjects aged 50 years or older using reported fractures as an outcome. Treatment with vitamin D and calcium was associated with a 12% risk reduction in fractures of all types (RR 0.88, 95% CI 0.83 to 0.95). The fracture risk reduction was significantly greater (24%) in trials in which the compliance rate was high. The treatment effect was better with calcium doses of 1200 mg or more than with doses less than 1200 mg (0.80 vs 0.94, p=0.006) and with vitamin D doses of 800 IU or more than with doses less than 800 IU (0.94 vs 0.87, p=0.03). The NNT for preventing one fracture over 3.5 years was 64.
A systematic review 2 including 7 trials assessed the effectiveness of oral vitamin D supplementation with or without calcium supplement in preventing hip and nonvertebral fractures in older people (mean age of at least 60 years), with a total of 9 820 subjects. Five studies used cholecalciferol 700 to 800 IU/day (4 with calcium supplement). Two trials with lower dose of cholecalsiferol did not use calcium supplement,
There was a statistically significant reduction of hip fractures (RR 0.74, 95% CI 0.61 to 0.88; 3 trials) for patients receiving 700 to 800 IU/day oral vitamin D supplementation with (4 studies) or without (1 study) calcium supplement, with no significant heterogeneity between studies (P=0.74). The pooled risk difference was 2% (95% CI 1 to 4, P<0.001), therefore the NNT was 45 (95% CI 28 to 114) for a treatment duration of 24 to 60 months. For patients receiving 400 IU/day oral vitamin D supplementation without calcium, there was no reduction in the RR of hip fracture (RR 1.15, 95% CI 0.88 to 1.50; 2 trials). When all studies were pooled together, there was no statistically significant reduction in the RR of hip fracture (RR 0.88, 95% CI 0.69 to 1.13; 5 trials) but significant heterogeneity between studies (P=0.09).
For any nonvertebral fracture, there was a statistically significant reduction (RR 0.77, 95% CI 0.68 to 0.87; 5 trials) for patients receiving 700 to 800 IU/day oral vitamin D supplementation with (4 studies) or without (1 study) calcium supplement, with no significant heterogeneity between studies (P=0.41). The pooled risk difference was 4% (95% CI 2 to 5), therefore the NNT was 27 (95% CI 19 to 49) for a treatment duration of 12 to 60 months. For patients receiving 400 IU/day oral vitamin D supplementation without calcium, there was no reduction in the RR of any nonvertebral fracture (RR 1.03, 95% CI 0.86 to 1.24; 2 trials). When all studies were pooled together, there was a statistically significant reduction in the RR of any nonvertebral fracture (RR 0.83, 95% CI 0.70 to 0.98; 7 trials) but significant heterogeneity between studies (P=0.07).
In a patient level analysis 4 seven major randomised trials of vitamin D with calcium or vitamin D alone were pooled, yielding a total of 68 517 participants (mean age 69.9 years, range 47-107 years, 14.7% men). Trials using vitamin D with calcium showed a reduced overall risk of fracture (hazard ratio 0.92, 95% confidence interval 0.86 to 0.99, P=0.025) and hip fracture (all studies: 0.84, 0.70 to 1.01, P=0.07; studies using 10 microg of vitamin D given with calcium: 0.74, 0.60 to 0.91, P=0.005). For vitamin D alone in daily doses of 10 microg or 20 microg, no significant effects were found.
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