Vitamin D and Health

RCTs (n=40,886) on hip fractures (Bischoff-Ferrari et al., 2009b). The pooled relative risk was 0.86
(95% CI, 0.77-0.96) for prevention of non-vertebral fractures and 0.91 (95% CI, 0.78-1.05) for
prevention of hip fractures but there was significant heterogeneity for both end points. The pooled
relative risk of trials which administered doses above 10 µg/d (400 IU/d) was 0.80 (95% CI, 0.72-0.89;
9 trials; n=33,265) for non-vertebral fractures and 0.82 (95% CI, 0.69-0.97; 5 trials; n=31,872) for hip
fractures. The higher dose reduced non-vertebral fractures in community dwelling (29%) and
institutionalised individuals (15%).
6.112 Bolland et al. (2014) conducted a trial sequential meta-analysis 48 on the effect of vitamin D
supplementation (alone and with calcium) on skeletal outcomes (total fracture & hip fracture; 22
trials; n=76,497; mean age, 53-89y), using a risk reduction threshold of 15%. There was statistically
significant heterogeneity between the results of trials of vitamin D and trials of vitamin D plus calcium
for hip fracture (p=0.004) but not for total fracture (p=0.4). Vitamin D alone did not reduce hip
fracture by 15% or more (12 trials; n=27,834). Vitamin D plus calcium reduced hip fracture in
institutionalised individuals (2 trials; n=3,853) but did not reduce the risk of hip fracture by 15% or
more in community-dwelling individuals (7 trials; n=46,237).
6.113 A Cochrane review of 53 trials (n=91,791; mean/median age, > 65 y) examined the effect of vitamin D
and its analogues (1,25(OH) 2 D) on fracture prevention (Avenell et al., 2014). Vitamin D alone (in the
forms and doses tested) vs placebo or no treatment had no effect on: hip fracture (RR=1.12; 95% CI,
0.98-1.29; 11 trials; n=27,693); non-vertebral fractures (RR, 1.05; 95% CI, 0.96-1.14; 12 trials;
n=22,930;); vertebral fractures (RR=1.03; 95% CI, 0.76-1.39; 6 trials, n=11,396); or any new fracture
(RR=1.03; 95% CI, 0.96-1.11; 15 trials; n=28,271;). Vitamin D plus calcium was no more effective than
calcium alone for: hip fracture (RR=0.84; 95% CI, 0.63-1.13; 7 trials, n=7411); any non-vertebral
fracture (RR=0.96; 95% CI, 0.76-1.16; 6 trials, n=3336); and vertebral fracture (RR=0.14; 95% CI, 0.01-
2.77; 2 trials, n=2681). Vitamin D plus calcium vs placebo or no treatment resulted in a statistically
significant reduction in: risk of hip fracture (RR=0.84; 95% CI, 0.74-0.96; 9 trials; n=49,853); incidence
of new non-vertebral fractures (RR=0.86; 95% CI, 0.78-0.96; 8 trials; n=10,380); incidence of any
fracture (RR=0.95; 95% CI, 0.9-0.99; 10 trials, n=49,976). There was evidence of a statistically
significant preventive effect of vitamin D plus calcium vs placebo or no treatment on clinical vertebral
fractures (RR=0.89; 95% CI, 0.74-1.09; 4 trials, n=42,185).
Intervention studies
6.114 Sanders et al. (2010) examined the effect of a single high annual dose of vitamin D 3
(12,500 µg/500,000 IU) for 3-5 years on fracture reduction in community dwelling women in Australia
(n=2256; median age, 76y). They reported an increased risk of fractures in the vitamin D
supplemented group compared to the placebo group (RR=1.26; 95% CI, 1.00-1.59; p=0.047). Risk of
falls was also increased in the vitamin D supplemented group (see paragraph 6.144).
Cohort studies
6.115 A nested case-control study within a prospective cohort study in the US (Cauley et al., 2010) examined
associations between serum 25(OH)D concentration and fracture risk in men aged ≥ 65y followed over
an average of 5 years. Men with incident non-spine fractures (n=436) including hip fractures (n=81)
were compared with a subcohort (n=1608). One SD decrease in total serum 25(OH)D concentration
was associated with an increased risk of hip fracture (multivariate HR=1.60; 95% CI, 1.18-2.17).
48 Trial sequential analysis performs a cumulative meta-analysis but reduces the risk of false positive results from repetitive statistical testing by
maintaining the overall risk of type 1 error at 5%.
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