Vitamin D and Health

Evidence considered (Tables 16-18, Annex 2)
Intervention studies
6.95 Lappe et al. (2008) investigated the effect of vitamin D (20 µg/800 IU) and calcium (2000 mg)
supplementation vs placebo for 8 weeks on stress fracture incidence in female Navy recruits (n=5201;
age, 17-35y). Based on an intention to treat analysis, the calcium and vitamin D supplemented group
had a 20% lower incidence of stress fracture than the control group (5.3% vs. 6.6%; p < 0.0026). Per
protocol analysis of recruits who completed the study (n=3700) reported a 21% lower incidence of
fractures in the supplemented vs the control groups (6.8% vs. 8.6% respectively; p < 0.02). Although
the results indicate a protective effect of vitamin D, no information was available on baseline or final
serum 25(OH)D concentrations and the data are confounded because the supplement also included
calcium. History of exercise was also inversely correlated with fracture risk; participants who
exercised ≥ 3 times/week had a 30% lower risk of stress fracture than those who exercised less
(p=0.004). Other studies of military recruits have also reported decreased risk of fracture associated
with regular physical activity (Rauh et al., 2006; Shaffer et al., 2006).
Cohort studies
6.96 A systematic review and meta-analysis of 8 observational studies (5 prospective cohort; 2 nested case
control; 1 case-control) examined the association between serum 25(OH)D concentration and stress
fractures in military personnel (n=2634; age, 18-30y) (Dao et al., 2015). In the individual studies,
mean/median serum 25(OH)D concentration ranged between 45 and 82 nmol/L in stress fracture
cases and 52 and 109 nmol/L in controls. In the 3 case control studies which measured serum
25(OH)D concentration at time of stress fracture diagnosis, the pooled mean difference was
significantly lower in stress fracture cases compared with controls (-5.6 nmol/L; 95% CI, -9.7 to -1.6;
p=0.007). In the 5 prospective cohort studies which measured serum 25(OH)D concentration at
baseline, the pooled mean difference was not significantly lower in stress fracture cases than controls
(-6.6 nmol/L; 95% CI, -14.5 to 1.3; p=0.1).
6.97 A subsequent cohort study (Davey et al., 2016) which prospectively followed Royal Marine (RM)
recruits (n=1082 males; age, 16-32y) through a 32 week training programme reported that the Odds
Ratio of stress fracture for recruits with baseline serum 25(OH)D concentration < 50 nmol/L compared
with ≥ 50 nmol/L was 1.6 (95% CI, 1.0-2.6).
6.98 Associations between serum 25(OH)D concentration and reduced stress fracture risk in observational
studies could be confounded by the association observed between exercise and reduced stress
fracture risk (Lappe et al., 2008). People who regularly exercise are likely to spend more time
outdoors and have higher serum 25(OH)D concentration as a consequence of greater UVB exposure.
6.99 Data for an association between serum 25(OH)D concentration and stress fractures in younger nonmilitary
populations are mainly observational, sparse and inconsistent.
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