69–0.97) . Analysis also showed that for both hip and non-vertebral
fractures, the anti-fracture efficacy increased significantly with a higher received dose (metaregression: ß = −0.001; P = .07) and higher achieved 25-hydroxyvitamin D levels (metaregression: ß = −0.009; P = .01). The received dose of vitamin D was determined from cross-product of dose and percentage compliance with supplementation. Most studies of calcium supplementation prescribe a daily calcium dose of 1,000–1,200 mg [32–35]. In contrast to vitamin D supplementation, meta-analysis of prospective cohort studies and clinical trials did not show a higher fracture risk reduction with a higher calcium intake . In addition, a randomized controlled trial of elemental calcium supplementation Selleck Veliparib at a dose selleck chemicals of 1,000 mg/day showed an increase in relative risk of 47% (95% CI 0.97, 2.23) in combined cardiovascular endpoints (defined as sudden death, myocardial infarction, angina, or chest
pain) when compared with placebo . In the WHI study, those who received calcium 1,000 mg daily had a 17% increase in the incidence of renal stones or renal insufficiency compared with placebo group . At present, the exact calcium requirement remains a matter for debate although a total daily calcium intake (diet plus supplementation) of approximately 1,000 mg/day is likely to be sufficient and safe. Relationship between vitamin D, falls and fracture prevention Approximately 5% to 10% of all falls will result in a fracture and 90% of all fractures are results of falls [42, 43]. A low level of vitamin D is associated with an increased incidence of falls in the elderly [44, 45]. Possible mechanisms include the effect of vitamin D on calcium homeostasis, muscle strength , and physical performance [47, 48]. An increased risk of fall occurs when 25(OH)D falls below 25 nmol/L . Body sway is also noted to increase when 25(OH)D falls below 50 nmol/L . Lower limb physical performance declines markedly when serum 25(OH)D falls
below 50 nmol/L . buy Anlotinib Interestingly, systematic review demonstrates that use of vitamin D, alone or in combination with calcium, does not significantly Ureohydrolase reduce falls (both rate of falls or number of fallers) or incidence of fracture following fall . Nonetheless, subgroup analysis reveals that falls can be reduced in those with low-baseline 25(OH)D level with risk ratio of 0.57 (95% CI 0.37,0.89) compared with those with high-baseline 25(OH) D and risk ratio of 1.02 (95% CI, 0.88,1.19) . Another meta-analysis of pooled data from seven randomized controlled trials that recruited 1,921 subjects demonstrated that use of Vitamin D 700–1,000 IU daily could reduce falls with a risk ratio of 0.81 (95% CI 0.71,0.92).