Vitamin D and osteoporosis

The active vitamin D metabolite, 1,25(OH)2D, acts on the intestine to stimulate calcium and phosphorus absorption, a nonredundant target. It also directly acts on osteoblasts to stimulate bone formation and mineralization and to reduce osteoclast recruitment and increase their activity, while at the same time acting on the osteoclast pathway to increase osteoclast recruitment. While these effects suggest a role for vitamin D on osteoporosis prevention and treatment, allelic variation in the vitamin D receptor was also the first nonstructural gene associated with osteoporosis. In large-scale epidemiological data, serum 25-hydroxyvitamin D (25(OH)D) levels are associated with bone mineral density (BMD) in both men and women. However, evidence is mixed on the effectiveness of vitamin D supplementation for the prevention of bone loss and minimal trauma fractures in postmenopausal women and older men. This may be explained by vitamin D being a threshold nutrient, with a threshold in vitamin D status below which disease risk increases and vitamin supplementation is beneficial. In this regard, two recent randomized controlled trials (RCTs) have shown vitamin D supplementation increases BMD in individuals with baseline serum 25(OH)D concentrations <30 nmol/L. There is also likely to be a benefit on primary fracture prevention for those with the highest background fracture risk, including those patients who are vitamin D deficient and institutionalized patients, but only when combined with calcium. Daily doses of vitamin D alone do not prevent fractures in community-dwelling, vitamin D–replete older adults, nor can the combination of calcium and vitamin D, or either alone, prevent fractures in patients with preexisting minimal trauma fractures. Daily doses of ≥4000 IU may be harmful for bone in postmenopausal women. As large RCTs assessing fracture reduction in vitamin D–deficient individuals would be prohibitively expensive and not feasible, Mendelian randomization studies create new opportunities to examine the effects of vitamin D on bone health.