Vitamin D and bone health: Epidemiologic studies.

Allelic variation in the vitamin D receptor was the first non-structural gene to be associated with osteoporosis, and together with the effects of the vitamin D system on bone homeostasis, suggested that this vitamin might have a strong role in bone health. However, controversy exists regarding what level of serum 25-hydroxyvitamin D (25(OH)D) is optimal. Current data from biochemical, observational and randomized controlled trials (RCTs), indicate serum 25(OH)D levels of at least 50 nmol l(-1) are required for normalization of parathyroid hormone (PTH) levels, to minimize the risk of osteomalacia and for optimal bone cell function. The skeletal consequences of 25(OH)D insufficiency include secondary hyperparathyroidism, increased bone turnover and bone loss and an increased risk of minimal trauma fractures. In large scale epidemiological studies, serum 25(OH)D levels are associated with bone mineral density in both men and women. However, there is mixed evidence on the effectiveness of optimizing serum 25(OH)D levels for the prevention of bone loss and minimal trauma fractures in postmenopausal women and older men. There may be some benefit on primary fracture prevention for those who have inadequate serum levels of 25(OH)D, particularly in institutionalised elderly patients, but only when combined with calcium supplements. For optimal bone health, evidence from RCTs suggests vitamin D may be considered a threshold nutrient with few further bone benefits observed at levels of 25(OH)D above which PTH is normalized. An adequate calcium intake is also imperative to gain optimum benefit from an improved vitamin D status in those with insufficient 25(OH)D levels, with an increased calcium intake being associated with suppression of PTH levels.