Vitamin D is critical for
calcium homeostasis. Following cutaneous synthesis or ingestion,
vitamin D is metabolized to 25(
OH)D and then to the active form 1,25(
OH)2D. Low serum
vitamin D levels are common in the general population and cause a decline in
calcium absorption, leading to low serum levels of ionized
calcium, which in turn trigger the release of
parathyroid hormone, promoting skeletal resorption and, eventually, bone loss or
osteomalacia.
Vitamin D deficiency is generally defined as a serum 25(
OH)D concentration <25-37 nmol/l (<10-15 ng/ml), but the definition of the milder state of
vitamin D insufficiency is controversial. Three recent meta-analyses concluded that
vitamin D must be administered in combination with
calcium in order to substantially reduce the risk of nonvertebral fracture in adults over the age of 50 years. Fracture protection is optimal when patient adherence to medication exceeds 80% and
vitamin D doses exceed 700 IU/day. In addition to disordered
calcium homeostasis, low
vitamin D levels might have effects on cell proliferation and differentiation and immune function. Randomized, double-blind, placebo-controlled trials are needed to clarify whether
vitamin D supplementation is beneficial in
cancer,
autoimmune disease and
infection. This Review focuses on the pathophysiology, clinical correlates, evaluation and treatment of hypovitaminosis D.