Vitamin D and musculoskeletal health


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.

Key Points

  • Hypovitaminosis D, encompassing both vitamin D insufficiency and deficiency, is common in the general population

  • The optimal serum 25(OH)D level required for calcium homeostasis and skeletal health is debated

  • Evidence indicates that vitamin D must be administered with calcium to increase bone mineral density in adults

  • Three recent meta-analyses concluded that vitamin D must be administered with calcium to reduce the risk of fracture in adults over age 50 years

  • Hypovitaminosis D causes sarcopenia, muscle weakness, and contributes to an increased risk of falls

  • Recent research suggests that vitamin D has a role in cancer risk and innate immunity

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Figure 1: The vitamin D metabolic pathway.
Figure 2: A strategy for assessing vitamin D status in patients with normal renal function.
Figure 3: Simplified example of a pathway by which vitamin D might stimulate innate immunity and enhance antimicrobial activity via interaction with TLRs.


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Désirée Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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Correspondence to Karen E Hansen.

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Wolff, A., Jones, A. & Hansen, K. Vitamin D and musculoskeletal health. Nat Rev Rheumatol 4, 580–588 (2008).

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