Interest in vitamin D has intensified with the association of vitamin D deficiency (VDD) with many diseases. This review will outline the limitations of current 25 hydroxyvitamin D (25OHD) methods, the target treatment threshold, and review the classical (endocrine/bone) and non-classical (paracrine/non-bone) actions of vitamin D. Recent standardisation by the National Institutes of Standards and Technology and use of LC tandem mass methodology has reduced inter-method bias but insensitivity and imprecision of automated methods have challenged assay performance. Many diseases are associated with VDD but randomised clinical trial data demonstrating the benefit of un-activated sterol supplementation only exists for the prevention of falls and fractures. Consequently, 25OHD measurement should be restricted to high falls or fracture risk patients. Controversy regarding the 25OHD target of therapy requires consensus. Until resolved, widespread adoption of screening programmes and measurement of 25OHD in patients at risk of non-musculoskeletal disease is premature, costly and not supported by evidence.
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