Controversy and consensus regarding vitamin D: Recent methodological changes and the risks and benefits of vitamin D supplementation.

A dramatic and sustained surge in vitamin D test numbers has been attributed to the extraskeletal and probable intra/paracrine effects of vitamin D and not the important role of vitamin D in the regulation of extracellular calcium homeostasis and bone metabolism. This review summarizes recent data regarding the skeletal and extraskeletal effects of vitamin D, provides an overview of current methods of 25-hydroxyvitamin D measurement and includes the beneficial and adverse effects of vitamin D replacement. The role of 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, vitamin D binding protein and free hormone levels are explored and potential future developments in this area are discussed. The adoption of a reference method for the measurement of 25-hydroxyvitamin D, certified reference standards and an independent certification program administered by the Centre of Disease Control is expected to improve routine analytical performance and is a major, crucial step forward. Improvements in accuracy, precision and sensitivity of 25-hydroxyvitamin D measurement is an important prelude to accurately defining the desirable level of 25-hydroxyvitamin D that is associated with the lowest risk for falls and fractures. Finally, the results of ongoing large, prospective, randomized clinical trials such as the Australian D-Health study should clarify the role of vitamin D supplementation in the prevention and management of skeletal and nonskeletal disorders, including vitamin D effects on mortality risk.