This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author's clinical recommendations.
A healthy 61-year-old white woman is concerned about a low vitamin D level detected during an assessment of her skeletal health. Her menopause began at 54 years of age. She has no history of falls, and there is no family history of hip fracture. She takes no medications or supplements. Her height is 157.5 cm (5 ft 2 in.), and her weight 59.1 kg (130 lb). The results of a physical examination are unremarkable, and the findings on laboratory studies are normal. The T score for bone mineral density at the hip is −1.5, and the serum level of 25-hydroxyvitamin D is 21 ng per milliliter (53 nmol per liter). What do you advise?
THE CLINICAL PROBLEM
Whereas frank vitamin D deficiency (serum level of 25-hydroxyvitamin D below 10 ng per milliliter [25 nmol per liter]) has long been recognized as a medical condition characterized by muscle weakness, bone pain, and fragility fractures, vitamin D “insufficiency,” characterized as a serum level of 25-hydroxyvitamin D of 10 to 30 ng per milliliter (25 to 75 nmol per liter), without overt clinical symptoms, has recently become a concern on the part of physicians and patients.1 Increased attention to this new “syndrome” and its potential complications has led to a substantial increase in testing for the metabolite 25-hydroxyvitamin D, the best clinical measure of vitamin D stores. The number of 25-hydroxyvitamin D assays performed by one major reference laboratory increased by 50% in the fourth quarter of 2009 as compared with the same quarter in 2008, and it is expected that several million tests will be performed this year.2
The implications of vitamin D levels that are below the normal reference range but not markedly reduced and the value of supplementation are incompletely understood. Vitamin D is critical for skeletal mineralization, and numerous observational studies have linked low levels of 25-hydroxyvitamin D to fractures.3-7 Therefore it is not surprising that most observational and randomized, placebo-controlled trials concerning vitamin D insufficiency have focused on skeletal health outcomes. In the past several years, attention has turned to nonskeletal effects of vitamin D insufficiency, particularly in relation to cardiovascular disease, diabetes mellitus, cancer, and immune dysfunction.8-11 This review summarizes the current understanding and uncertainties regarding vitamin D insufficiency and the effects of vitamin D supplementation on health outcomes.