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Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment

Bess Dawson-Hughes, MD
Section Editors
Marc K Drezner, MD
Clifford J Rosen, MD
Deputy Editor
Jean E Mulder, MD


Overt vitamin D deficiency, characterized by hypocalcemia and/or hypophosphatemia and rickets and osteomalacia in children and osteomalacia in adults, is now uncommon in most developed countries (see "Epidemiology and etiology of osteomalacia" and "Clinical manifestations, diagnosis, and treatment of osteomalacia"). However, subclinical vitamin D deficiency occurs even in developed countries and is associated with osteoporosis, increased risk of falls, and possibly fractures. Vitamin D stores decline with age, especially in the winter [1-3]. In temperate areas such as Boston and Edmonton, for example, cutaneous production of vitamin D virtually ceases in winter [2]. Thus, identification and treatment of vitamin D deficiency is important for musculoskeletal health and possibly even extraskeletal health, including the immune and cardiovascular systems. (See "Vitamin D and extraskeletal health".)

This topic will review the definition, clinical manifestations and treatment of vitamin D deficiency in adults. The causes of vitamin D deficiency, vitamin D supplementation in osteoporosis, and the treatment of vitamin D deficiency in children are reviewed separately. (See "Causes of vitamin D deficiency and resistance" and "Calcium and vitamin D supplementation in osteoporosis" and "Vitamin D insufficiency and deficiency in children and adolescents".)


Serum 25-hydroxyvitamin D — Vitamin D sufficiency is estimated by measuring 25-hydroxyvitamin D (25[OH]D or calcidiol) concentrations. The optimal serum 25(OH)D concentration for skeletal health is controversial. Based upon the trials of vitamin D supplementation [4-7] and the Institute of Medicine (IOM) systematic review [8], some experts, including some UpToDate editors, favor maintaining the serum 25(OH)D concentration between 20 and 40 ng/mL (50 to 100 nmol/L), whereas other experts, including other UpToDate editors and the author of this topic, favor maintaining 25(OH)D levels between 30 and 50 ng/mL (75 to 125 nmol/L). Thus, the range of common agreement is 30 to 40 ng/mL (75 to 100 nmol/L). Experts agree that levels lower than 20 ng/mL are suboptimal for skeletal health. The optimal serum 25(OH)D concentrations for extraskeletal health have not been established. (See "Vitamin D and extraskeletal health".)

The IOM supports 25(OH)D concentrations above 20 ng/mL (50 nmol/L) [8]. These recommendations are based upon evidence related to bone health. Other experts (the Endocrine Society [ENDO], the National Osteoporosis Foundation [NOF], the International Osteoporosis Foundation [IOF], the American Geriatric Society [AGS]) suggest that a minimum level of 30 ng/mL (75 nmol/L) is necessary in older adults to minimize the risk of falls and fracture [9-13]. The systematic review by the IOM also concluded there are insufficient data to determine the safe upper limit of serum 25(OH)D [8]. However, there was some concern at serum 25(OH)D concentrations above 50 ng/mL (125 nmol/L). These concerns were based upon the increase in fracture in patients treated with high dose vitamin D [7] and conflicting studies describing a potential increased risk for some cancers (eg, pancreatic, prostate) and mortality with levels above 30 to 48 ng/mL (75 to 120 nmol/L). (See "Vitamin D and extraskeletal health", section on 'Cancer' and "Vitamin D and extraskeletal health", section on 'Mortality'.)

Assay issues — Commercial assays measure total 25(OH)D, but some laboratories report 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 values separately (figure 1). It is the total 25(OH)D concentration that is clinically important.


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Literature review current through: Sep 2016. | This topic last updated: May 2, 2016.
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