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. 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.Related Putting Prevention into Practice: Vitamin D and Calcium Supplementation to Prevent Fractures in Adults.Summary of Recommendations and EvidenceThe U.S. Preventive Services Task Force (USPSTF) concludes that the current evidence is insufficient to assess the balance of the benefits and harms of combined vitamin D and calcium supplementation for the primary prevention of fractures in premenopausal women or in men (Table 1). View/Print TableVitamin D and Calcium Supplementation to Prevent Fractures in Adults: Clinical Summary of the USPSTF RecommendationPopulationMen or premenopausal womenCommunity-dwelling postmenopausal women at doses > 400 IU of vitamin D3 and > 1,000 mg of calciumCommunity-dwelling postmenopausal women at doses ≤ 400 IU of vitamin D3 and ≤ 1,000 mg of calciumRecommendationNo recommendationNo recommendationDo not supplementGrade: I statementGrade: I statementGrade: D recommendationBehavioral counseling interventionsAppropriate intake of vitamin D and calcium is essential to overall health.
However, there is inadequate evidence to determine the effect of combined vitamin D and calcium supplementation on the incidence of fractures in men or premenopausal women.There is adequate evidence that daily supplementation with 400 IU of vitamin D3 and 1,000 mg of calcium has no effect on the incidence of fractures in postmenopausal women.There is inadequate evidence regarding the effect of higher doses of combined vitamin D and calcium supplementation on fracture incidence in community-dwelling postmenopausal women.Balance of benefits and harmsEvidence is lacking regarding the benefit of daily vitamin D and calcium supplementation for the primary prevention of fractures, and the balance of benefits and harms cannot be determined.Evidence is lacking regarding the benefit of daily supplementation with > 400 IU of vitamin D3 and > 1,000 mg of calcium for the primary prevention of fractures in postmenopausal women, and the balance of benefits and harms cannot be determined.Daily supplementation with ≤ 400 IU of vitamin D3 and ≤ 1,000 mg of calcium has no net benefit for the primary prevention of fractures.
Other relevant USPSTF recommendationsThe USPSTF has made recommendations on screening for osteoporosis and vitamin D supplementation to prevent falls in community-dwelling older adults. .Vitamin D and Calcium Supplementation to Prevent Fractures in Adults: Clinical Summary of the USPSTF RecommendationPopulationMen or premenopausal womenCommunity-dwelling postmenopausal women at doses > 400 IU of vitamin D3 and > 1,000 mg of calciumCommunity-dwelling postmenopausal women at doses ≤ 400 IU of vitamin D3 and ≤ 1,000 mg of calciumRecommendationNo recommendationNo recommendationDo not supplementGrade: I statementGrade: I statementGrade: D recommendationBehavioral counseling interventionsAppropriate intake of vitamin D and calcium is essential to overall health. .The USPSTF concludes that the current evidence is insufficient to assess the balance of the benefits and harms of daily supplementation with greater than 400 IU of vitamin D3 and greater than 1,000 mg of calcium for the primary prevention of fractures in noninstitutionalized postmenopausal women.
The USPSTF recommends against daily supplementation with 400 IU or less of vitamin D3 and 1,000 mg or less of calcium for the primary prevention of fractures in noninstitutionalized postmenopausal women. Go to the Clinical Considerations section for suggestions regarding the I statements.RationaleIMPORTANCEFractures, particularly hip fractures, are associated with chronic pain and disability, loss of independence, decreased quality of life, and increased mortality.1 One-half of all postmenopausal women will have an osteoporosis-related fracture during their lifetime.Appropriate intake of vitamin D and calcium is essential to overall health. The Institute of Medicine has published recommended dietary allowances (Table 22,3). However, the benefits and harms of daily supplementation with greater than 400 IU of vitamin D3 and greater than 1,000 mg of calcium to prevent fractures are not clearly understood.View/Print TableInstitute of Medicine 2011 Recommended Dietary Allowances for Vitamin D and CalciumWomen19 to 50 years6001,00051 to 70 years6001,200> 70 years8001,200Pregnant women≤18 years6001,300> 18 years6001,000Breastfeeding women≤ 18 years6001,300> 18 years6001,000Men19 to 50 years6001,00051 to 70 years6001,000> 70 years8001,200Institute of Medicine 2011 Recommended Dietary Allowances for Vitamin D and CalciumWomen19 to 50 years6001
,00051 to 70 years6001,200> 70 years8001,200Pregnant women≤18 years6001,300> 18 years6001,000Breastfeeding women≤ 18 years6001,300> 18 years6001,000Men19 to 50 years6001,00051 to 70 years6001,000> 70 years8001,200BENEFITS OF PREVENTIVE MEDICATIONIn premenopausal women and in men, there is inadequate evidence to determine the effect of combined vitamin D and calcium supplementation on the incidence of fractures. In postmenopausal women, there is adequate evidence that daily supplementation with 400 IU of vitamin D3 combined with 1,000 mg of calcium has no effect on the incidence of fractures. However, there is inadequate evidence about the effect of higher doses of combined vitamin D and calcium supplementation on fracture incidence in noninstitutionalized postmenopausal women.HARMS OF PREVENTIVE MEDICATIONAdequate evidence indicates that supplementation with 400 IU or less of vitamin D3 and 1,000 mg or less of calcium increases the incidence of renal stones. The USPSTF assessed the magnitude of this harm as small.
USPSTF ASSESSMENTNoninstitutionalized, Community-Dwelling Postmenopausal Women. The USPSTF concludes that evidence is lacking about the benefit of daily supplementation with greater than 400 IU of vitamin D3 and greater than 1,000 mg of calcium for the primary prevention of fractures, and the balance of benefits and harms cannot be determined.The USPSTF concludes with moderate certainty that daily supplementation with 400 IU or less of vitamin D3 and 1,000 mg or less of calcium has no net benefit for the primary prevention of fractures.Men and Premenopausal Women. The USPSTF concludes that evidence is lacking about the benefit of vitamin D supplementation with or without calcium for the primary prevention of fractures, and the balance of benefits and harms cannot be determined.Clinical ConsiderationsPATIENT POPULATIONThis recommendation applies to noninstitutionalized or community-dwelling asymptomatic adults without a history of fractures. Community-dwelling is defined as not residing in an assisted living facility, nursing home, or other institutional care setting.
This recommendation does not apply to persons with osteoporosis or vitamin D deficiency.CONSIDERATIONS FOR PRACTICE REGARDING THE I STATEMENTSPotential Preventable Burden. The health burden of fractures is substantial in the older adult population.In the Women's Health Initiative, a statistically increased incidence of renal stones occurred in women taking supplemental vitamin D and calcium. One woman was diagnosed with a urinary tract stone for every 273 women who received supplementation over a seven-year follow-up period.Vitamin D and calcium supplements are inexpensive and readily available without a prescription.Vitamin D and calcium supplementation is often recommended for women, especially postmenopausal women, to prevent fractures. Surveys estimate that 56% of women 60 years and older take supplemental vitamin D, and 60% take a supplement containing calcium. The exact dosage is not known.4OTHER APPROACHES TO PREVENTIONThe USPSTF recommends screening for osteoporosis in women 65 years or older and in younger women whose fracture risk is equal to or greater than that of a 65-year-old white woman who has no additional risk factors.