Grade: I The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. Read the clinical considerations section of USPSTF Recommendation Statement. If the service is offered, patients should understand the uncertainty about the balance of benefits and harms.
The USPSTF concludes that the current evidence is insufficient to assess the balance of the benefits and harms of vitamin D and calcium supplementation, alone or combined, for the primary prevention of fractures in men and premenopausal women.
Frequency of Service
No information available.
Risk Factor Information
No information available.
These recommendations apply to community-dwelling, asymptomatic adults. “Community-dwelling” is defined as not living in a nursing home or other institutional care setting. These recommendations do not apply to persons with a history of osteoporotic fractures, increased risk for falls, or a diagnosis of osteoporosis or vitamin D deficiency.
Suggestions for Practice Regarding the I Statements
Potential Preventable Burden
Approximately 2 million osteoporotic fractures occurred in the United States in 2005.2 The health burden of fractures is substantial in the older adult population. Twenty percent to 30% of patients die within 1 year of a hip fracture, with significantly higher mortality rates in men than in women.5 Nearly 40% of persons who experience a fracture are unable to walk independently at 1 year, and 60% require assistance with at least 1 essential activity of daily living.3, 4
Low bone mass, older age, and history of falls are major risk factors for incident osteoporotic fractures.1, 6 Ten percent to 15% of falls result in fractures,6 and nearly all hip fractures are related to a fall.7 Other risks factors for low bone mass and fractures include female sex, smoking, use of glucocorticoids, and use of other medications that impair bone metabolism (eg, aromatase inhibitors).8-11 Most fractures (71%) occur among women,2 and an estimated 74% of all fractures that occur in women are among those 65 years or older.6 Although the risk for fractures in premenopausal women increases with lower peak bone mass, absolute fracture risk in premenopausal women is very low compared with that in postmenopausal women.12 Although fractures occur more frequently in women, mortality rates after a hip fracture are significantly higher in men than in women.2, 13
The large Women’s Health Initiative (WHI) trial (n=36,282), which studied daily supplementation with 400 IU of vitamin D3 (cholecalciferol) and 1000 mg of calcium, reported no significant reduction in any fracture outcome;14 thus, the USPSTF concluded that supplementation with 400 IU or less of vitamin D and 1000 mg or less of calcium does not prevent fractures. Studies of supplementation with higher doses of vitamin D and calcium (alone or combined) showed inconsistent results and were frequently underpowered to detect differences; thus, the USPSTF concluded that the evidence on supplementation with higher doses of vitamin D and calcium to prevent fractures is inadequate.
The WHI trial found a statistically significant increase in the incidence of kidney stones in women taking vitamin D and calcium compared with women taking placebo.14 For every 273 women who received supplementation over a 7-year follow-up period, 1 woman was diagnosed with a urinary tract stone. In addition, a recent study15 of combined vitamin D and calcium supplementation found findings consistent with those from the WHI trial, although the increase was not statistically significant. Another recent study16, 17 found no increase in incident cardiovascular disease with high-dose vitamin D supplementation.
In a separate recommendation statement,18 the USPSTF found that vitamin D supplementation does not reduce the number of falls or the number of persons who experience a fall. A single study suggested that an annual high dose of vitamin D (500,000 IU) may even be associated with a greater number of injurious falls and a greater number of persons experiencing falls and fractures.19 The USPSTF now recommends against vitamin D supplementation to prevent falls in community-dwelling older adults.18
Vitamin D and calcium supplementation are often recommended for women, especially postmenopausal women, to prevent fractures, although actual use is uncertain. Based on 2011–2012 data from the National Health and Nutrition Examination Survey, an estimated 27% of men and 35% of women older than 20 years take a vitamin D supplement, and 26% of men and 33% of women take a calcium supplement.20 The exact dosage of supplementation is not known.
Other Approaches to Prevention
The USPSTF recommends screening for osteoporosis in women 65 years or older and in younger women at increased risk.21 The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for vitamin D deficiency in asymptomatic adults.22
The USPSTF recently updated its recommendation on interventions to prevent falls in community-dwelling older adults.18 The USPSTF assessed the effect of vitamin D to prevent falls in older adults at average and increased risk for falls without vitamin D insufficiency or deficiency. The USPSTF found adequate evidence that vitamin D supplementation does not prevent falls. The USPSTF also found that exercise can prevent falls in community-dwelling older adults at increased risk for falls; multifactorial interventions may also be effective in some persons as well.18, 19
Approximately 2 million osteoporotic fractures occurred in the United States in 2005.1, 2 Within 1 year of experiencing a hip fracture, many patients are unable to walk independently, more than half require assistance with activities of daily living,3, 4 and 20% to 30% of patients will die.5
Benefits of Preventive Medication
The USPSTF found inadequate evidence to determine the effects of vitamin D and calcium supplementation, alone or combined, on the incidence of fractures in men and premenopausal women. The USPSTF found adequate evidence that daily supplementation with 400 IU or less of vitamin D combined with 1000 mg or less of calcium has no effect on the incidence of fractures in community-dwelling, postmenopausal women. The USPSTF found inadequate evidence regarding the effects of higher doses of vitamin D and calcium supplementation, alone or combined, on the incidence of fractures in community-dwelling, postmenopausal women.
Harms of Preventive Medication
The USPSTF found adequate evidence that supplementation with vitamin D and calcium increases the incidence of kidney stones. The USPSTF assessed the magnitude of this harm as small. The USPSTF found a few studies evaluating supplementation with vitamin D alone that suggested no increase in incident cardiovascular disease.
Community-Dwelling, Postmenopausal Women
The USPSTF concludes that the evidence on the benefit of daily supplementation with doses greater than 400 IU of vitamin D and greater than 1000 mg of calcium for the primary prevention of fractures in community-dwelling, postmenopausal women is lacking, 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 D and 1000 mg or less of calcium has no net benefit for the primary prevention of fractures in community-dwelling, postmenopausal women.
Men and Premenopausal Women
The USPSTF concludes that the evidence on the benefit of vitamin D and calcium supplementation, alone or combined, for the primary prevention of fractures in men and premenopausal women is lacking, and the balance of benefits and harms cannot be determined.
OTHER CONSIDERATIONS Research Needs and Gaps Research is needed to determine whether daily supplementation with doses greater than 400 IU of vitamin D and greater than 1000 mg of calcium reduces fracture incidence in postmenopausal women and in older men. Prospective studies should assess the potential benefits of vitamin D and calcium supplementation in premenopausal women on fracture incidence later in life. Studies need to be adequately powered and should evaluate consistent fracture outcomes. Studies are also needed to evaluate the effects of vitamin D supplementation on diverse populations. Because white women have the highest risk for osteoporotic fractures, most fracture prevention studies have been conducted in this population, and it is difficult to extrapolate results to nonwhite populations. In addition, more studies evaluating the potential harms of supplementation are needed, particularly studies on calcium and potential adverse cardiovascular outcomes. RECOMMENDATION OF OTHERS The Institute of Medicine (now the National Academy of Medicine)37 and the World Health Organization38 recommend standards for adequate daily intake of calcium and vitamin D as a part of overall health. Neither organization has recommendations specific to fracture prevention. The Institute of Medicine notes the challenge of determining dietary reference intakes given the complex interrelationship between calcium and vitamin D, the inconsistency of studies examining bone health outcomes, and the need to limit sun exposure to minimize skin cancer risk. The National Osteoporosis Foundation supports the Institute of Medicine’s recommendations regarding calcium consumption and recommends that adults 50 years or older consume 800 to 1000 IU of vitamin D daily.39 The Endocrine Society recommends that adults 65 years or older consume 800 IU of vitamin D daily for the prevention of falls and fractures.40 The American Geriatric Society recommends that adults 65 years or older take daily vitamin D supplementation of at least 1000 IU as well as calcium to reduce the risk for fractures and falls.41 UPDATE OF PREVIOUS USPSTF RECOMMENDATIONS This recommendation is consistent with the 2013 USPSTF recommendation on vitamin D supplementation, with or without calcium, to prevent fractures.36 The USPSTF added evidence on calcium supplementation alone to the evidence review for this recommendation; however, the evidence was too limited to make a separate recommendation about calcium supplementation alone. Evidence from more recent studies confirms that the evidence on fracture prevention with doses of vitamin D greater than 400 IU daily is inconsistent and inadequate, because of underpowering of studies at higher doses. Newer evidence confirms an increased risk for kidney stones with combined vitamin D and calcium supplementation and also suggests no increased incidence of cardiovascular disease with vitamin D supplementation.