Vitamin D, Calcium, or Combined Supplementation for the Primary Prevention of Falls and Fractures in Community-Dwelling Adults: Preventive Medication

The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without obvious related signs or symptoms to improve the health of people nationwide. 

It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment. 

The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms. 

The USPSTF is committed to mitigating the health inequities that prevent many people from fully benefiting from preventive services. Systemic or structural racism results in policies and practices, including healthcare delivery, that can lead to inequities in health. The USPSTF recognizes that race, ethnicity, and gender are all social rather than biological constructs. However, they are also often important predictors of health risk. The USPSTF is committed to helping reverse the negative impacts of systemic and structural racism, gender-based discrimination, bias, and other sources of health inequities, and their effects on health, throughout its work.

Although the age-standardized incidence of fragility fractures has been decreasing,¹ the absolute incidence of fragility fractures is increasing because the population is aging.² In 2016, 1,794,700 Medicare beneficiaries experienced one or more new fragility fractures, for an overall annual incidence of 332 new fractures per 10,000 beneficiaries.³ The morbidity and mortality associated with hip fractures are high; between 20% and 30% of patients die within 1 year of a hip fracture, with men experiencing a significantly higher mortality rate after fracture than women.⁴ Nearly 40% of those who experience a hip fracture are unable to walk independently at 1 year, and 60% require assistance with at least one essential activity of daily living.⁵

About 14 million adults age 65 years or older (27.6%) reported falling at least once in the previous year according to 2020 data from the Centers for Disease Control and Prevention’s (CDC’s) Behavioral Risk Factor Surveillance System.⁶ In 2021, 78 deaths per 100,000 persons were attributed to unintentional falls, making falls the leading cause of unintentional injury among older adults.⁶

The USPSTF concludes with moderate certainty that supplementation with vitamin D with or without calcium has no net benefit for the primary prevention of fractures in community-dwelling postmenopausal women and men age 60 years or older.

The USPSTF concludes with moderate certainty that supplementation with vitamin D has no net benefit for the prevention of falls in community-dwelling postmenopausal women and men age 60 years or older.

Go to Table 1 for more information on the USPSTF recommendation rationale and assessment. For more details on the methods the USPSTF uses to determine the net benefit, see the USPSTF Procedure Manual.⁷

Patient Population Under Consideration

These recommendations apply to community-dwelling, asymptomatic postmenopausal women and men age 60 years or older. “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, medical conditions associated with vitamin D deficiency or vitamin D malabsorption, or a diagnosis of osteoporosis or vitamin D deficiency. 

Definitions

Supplementation refers to the empiric use of dietary supplements without knowledge of or reference to an individual’s diet, nutritional status, or serum levels of micronutrients.

Although the evidence does not support supplementation with vitamin D with or without calcium for the prevention of fractures or falls in community-dwelling postmenopausal women and men age 60 years or older, ensuring adequate vitamin D and calcium intake is important for bone and overall health. The National Academy of Medicine has established recommended daily allowances for these nutrients, which range from 600 IU to 800 IU for vitamin D and 1,000 mg to 1,200 mg for calcium.^8,9 The recommended daily allowance refers to all dietary sources, including food, beverages, and dietary supplements, and it is important that all persons have vitamin D and calcium intake that meets the recommended daily allowance of these nutrients.

Treatment or Intervention

Vitamin D supplements are available as either vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol). Both forms must undergo further metabolism into calcitriol, the biologically active form of vitamin D. Calcium supplements are typically formulated as oral salts; calcium carbonate and calcium citrate are the most common preparations.¹⁰

Additional Tools and Resources

The CDC has information on preventing falls and hip fractures (https://www.cdc.gov/falls/prevention/index.html).

The CDC’s STEADI (Stopping Elderly Accidents, Death, and Injuries) initiative helps reduce fall risk among older patients (https://www.cdc.gov/steadi/index.html).

The National Institutes of Health has information on preventing falls and fractures in older adults (https://www.nia.nih.gov/health/falls-and-falls-prevention/falls-and-fractures-older-adults-causes-and-prevention).

Other Related USPSTF Recommendations

The USPSTF recommends screening for osteoporosis in women age 65 years or older and in younger women at increased risk.¹¹ The USPSTF recommends exercise interventions to prevent falls in community-dwelling adults age 65 years or older who are at increased risk for falls and individualizing the decision to offer multifactorial interventions to prevent falls to this group of persons.¹² 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.¹³

When final, this draft recommendation will replace the 2018 USPSTF recommendation on vitamin D, calcium, or combined supplementation for the primary prevention of fractures in community-dwelling adults. For the current update, the USPSTF also included the outcomes of falls in its review. In 2018, the USPSTF recommended against daily supplementation with 400 IU or less of vitamin D and 1,000 mg or less of calcium for the primary prevention of fractures in community-dwelling postmenopausal women. It found that the evidence was insufficient to assess the balance of the benefits and harms of daily supplementation with doses greater than 400 IU of vitamin D and greater than 1,000 mg of calcium for the primary prevention of fractures in community-dwelling postmenopausal women, or 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.¹⁴ In a separate recommendation in 2018, the USPSTF recommended against vitamin D supplementation to prevent falls in community-dwelling adults age 65 years or older.¹⁵ For this update, the USPSTF reviewed new evidence that showed there was no benefit of vitamin D with or without calcium across a broad range of doses to prevent fractures or of vitamin D to prevent falls.¹⁰ The USPSTF thus recommends against supplementation with vitamin D with or without calcium for the primary prevention of fractures and against supplementation with vitamin D for the prevention of falls in community-dwelling postmenopausal women and men age 60 years or older.

Scope of Review

The USPSTF commissioned a systematic evidence review on the benefits and harms of vitamin D, calcium, or combined supplementation for the prevention of fractures and falls in community-dwelling adults.¹⁰ The review excluded studies conducted in populations with a known disorder related to bone metabolism (e.g., osteoporosis or vitamin D deficiency) or taking medication known to be associated with osteoporosis (e.g., long-term steroids).

Benefits of Interventions

The USPSTF found 19 randomized clinical trials (RCTs) that reported on fracture, fall, or all-cause mortality outcomes with vitamin D or calcium supplementation, or both, over 9 months to 7 years of followup. Across trials, the mean age of participants ranged from 52.7¹⁶ to 80.0 years,¹⁷ although the mean age of participants was 60 years or older in 18 of these trials. Eight trials were conducted exclusively among postmenopausal women, while 11 were conducted among mixed populations of men and women in which the proportion of women ranged from 24% to 74%. Five trials compared vitamin D plus calcium with placebo or no treatment, one trial compared vitamin D plus calcium with calcium alone, and 13 RCTs compared vitamin D alone with placebo. Vitamin D dosages ranged from 300 to 4,000 IU per day or daily dose equivalent, and calcium dosages ranged from 93 to 1,600 mg/day. Several studies allowed for the use of personal vitamin D supplements during the study but restricted the maximum allowable dosage (range, 400 to 2,000 IU/day), while other studies prohibited personal use of supplements.¹⁰

Seven trials reported on hip fracture outcomes. Four trials evaluated vitamin D compared with placebo, one compared vitamin D and calcium with calcium alone, and two evaluated vitamin D and calcium compared with placebo. A pooled analysis found no statistically significant difference in the relative risk (RR) of hip fracture for vitamin D with or without calcium compared with the control (RR, 0.99 [95% confidence interval (CI), 0.86 to 1.13]; 7 RCTs; 88,364 participants) over 3 to 7 years of followup. This corresponds to an absolute risk difference (ARD) of zero hip fractures per 1,000 persons supplemented (95% CI, from 1 fewer to 1 more). There were no statistically significant differences between the pooled estimates for trials with and without the use of calcium, or when analyses were stratified by vitamin D dose (≤400 vs. >400 IU) or by personal supplement use during study.¹⁰

Three trials reported on major osteoporotic fracture outcomes (defined as a fracture of the hip, spine, wrist, or shoulder); all these trials evaluated vitamin D alone. A pooled analysis found no statistically significant difference in the RR of major osteoporotic fracture for vitamin D compared with the control (RR, 0.93 [95% CI, 0.78 to 1.10]; 3 RCTs; 48,883 participants) over 5 to 5.3 years of followup. This corresponds to an ARD of 2 fewer major osteoporotic fractures per 1,000 persons supplemented (95% CI, from 6 fewer to 3 more). Two trials reported on clinical vertebral fracture outcomes. A pooled analysis found no statistically significant difference in the RR of clinical vertebral fracture for vitamin D with or without calcium compared with the control (RR, 0.86 [95% CI, 0.65 to 1.12]; 2 studies; 38,968 participants) over 5 to 7 years of followup. This corresponds to an ARD of 2 fewer clinical vertebral fractures per 1,000 persons supplemented (95% CI, from 4 fewer to 1 more).¹⁰

Eight trials (N=54,584) reported on nonvertebral fracture outcomes. Five trials compared vitamin D alone with placebo, one compared vitamin D and calcium with placebo, one compared calcium alone with placebo, and one compared vitamin D and calcium with calcium alone. A pooled analysis found no statistically significant difference in the RR of nonvertebral fracture for vitamin D with or without calcium compared with the control (RR, 0.96 [95% CI, 0.86 to 1.09]; 6 RCTs; 52,191 participants) over 1 to 5.7 years of followup. This corresponds to an ARD of 2 fewer nonvertebral fractures per 1,000 persons treated (95% CI, from 8 fewer to 5 more).¹⁰ One trial only reported the number and rate of fractures and not unique participants with fractures. Findings from this trial (adjusted incidence rate ratio, 1.03 [99% CI, 0.75 to 1.43] at 3 years followup) were consistent with the pooled RR estimate.¹⁸ In the one trial comparing calcium alone with placebo, 11 (9.2%) participants had nonvertebral fractures in the calcium group compared with 12 (10.3%) participants in the placebo group (calculated RR, 0.90 [95% CI, 0.41 to 1.96]; ARD, 10 fewer nonvertebral fractures per 1,000 participants [95% CI, from 61 fewer to 98 more]).¹⁹

Seven trials reported on participants with any fracture. One trial evaluated vitamin D and calcium compared with placebo and six evaluated vitamin D alone compared with placebo. A pooled analysis found no statistically significant difference in the RR of any fracture for vitamin D with or without calcium compared with the control (RR, 0.96 [95% CI, 0.92 to 1.00]; 5 RCTs; 85,429 participants) over 1 to 7 years of followup. This corresponds to an ARD of 3 fewer fractures per 1,000 persons supplemented (95% CI, from 7 fewer to 0 more). Analyses stratified by vitamin D dosage (≤400 IU daily dose equivalent vs. >400 IU) and by personal supplement use found no statistically significant differences in the RR of any fracture.¹⁰

Nine trials reported fall-related outcomes. One trial evaluated vitamin D and calcium compared with placebo and eight evaluated vitamin D alone compared with placebo. For the incidence of participants with one or more falls (“fallers”), the pooled RR for vitamin D with or without calcium compared with placebo was 0.99 (95% CI, 0.97 to 1.01; 8 RCTs; 36,744 participants) over 9 months to 5.3 years of followup, corresponding to an ARD of 5 fewer fallers per 1,000 persons treated (95% CI, from 15 fewer to 5 more).¹⁰ One study was not included in the pooled analysis because the method of fall ascertainment varied substantively from the other studies, although the results of this study were consistent with the overall pooled analysis (odds ratio, 1.07 [95% CI, 0.84 to 1.36]; 2,093 participants).²⁰ Analyses stratified by vitamin D dosage (≤400 IU daily dose equivalent vs. >400 IU) and by personal supplement use found no statistically significant differences in the incidence of participants with falls.¹⁰

Five trials reported the rate of falls, which includes first falls and recurrent falls. All these trials compared vitamin D with placebo. The pooled incidence rate ratio for vitamin D with or without calcium compared with placebo was 0.98 (95% CI, 0.94 to 1.03; 4 RCTs; 28,519 participants).¹⁰ One trial that was not included in the pooled analysis because it used a different method of fall ascertainment also reported no statistically significant difference in the rate of falls between participants randomized to vitamin D compared with placebo.²⁰

Seventeen trials reported on all-cause mortality; however, one trial did not report mortality separately by intervention vs. control group. A pooled analysis found no statistically significant difference in the RR of all-cause mortality for vitamin D with or without calcium compared with the control (RR, 0.96 [95% CI, 0.91 to 1.02]; 16 RCTs; 109,782 participants) over 2 to 7 years of followup. This corresponds to an ARD of 2 fewer deaths per 1,000 persons supplemented (95% CI, from 4 fewer to 1 more).¹⁰ The Women’s Health Initiative calcium and vitamin D trial (N=36,282) recently reported no statistically significant difference in all-cause mortality among participants randomized to vitamin D plus calcium compared with placebo after a median followup of 22.3 years (hazard ratio, 1.00 [95% CI, 0.97 to 1.03]).²¹ The pooled estimates for all-cause mortality were similar among the trials with and without the use of calcium, and there were no statistically significant differences in the RR of all-cause mortality between dosage strata of vitamin D (≤400 IU daily dose equivalent vs. >400 IU) or by personal supplement use.¹⁰

Harms of Interventions

Fifteen trials reviewed by the USPSTF reported on one or more harm outcomes. There were no significant differences in adverse events or serious adverse events in participants randomized to vitamin D with or without calcium compared with placebo. However, only a minority of trials reported these outcomes, and ascertainment methods and details provided related to adverse or serious adverse events varied among trials.¹⁰

Eleven trials reported on the incidence of participants with kidney stones. Three trials evaluated vitamin D and calcium compared with placebo, two evaluated calcium alone compared with placebo, and seven RCTs evaluated vitamin D alone compared with placebo. The pooled RR for vitamin D with or without calcium compared with placebo was 1.11 (95% CI, 1.03 to 1.21; 10 RCTs; 99,036 participants) over 2.5 to 7 years of followup, corresponding to an ARD of 2 more participants with kidney stones per 1,000 persons treated (95% CI, from 1 more to 5 more). Two trials compared calcium alone with placebo, but the sample sizes were small and events were rare, so the pooled estimate was imprecise (pooled RR, 1.07 [95% CI, 0.17 to 6.77]; 2 RCTs; 969 participants).¹⁰

The National Academy of Medicine recommends a dietary intake of 600 IU of vitamin D and 1,000 mg of calcium for adults ages 19 to 50 years and males ages 51 to 70 years, 600 IU of vitamin D and 1,200 mg of calcium for females ages 51 to 70 years, and 800 IU of vitamin D and 1,200 mg of calcium for adults age 70 years or older, for overall health. The National Academy of Medicine’s recommended daily allowance includes all sources of calcium and vitamin D dietary sources, including food, beverages, and dietary supplements.^8,9 The American Academy of Family Physicians endorses the USPSTF recommendation on this topic from 2013, which is the same as the 2018 recommendation.²² The American College of Obstetricians and Gynecologists recommends counseling patients to consume the recommended daily allowance of dietary calcium and vitamin D for bone health and general health.²³