4 Vitamin D Deficiency

Suggested citation:  Endocrine Society. Endocrine Facts and Figures: Bone and Mineral. First Edition. 2016.

In 2011, the Endocrine Society reported that between 20-100% of US, Canadian, and European elderly men and women suffered from vitamin D (25-hydroxyvitamin D, or 25[OH]D) deficiency. It also reported that children and young- and middle-aged adults worldwide were equally at risk of vitamin D deficiency.69 In addition, national surveillance data has shown an increase in vitamin D insufficiency and deficiency within the US population.70 However, the US Preventive Services Task Force recently concluded that the current evidence remains insufficient to recommend universal vitamin D screening71. There is an additional evidence gap in understanding the effects of and needs for vitamin D supplementation, particularly in establishing risk-benefit ratios for various populations.72 Researchers seem to agree, in principle, that the adequate intake of vitamin D and calcium along with moderate weight-bearing exercise is helpful in preventing and treating osteoporosis,2,27,54,73 but opinions differ with respect to the target level for Vitamin D adequacy.

4.1 PREVALENCE AND INCIDENCE

Estimates of prevalence and incidence are impacted by the cutoffs used to define vitamin D deficiency and insufficiency. There are some areas of disagreement, most notably between the 2011 clinical practice guideline from the Endocrine Society69 and the 2011 dietary reference intake guideline from the Institute of Medicine (IOM).74 Table 16 summarizes these discrepancies.

Table 16. Comparison of Endocrine Society and Institute of Medicine cutoffs for serum 25-hydroxyvitamin D levels used to define deficiency, insufficiency, and sufficiency.
Guideline Year Serum 25-Hydroxyvitamin D Concentration
Deficiency Insufficiency Sufficiency
Endocrine Society 2011 ≤ 20 ng/ml 21-29 ng/ml 30-100 ng/ml
Institute of Medicine 2011 < 12 ng/ml 12-20 ng/ml 20-50 ng/ml

 Applying the IOM cutoffs to the NHANES dataset (2001-2006), researchers estimate that two-thirds of the US population had sufficient levels of serum 25-hydroxyvitamin D [25(OH)D] (Table 17).75

Table 17. Prevalence of vitamin D deficiency in the general United States population based on Institute of Medicine criteria.
Data Source Population Serum 25-Hydroxyvitamin D Concentration
Deficient  (< 12 ng/mL) Insufficient (12-20ng/mL) Sufficient (20-50 ng/mL) Excessive, Potentially Harmful           (> 50 ng/mL)
NHANES 2001-2006 US population, ages 1 year and older 8% 24% 67% 1%
Abbreviations: US, United States; NHANES, National Health and Nutrition Examination Survey

Source: Looker et al. 201175

Table 18 lists the most recent epidemiological data for children and adolescents (published prior to the most recent guidelines).76

Table 18. Prevalence of vitamin D deficiency in United States adolescents.
Data Source Population Serum 25-Hydroxyvitamin D Concentration
Deficient  (< 15 ng/mL) Insufficient   (≤ 20 ng/mL)
Youth and Adolescent Questionnaire, 2001-2003 Boston Children’s Hospital patients, age 11-18 years 24.1% 42.0%

Source: Gordon et al. 200476

4.2 DEMOGRAPHIC DIFFERENCES

The prevalence of vitamin D deficiency increases significantly with age until age 30 in men and age 18 in women. After adjusting for age and season, women are at higher risk for vitamin D deficiency than men. However, there were no notable sex differences in risk for vitamin D insufficiency (Table 19).

Table 19. Prevalence of vitamin D deficiency and insufficiency in the United States population age 1 year and older by sex based on Institute of Medicine criteria.
Data Source Population Serum 25-Hydroxyvitamin D Concentration
Deficient                    (<12 ng/ml) Insufficient            (12-20 mg/ml)
    Men Women Men Women
NHANES 2001-2006 US, age 1 year 6% 10% 23% 24%
Abbreviations: US, United States; NHANES, National Health and Nutrition Examination Survey

Source: Looker et al. 201175

The Centers for Disease Control has reported, based on IOM cutoffs, that non-Hispanic African Americans and Mexican Americans are at higher risk of vitamin D deficiency and insufficiency than non-Hispanic Caucasians (Table 20). However, the IOM has noted that caution should be used when interpreting serum 25(OH)D levels in non-Caucasian populations, as they may have better skeletal status despite lower serum 25(OH)D values.74

Table 20. Prevalence of vitamin D deficiency and insufficiency in the US population by race and ethnicity based on Institute of Medicine criteria.
Data Source

 

Population Serum 25-Hydroxyvitamin D Concentration
Deficient (<12 ng/mL) Insufficient (12-20 ng/mL)
Non-Hispanic Caucasian Non-Hispanic African American Mexican American Non-Hispanic Caucasian Non-Hispanic African American Mexican American
NHANES 2001-2006 US, age ≥ 1 year 3% 32% 9% 18% 41% 33%
Abbreviations: US, United States; NHANES, National Health and Nutrition Examination Survey

Source: Looker et al. 201175

A study of adolescents at Boston Children’s Hospital revealed a higher prevalence of vitamin D deficiency in African American adolescents compared to their Hispanic, Asian, and non-Hispanic Caucasian counterparts (Table 21).76 No statistically significant differences in the prevalence of vitamin D deficiency between female (26.0%) and male (20.6%) adolescents were noted in this study.

Table 21. Prevalence of vitamin D deficiency in United States adolescents by race and ethnicity.
Data Source Population Vitamin D Deficient (Serum 25-OH VitD ≤ 15 ng/mL)
    Non-Hispanic Caucasian Hispanic Asian African American
Youth and Adolescent Questionnaire, 2001-2003 Boston Children’s Hospital patients, age 11-18 years 6.1% 21.8% 16.7% 35.9%

Source: Gordon et al. 200476

4.3 LIFE EXPECTANCY AND MORTALITY

A Cochrane Review examined the use of vitamin D and its analogues for preventing fractures in older men and postmenopausal women and included 53 trials that enrolled 91,791 patients.28 The primary outcome was hip fracture. The authors found high-quality evidence that vitamin D plus calcium supplementation was associated with a small reduction in hip fracture (9 trials, 49,853 patients, RR 0.84, 95% CI 0.74–0.96, P = .01). Still, the authors concluded that supplementation with vitamin D alone is not likely to prevent fractures (at least in the doses and formulations currently used), but supplementation with vitamin D and calcium may help to prevent them.

The IOM and Endocrine Society guidelines agree that vitamin D does not seem to be associated with non-skeletal outcomes such as death, cardiovascular disease, or quality of life, and that routine screening of the general population is unnecessary.77

4.4 KEY TRENDS AND HEALTH OUTCOMES

Vitamin D can be obtained through sun exposure, but throughout the world, the sun, for a variety of reasons, is no longer a primary source of vitamin D. Dietary sources of vitamin D are also potentially available but they are generally limited. The Centers for Disease Control reports that the use of vitamin D supplements increased from 1988 to 2006, regardless of age or sex (Table 22).

Table 22. Use of vitamin D supplements among United States adults by sex and age.
Age Men Women
1988-1994 2003-2006 1988-1994 2003-2006
20-39 years 22.2% 26.5% 30.3% 33.8%
40-59 years 26.0% 38.0% 31.1% 45.0%
60+ years 23.7% 44.0% 29.7% 56.3%

Source: Gahche et al. 201178

However, it is likely that there are many patients with vitamin D deficiency who are not receiving vitamin D supplements. An analysis of the Research Patient Data Registry at the Partners HealthCare System (Boston, MA) showed that two-thirds of primary care patients with vitamin D deficiency (defined using the IOM cutoff of 25(OH)D < 20 ng/ml) did not receive a prescription for vitamin D supplements.79 Some sex and racial/ethnic differences in prescription rates were also noted in the study, as summarized in Table 23. However, since doses of vitamin D are generally available without a prescription, these findings do not mean that subjects with vitamin D deficiency did not take supplements.

Table 23. Percentage of patients with vitamin D deficiency that received a vitamin D prescription.
Patients with Vitamin D Deficiency who were Prescribed Supplements Overall Non-Hispanic Caucasian Non-Hispanic African American Hispanic
All 33.8% 30.9% 37.8% 38.4%
Male 7.5% 28.0% 37.9% 31.8%
Female 26.3% 32.1% 37.8% 40%

Source: Chandler et al. 201479

Even though universal screening for vitamin D deficiency is not currently recommended, the frequency of vitamin D testing has increased markedly in recent years. An analysis of Medicare Part B reimbursements for laboratory tests showed an 83-fold increase in vitamin D test reimbursements from 2000 to 2010.80

To determine the effectiveness of vitamin D supplementation for improving BMD in children, researchers examined six randomized, placebo-controlled clinical trials that lasted at least 3 months and involved healthy children and adolescents (ages 1 month to < 20 years) with bone density outcomes. Subgroup analyses were based on sex, stage of puberty, dose of vitamin D, and baseline serum vitamin D levels among 343 patients who received placebo and 541 who received vitamin D with or without calcium. The authors reported non-significant trends toward increased lumbar spine BMD in patients who received supplemental vitamin D, and similarly small effects on total bone mineral content. In patients with low serum vitamin D levels, supplementation was associated with statistically significant effects on bone mineral content and lumbar spine BMD (approximately equivalent to increases of 2.6% and 1.7%, respectively). Based on these findings the authors suggested vitamin D supplementation may be beneficial in children with low serum vitamin D levels.81

Table 24 summarizes findings following vitamin D supplementation in selected groups.

Table 24. Results of vitamin D studies in various groups.
Group Observation/Intervention Outcomes Reference
Postmenopausal women (Women’s Health Initiative) Identified 11 clinically relevant risk factors: age, race (ethnicity), self-reported health, weight, height, physical activity, parental hip fracture, fracture history after age 54, current smoking, corticosteroid use, and treatment for diabetes Small but significant positive effect on hip bone density after supplementation with vitamin D and calcium; an intention-to-treat analysis found no significant reduction in fractures Jackson et al. 201482; Clarke et al. 201283
Men 70 years and men 50-69 years (Endocrine Society) Risk factors for men in the younger cohort included low body weight, fracture during adulthood, smoking, alcohol abuse Recommended pharmacologic treatments, lifestyle modifications, follow-up with DXA Watts et al. 201284
3-year RCT in 208 healthy postmenopausal African American women (50-75 years) Placebo, 20 µg/day (800 IU) vitamin D3 with calcium supplementation (intake of 1200-1500 mg/day); after 2 years, the supplemented group’s vitamin D3 dose was increased to 50 µg/day BMD measured at 6-month intervals; no observed effect of vitamin D supplementation on bone loss or turnover Aloia et al. 200585
2-year double-blind RCT in 103 postmenopausal African American women Vitamin D supplementation (1000 IU/day); monitored parathyroid hormone levels and determined vitamin D receptor polymorphisms No difference in BMD between placebo and supplemented groups; femoral neck BMD increased in those with the FF polymorphism Nieves et al. 201286
International

meta-analysis

4,082 patients in 23 studies No effect of ethnic differences in response to vitamin D supplementation Reid et al. 201487

Abbreviations: DXA, dual-energy x-ray absorptiometry; RCT, randomized controlled clinical trial; BMD, bone mineral density

Evidence gaps and data inconsistencies have led to differing opinions regarding the outcomes resulting from vitamin D deficiency and supplementation. As noted in Table 16 above, the IOM and the Endocrine Society provide different cutoffs for the diagnosis of vitamin D insufficiency and deficiency. Reactions to these guidelines and areas of disagreement are summarized in Table 25.

Table 25. Differences in expert recommendations regarding vitamin D.
Data Source Recommendation Comments Reference
Heaney and Holick (2011) Agree with Endocrine Society that serum levels of vitamin D should be 30 ng/mL Note that supplementation with 600 IU/day, if the body’s only source, would not produce serum 25-hydroxyvitamin D level of 10 ng/mL Heaney et al. 201188
IOM response to Endocrine Society (2012) Three main areas of disagreement Dispute benefits of serum 25-hydroxyvitamin D levels of 30 vs. 20 ng/mL for general and at-risk populations; disagree with definition of vitamin D deficiency as < 20 ng/mL; disagree about definitions and characteristics of at-risk subgroups Rosen et al. 201277

Abbreviations: IOM, Institute of Medicine

When discussing breakthroughs in the field of vitamin D deficiency, meta-analyses, treatment guidelines, and other research reports often identify the lack of high-quality, long-term, placebo-controlled studies as obstacles that prevent firm conclusions about treatment outcomes.28,69,77,81,82,86 Indeed, some researchers have cautioned against the use of a single cutoff value to determine vitamin D deficiency because of the wide individual variability in response to vitamin D and interactions with calcium.89 Furthermore, these researchers noted that most of the evidence that supported the beneficial effects of vitamin D supplementation was based on observational studies, whereas controlled clinical trials are required for the conclusive demonstration of such benefits. Similarly, the US Preventive Services Task Force recommendations for vitamin D and calcium to prevent fractures (2013) found most of the evidence in favor of supplementation insufficient, except for data regarding community-dwelling adults age ≥65 years who are at increased risk of falls. 90,91

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