USPSTF: No Evidence for Routine Vitamin D Screening

Nancy A Melville

November 24, 2014

The US Preventive Services Task Force (USPSTF) has issued its first-ever guidance on the routine screening of asymptomatic patients for vitamin D deficiency. The recommendation is now final following the issue of draft guidance in June.

There simply is no evidence on the specific pros and cons of screening for vitamin D deficiency, so routine screening cannot be advised at the current time, say the authors of the recommendation statement, led by Dr Michael L LeFevre (University of Missouri, Columbia) and colleagues.

The statement and a review of the data on screening and treatment with vitamin D in asymptomatic individuals, by Dr Erin S LeBlanc (Kaiser Permanente Center for Health Research, Portland, Oregon) and colleagues, are published today in the Annals of Internal Medicine.

The review excluded conditions for which there is already consensus that vitamin D screening should be a part of patient management, including bone, endocrine, or autoimmune diseases or pregnancy.

The USPSTF stance is similar to that of the American Academy of Family Physicians (AAFP), which also concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for vitamin D deficiency.

AAFP president Dr Robert L Wergin emphasizes that the statements refer only to the issue of routine screening, however — not the many situations in which screening may indeed be necessary.

"The USPSTF recommendation is that vitamin D screening should not be routine, but they didn't say you shouldn't do it at all," Dr Wergin told Medscape Medical News.

"If patients show signs or have comorbidities such as osteoporosis or malabsorption disorders that predispose them to problems, then that is certainly something the patients should discuss with their doctor," said Dr Wergin, who is a family practitioner in Milford, Nebraska.

No Consensus on "Optimal" Vitamin D Levels

In the data review by Dr LeBlanc and colleagues, a pooled analysis of 11 trials did show that vitamin D treatment reduced mortality vs placebo or no treatment, but only among institutionalized elderly adults.

Treatment of deficiency with vitamin D was also associated with a reduction in falls but not fractures in five studies.

"On the basis of the current available science, the USPSTF concludes that…the balance of benefits and harms of screening and early intervention cannot be determined," they state.

In an editorial accompanying the USPSTF recommendation statement and data review, Drs Robert P Heaney and Laura AG Armas (Creighton University, Omaha, Nebraska) note that the field of nutrition is a tricky one to navigate.

"Only very recently has the USPSTF ventured into the field, or perhaps the minefield, of nutrition, a territory distant from screening tests and risk assessment, with different and unfamiliar landmarks," they write.

"The reason it's a minefield is that the nutrition community has no a priori notion of 'normal' for most nutrients," Dr Heaney told Medscape Medical News. "How can you recognize 'abnormal' if you can't define 'normal?' " he asserted.

That obstacle was in fact central to the USPSTF's conclusion of insufficient data.

While there is general consensus that serum 25-(OH) D levels lower than 50 nmol/L (20 ng/mL) can compromise bone health, the issue of whether levels above that represent "optimal" remains uncertain.

For the purpose of the recommendation statement, the USPSTF referred to vitamin D deficiency according to study populations with levels of 30 ng/mL or less or subpopulations with levels of less than 20 ng/mL.

Data from the National Health and Nutrition Examination Survey (NHANES) at least gives a general idea of where Americans stand, indicating that, from 2003 through 2006, as much as 33% of the US population was at risk of 25-(OH)D levels below 50 nmol/L (20 ng/mL), and 77% had 25-(OH)D levels below 75 nmol/L (30 ng/mL).

Even if there were consensus on optimal vitamin D levels, however, accurately measuring them would remain a challenge due to the lack of a standardized screening tool.

No Consistency of Screening Tests, Reference Standards, for Vitamin D

Despite the availability of many tests that measure total serum 25-(OH)D levels, there is no internationally recognized, commutable reference standard, the USPSTF asserts.

Some headway is being made in tackling the issue, with the establishment in 2010 by the National Institutes of Health (NIH) of the Vitamin D Standardization Program (VDSP), an international collaboration to standardize laboratory measurement of vitamin D status.

While those efforts continue, a standardized measure has yet to make its way to widespread adoption in clinical trials, said Dr LeBlanc.

"The Vitamin D Standardization Program has developed protocols for measuring vitamin D in some research studies, but these protocols are not yet available for commercial use or for all research studies," she told Medscape Medical News.

"In my opinion, being able to more precisely define an individual's vitamin D status as being deficient is a key part of determining whether giving vitamin D to those who are deficient makes them healthier," she observed.

Safety Issues Examined

The new data review also assessed 24 clinical trials involving nearly 5000 vitamin D deficient patients between the ages of 31 and 85 that examined potential harms of vitamin D supplementation, but no significant safety issues emerged. Patients were treated with doses of 400 to 7000 IU/day or 8400 to 54 000 IU/week for 6 weeks to 4 years.

Previous studies have suggested that vitamin D treatment can cause hypercalcemia, hyperphosphatemia, suppressed parathyroid-hormone levels, and hypercalciuria.

The review found no significant differences in adverse events, including serious adverse events — for example, hypercalcemia, kidney stones, or gastrointestinal symptoms were no higher in the vitamin D treatment groups compared with placebo or no treatment.

Ongoing Trials Watched for Answers

While existing data fail to adequately provide answers on the benefits of vitamin D, some ongoing trials should eventually shed more light on the issue.

Among them is the Vitamin D and Omega-3 Trial (VITAL), a large randomized, double-blind, placebo-controlled trial that is evaluating the effect of vitamin D supplementation on the prevention of cancer and cardiovascular disease in a multiethnic study population.

Because a large portion of the study population will have baseline 25-(OH)D levels measured, the study should provide information on whether supplementation in vitamin D–deficient populations is beneficial.

Other Recommendations on Vitamin D Screening

The USPSTF is meanwhile not alone in its position — in fact, no national primary care professional organizations currently recommend routine, populationwide screening for vitamin D deficiency.

Other organizations' recommendations regarding vitamin D screening do differ, however, and are as follows, according to the USPSTF

•   The American Congress of Obstetricians and Gynecologists, the American Geriatric Society, and the National Osteoporosis Foundation recommend testing for vitamin D as part of osteoporosis management or falls prevention.

•   The Endocrine Society recommends vitamin D deficiency screening only among patients at risk. According to that group, vitamin D deficiency is defined as total serum 25-(OH)D levels of less than 50 nmol/L (<20 ng/mL) and vitamin D insufficiency as 52.5 to 72.5 nmol/L (21 to 29 ng/mL). The society does recommend treatment of persons with a vitamin D deficiency.

•   The Institute of Medicine (IOM) has no formal guidelines on screening for vitamin D deficiency, but it has published a report on the recommended dietary allowance (RDA) for vitamin D, an estimated amount necessary to meet or exceed the vitamin D needs of 97.5% of the adult population. Assuming minimal sun exposure, the IOM's RDA for vitamin D is 600 IU/day for adults aged 19 to 70 years and 800 IU/day for adults older than 70 years. The IOM also concluded that total serum 25-(OH)D levels of 40 nmol/L (16 ng/mL) are sufficient to meet the needs of approximately half of the population, and levels of 50 nmol/L (20 ng/mL) or greater meet the needs of nearly all of the population.

In their editorial, Drs Heaney and Armas say: "Whether the practitioner adheres to the widely divergent guidelines of the IOM, the Endocrine Society, or the American Geriatrics Society, measuring vitamin D status would seem to be warranted, not so much to diagnose deficiency but to determine patient status relative to the selected guideline."

Vitamin D Screening, Testing, Has Soared in Recent Years

Dr Wergin notes that interest in vitamin D screening among patients and providers alike in the US has soared in recent years amid increased research and media coverage of the issue.

According to the USPSTF review, estimates of screening rates in primary-care settings are not available; however, a recent study did show the annual rate of outpatient visits that were associated with a diagnosis code for vitamin D deficiency more than tripled between 2008 and 2010.

In addition, a 2009 survey showed that testing in clinical laboratories for total serum 25-(OH)D increased by at least 50% compared with the previous year in more than half of the laboratories surveyed.

Dr Heaney agreed that patient vitamin D status is high on clinicians' radars, but he noted that the testing too often is not reimbursed by insurance companies.

"Most [physicians] I talk to want to know their patients' vitamin status values, and they seem frustrated at the refusal of many insurers to cover the cost of the test," he said.

Dr Wergin agreed that all eyes will be on the results of ongoing clinical trials in looking for more concrete evidence of the benefits of screening and the effects of treatment.

"Sometimes recommendations like this generate more questions than answers, and I think some of the key questions are which patients should be screened and which should be treated and what are the positive and negative effects of treatment," he said.

"But right now, we're in agreement that routine vitamin screening in people who are not at risk is not recommended, but screening should be targeted instead to those who are at risk."

The research was funded by the Agency for Healthcare Research and Quality (AHRQ) under a contract to support the work of the USPSTF. Dr LeFevre reports he has no relevant financial relationships; disclosures for the coauthors are listed in the article. Dr LeBlanc reports grants from AHRQ and grants to her institute from Amgen, Bristol-Meyers Squibb, and AstraZeneca; disclosures for the coauthors are listed here. Dr Wergin reported he had no relevant financial relationships. Dr Heaney is on the medical advisory board for the International Dairy Foods Association and is an advisor for GrassRootsHealth, a public group disseminating knowledge about nutrition, including vitamin D. He has received grants for clinical research from GlaxoSmithKline, General Mills, the National Dairy Council, Eli Lilly, P&P Pharmaceuticals, Rhodia, Lane Labs, and Roots. He has served as an advisor or consultant for GlaxoSmithKline, General Mills, National Dairy Council, and Bayer. Disclosures were not available for Dr Armas.

Ann Intern Med. Published online November 24, 2014. Available at: https://annals.org.

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