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Horizon BCBSNJ
Uniform Medical Policy ManualSection:Pathology
Policy Number:126
Effective Date: 06/15/2016
Original Policy Date:07/28/2015
Last Review Date:01/14/2020
Date Published to Web: 03/17/2016
Subject:
Testing Serum Vitamin D Levels

Description:
_______________________________________________________________________________________

IMPORTANT NOTE:

The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.

Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.

__________________________________________________________________________________________________________________________

Vitamin D, also known as calciferol, is a fat-soluble vitamin that has a variety of physiologic effects, most prominently in calcium homeostasis and bone metabolism. In addition to the role it plays in bone metabolism, other physiologic effects include inhibition of smooth muscle proliferation, regulation of the renin-angiotensin system, a decrease in coagulation, and a decrease in inflammatory markers.

PopulationsInterventionsComparatorsOutcomes
Individuals:
    • Who are asymptomatic without conditions or risk factors for which vitamin D treatment is recommended
Interventions of interest are:
    • Testing of vitamin D levels
Comparators of interest are:
    • Routine care without testing vitamin D levels
Relevant outcomes include:
    • Overall survival
    • Test validity
    • Symptoms
    • Morbid events
    • Treatment-related morbidity

BACKGROUND

Vitamin D

Vitamin D, also known as calciferol, is a fat-soluble vitamin that has a variety of physiologic effects, most prominently in calcium homeostasis and bone metabolism. In addition to the role vitamin D plays in bone metabolism, other physiologic effects include inhibition of smooth muscle proliferation, regulation of the renin-angiotensin system, a decrease in coagulation, and a decrease in inflammatory markers.1,

Vitamin D Replacement

The Institute of Medicine has recommended reference values for the intake of vitamin D and serum levels, based on available literature and expert consensus.2, Recommended daily allowances are 600 IU/d for individuals between 1 and 70 years of age, and 800 IU/d for individuals older than 70 years.

Estimates of vitamin D requirements are complicated by the many other factors that affect serum levels. Sun exposure is the most prominent of factors that affect serum levels, and this is because individuals can meet their vitamin D needs entirely through adequate sun exposure. Other factors such as age, skin pigmentation, obesity, physical activity, and nutritional status also affect vitamin D levels and can result in variable dietary intake requirements to maintain adequate serum levels.

Excessive intake of vitamin D can be toxic. Toxic effects are usually due to hypercalcemia and may include confusion, weakness, polyuria, polydipsia, anorexia, and vomiting. In addition, high levels of vitamin D may promote calcium deposition and has the potential to exacerbate conditions such as calcium kidney stones and atherosclerotic vascular disease.

The Institute of Medicine defined three parameters of nutritional needs for vitamin D, on the assumption of minimal sun exposure. These parameters were the estimated average requirement, defined as the minimum intake required to maintain adequate levels; the recommended daily allowance, defined as the optimal dose for replacement therapy; and the upper-level intake, defined as the maximum daily dose to avoid toxicity. These recommendations are summarized in Table 1.

Table 1. Institute of Medicine Recommendations for Vitamin D Dietary Intake
Patient GroupEstimated Average Requirement, IU/dRecommended Daily Allowance, IU/dUpper Limit Intake, IU/d
1-3 years old
400
600
2500
4-8 years old
400
600
3000
9-70 years old
400
600
4000
>70 years old
400
800
4000
Adapted from Institute of Medicine (2011).2,

Regulatory Status

The U.S. Food and Drug Administration has cleared a number of immunoassays in vitro diagnostic devices for the quantitative measurement of total 25-hydroxyvitamin D through the 510(k) process.

Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments. Lab tests for vitamin D are available under the auspices of the Clinical Laboratory Improvement Amendments. Laboratories that offer laboratory-developed tests must be licensed by the Clinical Laboratory Improvement Amendments for high-complexity testing. To date, the U.S. Food and Drug Administration has chosen not to require any regulatory review of this test.

Related Policies

  • None

Policy:
NOTE: (For Medicare Advantage, Medicaid and FIDE-SNP, please refer to the Coverage Sections below for coverage guidance.)

1. Testing vitamin D levels in members with signs and/or symptoms of vitamin D deficiency or toxicity (see Policy Guidelines section) is considered medically necessary.

2. Testing vitamin D levels in asymptomatic members is considered medically necessary in the following patient populations:
    · Individuals who have risk factors for vitamin D deficiency (see Policy Guidelines section)
    · Institutionalized members (see Policy Guidelines section)
    · Individuals who are at risk for developing complications related to vitamin D deficiency

3. Testing vitamin D levels in asymptomatic members is not considered medically necessary when the above criteria are not met.


Medicare Coverage:
Medicare generally considers vitamin assay panels (more than one vitamin assay) a screening procedure and therefore, non-covered. There is no National Coverage Determination (NCD) for Testing Serum Vitamin D Levels. In the absence of an NCD, coverage decisions are left to the discretion of Local Medicare Carriers. Novitas Solutions, Inc, the Local Medicare Carrier for jurisdiction JL, provides limited coverage for testing serum vitamin D levels when the LCD L34914 criteria is met. For additional information and eligibility, refer to Local Coverage Determination (LCD): Assays for Vitamins and Metabolic Function (L34914). Available at: https://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId=34914&ver=48&name=314*1&UpdatePeriod=749&bc=AAAAEAAAAAAAAA%3d%3d&.

Medicaid Coverage:

For members enrolled in Medicaid and NJ FamilyCare plans, Horizon BCBSNJ applies the above medical policy.

FIDE SNP:

For members enrolled in a Fully Integrated Dual Eligible Special Needs Plan (FIDE-SNP): (1) to the extent the service is covered under the Medicare portion of the member’s benefit package, the above Medicare Coverage statement applies; and (2) to the extent the service is not covered under the Medicare portion of the member’s benefit package, the above Medicaid Coverage statement applies.

Policy Guidelines: (Information to guide medical necessity determination based on the criteria contained within the policy statements above.)

Signs and symptoms of vitamin D deficiency are largely manifested by changes in bone health and biochemical markers associated with bone production and resorption. In most cases, a clinical diagnosis of an abnormality in bone health (eg, rickets, osteomalacia, osteoporosis) will lead to a decision to test vitamin D levels. Symptoms related to the clinical condition may be present (eg, pain, low-impact fractures), but these symptoms are usually not indications for testing prior to a specific diagnosis. Some biochemical markers of bone health may indicate an increased risk for vitamin D deficiency, and testing of vitamin D levels may therefore be appropriate. These biochemical markers include unexplained abnormalities in serum calcium, phosphorous, alkaline phosphatase, and/or parathyroid hormone.

Signs and symptoms of vitamin D toxicity (hypervitaminosis D) generally result from induced hypercalcemia. Acute intoxication can cause symptoms of confusion, anorexia, vomiting, weakness, polydipsia, and polyuria. Chronic intoxication can cause bone demineralization, kidney stones, and bone pain.

“Institutionalized” as used herein refers to patients who reside at long-term facilities where some degree of medical care is provided. These circumstances and facilities can include long-term hospital stays, nursing homes, assisted living facilities, and similar environments.

There are no standardized lists of factors denoting high risk for vitamin D deficiency, and published lists of high-risk factors differ considerably. Certain factors tend to be present on most lists, however, and they may constitute a core set of factors for which there is general agreement that testing is indicated. The Endocrine Society guidelines form the basis for the following list of high-risk factors for vitamin D deficiency (Holick et al [2011]).

·         Chronic kidney disease stage ≥3

·         Cirrhosis and chronic liver disease

·         Malabsorption states

·         Osteomalacia

·         Osteoporosis

·         Rickets

·         Hypo- or hypercalcemia

·         Granulomatous diseases

·         Vitamin D deficiency, on replacement

·         Obstructive jaundice and biliary tract disease

·         Osteogenesis imperfecta

·         Osteosclerosis and osteopetrosis

·         Chronic use of anticonvulsant medication or corticosteroids

·         Parathyroid disorders

·         Osteopenia.

The need for repeat testing may vary by condition. A single test may be indicated for diagnostic purposes; a repeat test may be appropriate to determine whether supplementation has been successful in restoring normal serum levels. More than 1 repeat test may occasionally be indicated, such as in cases where supplementation has not been successful in restoring levels (another example might include an instance in which continued or recurrent signs and symptoms may indicate ongoing deficiency, and/or when inadequate absorption or noncompliance with replacement therapy is suspected).


[RATIONALE: This policy was created in 2015 and has been updated regularly with searches of the MEDLINE database. The most recent literature update was performed through October 14, 2019.

Evidence reviews assess whether a medical test is clinically useful. A useful test provides information to make a clinical management decision that improves the net health outcome. That is, the balance of benefits and harms is better when the test is used to manage the condition than when another test or no test is used to manage the condition.

The first step in assessing a medical test is to formulate the clinical context and purpose of the test. The test must be technically reliable, clinically valid, and clinically useful for that purpose. Evidence reviews assess the evidence on whether a test is clinically valid and clinically useful. Technical reliability is outside the scope of these reviews, and credible information on technical reliability is available from other sources.

Vitamin D Deficiency

Vitamin D deficiency is best assessed by measuring serum levels of 25-hydroxyvitamin D. However, there is no consensus on the minimum vitamin D level or on the optimal serum level for overall health. A 2011 Institute of Medicine (IOM) report concluded that a serum level of 20 ng/mL is sufficient for most healthy adults.2, Some experts, such as the National Osteoporosis Foundation and the American Geriatrics Society, have recommended a higher level (30 ng/mL).2,

Vitamin D deficiency, as defined by suboptimal serum levels, is common in the U. S. In the National Health and Nutrition Examination Survey covering the period of 2000-2004, 30% of individuals over the age of 12 had 25-hydroxyvitamin D levels less than 20 ng/mL.3, Vitamin D deficiency occurs most commonly as a result of inadequate dietary intake coupled with inadequate sun exposure. Evidence from the National Nutrition Monitoring System and the National Health and Nutrition Examination Survey have indicated that the average consumption is below recommended levels of intake. Yetley (2008) estimated that the average daily intake for U.S. adults ranged from 228 to 335 IU/d, depending on gender and ethnicity.3, This level is below the average daily requirement, estimated by IOM (400 IU/d for healthy adults), and well below IOM’s required daily allowance (estimated to be 600 IU for nonelderly adults and 800 IU for elderly adults).

Vitamin D deficiency may occur less commonly for other reasons. Kidney or liver disease can cause deficiency as a result of the impaired conversion of inactive vitamin D to its active products. In rare situations, there is vitamin D resistance at the tissue level, which causes a functional vitamin D deficiency despite "adequate" serum levels.

The safe upper level for serum vitamin D is also not standardized. The IOM report concluded there is potential harm associated with levels greater than 50 ng/mL and recommended that serum levels be maintained in the 20- to 40-ng/mL range.2, However, conclusions on this point have differed. A 2011 Agency for Healthcare Research and Quality systematic review of vitamin D and bone health concluded that “There is little evidence from existing trials that vitamin D above current reference intakes is harmful.”4, The Women’s Health Initiative concluded that hypercalcemia and hypercalciuria in patients receiving calcium and vitamin D were not associated with adverse clinical events.5, The Women’s Health Initiative did find a small increase in kidney stones for women ages 50 to 79 years who received vitamin D and calcium.

Associations of vitamin D levels with various aspects of health have been noted over the last several decades,6,7,8,9,10, and these findings have led to the question of whether supplementation improves health outcomes. For example, a relation between vitamin D levels and overall mortality has been reported in most observational studies examining this association.11,12, Mortality is lowest at vitamin D levels in the 25- to 40-nmol/L range. At lower levels of serum vitamin D, mortality increases steeply, and overall mortality in the lowest quintile was more than three times that in the middle quintiles. Theodoratou et al (2014) identified 107 systematic reviews of observational studies examining the association between vitamin D levels and more than 100 different outcomes.13,

Clinical Context and Test Purpose

The purpose of testing of vitamin D levels is to provide a treatment option that is an alternative to or an improvement on existing therapies in patients who are asymptomatic without conditions or risk factors for which vitamin D treatment is recommended.

The question addressed in this policy is: Does testing for vitamin D deficiency in asymptomatic patients improve the net health outcome?

The following PICOs were used to select literature to inform this review.

Patients

The relevant population of interest are individuals who are asymptomatic without conditions or risk factors for which vitamin D treatment is recommended.

Interventions

The therapy being considered is testing of vitamin D levels.

Patients with vitamin D deficiency are managed by primary care providers in an outpatient setting.

Comparators

The following practice is currently being used to manage vitamin D deficiency: routine care without testing for vitamin D deficiency. Routine care may include recommendations for increased ultraviolet B exposure, dietary intake of vitamin D, or vitamin D supplementation even in the absence of known vitamin D deficiency.

Patients with vitamin D deficiency are managed by primary care providers in an outpatient setting.

Outcomes

The general outcomes of interest are overall survival, test validity, symptoms, morbid events. and treatment-related morbidity.

The length of time needed to correct subclinical vitamin D deficiency and improve outcomes is unknown and probably varies between outcomes.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

    • The study population represents the population of interest. Eligibility and selection are described.
    • The test is compared with a credible reference standard.
    • If the test is intended to replace or be an adjunct to an existing test; it should also be compared with that test.
    • Studies should report sensitivity, specificity, and predictive values. Studies that completely report true- and false-positive results are ideal. Studies reporting other measures (eg, receiver operating characteristic, area under receiver operating characteristic, c-statistic, likelihood ratios) may be included but are less informative.
    • Studies should also report reclassification of diagnostic or risk category.
Analytic Framework

Figure 1 summarizes the approach to this policy. The diagram demonstrates the framework for how vitamin D testing affects outcomes. Using this framework, the main question is whether testing individuals for vitamin D deficiency improves outcomes.

Figure 1. Analytic Framework

Based on this analytic framework, the most relevant studies for showing the clinical utility of vitamin D testing are trials that directly compare care including testing vitamin D levels against care without testing vitamin D levels. Should vitamin D screening in asymptomatic, general population be shown to be effective, guidelines would then be needed to establish criteria for screening, screening intervals, and appropriate follow-up for positive tests. Indirect evidence of the utility of vitamin D testing would include evidence of the effectiveness of supplementation from trials testing supplementation to no supplementation in patients who are vitamin D-deficient. Many of the existing randomized controlled trials (RCTs), including the largest trial (Women’s Health Initiative), did not test vitamin D levels prior to treatment. Rather, they treated all patients enrolled regardless of vitamin D levels. Results of some of the main systematic reviews that take this approach will be reviewed, but this evidence is indirect and must be extrapolated from the treatment of all patients to the treatment of patients who are vitamin D-deficient.

Technically Reliable

Assessment of technical reliability focuses on specific tests and operators and requires a review of unpublished and often proprietary information. Review of specific tests, operators, and unpublished data are outside the scope of this policy and alternative sources exist. This policy focuses on the clinical validity and clinical utility.

Clinically Valid

A test must detect the presence or absence of a condition, the risk of developing a condition in the future, or treatment response (beneficial or adverse).

There is no consensus on how to define vitamin D deficiency or inadequacy, and there is no accepted reference standard. Available cutoffs for deficiency are neither standardized nor based on rigorous scientific studies.14, Therefore, despite the availability of many tests that measure total serum 25-hydroxyvitamin D (25(OH)D) levels, their sensitivities and specificities for detecting clinically important deficiency are currently unknown.

Clinically Useful

A test is clinically useful if the use of the results informs management decisions that improve the net health outcome of care. The net health outcome can be improved if patients receive correct therapy, or more effective therapy, or avoid unnecessary therapy, or avoid unnecessary testing.

No RCTs were found that evaluated clinical outcomes or harms in patients tested for vitamin D deficiency vs not tested for vitamin D deficiency. In the absence of direct evidence of the utility of testing, evidence of the effectiveness of vitamin D supplementation could indirectly support the utility of testing by identifying a group of patients in which baseline serum 25(OH)D is a predictor of supplement effect so that testing might be useful.

A large number of RCTs have evaluated the impact of vitamin D supplementation on outcomes. Theodoratou et al (2014) identified 87 meta-analyses of RCTs on vitamin D supplementation13,; there were 21 meta-analyses on skeletal health, 7 on metabolic disease, 4 on pediatric outcomes, 3 on cardiovascular disease, 3 on pregnancy-related outcomes, and 18 on other outcomes. Because of the large literature base, this review of evidence will focus on the largest and most recent systematic reviews and meta-analyses of RCTs. Individual trials will be reviewed separately if they were not included in the meta-analyses or if particular features need highlighting.

Skeletal Health

Systematic Reviews

Numerous systematic reviews and meta-analyses of RCTs have been published evaluating the impact of vitamin D supplementation on skeletal health outcomes. The relevant health outcomes considered for this policy include fractures and falls. Studies that looked at the bone mineral density and/or other physiologic measures of bone health were not included. Table 2 summarizes the results of systematic reviews performing quantitative meta-analyses on the relevant outcomes.

Among the trials included in the meta-analyses, few were large studies; most were small or moderate in size and limited by a small number of outcomes events. Doses of vitamin D varied widely from 400 to 4800 IU/d; treatment and follow-up durations varied from 2 months to 7 years. Some studies limited enrollment to participants with low serum vitamin D. Most studies excluded institutionalized patients, but some included them. There was inconsistency in the results, especially for studies of fracture prevention, as evidenced by the relatively large degree of heterogeneity among studies.

Table 2. Systematic Reviews Assessing the Impact of Vitamin D Supplementation on Skeletal Health
StudyOutcomeNo. of StudiesNo. of ParticipantsI2, %aRR for Outcome (95% CI)
Patients with vitamin D deficiency
LeBlanc et al (2015)15,Any fracture
5
3551
32
0.98 (0.82 to 1.16)
Hip fracture
4
1619
46
0.96 (0.72 to 1.29)
Falls: total
5
1677
70
0.84 (0.69 to 1.02)
Falls: person
5
1809
64.5
0.66 (0.50 to 0.88)
All patients
Cranney et al (2011)4,; AHRQAny fracture
14
58,712
48.3
0.90 (0.81 to 1.01)
Hip fracture
8
46,072
16.2
0.83 (0.68 to 1.0)
Falls
9
9262
0
0.84 (0.76 to 0.93)
Avenell et al (2009)16,All fractures
10
25,016
NR
1.01 (0.93 to 1.09)
Hip fractures
9
24,749
NR
1.15 (0.99 to 1.33)
Vertebral fracture
5
9138
NR
0.90 (0.97 to 1.1)
Bischoff-Ferrari et al (2009)17,Non-vertebral fracture
5
7130
NR
0.79 (0.63 to 0.99)
Palmer et al (2009)18,All fractures (CKD-RD)
4
181
NR
1.0 (0.06 to 15.41)
Bischoff-Ferrari et al (2005)19,Hip fracture
700-800 IU/d
3
5572
NR
0.74 (0.61 to 0.88)
400 IU/d
2
3722
NR
1.15 (0.88 to 1.50)
Non-vertebral fracture
700-800 IU/d
5
6098
NR
0.77 (0.68 to 0.87)
400 IU/d
2
3722
NR
1.03 (0.86 to 1.24)
AHRQ: Agency for Healthcare Research and Quality; CI: confidence interval; CKD-RD: chronic kidney disease on renal dialysis; NR: not reported;RR: relative risk.
a
Heterogeneity value.

Cranney et al (2011) conducted a review for the Agency for Healthcare Research and Quality (AHRQ) on the effectiveness and safety of vitamin D in relation to bone health.4, Reviewers concluded that:

    • The evidence on the reduction in fractures was inconsistent. The combined results of trials using vitamin Dwith calcium were consistent with a benefit on fractures, although the benefit was primarily found in the subgroup of elderly institutionalized women, which was a subgroup not included in this review.
    • The evidence on a benefit in fall risk was also inconsistent. The results showed benefit in subgroups of postmenopausal women and in trials that used vitamin D in combination with calcium. There was a reduction in fall risk with vitamin D when six trials that adequately ascertained falls were combined.
A meta-analysis of double-blind RCTs by Bischoff-Ferrari et al (2005) estimated the benefit of vitamin D supplementation on fracture risk and examined the dose-response relation between vitamin D and outcomes.19, Based on a meta-analysis of 5 RCTs that used high-dose vitamin D, reviewers concluded that supplementation at 700 to 800 IU/d reduced the incidence of hip fractures by 26%, and reduced any non-vertebral fracture by 23%. In this same review, based on the results of 2 RCTs, lower doses of vitamin D at 400 IU/d did not significantly reduce the fracture risk.

Randomized Controlled Trials

An RCT not included in most of the systematic reviews (by Sanders et al [2010]20,) reported results inconsistent with some of the previous trials and conclusions of meta-analyses. In this trial, 2256 community-dwelling elderly individuals at high-risk for falls were treated with high-dose vitamin D¾500000 IU orally once per year for 3 to 5 years. There was a 15% increase in falls for the group treated with vitamin D (p=0.03) and a 26% increase in fractures (p=0.02). In addition, there was a temporal relation to the increase in fall risk, with the greatest risk in the period immediately after vitamin D administration. It is unclear whether the specific regimen used in this study (eg, high-dose vitamin D once/year) was responsible for the different results seen in this study compared with prior research.

Section Summary: Skeletal Health

Numerous RCTs and meta-analyses of RCTs have been published on the effect of vitamin D supplementation on skeletal health. The most direct evidence consists of trials that selected patients for vitamin D deficiency and randomize patients to vitamin D or placebo. A meta-analysis of these trials showed no reduction in fractures and an uncertain reduction in falls. In meta-analyses that treated all patients regardless of vitamin D levels, there are inconsistent findings on the effect of supplementation on fractures and falls. There is some evidence that subgroups (eg, elderly women) may benefit from supplementation and that higher doses may provide a benefit whereas lower doses do not; however, very high doses may increase the risk of falls. The results of one RCT indicated that bone mineral density in elderly black American women is not affected by increased dosages of vitamin D3.Therefore, the evidence does not convincingly demonstrate an improvement in skeletal health outcomes with vitamin D supplementation.

Cardiovascular Disease

A large number of trials have reported on the impact of vitamin D supplementation on cardiovascular events. A number of systematic reviews have examined the relation between vitamin D and cardiovascular outcomes.

Elamin et al (2011) published a systematic review and meta-analysis evaluating cardiovascular outcomes.21, It included 51 trials that used various forms of vitamin D with or without calcium. There was minimal heterogeneity among the studies. Combined analysis showed no significant impact on cardiovascular death (relative risk [RR], 0.96; 95% confidence interval [CI], 0.93 to 1.0), myocardial infarction (RR=1.02; 95% CI, 0.93 to 1.13), or stroke (RR=1.05; 95% CI, 0.88 to 1.25). No significant effects were found on the physiologic outcomes of lipids, glucose, or blood pressure.

A systematic review by Pittas et al (2010) assessed 5 RCTs evaluating the impact of vitamin D supplementation on incident cardiovascular disease.22, None of the five trials reported a significant reduction in cardiovascular outcomes in the vitamin D group. Combined analysis of these trials found a RR for cardiovascular outcomes of 1.08 (95% CI, 0.99 to 1.19) in the vitamin D group.

An AHRQ report by Chung et al (2009) concluded that23,:

    • The evidence on the impact of vitamin D on cardiovascular outcomes is inconsistent, and conclusions are difficult to make because of the marked heterogeneity of the evidence.
    • The RCTs that have evaluated the impact of vitamin D on cardiovascular outcomes use cardiovascular events as a secondary outcome, not as a prespecified primary outcome.
    • These analyses have been hampered by low numbers of cardiovascular events and imperfect methods for the ascertainment of cardiovascular events.
Wang et al (2008) also performed a systematic review of whether vitamin D and calcium prevent cardiovascular events.24, Eight RCTs of vitamin D supplementation in the general population evaluated cardiovascular outcomes as a secondary outcome. A combined analysis of studies that used high-dose vitamin D supplementation (»1000 IU/d) found a 10% reduction in cardiovascular events, but this reduction was not statistically significant (RR=0.90; 95% CI, 0.77 to 1.05). When studies that combined vitamin D plus calcium supplementation were included, there was no trend toward a benefit (RR=1.04; 95% CI, 0.92 to 1.18).

Section Summary: Cardiovascular Disease

The available evidence does not support a benefit of vitamin D supplementation on cardiovascular events. Numerous RCTs have assessed this outcome-however, in most studies, it is a secondary outcome with a limited number of events, thus limiting the power to detect a difference. Furthermore, it is difficult to separate the impact of vitamin D from the impact of calcium in many of these studies. It is common to use vitamin D and calcium supplementation together. Research has also highlighted a potential increase in cardiovascular outcomes associated with calcium supplementation.25, Thus, if there are beneficial effects of vitamin D, they may be obscured or attenuated by the concomitant administration of calcium supplements. Another possibility is that vitamin D and calcium act synergistically, promoting either a greater protective effect against cardiovascular disease or an increase in cardiovascular risk.

Hypertension

A systematic review by Pittas et al (2010) included 10 intervention trials that evaluated the relation between vitamin D and hypertension.22,Most did not report a decrease in incident hypertension associated with vitamin D supplementation. The largest trial with the longest follow-up was the Women’s Health Initiative, which included over 36000 patients.26, The Women’s Health Initiative trial did not show a reduction in the incidence of hypertension in vitamin D-treated individuals. There was a small, nonsignificant decrease in systolic blood pressure for patients in the vitamin D group (-1.9 mmHg; 95% CI, -4.2 to 0.4 mm Hg) and no change in diastolic blood pressure (-0.1 mm Hg; 95% CI, -0.7 to 0.5 mm Hg).

Cancer

Systematic Reviews

A Cochrane systematic review by Bjelakovic et al (2014) assessed the benefits and harms of vitamin D supplementation on the prevention of cancer in adults.27, Reviewers included 18 RCTs (50623 participants) that compared vitamin D at any dose, duration, and route of administration with placebo or no intervention in healthy adults or diagnosed with a specific disease. Cancer occurred in 1927 (7.6%) of 25275 participants assigned to vitamin D and in 1943 (7.7%) of 25348 participants assigned to control interventions (RR=1.00; 95% CI, 0.94 to 1.06) based on GRADE moderate-quality evidence. There was no substantial difference in the effect of vitamin D on cancer in subgroup analyses of trials only including participants with vitamin D levels less than 20 ng/mL at enrollment compared with trials including participants with vitamin D levels of 20 ng/mL or greater at enrollment. Vitamin D₃ combined with calcium was associated with increased nephrolithiasis (RR=1.17; 95% CI, 1.03 to 1.34).

An AHRQ report by Newberry et al (2014) summarized the evidence on vitamin D supplementation and cancer outcomes.28, Based on a limited number of RCTs, the following conclusions were made:

    • One RCT reported no effect of vitamin D on overall cancer mortality in healthy postmenopausal women.
    • One RCT reported no effect of vitamin D on overall cancer mortality for elderly men or women.
The evidence on the association between vitamin D levels and cancer was reviewed by the Institute of Medicine in 2011, with the following conclusions2,:
    • A small number of studies addressed this question and they showed a lack of consistency in associations between vitamin D intake, or levels, and all cancer mortality.
    • Most available RCTs did not have cancer as a prespecified primary outcome; thus, the validity of the data was less than optimal.
    • Overall, the evidence was insufficient to form conclusions about the association of vitamin D with cancer.
Randomized Controlled Trials

Lappe et al (2017) reported the results of the Clinical Trial of Vitamin D3 to Reduce Cancer Risk in Postmenopausal Women (CAPS). CAPS wasa double-blind, placebo-controlled randomized trial of vitamin D3 and calcium including 2303 healthy, postmenopausal, noninstitutionalized women in 31 rural counties in Nebraska.29, The women were randomized to vitamin D 2000 IU/d plus calcium 1500 mg/d (n=1156) or matching placebos (n=1147) for a period of 4 years. The primary outcome was time to the first diagnosis of any type of cancer (excluding nonmelanoma skin cancers) over four years. The trial was conducted from June 2009 to August 2015. A total of 2064 (90%) women completed the 4 years of study and 2197 (95%) provided at least 6 months of follow-up data. Mean baseline 25(OH)D level was 32.8 ng/mL. Mean achieved 25(OH)D levels during follow-up were 43.6 ng/mL (95% CI, 42.9 to 44.3 ng/mL) in the vitamin D3 plus calcium group and 31.6 ng/mL (95% CI, 31.0 to 32.2 ng/mL) in the placebo group. Ninety-three women in the vitamin D3 plus calcium group discontinued their intervention early due to adverse events compared with 76 in the placebo group. Kaplan-Meier estimated cancer incidence was 4.2% (95% CI, 3.2% to 5.6%) in the vitamin D3 plus calcium group and 6.0% (95% CI, 4.8% to 7.6%) in the placebo group (hazard ratio [HR], 0.70; 95% CI, 0.47 to 1.02; p=0.06). In a post hoc analysis of achieved 25(OH)D levels, the estimated HR for cancer incidence for 25(OH)D levels between 30 ng/mL and 55 ng/mL compared with 30 ng/mL was 0.65 (95% CI, 0.44 to 0.97). Breast cancer was the most commonly first diagnosed cancer, with 16 diagnoses in the vitamin D3 plus calcium group and 23 diagnoses in the placebo group. There were no serious supplement-related adverse events. Because of the study design, the separate effects of interventional calcium and vitamin D3 cannot be assessed. The women in this trial had higher baseline 25(OH)D levels than the U.S. population based on the U.S. National Health and Nutrition Examination Surveys and therefore might not be representative of the target population. Moreover, the participants were almost entirely non-Hispanic, white women, which limits generalizability to men and other racial/ethnic groups. The trial was powered to detect a 50% risk reduction; however, a 50% reduction is unlikely to be the minimally clinically important difference. Smaller risk reductions in all-cause cancer (eg, the 30% estimated reduction) would also be clinically important.

Baron et al (2015) published results of a 2×2 factorial RCT of supplementation with vitamin D and/or calcium for the prevention of colorectal adenomas.30, The trial enrolled 2259 patients with recently diagnosed adenomas and no known colorectal polyps remaining after complete colonoscopy. Patients received treatment and continued follow-up for three to five years and the primary outcome was adenomas diagnosed through colonoscopy. Overall, 1301 (43%) of patients had 1 or more adenomas. The RRs for recurrent adenomas were adjusted for age, clinical center, anticipated surveillance interval (three or five years), sex, type of randomization, and a number of baseline adenomas. The adjusted RR for recurrent adenomas was 0.99 (95% CI, 0.89 to 1.09) with vitamin D vs no vitamin D. The findings for advanced adenomas were similar. There were few serious adverse events, and rates of hypercalcemia did not differ between vitamin D and no vitamin D.

Section Summary: Cancer

Many RCTs have been examined the effect of vitamin D supplementation on cancer outcomes, although cancer was not the prespecified primary outcome in most. The CAPS trial was designed with all-cause cancer as the primary outcome. The current evidence does not demonstrate that vitamin D supplementation reduces the incidence of cancer.

Asthma

Systematic Reviews

Several systematic reviews of vitamin D supplementation for the prevention of asthma exacerbations have been published. Three recent reviews are summarized in Tables 3 and 4. Thirteen unique RCTs were included in the three systematic reviews (see Table 5). Reviews by Jolliffe et al (2017)31, and Martineau et al (2016)32, concluded that the RCTs were generally at low risk of bias. The RCTs included children and adults, as well as variable doses of vitamin D, routes and lengths of administration, and variable levels of asthma severity. The RCTs also included patients with variable baseline 25(OH)D levels and patients were not generally selected by baseline 25(OH)D. The Jolliffe et al (2017) and Martineau et al (2016) reviews found that vitamin D supplementation reduced the rate (or proportion) of asthma exacerbations requiring treatment with systemic corticosteroids. The reviews by Martineau et al (2016)32, and Luo et al (2015)33, found that vitamin D had no effect on Asthma Control Test scores, forced expiratory volume in 1-second outcomes, or rates of adverse events. The review by Jolliffe et al (2017) used individual participant data and was, therefore, able to test for patient-level subgroup effects. For the outcome of “rate of asthma exacerbations treated with systemic corticosteroids,” the protective effect of vitamin D was larger in patients with a baseline 25(OH)D levels of less than 25 nmol/L (rate ratio, 0.33; 95% CI, 0.11 to 0.98) compared with patients who had higher a baseline 25(OH)D levels (rate ratio, 0.77; 95% CI, 0.58 to 1.03). However, the subgroup by treatment group interaction was not statistically significant (p=0.25).

Table 3. Characteristics of Systematic Review Assessing Vitamin D and Asthma
Study; TrialDatesTrialsParticipantsNDesignDuration
Jolliffe et al (2017)31,; PROSPERO CRD42014013953To Oct 20168People with asthma, all ages, and baseline 25(OH)D levels included1078Randomized, double-blind, placebo-controlled15 wk to 12 mo
Martineau et al (2016)32,To Jan 20169People with asthma, all ages, and baseline 25(OH)D levels included1093Randomized, double-blind, placebo-controlled4-12 mo
Luo et al (2015)33,1946-20157People with asthma, all ages, and baseline 25(OH)D levels included903RCT9 wk to 12 mo
RCT: randomized controlled trial; 25-(OH)D: 25-hydroxyvitamin D.

Table 4. Results of Systematic Review Assessing Vitamin D and Asthma
StudyAsthma ExacerbationAsthma Exacerbation Requiring SCSACT ScoreFEV1Proportion of Patients With AEs
Jolliffe et al (2017)31,
Total N868955NRNR955
Pooled effectHR=0.78RR=0.74OR=0.87d
95% CI0.55 to 1.100.56 to 0.970.46 to 1.63
I2NANA
Martineau et al (2016)32,
Total N999963713387879
Pooled effectOR=0.53OR=0.39aDiff = -0.08Diff=0.48%bOR=1.01d
95% CI0.28 to 0.99, favoring vitamin D0.19 to 0.78, favoring vitamin D-0.70 to 0.540.93 to 1.890.54 to 1.89
I265%0%21%0%0%
Luo et al (2015)33,
Total N820NR250316326
Pooled effectOR=0.66Diff = -0.05Diff = -0.02cOR=1.16
95% CI0.32 to 1.37-0.30 to 0.20-0.15 to 0.110.74 to 1.81
I281%NA0%0%
ACT: Asthma Control Test; AE: adverse event; Diff: difference; CI: confidence interval; FEV1: forced expiratory volume in 1 second; HR: hazard ratio; NA: not applicable; NR: not reported; OR: odds ratio; RR: relative risk; SCS: systemic corticosteroid.
a
Outcome was proportion with ≥1 exacerbation.
b
FEV1, % predicted.
c
At 12 months.
d
Serious adverse events.

Table 5. Comparison of Randomized Controlled Trials Included in the Systematic Reviews
Primary Study (Year)Jolliffe et al (2017)31,Martineau et al (2016)32,Luo et al (2015)33,
Worth et al (1994)34,
Majak et al (2009)35,
Urashima et al (2010)36,
Majak et al (2011)37,
Lewis et al (2012)38,
Baris et al (2014)39,
Castro et al (2014)40,
Yadav et al (2014)41,
de Groot et al (2015)42,
Martineau et al (2015)43,
Tachimoto et al (2016)44,
Jensen et al (2016)45,
Kerley et al (2016)46,
Randomized Controlled Trials

An RCT of prenatal supplementation in 881 pregnant women at high-risk of having children with asthma was published in 2016.47, Women between gestational ages of 10 and 18 weeks were randomized to daily vitamin D 4000 IU plus a multivitamin containing vitamin D 400 IU (4400 IU group) or daily placebo vitamin D plus a multivitamin containing vitamin D 400 IU (400 IU group). Coprimary outcomes were (1) parental report of physician-diagnosed asthma or recurrent wheezing through 3 years of age and (2) third trimester maternal 25-OH(D) levels. Analysis of infant outcomes included 806 infants, 218 of whom developed asthma by age 3. The proportion of infants with asthma or recurrent wheeze was 24% in the 4400 IU group vs 30% in the 400 IU group (difference, -6%; 95% CI, -30% to 18%). There were no differences in the proportion of infants experiencing eczema or lower respiratory tract infections.

Section Summary: Asthma

Results of RCTs have reported mixed findings with respect to the effect of vitamin D supplementation on asthma outcomes. Populations included in studies varied by baseline vitamin D deficiency levels, administration of vitamin D, and the severity of asthma. In general, patients were not selected based on a low baseline 25(OH)D level. While there is some evidence that vitamin D supplementation reduces the rate of asthma exacerbations, it is unclear if baseline 25(OH)D level is related to treatment benefit. The current evidence is insufficient to determine the effect of vitamin D supplementation on asthma outcomes.

Multiple Sclerosis

Three systematic reviews have examined the effect of vitamin D supplementation in patients with MS.48,49,50, Reviewers described 6 RCTs, all of which were small (n<100). Patient follow-up ranged from six months to two years, and the dosing and administration of vitamin D varied. None of the trials reported improvement in MS relapse rates; most trials showed no effect of vitamin D on any of the surrogate or clinical outcomes. Onlyone trial reported improvement in magnetic resonance imaging of lesions in the vitamin D supplementation group. The evidence for vitamin D supplementation in MS is poor.

Overall Mortality

A number of meta-analyses of RCTs of vitamin D supplementation have examined the benefit of vitamin D supplementation on overall mortality. Table 6 summarizes the most recent meta-analyses. The individual studies ranged in size from fewer than 100 to several thousand patients. No significant heterogeneity was reported for these trials.

The most relevant information comes from a meta-analysis of patients with vitamin D deficiency by LeBlanc et al (2015).51, This report included 11 studies and found a marginally significant reduction in overall mortality, with a CI that approached 1.0. When the subgroup analysis was performed, it became apparent that most of the benefit was specific to institutionalized patients-whereas, in community-dwelling patients, the data revealed no reduction in mortality.

The AHRQ report by Newberry et al (2014),28, assessing the health effects of vitamin D supplementation, updated the original 2007 report. A quantitative synthesis of all trials was not performed in the 2014 update. Rather reviewers identified areas where the new trials might change previous conclusions. Their main conclusions were that the results did not support a benefit on overall mortality associated with vitamin D supplementation. No important trials identified in the update would potentially change this conclusion.

For meta-analyses including RCTs that treated all patients with vitamin D, most analyses have not shown a significant reduction in mortality. The single analysis that did show a significant reduction was that by Chowdhury et al (2014), who reported a marginally significant result for vitamin Dsupplementation but not for vitamin Dsupplementation.52,

Table 6. Results of Systematic Reviews of RCTs Assessing the Impact of Vitamin D Supplementation on Mortality
StudyOutcomeNo. of StudiesNo. of ParticipantsI2, %aRR for Outcome (95% CI)
Patients with vitamin D deficiency
Leblanc et al (2015)51,Mortality (all patients)11412600.83 (0.70 to 0.99)
Mortality (noninstitutionalized patients)8294700.93 (0.73 to 1.18)
All patients
Chowdhury et al (2014)52,Mortality (vitamin D3)1413,36700.89 (0.80 to 0.99)
Mortality (vitamin D2)817,07901.04 (0.97 to 1.11)
Bjelakovic et al (2011)53,Mortality (vitamin D2)817,0791.04 (0.97 to 1.11)
Mortality (vitamin D3)912,8240.91 (0.82 to 1.02)
Palmer et al (2009)18,Mortality (CKD-RD)52331.34 (0.34 to 5.24)
Palmer et al (2009)54,Mortality (CKD)44771.40 (0.38 to 5.15)
CI: confidence interval; CKD: chronic kidney disease; CKD-RD: chronic kidney disease on renal dialysis; RCT: randomized controlled trial; RR: relative risk.
a
Heterogeneity value.

Section Summary: Overall Mortality

Evidence from a number of systematic reviews and meta-analyses does not support a benefit on overall mortality for the general, noninstitutionalized population. Populations included in the studies varied by baseline vitamin D deficiency and administration of vitamin D.

Summary of Evidence

For individuals who are asymptomatic without conditions or risk factors for which vitamin D treatment is recommended who receive testing of vitamin D levels, the evidence includes no RCTs of clinical utility (ie, evidence that patient care including testing vitamin D levels vs care without testing vitamin D levels improves outcomes). The relevant outcomes are overall survival, test validity, symptoms, morbid events, and treatment-related morbidity. Indirect evidence of the potential utility of testing includes many RCTs and systematic reviews of vitamin D supplementation. There is a lack of standardized vitamin D testing strategies and cutoffs for vitamin D deficiency are not standardized or evidence-based. In addition, despite the large quantity of evidence, considerable uncertainty remains about the beneficial health effects of vitamin D supplementation. Many RCTs have included participants who were not vitamin D deficient at baseline and did not stratify results by baseline 25-hydroxyvitamin D level. Nonwhite race/ethnic groups are underrepresented in RCTs but have an increased risk of vitamin D deficiency. For skeletal health, there may be a small effect of vitamin D supplementation on falls, but there does not appear to be an impact on reducing fractures for the general population. The effect on fracture reduction may be significant in elderly women, and with higher doses of vitamin D. For patients with asthma, there may be a reduction in severe exacerbations with vitamin D supplementation, but there does not appear to be an effect on other asthma outcomes. For overall mortality, there is also no benefit to the general population. RCTs evaluating extraskeletal, cancer, cardiovascular, and multiple sclerosis outcomes have not reported a statistically significant benefit for vitamin D supplementation. Although vitamin D toxicity and adverse events appear to be rare, few data on risks have been reported. The evidence is insufficient to determine the effects of the technology on health outcomes.

SUPPLEMENTAL INFORMATION

Practice Guidelines and Position Statements

Endocrine Society

The Endocrine Society (2011) published clinical practice guidelines on the evaluation, treatment, and prevention of vitamin D deficiency.55, The following recommendations were made regarding testing vitamin D levels:

    • 25-hydroxy vitamin D serum level testing is recommended: “to evaluate vitamin D status only in patients who are at risk of deficiency.” The guideline did not recommend screening of individuals not at risk of vitamin D deficiency.
    • 1,25-dihydroxyvitamin D testing was not recommended to evaluate vitamin D status. However, the guideline did recommend monitoring calcitriol levels under certain conditions.
American College of Obstetrics and Gynecology

The American College of Obstetrics and Gynecology (2011, reaffirmed 2017, 2019) issued a committee opinion on the testing of vitamin D levels and vitamin D supplementation in pregnant women.56, The following recommendation was made concerning testing vitamin D levels:

“At this time there is insufficient evidence to support a recommendation for screening all pregnant women for vitamin D deficiency. For pregnant women thought to be at increased risk of vitamin D deficiency, maternal serum 25-hydroxyvitamin D levels can be considered and should be interpreted in the context of the individual clinical circumstance. When vitamin D deficiency is identified during pregnancy, most experts agree that 1,000-2,000 international units per day of vitamin D is safe.”

American Academy of Family Physicians

The American Academy of Family Physicians (2014) concluded that the current evidence was insufficient to assess the balance of benefits and harms of screening for vitamin D deficiency.57,

In 2018, key recommendations for practice concluded that there was insufficient information to recommend screening the general population for vitamin D deficiency and that treating asymptomatic individuals with identified deficiency has not been shown to improve health.58,

U.S. Preventive Services Task Force Recommendations

The U.S. Preventive Services Task Force published a recommendation in 201459, and associated guidelines in 201560, on vitamin D screening. The Task Force concluded that the current evidence was insufficient to assess the balance of benefits and harms of screening for vitamin D deficiency in asymptomatic individuals (grade I [insufficient evidence]).As of December 2016, the final recommendation upholds the same conclusion and an update is currently in progress.61,

Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this review are listed in Table 7.

Table 7. Summary of Key Trials
NCT No.Trial Name
Planned Enrollment
Completion Date
Ongoing
NCT01169259Vitamin D and Omega-3 Trial (VITAL)
25,871
Nov 2020
NCT01490502A Randomized Controlled Trial of Vitamin D Supplementation in Multiple Sclerosis (VIDAMS)
172
Mar 2021
NCT00920621Randomized Trial: Maternal Vitamin D Supplementation to Prevent Childhood Asthma (VDAART)
876
Feb 2024
NCT02166333Vitamin D Supplements to Prevent Falls in Older Adults: A Dose-Response Trial (STURDY)
1200

enrollment terminated at 688

Jun 2019
Unpublished
NCT02750293The Effect of Vitamin D Supplementation on Cardiovascular Risk Factors in Subjects With Low Serum 25-hydroxyvitamin D Levels (D-COR)
411
Sep 2017
(completed; last update posted 10/26/17)
NCT02424552EVITA Trial: Effect of VItamin D as add-on Therapy for Vitamin D Insufficient Patients With Severe Asthma: a Randomized, Double-blind, Placebo-controlled Trial
54
Mar 2017 (terminated due to recruitment difficulties)
NCT: national clinical trial.]
________________________________________________________________________________________

Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

___________________________________________________________________________________________________________________________

Index:
Testing Serum Vitamin D Levels
Vitamin D Testing
Vitamin D Deficiency
Testing for Vitamin D Deficiency
Vitamin D Deficiency Testing
25-hydroxyvitamin D
1,25-dihydroxyvitamin D
Calcidiol
Calcitriol
Ergocalciferol
Cholecalciferol

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52. Chowdhury R, Kunutsor S, Vitezova A, et al. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ. Apr 01 2014;348:g1903. PMID 24690623

53. Bjelakovic G, Gluud LL, Nikolova D, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. Jul 06 2011(7):CD007470. PMID 21735411

54. Palmer SC, McGregor DO, Craig JC, et al. Vitamin D compounds for people with chronic kidney disease not requiring dialysis. Cochrane Database Syst Rev. Oct 07 2009(4):CD008175. PMID 19821446

55. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. Jul 2011;96(7):1911-1930. PMID 21646368

56. American College of Obstetrics and Gynecology Committee on Obstetric Practice. ACOG Committee Opinion No. 495: Vitamin D: Screening and supplementation during pregnancy. Obstet Gynecol. Jul 2011;118(1):197- 198. PMID 21691184

57. American Academy of Family Physicians. Clinical preventive services recommendation: Vitamin D deficiency, screening. 2014; http://www.aafp.org/patient-care/clinical-recommendations/all/vitamin-D-deficiency.html. Accessed November 8, 2019.

58. LeFevre ML, LeFevre NM. Vitamin D Screening and Supplementation in Community-Dwelling Adults: Common Questions and Answers.. Am Fam Physician, 2018 Apr 20;97(4). PMID 29671532

59. U.S. Preventive Services Task Force (USPSTF). Vitamin D Deficiency: Screening. 2014; https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/vitamin-d-deficiency-screening. Accessed November 8, 2019.

60. LeFevre ML, U.S. Preventive Services Task Force. Screening for vitamin D deficiency in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. Jan 20 2015;162(2):133-140. PMID 25419853

61. Final Recommendation Statement: Vitamin D Deficiency: Screening. U.S. Preventive Services Task Force. December 2016. https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/vitamin-d-deficiency-screening. Accessed October 28, 2019.

62. Noridian Healthcare Solutions. Local Coverage Determination (LCD): Vitamin D Assay Testing (L36692). 2017; https://med.noridianmedicare.com/documents/10546/6990981/Vitamin+D+Assay+Testing+LCD. Accessed November 8, 2019.

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

    82306
    82652
    0038U
HCPCS

* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
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Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.

The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy

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