Hypovitaminosis D may result from inadequate intake, insufficient sunlight,
malabsorption, liver, kidney and genetic disease. It results in the inadequate
mineralization of bone. The CDC reported approximately 300,000 hip fractures,
60,000 fall-related deaths and 33 billion dollars in health care expenditures
in 2014. This LCD identifies the indications and limitations of Medicare
coverage for Vitamin D; 25 hydroxy and Vitamin D; 1, 25 dihydroxy laboratory
assays in the medical management of patients.  
  
 **Indications:**  
  
Measurement of 25-OH Vitamin D level is indicated for patients with:

  * chronic kidney disease stage III or greater
  * cirrhosis
  * hypocalcemia
  * hypercalcemia
  * hypercalciuria
  * hypervitaminosis D
  * parathyroid disorders
  * malabsorption states
  * obstructive jaundice
  * osteomalacia
  * osteoporosis if:   

i. T score on DEXA scan <-2.5 or

ii. History of fragility fractures or

iii. FRAX> 3% 10-year probability of hip fracture or 20% 10-year probability
of other major osteoporotic fracture or

iv. FRAX> 3% (any fracture) with T-score <-1.5 or

v. Initiating bisphosphanate therapy (Vitamin D level and serum calcium levels
should be determined and managed as necessary before bisphosphonate is
initiated.)

  * osteosclerosis/petrosis
  * rickets
  * vitamin D deficiency on replacement therapy related to a condition listed above; to monitor the efficacy of treatment.

Measurement of 1, 25-OH Vitamin D level is indicated for patients with:

  * unexplained hypercalcemia (suspected granulomatous disease or lymphoma)
  * unexplained hypercalciuria (suspected granulomatous disease or lymphoma)
  * suspected genetic childhood rickets
  * suspected tumor-induced osteomalacia
  * nephrolithiasis or hypercalciuria

  
**Limitations:**  
  

  * Both assays of vitamin D need not be performed for each of the above conditions.

  * Once a beneficiary has been shown to be vitamin D deficient, further testing may be medically necessary only to ensure adequate replacement has been accomplished.

  * If Vitamin D level is between 20 and 50 ng/ml and patient is clinically stable, repeat testing is often unnecessary; if performed, documentation must clearly indicate the necessity of the test.

  * If level <20 ng/ml or > 60 ng/ml are noted, a subsequent level(s) may be reimbursed until the level is within the normal range.

  * Testing may not be used for routine or other screening.

Routine use of laboratory assays to document Vitamin D deficiency remains
controversial. The current United States Preventive Health Service Task Force
recommendations consider current medical evidence insufficient to assess the
balance of benefits and harms of screening for Vitamin D deficiency in
asymptomatic adults. However, one major meta-analysis (one with five pooled
randomized controlled trials including 1237 patients) concluded that Vitamin D
supplementation reduced the risk of falls among ambulatory and
institutionalized older individuals with stable health by more than 20%.

A second meta-analysis pooled 12 randomized controlled trials, all using
cholecalciferol supplementation therapy between 700-800 IU/d. The results
demonstrated a reduction in fractures of the hip of 26%, and non-vertebral
fractures of 23%, in both ambulatory and institutionalized elderly persons.

There is also controversy as to the definition of vitamin D sufficiency,
although many authors accept a level of 25(OH)D of at least 30 ng/ml.
Accepting this metric, 25-50% of nursing home or homebound patients, greater
than 50% of hospitalized patients and 30% of women with osteoporosis may still
have Vitamin D deficiency despite a growing societal awareness of that
deficiency as a contributing factor.

In 2009, the Agency for Healthcare Research and Quality, through the Tufts
Evidenced Based Practice Center, conducted a systematic review of the
scientific literature on Vitamin D and calcium intake as related to status
indicators and health outcomes. This original report summarized 165 articles
and 11 systematic reviews that incorporated 200 additional primary articles.
In 2013, in preparation for a project in conjunction with the NIH Office of
Dietary Supplements, the report was updated to include 154 new articles.
Despite this effort, disagreement exists regarding Vitamin D optimum dosing,
target 25(OH) vitamin D levels and the reported associations with health
outcomes. Associations with cardiovascular disease, major cancers breast,
prostate, colorectal and pancreatic were mixed and inconclusive. One RCT found
a small effect on fall risk among older adults. As described in the original
report, both the Tufts EPC and the Ottawa EPC data found good evidence that
combined Vitamin D3 (200-800 IU/d) plus calcium 500mg/d supplementation
resulted in a small increase in Bone Mineral Density of the spine, the total
body, femoral neck and total hip.

Another AHRQ funded study, LeBlanc et al Screening for Vitamin D deficiency: A
Systematic Review for the US Preventive Services Task Force (Jan. 2015)
concluded that screening for Vitamin D levels in asymptomatic persons might
reduce mortality risk in institutionalized elderly persons and risk for falls,
but not fractures. The authors noted the inconsistency of laboratory
methodology and reporting, and a lack of consensus regarding optimal 25(OH) D
levels.

In its 2011 report, the Institute of Medicine shared the concerns that a
"reassessment of laboratory ranges for 25-hydroxyvitamin D" was needed to
decrease risks of over and under treatment of Vitamin D deficiency.

A pragmatic approach for patients and their physicians was developed by the
ABIM Foundation in its Choosing Wisely initiative. The patient friendly
literature reassures individuals that healthy diet and exercise maintain most
persons in an adequate range of Vitamin D level. It raises the possible
justification of empiric vitamin D supplementation without testing for those
patients without risk factors but may be thought to have inadequate sun
exposure or dietary intake, while outlining those clinical risk factors that
warrant baseline diagnostic assays.

It is established that 25-hydroxyvitamin D is more reflective of total body
stores of vitamin D than the shorter lived, active metabolite, 1,25
dihydroxyvitamin D. Although lack of laboratory standardization is commonly
noted in most papers, it is the preferred initial assay in the evaluation of
most patients with hypovitaminosis D.  The 25-hydroxyvitamin D undergoes
additional hydroxylation in the kidney by 1- alphahydroxylase under the
influence of parathyroid hormone to produce the active metabolite. The 1,25
dihydroxyvitamin D assay is reserved for those patients where a contributory
medical illness generally related to kidney disease, but also possibly related
to liver, parathyroid or genetic diseases that may influence this normal
metabolism.  

The benefits of treatment of Vitamin D supplementation may be modest, and
those benefits made difficult to quantify by general health, habits such as
exercise and smoking, and other contributory factors such as ethnicity and
medication treatment regimens.  

However, the prevalence of osteoporosis, fall risk and skeletal fractures, and
the general tolerance of the current recommended daily requirements mitigate
for early supplementation in any individual uncertain regarding adequate
dietary intake and sunlight exposure.  

Once a beneficiary has been shown to be Vitamin D deficient, by assay or
clinical findings, the correctly chosen assay (25 hydroxyvitamin D, or 1,25
di-hydroxyvitamin D) may be used to assure correct supplementation to attain
the serum levels outlined in Limitations. Continued findings outside those
parameters (again outlined in the Limitations section) may warrant additional
testing.