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Point-of-care vitamin D testing is efficient and more accessible for patients
Vitamin D – long heralded for its role in maintaining bone and tooth health and protecting against osteoporosis – may have other important health-promoting effects and biological functions as well. Emerging evidence suggests that it can help protect the body from malignancy, cardiovascular disease (CVD), diabetes and various bone disorders.1 The broadening scope of vitamin D’s potential health benefits, combined with the recent and growing recognition that vitamin D deficiency may be more common across populations than was previously realized, is raising awareness of the risk factors for low vitamin D levels. It has also led to new guidelines for defining vitamin D insufficiency and deficiency, as well as for recommended daily vitamin D intake. Accompanying these trends has been a rising demand for vitamin D testing.
New methods for measuring vitamin D that are precise, accurate and easier to perform have become increasingly available in recent years. The continuing evolution in technology development, immunoassay methods and automation has helped standardize vitamin D testing. The rapid, quantitative analytical techniques available today are faster, more cost-effective and able to transition much more easily to the point-of-care (POC) setting. As with other types of test-and-treat options that have moved into clinics and physicians’ offices, POC vitamin D testing offers important advantages for both clinicians and patients.
The value of D
A steroid hormone, vitamin D is well known for a number of health-promoting effects and biological functions, and new benefits continue to be uncovered. People with low levels of vitamin D can develop soft, thin, brittle bones, leading to rickets in children, or osteomalacia in adults, and such symptoms as bone pain and weakness. In addition to its established role in maintaining bone and tooth health and protecting against osteoporosis, emerging evidence suggests that vitamin D can help protect the body from malignancy, CVD, diabetes, and various bone disorders.2 Genome-wide analysis has shown that vitamin D affects the expression of more than 2,000 human genes.2
In the human body, the liver metabolizes vitamin D to form 25-hydroxy (OH) vitamin D. The two most biologically relevant forms of vitamin D are 25-hydroxyvitamin D2 (ergocalciferol) and D3 (cholecalciferol). Measures of total 25-OH vitamin D typically include levels of both D2 and D3.
Traditionally, vitamin D has received far less attention than other vitamins, such as vitamin C and the B vitamins. However, recent studies suggesting that a substantial percentage of the U.S. population has low blood levels of 25-OH vitamin D (<30 ng/mL), with levels approaching the cut-off for vitamin D insufficiency, have drawn attention to the value of vitamin D. Populations that tend to have lower blood levels of 25-OH vitamin D include:
- Dark-skinned individuals, who cannot absorb as much vitamin D from the sun.
- Older adults.
- Breastfed infants.
- Obese children and adults.
- People with intestinal disorders, such as Crohn’s or celiac disease.
Furthermore, one’s risk of vitamin D deficiency increases with the use of certain therapeutic drugs, such as long-term steroids; antiepileptic agents; L-thyroxine; gonadotropin-releasing hormone agonists; chronic lithium therapy; thiazolidinediones for diabetes; antifungals, such as ketoconazole; medications for AIDS; and antacids, including omeprazole and lansoprazole..
How much Is enough?/strong>
Although most people cannot absorb or ingest enough vitamin D from sunlight exposure or nutritional intake to meet their daily needs, supplements can fill the gap. The Institute of Medicine of the National Academies released a consensus report recommending the following daily intake of vitamin D3:
- 600 IU/day for people 70 years of age and younger.
- 800 IU for people 71 years of age and older.
These recommended amounts correspond to a serum 25-OH vitamin D level of at least 20 ng/mL.3
In the evidence-based clinical guidelines entitled, “Evaluation, Treatment, and Prevention of Vitamin D Deficiency,” The Endocrine Society Task Force defines the range of sufficient 25-OH vitamin D as 20-50 ng/mL, with levels higher than 50 ng/mL considered to be toxic.4 The Task Force recommends use of the serum circulating 25-hydroxyvitamin D level, measured by a reliable assay, to assess vitamin D status in individuals at risk for vitamin D deficiency.
POC testing
Traditional methods of quantifying vitamin D have relied on competitive binding, using either high performance liquid chromatography (HPLC) or radioimmunoassay (RIA) with an antibody that targets 25-hydroxy vitamin D. In large reference laboratories with mass spectrometry (MS) capabilities, the use of LC-MS/MS has become the gold standard for vitamin D analysis. This technique measures the different forms of vitamin D that, when added together, provide the total vitamin D concentration. While this is useful as a reference and confirmatory method, LC-MS/MS requires complex, costly instrumentation and staff training, and it is not commonly available in a decentralized laboratory or as a point-of-care option.
The availability of HPLC test kits has simplified the use – and reduced the cost – of HPLC-based analytical methods, which are substantially more sensitive and user-friendly than traditional testing. In addition, immunoassay-based vitamin D testing offers multiple advantages. For instance, the results tend to correlate more closely with LC-MS/MS than do HPLC-based vitamin D assays. Immunoassays that provide rapid and accurate measurement of 25-OH vitamin D in plasma or serum are readily available in kit form and are cost-effective and easy to perform. Designed for use on the manufacturer’s analytical platform, immunoassays measure vitamins D2 and D3, either equally or with different degrees of cross-reactivity, depending on the specificity of the antibody used.
Over the past few years, the precision and accuracy of automated immunoassays have continued to improve.1 They are proven to provide the quality results of a centralized laboratory, which uses compact, automated technology that does not require specialized expertise and yields rapid turnaround, making vitamin D immunoassays an ideal POC offering. A test result available for the patient in 12-15 minutes while he or she is still at the physician’s office – compared to hours later if a sample must be sent out for testing – saves time for both healthcare providers and patients. On-demand testing means fewer return visits are needed, facilitating better quality of service and practice productivity, as well as increased patient satisfaction. It allows clinicians to test for vitamin D deficiency and treat it, or monitor vitamin D levels and adjust supplementation levels during the same face-to-face visit.
Onsite vitamin D testing has economic advantages as well, particularly in the United States. Physician practices that provide in-house testing receive reimbursement for each test, which translates into a faster return on investment.
Experts raise several points, such as the following, which support the value point-of-care testing of vitamin D can offer clinics and physician offices:
- A) “An increasing number of people are being advised to take vitamin D supplements or even to receive higher dosages of vitamin D through therapeutic treatment to lower their risk for skeletal and nonskeletal diseases such as malignant neoplasms or cardiovascular disease…. Therefore, precise and accurate test methods are crucial to distinguish insufficient levels based on undertreatment and toxic levels based on overtreatment.”1
- B) “Considering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the [Endocrine Society] Task Force recommended supplementation at suggested daily intake and tolerable upper limit levels, depending on age and clinical circumstances. The Task Force also suggested the measurement of serum 25-hydroxyvitamin D level by a reliable assay as the initial diagnostic test in patients at risk for deficiency.”4
- C)”There is emerging evidence that calcitriol [vitamin D] plays a role in the immune system that has not yet been clearly described.” Calcitriol has also been shown to consistently inhibit the growth of cancer cells and promote cell differentiation in vitro by regulating multiple pathways. The vitamin D receptor has been documented in a wide array of cancer cell types.3
- D) “Initially thought to play a restricted role in calcium homeostatis, the pleiotropic actions of vitamin D in biology and their clinical significance are only now becoming apparent…. After calcitriol [vitamin D] stimulation, we identified 2776 genomic positions occupied by the VDR [vitamin D receptor] and 229 genes with significant changes in expression in response to vitamin D…. Notable genes with VDR binding included IRF8, associated with MS [multiple sclerosis], and PTPN2 associated with Crohn’s disease and T1D [type 1 diabetes].”2
As rapid testing continues to help bring reliable, easy-to-use analytical methods as near to the patient as possible, experts expect to see fewer and fewer patient samples sent to labs for testing.
References
- Arneson WL, Arneson DL. Current methods for routine clinical laboratory testing of vitamin D levels. Lab Med 2013;44(1):e38-e42.
- Ramagopalan SV, Heger A, Berlanga AK, et al. A ChIP-seq defined genome-wide map of vitamin D receptor binding: Associations with disease and evolution. Genome Res 2010;20:1352-1360.
Task Force of The Endocrine Society. Evaluation, Treatment, and Prevention of Vitamin D Deficiency. An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96(7):1911-1930. - Institute of Medicine. Ross AC, Taylor CL, Yaktine AL, Del Valle HB (eds). Dietary reference intakes for calcium and vitamin D. Washington, DC: The National Academies Press, 2010. Available at: http://www.nap.edu/read/13050/chapter/1 (Last accessed August 2016)
- Task Force of The Endocrine Society. Evaluation, Treatment, and Prevention of Vitamin D Deficiency. An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96(7):1911-1930.