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Vitamin D Testing Methodologies: Assessment Issues and Therapeutic Management

Vitamin D Testing Methodologies: Assessment Issues and Therapeutic Management. Jimmy L. Boyd, Asst. Professor MLT Program Director Arkansas State University – Beebe. Learning Objectives. To provide an overview of the pathophysiology of Vitamin D metabolism

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Vitamin D Testing Methodologies: Assessment Issues and Therapeutic Management

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  1. Vitamin D Testing Methodologies: Assessment Issues and Therapeutic Management Jimmy L. Boyd, Asst. Professor MLT Program Director Arkansas State University – Beebe

  2. Learning Objectives • To provide an overview of the pathophysiology of Vitamin D metabolism • To differentiate the various available assay measures • To assess the serum/blood biomarkers associated with Vitamin D • To list various pros and cons to Vitamin D supplementation

  3. Reasoning & rationale A. Pandemic or Epidemic? B. Prohormone or Vitamin? C. Deficiency versus Insufficiency? D. “Gold Standard” Laboratory method?

  4. What is Vitamin D? Fat soluble, steroidal pro-hormone that is synthesized by the body as a precursor compound, which must be acted upon by UV-B rays (290 – 315 nm). Regulation: Ca+2 and P-3 Metabolism: D2 , D3 , and DTotal

  5. Vitamin D – Epidemiology No longer restricted to the disease: Rickets (Types) Post-menopausal women on HRT Elderly men and women (poor diets) Problematic and extensive world-wide Evolutionary/Historical Context

  6. Types of Rickets

  7. Synthesis of Vitamin D

  8. Vitamin D Risk Factors Lack of physical activity and adequate sun exposure, Dark skin pigmentation Excessive use of sunscreen lotions Lack of Dietary intake/inappropriate supplementation Obesity Bariatric Surgery and associated Fat-malabsorption, including Celiac, Crohns, CF, and GERD, and Sprue

  9. Medication-Related Risk Factors Vitamin-D Antagonists Antieptileptic Rx Corticosteroids Immunosuppressants HIV anti-retrovirals Co-Morbid Illnesses Renal Failure (ALL) Primary Hyper-PTH Liver Failure

  10. Biological Functions of Vitamin D Bone Homeostasis Bone Salts Intestinal Increased absorption Kidneys Inhibits loss of Ca+2

  11. Cancer Mechanisms MODALITY A. Cell Cycle Kinetics B. Immunomodulatory C. Oxidative Stress D. Inflammation E. Hormonal F. Other

  12. Mechanistic roles of action Modulates cell proliferation, differentiation, and apoptosis; regulation of steroid receptor genes; growth factor signaling, cell adhesion, Angiogenesis, DNA report Activity of NK cells and phagocyticfxn of macrophages; alpha-TNF in deficiency Oxidative DNA damage, CRP levels with supplements; COX-2 enzymes with supplements, expression of Aromatase Estrogen Receptor

  13. Vitamin D Receptor (VDR) VDR is expressed in all major body tissues, e.g., Adipose, Brain, Intestines, Lymphocytes, Muscles Adrenal Bone Breast Cartilage Colon Liver Lung Kidney Parotid, Pituitary, Placenta, Testes, and Stomach

  14. VDR Mediates Vitamin D Actions • Nuclear Hormone Receptor • Located in numerous body sites • Binds the active form of the hormone, leads to the formation of a heterodimer with retinoid-X receptor – facilitates binding to VDRE • Decrease/Increase gene regulation • Modulate signal transduction pathways • Differential effects based on the variations in the VDR activity

  15. Related Definitions Vitamin D Deficiency – serum D (total) is < 20 ng/mL Vitamin D Insufficiency – serum D (total) is 20 – 30 ng/mL Vitamin D Sufficiency – serum D (total) is 30 – 100 ng/mL Vitamin D Toxicity – serum D (total) is > 100 ng/mL D(Total) = serum levels of 25-hydroxyvitamin D

  16. Recommended IOM Guidelines Infants, Children, Adolescents, and Adults: Ages < 51 years – 200 IU/day Middle Age Adults: ages, 51 to 70 years – 400 IU/day Elder Adulthood: > 70 years – 600 IU/day with Calcium supplement (keep in mind the ½ life of Vit. D – 14 to 20 days)

  17. Laboratory Testing Methodologies Increased Testing Volumes 2006 – 19,000 2008 – 61,000 2010 – 120,000 2012 – 160,000 Random Reference Ranges D2 – Ergocalciferol, D3 – Cholecalciferol D (total) – Calcitriol (25-OH Vitamin-D) Analytical Challenges LC/MS ImmunoAssayChemiluminescence

  18. Related Analytical Studies Randomized Controlled Trials: Biscoff-Ferrari, Willett, Wong, et. al., 2005 (JAMA) DEQAS NIST SRM JCTLM Steerman & Svec (2009) Military Medicine Orelind, Feinglass, et al., (2012) South. Med. J. Zee, Fudge, Whiting, et al., (2012) Assn. Clin. Bioch. Carter, G. (2011) Accuracy of 25-OH Vit. D., Current Drug Targets

  19. Recommendations & Conclusions More physician-informed assay actions Re-assessment of insidious disease processes Balance of Safety, Efficacy, and Toxicity Need for International Standardization

  20. CONCLUSIONS Questions???? Answers!!! Thanks for your time…

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