Vitamin D Deficiency: Family Medicine Review 2012

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1 Vitamin D Deficiency: Family Medicine Review 2012 Don Chaffer, MD Program Director Nephrology Fellowship Division of Nephrology and Hypertension Scott and White Clinic Texas A&M University Health Science Center

2 Vitamin D Deficiency Risk Factors Ins5tu5onalized Dark skin pigment Limited sun exposure Obesity Being evaluated for osteoporosis Medica5ons e.g. Phenytoin accellerates metabolism of vitamin D Pregnant women Malabsorp5on

3 The evil that men do lives aoer them; the good is oo interred with their bones William Shakespeare Same As It Ever Was Russell Sunabe

4 UVB nm 35⁰ N Equator 35⁰ S

5 Skin UVB nm 7- dehydrocholesterol Cholecalciferol Vitamin D 3 Dietary Sources Ergocalciferol Vitamin D 2 Liver 25- hydroxylase Cholecalciferol Vitamin D 3 Calcidiol 25 OH- Vitamin D 3 Kidney 1 - hydroxylase Calcitriol 1-25 OH- Vitamin D 3 (+) PTH, phosphate (- ) FGF 23, phosphate plasma Ca plasma PO 4

6 Terms Used in Reference to Vitamin D Vitamin D Vitamin D 2 Vitamin D 3 also referred to as calciferol also referred to as ergocalciferol also referred to as cholecalciferol Supplementa5on/ Replacement 25OHD also referred to as calcidiol or calcifediol no dis5nc5on between D 2 (25OHD2) and D 3 (25OHD3) Laboratory/ Replacement in advanced liver disease 1,25- dihydroxyvitamin D 3 also referred to as calcitriol 1,25- dihydroxyvitamin D 2 (ercalcitriol) is most ooen also referred to as calcitriol There is no evidence to support the rou5ne tes5ng of ac5ve Vitamin D for replacement or supplementa5on purposes

7 IU = Interna5onal Unit Another Source of Terminology Confusion Measurement based on biological ac5vity or effect For dietary sources of cholecalciferol (vitamin D 3 ): 1 IU is defined = ac5vity of μg of cholecalciferol in animal model bioassays 40 IU of vitamin D 3 = 1 μg RDA for most age groups aoer 12 months of age is 600 IU

8 Prepara5ons Cholecalciferol (D 3 ) Forms: 400/800/1000/2000/5000/10,000/50,000 unit capsules Ergocalciferol (D 2 ) Forms: 400 and 50,000 unit capsules Calcidiol (25OHD) Forms: 20 and 50 mcg capsules Useful in senng of advanced liver disease, does not require 25 hydroxyla5on Total 25OHD < 20 ng/ml (50 nmol/l) should be replaced (1A) D 2 or D 3 50,000 IU capsule q weekly x 6-8 weeks Follow with maintenance dose IU once daily Endocrine Society Clinical Prac5ce Guidelines: Maintenance: IU to maintain serum 25OHD 30 ng/ml (75 nmol/l) In advance liver disease: calcidiol mcg once daily

9 Food Sources of Vitamin D Naturally occurring faqy fish fish liver oil egg yolk mushrooms For5fica5on Milk: 400 IU per quart (form not specified) Infant formula: IU per 100 kcal

10 440 IU The Journal of Nutri5on. First published ahead of print April 18, 2012

11 1 tablespoon of cod liver oil contains ~1360 IU vitamin D 3 (and 13,000 IU vitamin A)

12 Infant Vitamin D Deficiency and Rickets Risk Factors: Exclusively breast fed AAP recommenda5on 400 IU beginning first few days of life con5nuing un5l weaned and taking at least 1L or 1 quart of for5fied milk or formula Northern la5tudes Typically symptoma5c by 20 months of age Vitamin D replacement cura5ve only if treated early before growth plates begin to close

13 Consensus Report: Dietary Reference Intakes for Calcium and Vitamin D. Inst. Of Med. Nov

14 Other Ac5ons of Vitamin D Vitamin D Receptor (VDR) present in many 5ssues: Epidermal kera5nocytes Ac5vated T cells An5gen presen5ng cells Macrophages Monocytes Cytotoxic T cells Vitamin D regulates transcrip5on in up to 5% of human genome The role of Vitamin D in the preven5on of remains unclear: Peripheral insulin resistance Development of autoimmune disorders Cancer risk Cardiovascular disease Fall risk

15 Ins5tute of Medicine Consensus Report: Dietary Reference Intakes for Calcium and Vitamin D Ins5tute of Medicine Recommenda5ons: Daily and weekly dosing have similar efficacy. Monthly or annual replacement dosing regimens may be associated with adverse events Suppor5ve of 25OHD (total) 20 ng/ml (50 nmol/l) Safety concerns surrounding 25OHD levels > 50 ng/ml (125 nmol/l) Possible increased fracture risk Some studies have suggested increased risk of prostate and pancrea5c cancer Upper limit of daily dosing: 4,000 IU

16 Lancet 2005; 365: N=5292 mobile pa;ents >70 years of age follow- up 60 months

17

18 Support the Ca 2+ Worry About the PO 4 1 Kidney 1 - hydroxylase Calcitriol 1-25 OH- Vitamin D 3 FGF- 23 urine PO 4 1. Intes5nal absorp5on of Ca and PO 4 2. PTH dependent bone resorp5on 3. PTH dependent renal tubular Ca reabsorp5on plasma Ca plasma PO 4

19 Nephrolithiasis Risk Significant increase at serum 25OHD levels > 88 ng/ml Calcium oxalate and calcium phosphate, 37% Calcium Oxalate, 26% Calcium Phosphate, 7% CysHne, 2% Struvite, 22% Uric Acid, 5%

20 QuesEons? Jung CG, The Red Book

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