Vitamin D Deficiency

Vitamin D Deficiency Synthesis and Metabolism: Prevalence: 1 billion people worldwide >40 % of U.S. and European elderly men and women > 50% of postmenopausal women taking medication for osteoporosis 25 hydroxyvitamin D < 10 ng/mL levels comparing 1988-1994 vs. 2001-2004 : 2% vs. 6% overall ; 9 % vs. 29% for non-Hispanic black Risk factors • • • • • • •

decreased skin synthesis (lack of sunlight) inadequate dietary or supplemental intake impaired gastrointestinal absorption impaired hepatic 25-hydroxylation impaired renal 1-alpha-hydroxylation of 25-hydroxyvitamin D3 rarely loss of vitamin D-binding protein defective target-organ response - vitamin D-dependent rickets, type 2 (abnormal vitamin D receptor)

Metabolic functions of vitamin D : intestinal calcium and phosphate absorption, bone calcification, stimulates PTH-mediated renal tubular reabsorption of calcium, vitamin D deficiency leads to deficient calcification of osteoid matrix which leads to rickets in children, osteomalacia in adults Possible extraskeletal functions under investigation - Role in immune function and cancer prevention, vascular, tissue repair etc Complications o o o o o

secondary hyperparathyroidism (with skeletal complications) osteomalacia (inadequate osteoid mineralization at sites of bone modelling and remodelling) osteoporosis possibly hip fracture Proximal myopathy

Associated conditions: • • •

low serum 25-hydroxyvitamin D levels associated with increased all-cause mortality in general population preliminary evidence suggestive of association with autoimmune disorders (e.g. rheumatoid arthritis, inflammatory bowel disease), MS low serum 25-hydroxyvitamin D levels associated with increased risk of colorectal cancer in meta-analysis of 5 observational studies (A 50% lower risk of

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associated with a serum 25(OH)D level > or =33 ng/mL, compared to < or =12 ng/mL) depression associated with decreased 25-hydroxyvitamin D levels in elderly

Diagnosis • • • •

25-hydroxyvitamin D3 levels renal function tests - BUN, creatinine Serum calcium, phosphate, and alkaline phosphatase not reliable predictors of hypovitaminosis D 1,25-dihydroxyvitamin D3 (the biologically active form) not recommended to diagnose deficiency, not a good measure of vitamin D storage

Treatment o o o

vitamin D 3,000-5,000 units (75-125 mcg) daily for minimum 6-12 weeks usually adequate for initial therapy maintenance therapy (for example, 1,000 units daily [25 mcg]) once serum 25-hydroxyvitamin D3 levels return to reference range high-dose therapy (ergocalciferol 50,000 units orally) once or twice weekly for 6-8 weeks is an alternative

Sunlight exposure Monitor PTH, calcium, and 25-hydroxyvitamin D3 levels if serum calcium and PTH levels abnormal (e.g. in moderate to severe deficiencies), starting 6-8 weeks after initiating therapy