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 secondary hyperparathyroidism (with skeletal complications)

o osteomalacia (inadequate osteoid mineralization at sites of bone modelling
and remodelling)
o osteoporosis
o possibly hip fracture
o 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
 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 vitamin D 3,000-5,000 units (75-125 mcg) daily for minimum 6-12 weeks
usually adequate for initial therapy
o maintenance therapy (for example, 1,000 units daily [25 mcg]) once serum
25-hydroxyvitamin D3 levels return to reference range
o 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