Vitamin D deficiency

Background

• AKA: Hypovitaminosis D
• Vitamin D
  • Lipid soluble
  • Acts as a hormone which:
    • Stimulates intestinal calcium absorption
    • Maintains adequate phosphate levels for bone development
    • Regulates cell growth proliferation and apoptosis
    • Modulates immune function and inflammation reduction
• Deficiency leads to impaired bone mineralization and disease such as:
  • Rickets in children
  • Osteomalacia and Osteoporosis in adults

Metabolism and Physiology of Vitamin D

• Vitamin D gained from diet, supplements, or sunlight exposure
• Vitamin D undergoes hydroxylation in the liver producing 25-hydroxyvitamin D
• A second hydroxylation occurs in the kidney producing 1,25-dihydroxyvitamin D which is the active form of vitamin D
  • This step can occur extrarenally
  • Regulated by PTH, serum calcium, and phosphorus levels

Etiology of Vitamin D Deficiency

• Inadequate intake
  • Dietary sources such as fortified foods and supplements are the mainstay of vitamin D intake
  • Foods rich in vitamin D include fatty fish, egg yolks, fish liver oil, and some mushrooms
• Inadequate sunlight exposure
  • Synthesis of vitamin D occurs in the skin through exposure to ultraviolet B radiation from sunlight
  • Factors associated with vitamin D deficiency include darker skin pigmentation, prolonged winter season, and skin coverage
• Disorders limiting vitamin D absorption
  • Crohn's disease
  • Cystic fibrosis
• Conditions preventing vitamin D conversion into active metabolites
  • Renal Failure
  • Liver failure

Clinical Features

• Bone pain and muscle weakness
• Brittle bones
  • Rickets in children
    • Soft bones, skeletal deformities
    • Craniotabe: abnormal softening or thinning of the skull
  • Osteomalacia and Osteoporosis in adults leading to increased risk of fractures
• Associated with advancement of cancers
  • Breast, colon, ovarian, and prostate

Differential Diagnosis

• Hypocalcemia
• Hyperparathyroidism
• Hypophosphatemia
• Malignancy

Evaluation

• Diagnosed by measuring the concentration of 25-hydroxyvitamin D
  • This is the pre hormone, calcidiol, which is a precursor to the active form 1,25-dihydroxyvitamin D
• Insufficient vitamin D defined as a 25-hydroxyvitamin level 25-75 nmol/L (normal range 75-250 nmol/L)
• Vitamin D deficiency defined as a 25-hydroxyvitamin level <20-25 nmol/L
• Screening adults not at risk and without symptoms not recommended

Management

• Supplemental vitamin D
  • Initial high-dosage treatment phase
    • 1,000 IU cholecalciferol per 10 nmol/L required serum increase given daily for 2-3 months
  • Followed by maintenance dosage
    • 400 IU daily for all age groups
    • Double dosage for premature infants, dark pigmented infants/children, children with limited sun exposure, and obese patients
  • Special populations may require higher dosing (i.e. parathyroid disease, chronic liver disease, renal failure, and malabsorption disorders

See Also

• Rickets
• Hypocalcemia
• Hypophosphatemia

References

• 1. <Health Quality Ontario. Clinical utility of vitamin d testing: an evidence-based analysis. Ont Health Technol Assess Ser. 2010;10(2): 1–93.>
• 2. <Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad H, and Weaver CM. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline. "J Clin Endocrinol Metab". Jul 2011; 96(7): 1911–1930.>