Vitamin D deficiency

Background

• AKA: Hypovitaminosis D
• Vitamin D deficiency leads to impaired bone mineralization and diseases such as:
  • Rickets in children
  • Osteomalacia and Osteoporosis in adults

Metabolism and Physiology of Vitamin D

• Gained from diet, supplements, or sunlight exposure
  • Fortified foods (mainstay), supplements, fatty fish, egg yolks, fish liver oil, and some mushrooms
  • Synthesis of vitamin D occurs in the skin through exposure to ultraviolet B radiation from sunlight
• Hydroxylated in liver→ 25-hydroxyvitamin D, which is further hydroxylated in kidney or extrarenally→ 1,25-dihydroxyvitamin D (active form)
  • Second hydroxylation regulated by PTH, serum calcium, and phosphorus levels
• Vitamin D acts to:
  • Stimulate intestinal calcium absorption
  • Maintain adequate phosphate levels for bone development
  • Regulate cell growth proliferation and apoptosis
  • Modulate immune function and inflammation reduction

Etiology of Vitamin D Deficiency

• Inadequate dietary intake, inadequate sunlight exposure
• Impaired vitamin D absorption
  • Crohn's disease, cystic fibrosis
• Impairment in conversion of vitamin D into active metabolites
  • Renal Failure, Liver failure

Clinical Features

• Bone pain
• 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, particularly of breast, colon, ovarian, and prostate

Differential Diagnosis

• Hypocalcemia
• Hyperparathyroidism
• Hypophosphatemia
• Malignancy
• Nonaccidental trauma

Evaluation

• Assess for fractures, if indicated
• BMP, Mg/Phos, serum calcium
• Vitamin D assessed by measuring serum concentration of 25-hydroxyvitamin D (precursor to hormonally active 1,25-dihydroxyvitamin D)
  • Normal range: 75-250 nmol/L
  • Insufficiency: 25-75 nmol/L
  • Deficiency: <25 nmol/L
  • Screening adults not at risk and without symptoms not recommended

Management

• Treat complications (e.g. fractures, pain)
• 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
  • Maintenance: 400 IU daily
    • Double dosage for premature infants, infants/children with dark pigmentation, children with limited sun exposure, and obese patients
  • Some 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.>