Vitamin D Deficiency in Adults

Background

• Vitamin D deficiency, caused by low levels of vitamin D in the blood, can cause abnormalities in calcium, phosphorus, and bone metabolism.
• There is no consensus cutoff for vitamin D deficiency, but generally considered as a serum 25-hydroxyvitamin D (25[OH]D) < 20 ng/mL (50 nmol/L).
• Serum 25(OH)D levels ≥ 20-30 ng/mL (50-75 nmol/L) generally considered normal.
• Types of vitamin D:
  • vitamin D2 (ergocalciferol) - present in some foods and dietary supplements
  • vitamin D3 (cholecalciferol) - formed in skin exposed to ultraviolet light and present in some foods and dietary supplements
  • 25-hydroxyvitamin D (25[OH]D, calcidiol) - major circulating form of vitamin D, created through hepatic metabolism of vitamin D2 and D3
  • 1,25 dihydroxyvitamin D (1,25-[OH]₂D3, calcitriol) - biologically active form of vitamin D (it promotes intestinal calcium and phosphate absorption, calcium homeostasis, and skeleton mineralization), created through renal metabolism of 25(OH)D
• Most vitamin D deficiency in adults is asymptomatic, but severe vitamin D deficiency may be associated with musculoskeletal symptoms such as pain or weakness. Untreated vitamin D deficiency can lead to complications such as osteomalacia, and secondary hyperparathyroidism.
• Common causes of vitamin D deficiency include decreased synthesis in the skin (for example, due to dark skin pigmentation, aging, or lack of sunlight exposure), inadequate dietary intake, impaired gastrointestinal absorption, nephrotic syndrome, medications, and impaired hepatic metabolism.

Evaluation

• Population-based screening for vitamin D deficiency is not recommended (Strong recommendation), but testing is recommended in patients at risk for vitamin D deficiency, such as patients with conditions including hypocalcemia, chronic kidney disease, osteoporosis, primary hyperparathyroidism, secondary hyperparathyroidism, granulomatous disorders, obesity or a malabsorption syndrome (Strong recommendation).
• Serum 25-hydroxyvitamin D (25[OH]D) measurement:
  • Measure serum 25(OH)D levels using a reliable assay to evaluate vitamin D status (Strong recommendation).
  • 1,25 dihydroxyvitamin (1,25[OH]₂ D3) levels may not accurately reflect total body stores.
• Perform thorough history and physical, including tests to identify underlying causes such as liver disease and conditions that lead to impaired gastrointestinal absorption such as celiac disease.
• Consider testing for effects of vitamin D deficiency which may include:
  • blood tests for parathyroid hormone, calcium, phosphorus, and alkaline phosphatase levels
  • imaging if clinically indicated

Management

• Consider vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol) for treatment of vitamin D deficiency (Weak recommendation).
• The treatment dose recommendation depends on the severity of vitamin D deficiency.
  • Consider an initial dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) 50,000 units orally (1,250 mcg) every 1-4 weeks or 3,000-6,000 units/day orally (75-150 mcg/day) for 6-12 weeks to achieve a 25-hydroxyvitamin D level > 30 ng/mL (75 nmol/L) (Weak recommendation).
  • Consider maintenance dosing of cholecalciferol 1,000-2,000 units/day orally (25-50 mcg/day (Weak recommendation).
  • Consider higher doses for patients who are obese, have a malabsorption syndrome, or are taking medications affecting vitamin D metabolism (antiseizure medications, glucocorticoids, antifungals, HIV medications) (Weak recommendation) if hypocalcemia present.
• Consider ultraviolet irradiation in institutionalized elderly patients with vitamin D deficiency.
• Consider alternative vitamin D formulations for vitamin D deficiency in special populations, including:
  • calcitriol (1,25-dihydroxycholecalciferol analog) orally or IV in patients with chronic renal failure, nephrotic syndrome, or severe malabsorption syndromes
  • calcifediol (calcidiol) in patients with severe liver disease or impaired hepatic metabolism due to drugs
  • intramuscular vitamin D in patients with malabsorption
• Monitoring treatment:
  • Consider checking serum 25-hydroxyvitamin D level 10-12 weeks after starting replacement therapy, and reassessing treatment if level is < 30 ng/mL (75 nmol/L).
  • Consider monitoring for possible toxicities associated with excessive serum vitamin D (> 100 ng/mL [250 nmol/L]) such as hypercalciuria, hypercalcemia, hyperphosphatemia, and possible increased risk of falls.