BASICS
- Vitamin D is a fat-soluble vitamin and hormone essential for calcium homeostasis and bone metabolism.
- Synthesized in skin (vitamin D3) via UVB exposure; vitamin D2 obtained from diet/supplements.
- Metabolized in liver to 25-hydroxyvitamin D (calcidiol), then in kidney to active 1,25-dihydroxyvitamin D (calcitriol).
- Active vitamin D increases intestinal calcium and phosphorus absorption, reduces renal excretion, and stimulates bone resorption.
EPIDEMIOLOGY
- Prevalence varies geographically, higher in northern latitudes and during winter months.
- Risk groups include infants, children, adolescents, elderly, individuals with dark skin pigmentation, cultural clothing coverage, obesity, and chronic diseases.
- Pediatric vitamin D deficiency is common; many children fail to meet recommended levels.
ETIOLOGY AND PATHOPHYSIOLOGY
- Causes: insufficient sunlight, low dietary intake (fatty fish, fortified foods), malabsorption (celiac, Crohn’s, liver disease).
- Obesity sequesters vitamin D in fat, reducing bioavailability.
- Medications affecting metabolism: anticonvulsants, glucocorticoids, weight-loss drugs.
- Chronic kidney disease impairs conversion to active form.
- Genetic disorders: Vitamin D-dependent rickets type I (1α-hydroxylase mutation).
- Increased vitamin D breakdown in liver disease and alcoholism.
RISK FACTORS
- Limited sun exposure due to lifestyle or cultural practices.
- Dark skin pigmentation.
- Obesity.
- Malabsorption syndromes.
- Certain medications.
- Pregnancy and lactation increasing vitamin D demand.
PREVENTION
- Adequate sun exposure and dietary intake.
- Recommended daily allowance (RDA):
- Infants (0-12 months): 400-1000 IU/day
- Children/adolescents (1-18 years): 600-1000 IU/day
- Adults (19-70 years): 600-800 IU/day
- Older adults (>71 years): 800-1000 IU/day
- Pregnant/lactating women: 600-800 IU/day
- AAP recommends 400 IU/day vitamin D for all breastfed infants starting within first days of life.
COMMONLY ASSOCIATED CONDITIONS
- Rickets and osteomalacia.
- Premenstrual syndrome.
- Osteoporosis.
- Chronic renal disease.
- Hypertension.
- Increased risk of myocardial infarction and all-cause mortality with deficiency.
DIAGNOSIS
History
- Assess risk factors: limited sun, dark skin, malabsorption, chronic illness.
- Symptoms: muscle weakness, bone pain, fractures, tetany, seizures.
- Consider demographic risk: elderly, pregnant, housebound.
Physical Exam
- Muscle weakness, gait abnormalities.
- Signs of hypocalcemia: Chvostek sign, Trousseau phenomenon.
- Bone deformities (in children): bowed legs.
Tests
- 25-hydroxyvitamin D (25-OH vitamin D) level: most sensitive test.
- Deficiency defined as <20 ng/mL (IOM), some guidelines suggest <30 ng/mL.
- Parathyroid hormone (PTH): elevated in secondary hyperparathyroidism.
- Serum calcium, phosphorus (low/normal), alkaline phosphatase (elevated in osteomalacia).
- Radiographs may show pseudofractures or Looser zones in osteomalacia.
TREATMENT
- Vitamin D supplementation:
- Adults: 800 to 2000 IU/day vitamin D2 or D3.
- For deficiency: 50,000 IU weekly for 8-12 weeks followed by maintenance dosing.
- Calcium intake via diet preferred; supplementation if dietary intake inadequate.
- Monitor levels and clinical response.
- Treat underlying causes such as malabsorption.
PEDIATRIC AND PREGNANCY CONSIDERATIONS
- Breastfed infants require supplementation (400 IU/day).
- Pregnancy safe supplementation up to 1000-2000 IU/day.
- Maternal deficiency affects neonatal stores.
ONGOING CARE
- Monitor clinical symptoms and vitamin D levels as indicated.
- Encourage lifestyle modifications for sun exposure and diet.
- Avoid excessive supplementation to prevent toxicity.
PROGNOSIS
- Vitamin D repletion improves symptoms and biochemical abnormalities.
- Adequate levels linked to decreased fracture risk, cardiovascular events, and mortality.
- Ongoing deficiency leads to bone deformities, fractures, and muscle weakness.
COMPLICATIONS
- Hypocalcemic tetany, seizures.
- Bone deformities and fractures.
- Vitamin D toxicity with hypercalcemia if overdosed.
REFERENCES
- Bjelakovic G, Gluud LL, Nikolova D, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 2011;(7):CD007470.
- Zhang Y, Fang F, Tang J, et al. Association between vitamin D supplementation and mortality: systematic review and meta-analysis. BMJ. 2019;366:l4673.
- LeBoff MS, Chou SH, Murata EM, et al. Supplemental vitamin D and incident fractures in midlife and older adults. N Engl J Med. 2022;387(4):299-309.
ICD10
- E55 Vitamin D deficiency
- E55.0 Rickets, active
- E55.9 Vitamin D deficiency, unspecified
Clinical Pearls
- 25-OH vitamin D is the preferred test for vitamin D status.
- Vitamin D deficiency is common in dark-skinned, obese, and housebound individuals.
- Supplementation up to 2000 IU/day is generally safe in adults.
- All breastfed infants should receive 400 IU/day vitamin D starting within days of birth.