Vitamin D Deficiency

Aka: Vitamin D Deficiency, Hypovitaminosis D

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II. Epidemiology

  1. Vitamin D Deficiency is common in U.S. (esp. in northern climates)
  2. Incidence increasing due to Sunscreen use and less Time Outdoors
  3. Age over 65 are associated worldwide with Vitamin D Deficiency in >50% of people

III. Precautions

  1. Vitamin D Testing has increased substantially increased since 2010, often for vague, unrelated symptoms
    1. Low Vitamin D levels result in a cascade of additional tests and referrals
    2. However, levels are often inaccurate, variable and with no universal defined lower limit of normal
  2. Vitamin D Replacement (esp. high dose) for asymptomatic, low Vitamin D typically offers little benefit
    1. Contrast with truly indicated replacement in severe Vitamin D Deficiency (e.g. Rickets, Osteomalacia)
  3. References
    1. Lazris (2024) Am Fam Physician 110(3): 302-4 [PubMed]

IV. Risk Factors: Infants

  1. Anticonvulsants
  2. Chronic disease with fat malabsorption
  3. Exclusively Breast-fed infant without Vitamin D Supplementation
  4. Low maternal Vitamin D levels
  5. Lack of Sun Exposure
    1. Direct sunlight avoidance is recommended by AAP for those under 6 months
    2. Darker skin pigmentation (requires 3-6 fold more Sun Exposure)

V. Risk Factors: Adults

  1. Age over 65 years
    1. Related to housebound status and decreased Vitamin D absorption
  2. Comorbid illness
  3. Malnourished
  4. Total Parenteral Nutrition
  5. Lack of Sun Exposure (or thorough sun screen use)
    1. Those with darker skin require 3-6 fold more exposure
  6. Renal disease (Renal Failure, Nephrotic Syndrome)
    1. Renal losses of Vitamin D
  7. Hepatic disease (Cirrhosis)
  8. Gastrointestinal malabsorption
    1. Gastric surgery (resection or Gastric Bypass)
    2. Crohn's Disease
    3. Cystic Fibrosis
    4. Celiac Disease
  9. Small Bowel Resection
  10. Medications
    1. Anticonvulsant use (e.g. Phenobarbital, Phenytoin)
      1. Requires 2-5 fold more Vitamin D intake daily
    2. Corticosteroids (long-term use) or other Immunosuppressants
    3. Rifampin
    4. Antiviral Medications

VI. Pathophysiology

  1. Effects of Vitamin D Deficiency
    1. Altered secretion of Parathyroid Hormone
    2. Altered mineral ion metabolism
      1. Hypocalcemia
      2. Hypophosphatemia
    3. Mineralization defects in skeleton
      1. Osteomalacia in adults
      2. Rickets in children
  2. Step-by-step outcome of Vitamin D Deficiency
    1. Malabsorption of Calcium and Phosphorus
      1. Calcium absorption drops to 10% of normal
      2. Phosphorus absorption drops to 60% of normal
    2. Inadequate intestinal Calcium absorption
      1. Results in Hypocalcemia
      2. Severe Hypocalcemia occurs in later deficiency
    3. PTH secreted to compensate for Hypocalcemia
      1. Results in secondary Hyperparathyroidism
      2. Osteoclasts dissolve bone to mobilize Calcium from bone
        1. Exacerbates Osteomalacia and Osteoporosis
    4. Increased PTH results in phosphate wasting
      1. Severe hypophophatemia results

VII. Symptoms

  1. Early
    1. Diffuse Myalgias (may be associated marked serum Creatine Phosphokinase or CPK elevations)
    2. Proximal Muscle Weakness
      1. Associated with increased Fall Risk
  2. Later
    1. Bone pain
      1. Low Back Pain (especially older women)
      2. Extremity pain
    2. Secondary Hyperparathyroidism
      1. Osteoporosis
      2. Osteomalacia
    3. Symptomatic mineral disturbance
      1. See Hypocalcemia
      2. See Hypophosphatemia
  3. Other symptoms
    1. Abdominal Pain
    2. Seizures

VIII. Signs

  1. Bone pain reproduced with pressure applied to Sternum or tibia

IX. Differential Diagnosis

  1. See Hypocalcemia
  2. See Hypophosphatemia
  3. See Hyperparathyroidism
  4. Myalgias
    1. See Polymyositis Differential Diagnosis
    2. Consider in those diagnosed with Fibromyalgia, Myositis, Malingering

X. Associated Conditions: Conditions linked to Vitamin D Deficiency

  1. Musculoskeletal Conditions
    1. Osteomalacia
    2. Osteoporosis
    3. Rickets
  2. Other associated conditions (but insufficient evidence that supplementation prevents these conditions)
    1. Fall Risk
    2. Cardiovascular Disease
    3. Colon Cancer
    4. Major Depression

XI. Labs

  1. Serum 25-Hyroxyvitamin D Level
    1. Routine screening is not recommended
    2. Vitamin D testing or supplementation is not indicated in Major Depression, Fatigue, Osteoarthritis or Chronic Pain
    3. Preferred test (but expensive)
    4. Levels <20 ng/ml suggest deficiency (<30 ng/ml per endocrine society)
  2. Ionized Serum Calcium
  3. Serum Phosphorus
  4. Serum Creatine Phosphokinase
    1. May increase significantly in Vitamin D Deficiency with myalgias
  5. Consider testing for Vitamin D Deficiency mimics in Differential Diagnosis
    1. Thyroid Stimulating Factor
    2. Rheumatoid Factor
    3. Serum Vitamin B12

XII. Management

  1. Treat Hypocalcemia
    1. Symptomatic Hypocalcemia or Ionized Calcium <3.2 mg/dl
  2. Treat Hypophosphatemia
  3. Vitamin D Replacement
    1. See Vitamin D Replacement
  4. Vitamin D maintenance
    1. Guidelines do not recommend routine Vitamin D screening (outside Hypercalcemia, Renal Insufficiency)
    2. Maintain Vitamin D at least above 20 ng/ml (and >29 ng/ml per endocrine society)
    3. See Vitamin D for maintainance doses

XIII. Prevention

  1. Adequate dosing depends on latitude
    1. In northern climates 1000-2000 IU daily may be more appropriate
    2. Higher doses may be required in those with risk factors above

XIV. References

  1. Rendon et al. (2017) Crit Dec Emerg Med 31(6): 15-21
  2. Bordelon (2009) Am Fam Physician 80(8): 841-6 [PubMed]
  3. Holick (2007) N Engl J Med. 357(3):266-81 [PubMed]
  4. Holick (2008) Am J Clin Nutr 87:1080S-1086S [PubMed]
  5. LeFevre (2018) Am Fam Physician 97(4): 254-60 [PubMed]

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