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Vitamin D Deficiency

para>NHANES data found 70% of children did not have sufficient 25-OH vitamin D serum levels (9% deficient and 61% insufficient), which was associated with an increase in BP and decrease in high-density lipoprotein (HDL) cholesterol. ‚

ETIOLOGY AND PATHOPHYSIOLOGY

  • Insufficient dietary intake of vitamin D and/or lack of UV-B exposure (in sunlight) results in low levels of vitamin D.This limits calcium absorption, causing excess PTH to be released.
  • PTH stimulates osteoclast activity, which helps to normalize calcium and phosphorous, but results in osteomalacia.
  • Dietary deficiencyInadequate vitamin D intake
  • Inadequate sunlight exposureInstitutionalized/hospitalized patients
  • Chronic illness: liver/kidney disease
  • Malabsorptive states

Genetics

Vitamin D " “dependant rickets type 1 occurs due to inactivating mutation of the 1 alpha hydroxylase gene; as a result, calcidiol is autosomal recessive not hydroxylated to calcitriol. ‚

RISK FACTORS

  • Inadequate sun exposure
  • Female
  • Dark skin
  • Immigrant populations
  • Low socioeconomic status
  • Latitudes higher than 38 degrees
  • Elderly
  • Institutionalized
  • Depression
  • Medications (phenobarbital, phenytoin)
  • Gastric bypass surgery
  • Obesity

GENERAL PREVENTION

  • Adequate exposure to sunlight and dietary sources of vitamin D (plants, fish); many foods are fortified with vitamin D2 and D3.
  • Recommended minimum daily requirement from the 2010 Institute of Medicine Report is minimally 600 IU/day for those 1 to 70 years of age and 800 IU/day for those >70 years of age. Up to 4,000 IU/day is safe in healthy adults without risk of toxicity.
  • Higher intake of vitamin D recommended for age >50 years
  • 2005 and 2009: Meta-analysis demonstrated for ages 51 to 70 years, minimally recommended supplementation is 800 IU/day to prevent nonvertebral fractures.

Pediatric Considerations

The American Academy of Pediatrics recommends all breast-fed babies receive 400 IU/day of vitamin D beginning "within the first few days of life. " ¯

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Pregnancy Considerations

ACOG recommends data insufficient to screen all pregnancies; only those "at risk " ¯ and states it is safe to take 1,000 to 2,000 IU/day during pregnancy (1)[B].

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Geriatric Considerations

U.S. Preventive Services Task Force recommends seniors take at least 800 IU/day vitamin D to reduce risk of falls in community-dwelling older adults (2)[A].

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COMMONLY ASSOCIATED CONDITIONS

  • Osteomalacia, osteoporosis
  • Premenstrual syndrome
  • Rickets
  • Celiac disease
  • Gastric bypass
  • Chronic renal disease
  • Bacterial vaginosis in pregnant women
  • Hypertension

ALERT

VDD is associated with risk of myocardial infarction (MI) and all-cause mortality (3)[A].

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DIAGNOSIS

  • Nonspecific musculoskeletal complaints
  • Weak antigravity muscles
  • Fracture with minimal trauma

HISTORY

  • Senior citizens at risk of falling
  • Renal disease
  • GI (malabsorption) disorders
  • Liver dysfunction
  • Immigration from tropical to colder climates
  • Dark-skinned/veiled individuals
  • Housebound patients
  • Women at perimenopause

PHYSICAL EXAM

  • Vague neurologic signs: numbness, proximal myopathy, paresthesias, muscle cramps, laryngospasm
  • Chvostek sign: contraction of the facial muscles by tapping along the facial nerve
  • Trousseau phenomenon: carpal spasms and paraesthesia produced by pressure on nerves and vessels of the upper arm, by inflation of a BP cuff
  • Tetany, seizures

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

  • 25-OH vitamin D (most sensitive measure of vitamin D status)
  • Vitamin D deficiency
  • PTH elevation: not routinely obtained unless severe deficiency
  • Low-normal/low calcium and phosphorous
  • Elevated alkaline phosphatase (in later disease)
  • Plain radiographs: If atypical fracture, radiographs may show osteomalacia (pseudofractures/looser zones) in pelvis, femur, and fibula.
  • Osteoporosis screenWomen ≥65 years with no risk factorsWomen ≥60 years at risk: body weight <70 kg (best predictor)Less evidence: smoking, low body mass index, family history, decreased activity, alcohol or caffeine useAfrican American women have higher bone density than Caucasians.

TREATMENT

  • Treatment goals remain unclear, but current "normal " ¯ 25-OH vitamin D levels are based on suppression of PTH.
  • Obesity: Treatment of VDD in obesity, especially those who are obese and depressed, improves depressive symptoms and may improve weight loss (4)[B].

ALERT

All-cause mortality: Cochrane Systematic Review found vitamin D supplementation lowers all-cause mortality (5)[A].

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Geriatric Considerations

In senior citizens, serum 25-OH vitamin D of 20 ng/mL resulted in improved physical performance scores; recent data suggests supplementation may not improve fracture risk and remains unclear about a true benefit.

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MEDICATION

  • Vitamin D sufficient (25-OH vitamin D ≥20 ng/mL)Vitamin D 800 to 4,000 IU/day D2/D3 (6)[A]D3 (animal derived) may be slightly more effective than D2 (plant derived), but clinical significance is uncertain.Calcium supplementation: Unclear benefit and may increase some CHD risk in patients. No supplementation currently required (see below).
  • Vitamin D deficiency (25-OH vitamin D <20 ng/mL)D2 50,000 IU/week for 8 to 12 weeks, followed by 800 to 2,000 IU/day of vitamin D3 (6)[A]
  • Calcium: meta-analysis data supportDietary intake of ~700 mg/day leads to best outcomes; higher doses did NOT decrease risk of osteoporotic fractures.Dietary calcium may be more beneficial than calcium supplementation.Supplementary calcium associated with an increased risk of MI, especially in women (7)[A], but this data remains controversial (8)[C].

ISSUES FOR REFERRAL

Endocrinology if no response to treatment ‚

ADDITIONAL THERAPIES

Aggressive calcium in ICU patients with ionized calcium <3.2 mg/dL or if symptomatic (tetany, seizures, QT prolongation, bradycardia, or hypotension, or ventilated patient with decreased diaphragmatic function) ‚

INPATIENT CONSIDERATIONS

Admission Criteria/Initial Stabilization

  • Symptoms of severe hypocalcemia or
  • Malabsorption syndromes

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Follow-up of abnormal 25-OH vitamin D not required ‚

DIET

  • Cod liver oil is most potent source of vitamin D and has ~1,300 IU vitamin D/tablet/tablespoon.
  • Fatty fish (tuna, salmon)
  • Fortified milk (100 IU/8 oz), cereal, and foods

PROGNOSIS

  • Systematic review of 63 observational studies found adequate 25-OH vitamin D levels correlate with lower rates of colon, breast, and prostate cancer.
  • Cohort study found that vitamin D deficiency is correlated with increased risk of all-cause mortality.

ALERT

Meta-analysis data support supplementation of >500 IU/day lowered the risk of all-cause mortality (5,9)[A] but remains controversial.

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REFERENCES

11 ACOG Committee on Obstetric Practice. ACOG Committee Opinion no. 495: vitamin D: screening and supplementation during pregnancy. Obstet Gynecol. 2011;118(1):197 " “198.22 Moyer ‚ VA; U.S. Preventive Services Task Force. Prevention of falls in community-dwelling older adults: U.S. Preventive Task Force recommendation statement. Ann Intern Med. 2012;157(3):197 " “204.33 Correia ‚ LC, Sodre ‚ F, Garcia ‚ G, et al. Relationship of severe deficiency of vitamin D to cardiovascular mortality during acute coronary syndromes. Am J Cardiol. 2013;111(3):324 " “327.44 Vimaleswaran ‚ KS, Berry ‚ DJ, Lu ‚ C, et al. Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Med. 2013;10(2):e1001383.55 Bjelakovic ‚ G, Gluud ‚ LL, Nikolova ‚ D, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 2011;(7):CD007470.66 Holick ‚ MF, Binkley ‚ NC, Bischoff-Ferrari ‚ HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911 " “1930.77 Bolland ‚ MJ, Avenell ‚ A, Baron ‚ JA, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ. 2010;341:c3691.88 Chrysant ‚ SG, Chrysant ‚ GS. Controversy regarding the association of high calcium intake and increased risk for cardiovascular disease. J Clin Hypertens (Greenwich). 2014;16(8):545 " “550.99 Chowdhury ‚ R, Kunutsor ‚ S, Vitezova ‚ A, et al. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ. 2014;348:g1903.

CODES

ICD10

  • E55.9 Vitamin D deficiency, unspecified
  • M83.8 Other adult osteomalacia

ICD9

  • 268.9 Unspecified vitamin D deficiency
  • 268.2 Osteomalacia, unspecified

SNOMED

  • 34713006 Vitamin D deficiency (disorder)
  • 386072000 Deficiency of vitamin D3 (disorder)
  • 386070008 Deficiency of vitamin D2 (disorder)
  • 4598005 Osteomalacia (disorder)

CLINICAL PEARLS

  • Risk factors for VDD: senior citizen, renal disease, GI (malabsorption) disorders, liver dysfunction, immigration from tropical to colder climates, dark-skinned/veiled individuals, housebound patients, perimenopause
  • Diagnosis: 25-OH vitamin D (most sensitive measure of vitamin D status)
  • Vitamin D deficiency: <20 ng/mL
  • Up to 4,000 IU/day is safe in healthy adults without risk of toxicity.
  • 2005 and 2009: Meta-analysis demonstrated for ages 51 to 70 years minimally recommended supplementation is 800 IU/day to prevent nonvertebral fractures.
  • The American Academy of Pediatrics recommends all breast-fed babies receive 400 IU/day of vitamin D beginning within a few days of birth.