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 deficiency
- Inadequate vitamin D intake
- Inadequate sunlight exposure
- Institutionalized/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. " ¯
‚
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].
‚
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].
‚
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].
‚
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 screen
- Women ≥65 years with no risk factors
- Women ≥60 years at risk: body weight <70 kg (best predictor)
- Less evidence: smoking, low body mass index, family history, decreased activity, alcohol or caffeine use
- African 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].
‚
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.
‚
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 support
- Dietary 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.
‚
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.