vitamin d deficiency elaine wendt, md january 4, 2010
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Vitamin D DeficiencyVitamin D Deficiency
Elaine Wendt, MDJanuary 4, 2010
Importance of vitamin D Importance of vitamin D DeficiencyDeficiency
In utero and during childhood, can cause growth retardation and skeletal deformities
In adulthood, can cause osteopenia, osteoporosis, osteomalacia, muscle weakness and increase risk of fracture
Other risk associationsOther risk associationsCommon cancers such as breast,
prostate, colon, and NH lymphomaAutoimmune diseases such as
multiple sclerosis, rheumatoid arthritis, Type 1diabetes, and Crohn’s disease
Infectious diseases such as TBCardiovascular disease such as HTN
and CHFMuscle aches and bone painsMental illness such as schizophrenia
and depression
Holick M. N Engl J Med 2007;357:266-281
Metabolism of 25-Hydroxyvitamin D to 1,25-Dihydroxyvitamin D for Nonskeletal Functions
Functions of 1,25 Dihydroxyvitamin Functions of 1,25 Dihydroxyvitamin DDRegulates cellular proliferation,
differentiation, apoptosis, and angiogenesis
Potent immunomodulatorInhibits renin synthesisIncreases insulin productionIncreases myocardial contractility
Prevalence of Vitamin D Prevalence of Vitamin D DeficiencyDeficiencyElderly in US and Europe 40-
100%Children 30-50%Adult inpatients over 80%
Vitamin D Status in Relation Vitamin D Status in Relation to 25 (OH)-D Levelsto 25 (OH)-D Levels
Vitamin D Status 25 (OH)- D Level, nmol/L (ng/ml)
Severe Deficiency < 12.5 (5)
Deficiency < 37.5 (15)
Insufficiency 37.5 – 50 (15-20)
Sufficiency 50-250 (20-100)
Excess >250 (100)
Intoxication > 375 (150)
Causes of Vitamin D Causes of Vitamin D DeficiencyDeficiencyReduced skin synthesisDecreased bioavailabilityIncreased catabolismBreast-feedingDecreased synthesis of 25-OH Vit DIncreased urinary loss of 25-OH Vit
DDecreased synthesis of 1,25
dihydroxyvitamin D
Causes of Vitamin D Causes of Vitamin D DeficiencyDeficiencyHeritable disorders- ricketsAcquired disorders
Holick M. N Engl J Med 2007;357:266-281
Synthesis and Metabolism of Vitamin D in the Regulation of Calcium, Phosphorus, and Bone Metabolism
Reduced Skin SynthesisReduced Skin SynthesisSunscreen useSkin pigmentationAgingSeason, latitude, and time of dayPatients with skin grafts for burns
Inadequate sun exposure or Inadequate sun exposure or supplementationsupplementation Children
Preventative
400- 1000 IU D3 daily
sensible sun exposure
1000-2000 IU D3 daily is safe
Treatment of Deficiency
50000 IU of D2 every week for 8
weeks
Adults (non lactating)
Preventative
800-1000 IU D3 daily
50000 IU of D2 every 2-4 weeks
Sensible sun exposure
Use of a tanning bed or UVB radiation device
10000 IU of D3 daily is safe for 5 months
Treatment of deficiency
50000 IU of D2 every week for 8 weeks, repeat for another 8 weeks if 25, OH Vitamin D level < 30 ng/ml
Pregnant or lactating Pregnant or lactating adultsadults
Preventative
1000-2000 IU of D3 daily
50000 IU of D2 every 2 weeks
up 4000 IU of D3 is safe for 5 months
Maintenance dose is 50000 IU of D2 every 2-4 weeks
Treatment of Deficiency
50000 IU of D2 every week for 8 weeks
Repeat for another 8 weeks if 25-OH vitamin D level <30 ng/ml
Decreased bioavailabilityDecreased bioavailabilityMalabsorption from disease or
cholesterol medicationsObesity- sequestration of vitamin
D in body fat
Holick M. N Engl J Med 2007;357:266-281
Synthesis and Metabolism of Vitamin D in the Regulation of Calcium, Phosphorus, and Bone Metabolism
Malabsorption SyndromesMalabsorption SyndromesPrevention
Adequate exposure to sun or UV radiation
50000 IU D2 daily, every other day, or every other week
Up to 10000 IU D3 daily is safe for 5 months
Maintenance is 50000 IU D2 weekly
◦ Treatment of Deficiency
UVB irradiation
50000 IU D2 every day or every other day
ObesityObesityPreventative
1000-2000 IU D3 daily
50000 IU of D2 every 1-2 weeks
Maintenance dos is 50000 IU D2 every 1, 2, or 4 weeks
Treatment of Deficiency
50000 IU D2 every week for 8-12 weeks
Repeat if 25-OH vitamin D level < 30 ng/ml
Increased CatabolismIncreased CatabolismAnticonvulsantsGlucocorticoidsHAARTAntirejection medications
Holick M. N Engl J Med 2007;357:266-281
Synthesis and Metabolism of Vitamin D in the Regulation of Calcium, Phosphorus, and Bone Metabolism
Drugs that activate steroid and xenobiotic Drugs that activate steroid and xenobiotic receptor, drugs used in transplantationreceptor, drugs used in transplantation
Preventative
50000 IU of vitamin D2 every other day or every week
Maintenance is 50000 IU of D2 every 1, 2, or 4 weeks
Treatment of Deficiency
50000 IU D2 every 2 weeks for 8- 10 weeks, or every week if 25-OH vitamin D level <30 ng/ml
Breast-feedingBreast-feedingPoor vitamin D content in human
milk
BreastfeedingBreastfeeding
Preventative
400 IU D3 daily
Sensible sun exposure
1000-2000 IU D3 daily safe
Maintenance dose is 400-1000 IU of D3 daily
Treatment of Deficiency
200000 IU D3 every 3 months
600000 IU D3 IM, repeat 12 weeks
1000-2000 IU D2 or D3 daily with calcium supplementation
Decreased synthesis of 25-Decreased synthesis of 25-OH vitamin DOH vitamin DLiver failure
Holick M. N Engl J Med 2007;357:266-281
Synthesis and Metabolism of Vitamin D in the Regulation of Calcium, Phosphorus, and Bone Metabolism
Increased Urinary Loss of 25-Increased Urinary Loss of 25-OH Vitamin DOH Vitamin DNephrotic Syndrome
Holick M. N Engl J Med 2007;357:266-281
Synthesis and Metabolism of Vitamin D in the Regulation of Calcium, Phosphorus, and Bone Metabolism
Nephrotic SyndromeNephrotic Syndrome
Preventive
1000-2000 IU D3 daily
50000 IU D2 once or twice weekly
Maintenance is 50000 IU D2 every 2 or 4 weeks
Treatment of Deficiency
50000 IU D2 weekly for 8-12 weeks
Repeat if 25-OH vitamin D level <30 ng/ml
Decreased Synthesis of 1,25- Decreased Synthesis of 1,25- dihydroxyvitamin Ddihydroxyvitamin DChronic kidney diseaseStages 2 and 3-
hyperphosphatemia increases fibroblast growth factor 23, which decreases 25 OH vitamin D-1-hydroxylase activity
Stages 4 and 5- inability to produce adequate amounts of 1,25- dihydroxy- vitamin D
Holick M. N Engl J Med 2007;357:266-281
Synthesis and Metabolism of Vitamin D in the Regulation of Calcium, Phosphorus, and Bone Metabolism
Chronic Kidney Disease Chronic Kidney Disease Stages 2 and 3 Stages 2 and 3 Prevention
Control serum phosphate
1000 IU D3 daily
50000 IU D2 every 2 weeks
Maintenance dose 50000 IU D2 every 2-4 weeks
May also need to treat with an active vitamin D analog when sufficiency is obtained
Treatment of Deficiency
50000 IU D2 once weekly for 8 weeks
Repeat if 25-OH vitamin D level <30 ng/ml
Chronic Kidney Disease Chronic Kidney Disease Stages 4 and 5Stages 4 and 5Prevention
1000 IU D3 daily50000 IU D2 every 2
weeksNeed to treat with
1,25 dihydroxyvitamin D3, or active analog
Treatment of Deficiency
0.25-1 ug calcitriol BID
1-2 ug paricalcitriol IV every 3 days
Doxecalciferol 10-20 ug three times weekly or 2-6 ug IV three times weekly
Heritable disorders- Heritable disorders- RicketsRicketsPseudovitamin D deficiency
ricketsVitamin D-resistant ricketsVitamin D-dependent rickets
Type 3Autosomal dominant
hypophosphatemic ricketsX-linked hypophosphatemic
rickets
Treatment of Vitamin D Treatment of Vitamin D Defiency RicketsDefiency RicketsVitamin D (ergocalciferol)Double dose vitamin D3: 800 IU daily for 3-4 months OR
Vitamin D 1000-10000 IU daily for 8-12 weeks, then 400-1000 IU daily
OR D2 100000- 600000 IU daily or 50000 D2 weekly for 8 weeks
Calcium30-75 mg/kg daily of elemental calcium in 3 divided doses
( start at higher dose and wean down over 2-4 weeks)
Monitoring of TherapyAt 1 month: calcium, phosphorus, alkaline phosphatase (ALP)
At 3 months: calcium, phosphorus, magnesium, ALP, PTH, 25(OH)-D, urine calcium/creatinine ratio, recheck radiographic findings
At 1 year and annually: 25(OH)-D
Acquired DisordersAcquired DisordersTumor- induced OsteomalaciaPrimary hyperparathyroidismGranulomatous DisordersHyperthyroidism
Primary or tertiary Primary or tertiary HyperparathyroidismHyperparathyroidismPrevention
800-1000 IU D3 daily50000 IU D2 every 2
weeksMaintenance 50000
IU D2 every 2-4 weeks
Treatment of deficiency
50000 IU D2 once weekly for 8 weeks,
Repeat is 25-OH vitamin D < 30 ng/ml
Granulomatous disorders Granulomatous disorders and some lymphomasand some lymphomasPrevention
400 IU D3 daily50000 IU D2 monthly
Treatment of Deficiency
50000 IU D2 weekly for 4 weeks, need to keep 25-OH vitamin D level between 20 and 30 ng/ml. >30 ng/ml can result in hypercalciuria and hypercalcemia
ReferencesReferences
N Engl J Med 2007;357:266-81.Pediatrics 2008;122:398-417.