Vitamin D Deficiency Elaine Wendt, MD January 4, 2010.

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.