Vitamin D Deficiency Elaine Wendt MD January 4

Vitamin D Deficiency Elaine Wendt, MD January 4, 2010

Importance of vitamin D Deficiency 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 associations Common cancers such as breast, prostate, colon, and NH lymphoma Autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, Type 1 diabetes, and Crohn’s disease Infectious diseases such as TB Cardiovascular disease such as HTN and CHF Muscle aches and bone pains Mental illness such as schizophrenia and depression

Metabolism of 25 -Hydroxyvitamin D to 1, 25 -Dihydroxyvitamin D for Nonskeletal Functions Holick M. N Engl J Med 2007; 357: 266 -281

Functions of 1, 25 Dihydroxyvitamin D Regulates cellular proliferation, differentiation, apoptosis, and angiogenesis Potent immunomodulator Inhibits renin synthesis Increases insulin production Increases myocardial contractility

Prevalence of Vitamin D Deficiency Elderly in US and Europe 40 -100% Children 30 -50% Adult inpatients over 80%

Vitamin D Status in Relation to 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 Deficiency Reduced skin synthesis Decreased bioavailability Increased catabolism Breast-feeding Decreased synthesis of 25 -OH Vit D Increased urinary loss of 25 -OH Vit D Decreased synthesis of 1, 25 dihydroxyvitamin D

Causes of Vitamin D Deficiency Heritable disorders- rickets Acquired disorders

Synthesis and Metabolism of Vitamin D in the Regulation of Calcium, Phosphorus, and Bone Metabolism Holick M. N Engl J Med 2007; 357: 266 -281

Reduced Skin Synthesis Sunscreen use Skin pigmentation Aging Season, latitude, and time of day Patients with skin grafts for burns

Inadequate sun exposure or supplementation Children Preventative Adults (non lactating) Preventative 800 -1000 IU D 3 daily 400 - 1000 IU D 3 daily 50000 IU of D 2 every 2 -4 weeks sensible sun exposure Sensible sun exposure 1000 -2000 IU D 3 daily is safe Use of a tanning bed or UVB radiation device 10000 IU of D 3 daily is safe for 5 months Treatment of Deficiency Treatment of deficiency 50000 IU of D 2 every week for 8 weeks, repeat for another 8 weeks if 25, OH Vitamin D level < 30 ng/ml weeks

Pregnant or lactating adults Preventative 1000 -2000 IU of D 3 daily 50000 IU of D 2 every 2 weeks up 4000 IU of D 3 is safe for 5 months Maintenance dose is 50000 IU of D 2 every 2 -4 weeks Treatment of Deficiency 50000 IU of D 2 every week for 8 weeks Repeat for another 8 weeks if 25 -OH vitamin D level <30 ng/ml

Decreased bioavailability Malabsorption from disease or cholesterol medications Obesity- sequestration of vitamin D in body fat

Synthesis and Metabolism of Vitamin D in the Regulation of Calcium, Phosphorus, and Bone Metabolism Holick M. N Engl J Med 2007; 357: 266 -281

Malabsorption Syndromes Prevention ◦ Treatment of Deficiency Adequate exposure to sun or UV radiation UVB irradiation 50000 IU D 2 daily, every other day, or every other week Up to 10000 IU D 3 daily is safe for 5 months Maintenance is 50000 IU D 2 weekly 50000 IU D 2 every day or every other day

Obesity Preventative Treatment of Deficiency 1000 -2000 IU D 3 daily 50000 IU of D 2 every 1 -2 weeks 50000 IU D 2 every week for 8 -12 weeks Maintenance dos is 50000 IU D 2 every 1, 2, or 4 weeks Repeat if 25 -OH vitamin D level < 30 ng/ml

Increased Catabolism Anticonvulsants Glucocorticoids HAART Antirejection medications

Synthesis and Metabolism of Vitamin D in the Regulation of Calcium, Phosphorus, and Bone Metabolism Holick M. N Engl J Med 2007; 357: 266 -281

Drugs that activate steroid and xenobiotic receptor, drugs used in transplantation Preventative Treatment of Deficiency 50000 IU of vitamin D 2 every other day or every week Maintenance is 50000 IU of D 2 every 1, 2, or 4 weeks 50000 IU D 2 every 2 weeks for 8 - 10 weeks, or every week if 25 -OH vitamin D level <30 ng/ml

Breast-feeding Poor vitamin D content in human milk

Breastfeeding Preventative Treatment of Deficiency 400 IU D 3 daily 200000 IU D 3 every 3 months Sensible sun exposure 1000 -2000 IU D 3 daily safe 600000 IU D 3 IM, repeat 12 weeks Maintenance dose is 400 -1000 IU of D 3 daily 1000 -2000 IU D 2 or D 3 daily with calcium supplementation

Decreased synthesis of 25 -OH vitamin D Liver failure

Synthesis and Metabolism of Vitamin D in the Regulation of Calcium, Phosphorus, and Bone Metabolism Holick M. N Engl J Med 2007; 357: 266 -281

Increased Urinary Loss of 25 -OH Vitamin D Nephrotic Syndrome

Synthesis and Metabolism of Vitamin D in the Regulation of Calcium, Phosphorus, and Bone Metabolism Holick M. N Engl J Med 2007; 357: 266 -281

Nephrotic Syndrome Preventive Treatment of Deficiency 1000 -2000 IU D 3 daily 50000 IU D 2 weekly for 8 -12 weeks 50000 IU D 2 once or twice weekly Maintenance is 50000 IU D 2 every 2 or 4 weeks Repeat if 25 -OH vitamin D level <30 ng/ml

Decreased Synthesis of 1, 25 dihydroxyvitamin D Chronic kidney disease Stages 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 - dihydroxyvitamin D

Synthesis and Metabolism of Vitamin D in the Regulation of Calcium, Phosphorus, and Bone Metabolism Holick M. N Engl J Med 2007; 357: 266 -281

Chronic Kidney Disease Stages 2 and 3 Prevention Treatment of Deficiency Control serum phosphate 50000 IU D 2 once weekly for 8 weeks 1000 IU D 3 daily 50000 IU D 2 every 2 weeks Maintenance dose 50000 IU D 2 every 2 -4 weeks May also need to treat with an active vitamin D analog when sufficiency is obtained Repeat if 25 -OH vitamin D level <30 ng/ml

Chronic Kidney Disease Stages 4 and 5 Prevention Treatment of Deficiency 1000 IU D 3 daily 50000 IU D 2 every 2 weeks Need to treat with 1, 25 dihydroxyvitamin D 3, or active analog 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- Rickets Pseudovitamin D deficiency rickets Vitamin D-resistant rickets Vitamin D-dependent rickets Type 3 Autosomal dominant hypophosphatemic rickets X-linked hypophosphatemic rickets

Treatment of Vitamin D Defiency Rickets Vitamin D (ergocalciferol) Double dose vitamin D 3: 800 IU daily for 3 -4 months OR Vitamin D 1000 -10000 IU daily for 8 -12 weeks, then 400 -1000 IU daily OR D 2 100000 - 600000 IU daily or 50000 D 2 weekly for 8 weeks Calcium 30 -75 mg/kg daily of elemental calcium in 3 divided doses ( start at higher dose and wean down over 2 -4 weeks) Monitoring of Therapy At 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 Disorders Tumor- induced Osteomalacia Primary hyperparathyroidism Granulomatous Disorders Hyperthyroidism

Primary or tertiary Hyperparathyroidism Prevention Treatment of deficiency 800 -1000 IU D 3 daily 50000 IU D 2 every 2 weeks Maintenance 50000 IU D 2 every 2 -4 weeks 50000 IU D 2 once weekly for 8 weeks, Repeat is 25 -OH vitamin D < 30 ng/ml

Granulomatous disorders and some lymphomas Prevention Treatment of Deficiency 400 IU D 3 daily 50000 IU D 2 monthly 50000 IU D 2 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

References N Engl J Med 2007; 357: 266 -81. Pediatrics 2008; 122: 398 -417.