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LTC Karen S. Vogt Pediatric Endocrinology, WRNMMCB March 2013.

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Presentation on theme: "LTC Karen S. Vogt Pediatric Endocrinology, WRNMMCB March 2013."— Presentation transcript:

1 LTC Karen S. Vogt Pediatric Endocrinology, WRNMMCB March 2013

2  Understand the necessity of adequate vitamin D intake in children and adolescents  Understand the necessity of calcium and phosphorous intake in children and adolescents  Know that hypocalcemia with hypophosphatemia suggests vitamin D deficiency

3  Understand the mechanism of rickets in children with hepatic disease  Plan the treatment of a child with familial hypophosphatemic rickets

4  Case  Nutritional rickets and Vitamin D deficiecy  Prevention  Other types of rickets  PREP Questions

5  9 month old female presents in January for her well baby visit

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7  Birth:  C-section at 34 weeks for placental abruption  Required PRBC transfusion x2  PDA - closed after indomethacin x 1  18 day NICU stay  PMH: healthy  Immunizations: up-to-date

8  Diet: exclusively breastfed until 6 months of age, now taking stage 2 baby foods and soft table foods  Meds: Poly-vi-sol in first 3 months of life, no current meds  Development: sits unsupported when placed, pulls to stand, cannot get from lying to sitting, immature pincer grasp, waves bye-bye, plays peek-a-boo, consonant babbling

9  Family History: parents healthy, mom no longer taking prenatal vitamins, mom is Filipino, dad is half caucasian/half Filipino  Physical Exam : Unremarkable

10  Weight check in one month  Mom comes back in 2 weeks for concern for difficulty feeding  Less appetite for solids than previously and no weight gain from well visit

11  TSH, CRP, Celiac Panel – unremarkable  Fecal fat, reducing substances and alpha-1- antitrypsin – normal  Sweat test – normal  CMP- Alk Phos 736 U/L( )  Calcium 9.2 mg/dl ( )  Albumin 4.0 g/dl (3.5-5)

12  CBC -WBC 12.6  Hgb 10.8  Hct 34.7  Plt 547  MCV 64.6 (70-86)

13  More History: Mom drinks no milk, occasional cheese, doesn’t like yogurt  Infant light skinned and born in early spring  Minimal time in the sun per mom – spent most of summer indoors  PE: subtle wrist widening, slight concavity of lateral chest walls, mild generalized low tone

14  Alk Phos: 568 U/L( )  Calcium:8.8 mg/dl( )  Albumin:4.7 g/dl(3.5-5)  Corrected Ca:8.24 mg/dl( )  Phosphorus:2.5 mg/dl ( )  PTH:346.1 pg/ml (13-75)  25 OH Vit D:< 4.0 ng/ml

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19  Rickets due to vitamin D deficiency  Treatment:  Ergocalciferol (Drisdol® 8000 IU/ml) 2000 IU daily  Calcium carbonate 40 mg/kg/day div bid

20 Pediatrics Aug 2008:122:

21  Failure in the mineralization of newly synthesized bone matrix (osteoid) in growing bone  Due to deficiencies in calcium, phosphorous, or both  Most common cause is Vitamin D deficiency

22  Osteomalacia – equivalent in mature bone  Contrast to osteoporosis  Low bone mass due to decreased mineralization and decreased bone matrix

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24  Dietary  Ergocalciferol (D2) – plant source  Cholecalciferol (D3) – animal source  UVB exposure  Promotes conversion of 7-dehydrocholesterol to cholecalciferol (D3) in the skin

25  Vitamin D is converted to 25(OH)D by 25- hydroxylase in the liver  25(OH)D  A.k.a calcidiol  Inactive form  Reflects total body stores (2-3 week ½ life)

26  25(OH)D is converted to 1,25(OH)2 D by 1α- hydroxylase in the kidney  1,25-OH2 D  A.k.a calcitriol  Active form  More tightly regulated (4-6 hour ½ life)

27  Stimulated by  PTH  Low phosphorous levels

28  Acts on the vitamin D receptor (nuclear receptor) at the target organs  Major effect: absorption of calcium and phosphorous from the GI tract  Immunomodulary effects

29  Actions: keep serum calcium normal  Bone – stimulates reabsorption  Kidney: ▪ Stimulates 1α-hydroxylase ▪ Increases calcium reabsorption ▪ Increases phosphate excretion  Stimulated by decreased serum calcium levels  Hypomagnesemia impairs its secretion

30  Produced by active osteoblasts, which form unmineralized matrix  Levels increase with increased osteoblast activity

31  Deficient GI absorption of :  Calcium → hypocalcemia → ↑PTH: ▪ Release of calcium and phosphorous from bones ▪ Activation of 1α-hydroxylase → increased formation of 1,25-OH 2 D ▪ Increase in renal phosphate loss  Phosphorous

32  Net effect: decreased calcium and phosphorous available for bone mineralization  Osteoid continues to form without mineralization  Expansion of the growth plate  Metaphyseal irregularities, fraying, flaring  Bones become “soft” and less rigid

33  Reasons for increasing prevalence  Exclusive breastfeeding  Breastfeeding moms with insufficient vitamin D stores  Increasing use of sunscreen  Less time spent outdoors Pediatrics 2008;122:

34  Prematurity  Exclusive breastfeeing for 6 months (although was on poly-vi-sol for the first 3 months)  Probable vitamin D deficient breastfeeding mother  Winter season  Minimal sun exposure

35  Nutritional  Dark skin  Malabsorption  Obesity (sequestration in body fat)  Liver or kidney disease

36  Anticonvulsants  Glucocorticoids  HIV medications  Rifampin  Isoniazide  Ketoconazole

37  Incidental finding  LE bowing  Delayed walking  Failure to thrive  Bone pain  Pathologic fracture  Hypocalcemia (to include seizure)  Weakness  Pneumonia, other respiratory infection  Anorexia  Restlessness/irritability

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44  Poor growth or weight gain  Delayed anterior fontanelle closure  Teeth: delayed eruption, enamel defects  Generalized muscular weakness/hypotonia

45  Wrist and/or knee films usually  Metaphyseal fraying, widening, flaring, cupping  Periosteum separated from the diaphysis  Generalized osteopenia

46  Iron deficiency anemia  Renal Fanconi syndrome

47  Who?  Nonspecific symptoms: poor growth, gross motor delays, unusual irritability  Dark skin infants in higher latitudes in the winter and spring  Children taking chronic glucocorticoids or anticonvulsants  Chronic diseases associated with malabsorption  Frequent fractures and low BMD Pediatrics 2008;122:

48  How?  Serum Alkaline Phosphatase (ALP)  If elevated: 25 OH Vitamin D, PTH, Calcium and Phosphorus  Films: ▪ Wrist ▪ Knee Pediatrics 2008;122:

49  < 1 month of age:1000 IU/day  1-12 months of age: IU/ day  > 12 months of age:>5000 IU/day  Teens/adults:50,ooo IU/week x 8 weeks  Consider Stoss therapy if compliance a concern (100,000 – 600,000 IU over 1-5 days) Pediatrics 2008;122:

50  Ergocalciferol = D2 (Drisdol®, Calciferol®)  Drops (8000 IU/mL)  Capsules (50,000 IU)  Injection (500,000 IU) – no longer available  Cholecalciferol = D3  Capsules (5000 IU)

51  Simultaneous calcium supplementation necessary  Concern for “Hungry Bone” hypocalcemia  mg/kg/day divided TID – elemental calcium  Symptomatic hypocalcemia requires parenteral calcium replacement  Calcitriol (Rocaltrol®) can help treat hypocalcemia associated with rickets but does NOT build up vitamin D stores Pediatrics 2008;122:

52  Vitamin D is fat soluble so must not overtreat  Hypercalcemia ▪ Weakness ▪ Polyuria ▪ Nephrocalcinosis

53  1 Month: Calcium, Phosphorus, ALP  3 Months:Calcium, Phosphorus, ALP PTH, 25 OH Vit D, Urine calcium/creatinine ratio Recheck films  Check 25 OH Vit D at one year and then annually Pediatrics 2008;122:

54  Alk phos may increase initially due to increased bone formation  Healing is usually complete by 4 months  Lack of response to treatment may indicate a different etiology (or lack of adherence)  Once healed, continue a maintenance dose of at least 600 IU vitamin D daily (often more)

55  Cardiovascular disease, BMI, Insulin resistance  Autoimmune disease  Cancers – breast, prostate, colon  Asthma  Schizophrenia, Mood disorders  Tuberculosis  Analogs used to treat psoriasis

56  No established reference range in children  2008 AAP Review> 20 ng/ml  IOM Report 2012> 20 ng/ml  Endocrine Society 2011 CPG  Deficiency< 20 ng/ml  Insufficiency< 30 ng/ml

57  Adequate dietary intake of calcium and vitamin D  Adequate sunlight exposure

58  Vitamin D supplementation (400 IU) for:  Breast-fed or partially breast-fed infants beginning in the first few days of life  Infants receiving <1000 ml formula/day (33 oz)  Older children/adolescents who don’t obtain 400 IU/day of Vit D through diet (milk, other foods)  IOM Nov 2010 recommends 600 IU for children and adolescents (RDA) Pediatrics 2008;122:

59  Breastmilk15-50 IU/L  Vit D sufficient mother  Infant formula400 IU/L  Prenatal vitamins400 IU

60  Released Nov 2010  Supplementation for healthy infants, children, and adults  Prevention  Not treatment recommendations  Assumed little to no sun exposure

61  Infants (0-12 months)400 IU  Children/Adolescents600 IU  Adults (19-70 years)600 IU  Upper level intakes  0-6 months1000 IU  6-12 months1500 IU  1-3 y/o2500 IU  4-8 y/o3000 IU  9-70 y/o4000 IU IOM Report Nov 2010

62 AGERDAUPPER INTAKE LEVEL 0-6 months200 mg (AI)1000 mg 6-12 months260 mg (AI)1500 mg 1-3 years700 mg2500 mg 4-8 years1000 mg2500 mg 9-18 years1300 mg3000 mg Adults years 1000 mg2500 mg IOM Report Nov 2010

63  Fish oils (salmon, mackerel, sardines)  Cod liver oil  Liver and organ meats  Egg yolks IU/yolk  Fortified milk/juice 400 IU/L  Fortified cereals 40 IU/serving

64 SOURCEMG CALCIUM Milk (2%)285 Per cup Plain low-fat yogurt415 Per cup Cheese220 Per oz Tofu163 Per ¼ firm block Sardines325 Per 3 oz Salmon181 Per 3 oz Spinach250 Per cup Almonds126 Per 1/3 cup

65  UVB nm – highest at 1200 noon ( )  Minimal Erythema Dose (MED, slight pink skin) → 10,000-20,000 IU vitamin D  40% body to ¼ MED → approx 1000 IU vitamin D Pediatrics 2008;122:

66  Formulary Cholecalciferol = D3  D-Vi-Sol® (400 IU/ml)  Poly-Vi-Sol® (400 IU/mL)  400 IU tab  1000 IU tab  OTC  Most standard multivitamins (400 IU)  Viactiv® chews (500 IU D3/chew)  Many other OTC vitamin D supplements

67  Calcium Carbonate – with food  Oral suspension (500 mg/5 mL)  500 mg tab  600 mg/tab IU D3  Calcium Citrate – absorbed with/without food  200 mg tab  Citracal® (315 mg/tab IU vit D3)

68  Tums®  Reg 500 mg/tab  Extra Strength 750 mg/tab  Viactiv® chews (500 mg IU vit D3)

69  1 α -hydroxylase deficiency  Vitamin D receptor mutation  Associated alopecia totalis  X-linked hypophosphatemic rickets  Other inherited hypophosphatemic rickets

70  Renal phosphate wasting  Defective 1 α -hydroxylase activity in kidney  Due to PHEX mutation  increased levels of FGF-23  X-linked dominant  Low serum phos, low/inappropriately normal 1,25-dihydroxyvitamin D  Treatment: phosphorous replacement, calcitriol (Rocaltrol®)

71  Prevention of vitamin D deficiency is key  Don’t forget about sunlight exposure  Supplement all breast-fed infants with 400 IU vitamin D within the first few days  Vitamin D RDA 600 IU for children and adolescents (IOM Report)  Vitamin D may be important for more than just bone health  If rickets is not responding to vitamin D treatment, consider other causes

72  A 12 year old boy presents to your office for follow-up after his third wrist fracture in 3 years. As part of his evaluation in the emergency department, a complete metabolic panel was obtained and revealed a low calcium (7.5 mg/dL), low phosphorous (2.8 mg/dL), normal magnesium (1.9 mg/dL), and normal albumin (4 g/dL).

73  With the exception of his fractures, the boy has had no other medical problems and has not been taking any long-term medications. His height and weight are both at the 75 th percentile. His physical exam is unremarkable except for his casted left wrist.  Of the following, the MOST appropriate next step in this boy’s evaluation and management is to measure:

74 A. Ionized calcium B. Serum 1,25-dihydroxyvitamin D C. Serum 25-hydroxyvitamin D D. Serum parathyroid hormone E. Urine N-telopeptide

75  A 14 y/o boy suffers a nondisplaced fracture of his left radius and ulna while playing soccer. He had a similar injury to his radius and ulna 9 months ago. Physical exam reveals SMR 2 pubic hair and testicular volume of 6 ml. A thorough review of his dietary history suggests that his daily intake of calcium and phosphorous are 800 mg each. He takes 400 IU of vitamin D supplement daily.

76  Serum calcium measures 7.9 mg/dL, serum phosphorous measures 2.7 mg/dL, and 25- hydroxyvitamin D measures 55 ng/mL (normal 30-80).  Of the following, the most appropriate recommendation for this boy is to increase his:

77 A. Calcium and phosphorous intake to 1300 mg/day B. Calcium and phosphorous intake to 2000 mg/day C. Calcium intake to 1000 mg/day D. Phosphorous intake to 1000 mg/day E. Vitamin D supplementation to 2000 IU/day

78  A 7-month-old child presents for a follow-up visit after undergoing a Kasai procedure for biliary atresia at 6 weeks of age. The mother states that the boy is irritable when his right arm is moved. On physical exam, the infant is jaundiced. You detect tenderness in the anterior radial head. Radiography of the affected region demonstrates metaphyseal fraying and a fracture.

79  The MOST appropriate laboratory studies to obtain next are: A. Calcium, phosphorous, bone densitometry (DEXA scan) B. Calcium, phosphorous, urinary calcium-to- creatinine ratio C. Calcium, phosphorous, 25-hydroxyvitamin D D. Calcium, phosphorous, magnesium E. Magnesium, phosphorous, parathyroid hormone

80  You diagnose familial hypophosphatemic rickets in a boy who presents with rickets and whose mother had rickets as a child and required osteotomies as an adult. You explain to the parents that treatment can help the boy reach normal height and lessen his rachitic bone changes.  Of the following, the most appropriate treatment is:

81 A. Daily injections of human growth hormone and oral calcium twice daily B. Oral calcitriol once daily C. Oral calcium twice daily with oral cholecalciferol once daily D. Oral neutral phosphate salts every 6 hours with calcitriol once or twice daily E. Oral neutral phosphate salts once daily

82  * Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M. Vitamin d deficiency in children and its management: review of current knowledge and recommendations. Pediatrics. 2008;122:  * Wagner CL, Greer FR. Prevention of rickets and vitamin d deficiency in infants, children, and adolescents. Pediatrics. 2008;122:  Institute of Medicine Report on Dietary Reference Intakes for Calcium and Vitamin D. Released 30 Nov Available at  Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:  Adams JS, Hewison M. Update in vitamin D. J Clin Endocrinol Metab. 2010;95:  Carpenter TO et al. A clinician’s guide to X-linked hypophosphatemia. JBMR. July 2011;26(7):


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