1. Dr. Hossein Moravej

2. Bone consists of : a protein matrix: osteoid a mineral phase, principally composed of calcium and phosphate: hydroxyapatite

3. Osteomalacia: Inadequate mineralization of bone osteoid; in children or adults Rickets: a disease of growing bone, due to unmineralized matrix at the growth plates.

4. . VITAMIN D PHYSIOLOGY

5. Cutaneous synthesis The most important source of vitamin D Conversion of 7-dehydrochlesterol to vitamin D 3 (3-cholecalciferol) by ultraviolet B radiation from the sun. Covering the skin with clothing or applying sunscreen, also decrease vitamin D synthesis. Children who spend less time outside have reduced vitamin D synthesis.

6. dietary sources Fish liver oils have a high vitamin D content. Other good dietary sources include fatty fish and egg yolks. Vitamin D fortified foods, especially formula Supplemental vitamin D may be vitamin D 2 (which comes from plants or yeast) or vitamin D 3 ; they are biologically equivalent. Breast milk has a low vitamin D content, approximately 12–60 IU/L.

7. Metabolism of Vit.D Vitamin D is transported to the liver and converts to 25-hydroxyvitamin D (25-D), the most abundant circulating form of vitamin D. In the kidney, 1α-hydroxylase adds a second hydroxyl group, resulting in 1,25- dihydroxyvitamin D (1,25-D). The 1α-hydroxylase activity is regulated by PTH, phosphate, and 1,25-D levels.

8. Action of Vit. D On GI: marked increase in calcium absorption, which is highly dependent on 1,25-D. phosphorus absorption, most dietary phosphorus absorption is vitamin D–independent. On bone, mediating resorption. Suppresses PTH secretion 1,25-D inhibits its own synthesis in the kidney.

9. Etiology of Rickets

11. Causes of rickets

12. Clinical Manifestations

15. The chief complaint in a child with rickets: skeletal deformities difficulty walking due to a combination of deformity and weakness. failure to thrive symptomatic hypocalcemia.

16. Clinical Manifestations Most manifestations of rickets are due to skeletal changes. Craniotabes, occiput or parietal Craniotabes may also be secondary to osteogenesis imperfecta, hydrocephalus, and syphilis. It is a normal finding in many newborns, but disappears within a few months of birth.

17. Clinical Manifestations Thickening of growth plate, causing widening of the wrists and ankles. general softening of the bones that causes them to bend easily when subject to

18. Clinical Manifestations Widening of the costochondral junctions results in a rachitic rosary; along the costochondral junctions

20. Growth plate widening causes enlargement at the wrists and ankles. Harrison groove: The horizontal depression along the lower anterior chest; occurs due to pulling of the softened ribs by the diaphragm during inspiration

22. Clinical Manifestations Softening of the ribs also impairs air movement and predisposes patients to atelectasis. The risk of pneumonia is elevated.

23. Clinical Manifestations There is some variation in the clinical presentation of rickets based on the etiology. Changes in the lower extremities tend to be the dominant feature in X-linked hypophosphatemic rickets. Symptoms secondary to hypocalcemia occur only in those forms of rickets associated with decreased serum calcium.

24. Clinical Manifestations Other manifestations: dental caries poor growth delayed walking waddling gait hypocalcemic symptoms.

25. Windswept deformity

26. Wrist enlargement

27. Bowing deformity

28. scoliosis

29. Rib beading (rachitic rosary)

30. Ankle enlargement

31. Bowleg deformity (genu varum)

32. Frontal bossing

33. Knock knee deformity (genu valgum )

34. Radiology Rachitic changes are most easily visualized on posteroanterior radiographs of the wrist: The edge of the metaphysis loses its sharp border, which is described as fraying. The edge of the metaphysis changes from a convex or flat surface to a more concave surface. This is termed cupping.

37. Laboratory findings Alk.ph is always elevated, except in zinc def. or protein def. Ph. is always decreased, except in renal failure. Ca. is always normal or decreased

39. Diagnosis Diagnosis is based on the presence of classic radiographic abnormalities, supported by physical examination and history and laboratory results.

40. Vit.D Deficient Rickets

41. . Vit.D deficient Rickets The most common cause of rickets globally and is prevalent, even in industrialized countries.

42. Vit.D deficient Rickets Etiology: Most commonly occurs in infancy due to a combination of poor intake and inadequate cutaneous synthesis. Transplacental transport of 25-D provides enough vitamin D for the 1st 2 mo of life unless there is severe maternal vitamin D deficiency.

43. Vit.D deficient Rickets Infants who receive formula receive adequate vitamin D, even without cutaneous synthesis. Breast-fed infants, because of the low vitamin D content of breast milk, rely on cutaneous synthesis or vitamin supplements.

44. Laboratory Findings. Hypocalcemia is a variable finding due to elevated PTH. Hypophosphatemia is due to increased PTH and decreased vit.D. Wide variation in 1,25-D levels (low, normal, or high) Some patients have a metabolic acidosis secondary to PTH-induced renal bicarbonate-wasting. There may also be generalized aminoaciduria.

45. Diagnosis and Differential Diagnosis Based on the combination of History of poor vitamin D intake and risk factors for decreased cutaneous synthesis, Radiographic changes consistent with rickets typical laboratory findings

46. Treatment 2 strategies for administration of vitamin D. Stoss therapy, 300,000–600,000 IU of vitamin D are administered orally or intramuscularly as 2–4 doses over 1 day. Alternative is daily, high-dose vitamin D, with doses ranging from 2,000–5,000 IU/day over 4–6 wk. Either strategy should be followed by daily vitamin D intake of 400 IU/day, as a multivitamin. Adequate dietary calcium and phosphorus; by milk, formula, and other dairy products.

47. Treatment Symptomatic hypocalcemia need intravenous calcium acutely, followed by oral calcium supplements, which typically can be tapered over 2–6 wk in children who receive adequate dietary calcium.

48. Prognosis Excellent response to treatment Radiologic healing within a few months, first finding is Z-P line. Normalization of laboratory test results : Ca and Ph after 5 to 7 days, Alk-ph after a few weeks

49. Prevention Daily multivitamin containing 200–400 IU of vitamin D to children who are breast-fed. For other children, the diet should be reviewed to ensure that there is a source of vitamin D.

50. SECONDARY VITAMIN D DEFICIENCY Etiology: inadequate absorption, decreased hydroxylation in the liver, and increased degradation in patients with liver and gastrointestinal diseases

51. SECONDARY VITAMIN D DEFICIENCY phenobarbital, phenytoin, isoniazid and rifampin increase degradation of vitamin D by inducing the P450 system.

52. VITAMIN D–DEPENDENT RICKETS, TYPE 1

53. VITAMIN D–DEPENDENT RICKETS, TYPE 1. Mutations in the gene encoding renal 1α- hydroxylase, preventing conversion of 25-D into 1,25-D. Present during the 1st 2 yr of life

54. Laboratory Findings. Most lab. Findings are similar to Vit. D def. rickets: Hypocalcemia is a variable finding due to elevated PTH. Hypophosphatemia is due to increased PTH and decreased vit.D. Wide variation in 1,25-D levels (low, normal, or high) Some patients have a metabolic acidosis secondary to PTH-induced renal bicarbonate-wasting. There may also be generalized aminoaciduria. But 1,25 D level is decreased.

55. VITAMIN D–DEPENDENT RICKETS, TYPE 1 Treatment: Long-term treatment with 1,25-D (calcitriol)

56. VITAMIN D–DEPENDENT RICKETS, TYPE 2

57. VITAMIN D–DEPENDENT RICKETS, TYPE 2. mutations in the gene encoding the vitamin D receptor, preventing a normal physiologic response to 1,25-D. Levels of 1,25-D are extremely elevated. Present during infancy 50–70% of children have alopecia.

58. VITAMIN D–DEPENDENT RICKETS, TYPE 2 Treatment Some respond to extremely high doses of vitamin D 2, 25-D, or 1,25-D, due to a partially functional vitamin D receptor.

60. X-LINKED HYPOPHOSPHATEMIC RICKETS Pathophysiology: Increased urinary phosphate wasting

61. X-LINKED HYPOPHOSPHATEMIC RICKETS Clinical Manifestations: These patients have rickets, but abnormalities of the lower extremities and poor growth are the dominant features.

62. CHRONIC RENAL FAILURE Decreased activity of 1α-hydroxylase in the kidney, leading to diminished production of 1,25- D. unlike the other causes of vitamin D deficiency, patients have hyperphosphatemia as a result of decreased renal excretion

63. Clinical Evaluation Initial evaluation should focus on a dietary history, emphasizing intake of vitamin D and calcium. ask about time spent outside, sunscreen use, and clothing.

64. Clinical Evaluation when a neonate or young infant has rachitic findings: Consider maternal risk factors for nutritional vitamin D deficiency, including diet and sun exposure.

65. Clinical Evaluation Take history of anticonvulsants use (phenobarbital and phenytoin), and aluminum- containing antacids.

66. Clinical Evaluation History of liver or intestinal disease, although occasionally, rickets may be the presenting complaint.

67. Clinical Evaluation A history of renal disease (proteinuria, hematuria, urinary tract infections.

68. Clinical Evaluation The family history is critical. Inquire about leg deformities, difficulties with walking, or unexplained short stature because some parents may be unaware of their diagnosis.

69. Clinical Evaluation Physical examination: Observe the child's gait, auscultate the lungs to detect atelectasis or pneumonia, and plot the patient's growth. Alopecia suggests vitamin D– dependent rickets type 2.

70. Clinical Evaluation The initial laboratory tests in a child with rickets should include: serum calcium; phosphorus; alkaline phosphatase; parathyroid hormone (PTH); 25- hydroxyvitamin D; 1,25-dihydroxyvitamin D 3 ; creatinine; and electrolytes. Urinalysis is useful for detecting the glycosuria and aminoaciduria.