2.  Calcium  Phosphate  PTH  Vitamin D  Calcitonin

3.  > 99% in bone  Muscle and nerve function  Clotting mechanisms  Free plasma Ca = Bound plasma Ca  Active transport absorption in the duodenum and passive diffusion in the jejunum  98% reabsorption in the kidney

4.  600 mg/day in children  1300 mg/day in adolescents and young adults  750 mg/day in adults  1500 mg/day in pregnant women  2000 mg/day in lactating women  1500 mg/day in postmenopausal women and patients with fractures

5.  Key component of bone mineral  Enzyme systems and molecular interactions  85% in bone  Plasma Phosphate is mostly unbound  1000-1500 mg/day

7. Vitamin D metabolism

8. Secondary role Other Hormones - Estrogen - Corticosteroids - Thyroxin Non-hormonal Factors - Mechanical stress - Prostaglandin E - Acid-base balance

10. Introduction Introduction  Normal bone growth & mineralization require adequate availability of calcium & phosphate.  Deficient mineralization can result in rickets and/or osteomalacia.  Rickets refers to the changes caused by deficient mineralization at the growth plate.  Osteomalacia refers to impaired mineralization of the bone matrix.  Rickets & osteomalacia usually occur together as long as the growth plates are open; only osteomalacia occurs after the growth plates have fused.

11.  Vitamin D disorders ◦ Nutritional vitamin D deficiency; Congenital vitamin D deficiency; Secondary vitamin D deficiency; Malabsorption ; Increased degradation; Decreased liver 25-hydroxylase; Vitamin D-dependent rickets type 1; Vitamin D-dependent rickets type 2; Chronic renal failure.  Calcium deficiency ◦ Low intake, Calcium deficient Diet, Premature infants (rickets of prematurity), Malabsorption, Dietary inhibitors of calcium absorption  Phosphorus deficiency ◦ Inadequate intake, Premature infants (rickets of prematurity), Aluminum-containing antacids

12.  RENAL LOSSES ◦ X-linked hypophosphatemic rickets; Autosomal dominant hypophosphatemic rickets; Hereditary hypophosphatemic rickets with hypercalciuria; Overproduction of phosphatonin (Tumor- induced rickets, McCune-Albright syndrome, Epidermal nevus syndrome, Neurofibromatosis), Fanconi syndrome, Dent disease  DISTAL RENAL TUBULAR ACIDOSIS

13.  GENERAL Failure to thrive; Listlessness; Protuding abdomen; Muscle weakness (especially proximal); Fractures.  HEAD Craniotabes; Frontal bossing; Delayed fontanelle closure; Delayed dentition; caries; Craniosynostosis  CHEST Rachitic rosary; Harrison groove; Respiratory infections and atelectasis  BACK Scoliosis,Kyphosis,Lordosis  EXTREMITIES Enlargement of wrists and ankles; Valgus or varus deformities Windswept deformity (combination of valgus deformity of 1 leg with varus deformity of the other leg); Anterior bowing of the tibia and femur; Coxa vara; Leg pain.  HYPOCALCEMIC SYMPTOMS Tetany ; Seizures; Stridor due to laryngeal spasm

14. Extra skeletal findings in Rickets  Extraskeletal manifestation of rickets vary depending upon the mineral deficiency.  Hypoplasia of the dental enamel is typical for hypocalcemic rickets, whereas abscesses of the teeth occur more often in phosphopenic rickets.  Hypocalcemic seizures, decreased muscle tone leading to delayed motor milestones, recurrent infections, increased sweating.

21. Diagnostic approach to suspected rickets

22. Diagnostic approach to hypocalcimic rickets

23. Diagnostic approach to hypophosphatemic rickets

24. Biochemical findings in rickets

25.  Alkaline phosphatase usually is ↑in all forms of rickets.  Serum phosphorus concentrations usually are↓ in both hypocalcemic and hypophosphatemic rickets.  Serum Ca is ↓only in hypocalcemic rickets.  Serum parathyroid hormone typically is ↑in hypocalcemic rickets, in contrast it is N in hypophosphatemic rickets.  25-OH vitamin D reflect the amount of vitamin D stored in the body, and is ↓in vit D deficiency.  1,25-OH2 vitamin D can be↓, N or ↑in hypocalcemic rickets and usually is N or slightly ↑in hypophosphatemic rickets.

26. Treatment of Rickets  Vitamin D. Stoss therapy: 300,000-600,000 IU orally or IM in 2-4 divided doses over one day.  High dose vit D 2000-5000 IU orally for 4-6wks followed by 400 IU daily orally as maintenance.  Adequate dietary Calcium & phosphorus provided by milk, formula & other dairy products.  Symptomatic hypocalcaemia need IV Cacl as 20mg/kg or Ca gluconate as 100mg/kg as a bolus, followed by oral calcium tapered over 2-6 weeks.

30. *Primary hyperplasia - adenoma - carcinoma *Secondary persistent hypocalcaemia *Tertiary secondary leads to hyperplasia

31. Pathology - PTH overproduction - Increased renal tubular absorption, intestinal absorption and bone resorption of Ca - Hypercalcaemia and hypercalciuria - Suppressed phosphate tubular reabsorption - Hypophosphataemia and hyperphosphaturia

32. Pathology *Hypercalcaemia calcinosis, stone formation, recurrent infection and soft tissue calcification *Bone resorption loss of bone substance, subperiosteal erosion osteitis fibrosa cystica and brown tumors

33. Symptoms & Signs *Hypercalcaemia anorexia, nausea, depression and polyuria *Bone rarefaction pain, pathological fractures and deformities *Biochemistry hypercalcaemia, hypophosphataemia, high alk. Phosphatase and serum PTH

35. X-rays - Subperiosteal bone resorption - Generalized decrease in bone density - Brown tumors - Chondrocalcinosis knee, wrist and shoulder

42. Treatment  Surgical excision of adenoma or hyperplastic parathyroid tissue  Hungry bone syndrome ◦ Treated by vitamin D

43. * Normal mineralization * Decrease bone mass (amount of bone per unit volume) * Age related * Associated or manifestation of other conditions

44. Causes * Idiopathic * Nutritional * Endocrine disorders * Drug induced * Malignant diseases * Miscellaneous

46. - Idiopathic osteoporosis - normal investigations - In old patients we have to role out malignancy and multiple myeloma - Younger patients must be fully investigated - Several causes may be involved - Osteoporosis can be associated with osteomalacia

47. Symptoms & Signs - Bony aches - Easy fractures spine - lower radius - femoral neck - Rib fracture, chest pain - Normal biochemistry

49. X-rays - Decrease bone density - Wedging or biconcave vertebrae - Thin cortex and deformities - Dexa Scan - Biopsy

56. Treatment - Treat underlying cause - Idiopathic, extremely difficult - Calcium and vitamin D - Fluoride and triple therapy - Calcitonin, Diphosphonate - Treat fractures

58. Prevention * Good diet * Exercise * Exposure to sun light * Ca supplement * Hormone therapy

59.  Diminished renal P excretion  Increased Ca excretion  Impaired synthesis of Vit D  Toxicity e.g. Aluminum and amyloidosis