Rickets

1. RICKETS

2. Clinical condition in which there is inadequate mineralisation of growing bone. Primarily due to Vit D deficiecy or a disturbance in its metabolism. Rickets – children Osteomalacia bones of adults.

3. VIT.D DEFICIENCY  decrease absorption of ca. & p from the gut  decrease ca. level in blood  increase PTH  mobilization of ca. & po4 from bones and decrease tubular reabsorption of p in kidneys  normal serum ca. & low serum po4  decrease ca. available for bones  ca. & po4 will be far below 40  failure of calcification around the mature cart. cells and osteoblasts in the ostoeid tissue.

4. Normal bone growth THERE ARE 4 ZONES : 1. ZONE OF RESTING CARTILAGE : 1 layer 2. ZONE OF PROLIFERATING CART. : 6 layers 3. zone OF PROVISSIONAL CALCIFICATION " epiphyseal line " : the cart. cells in this layer become mature, they containe alkaline phosphatase  release the phosphate in the matrix which already contains ca. & po4 in solution  increase production of ca. & po4  once the production exceeds 40  precipitation of ca.phosphate in the matrix around the cartilage cells  death of the cells. 4. ZONE OF BONE FORMATION : The layer of prov. calc. is invaded by capillaries and osteoblast which deposit a layer of organic bone matrix " osteoid tis .“  rapidly meniralized and the calcified cartilage ultimitly replaced by bone.

5. PATHOLOGY The mature cartilage cells will not die and the proliferating zone will be formed of many layers and invades the adjacent zone of of provis . calc.- irrIegularity of epiphseal line. The prov. calc. zone and newly formed ost . tis . will fail to calcify or will calcified irregularly.  wide irregular frayed zone of non rigid tis . " RACHITIC METAPHSIS " is produced. In the shaft the preformed bone is replaced by uncalcified ost .  soft rarified cortical bone  bone deformities & green stick fractures.

6. CAUSES Vitamin D deficiency Lack of sunlight exposure Dietry lack of meat & dairy products Malsbsorption Failure of 1,25 vit D synthesis Chronic renal failure Hyperphosphataemia & kidney damage Vit D dependent rickets ( type 1) - AR Inactivating mutation in 1,25,hydroxylase enzyme.

7. Vitamin D receptor defects Vit D dependent rickets type2 (AR) Mutation in vit D receptors Defects in phosphate metabolism Primary hypophosphataemic rickets(XLH) renal phosphate wasting. Fanconi syndromes Proximal renal tubular acidosis. Hypophosphatasia Mutation of bone specific ALP

8. NUTRITIONAL RICKETS VIT D DEFICIENCY 3-18 MONTHS LACK OF SUNLIGHT EXPOSURE & NO DIETARY SUPPLEMENTATION PROLONGED BREAST FEEDING CALCIUM DEFICIENT DIET BOTH VEGETARIANS WHO AVOID DAIRY PRODUCTS

9. GASTROINTESTINAL RICKETS ABSORPTION OF CALCIUM & VITAMIN D PREVENTED GLUTEN SENSITIVE ENTEROPATHY CROHNS DISEASE ULCERATIVE COLITIS SARCOIDOSIS SHORTGUTSYNDROMES LIVERDISEASE

10. X LINKED HYPOPHOSPHATEMIA MOST COMMON INHERITED ETIOLOGY X LINKED DOMONANT DISORDER DEFECT IN PHEX GENE(REGULATE TRANSPORT OF RENAL PHOSPHATES) RENALPHOSPHATE WASTING HYPOPHOSPHATEMIA RICKETS SHORT STATURE DENTAL ABSCESSES

11. McCUNE -ALBRIGHT SYNDROME HYPOPHOSPHATEMIC RICKETS CAFÉ AU LAIT SPOTS PRECOCIOUS PUBERTY FIBROUS DYSPLASIA OF MULTIPLE LONG BONES CONSTITUTIONAL ACTIVATION OF C-AMP-PKA SIGNALING PATHWAY DUE TO GENETIC DEFECTS IN G SIGNALING PROTEINS

12. 1 ALPHA HYDROXYLASE DEFICIENCY VITAMIN D DEPENDENT RICKETS <24WKS OF AGE WEAKNESS PNEMONIA SEIZURES BONEPAIN BONE CHANGES OF RICKETS

13. END ORGAN INSENSITIVITY 3 TO 30 FOLD HIGHER THAN NORMAL VALUE OF 1,25(OH)2VITD3 NEAR TOTAL LOSS OF HAIR FROM HEAD & BODY

14. FANCONIS SYNDROME(RENAL TUBULAR ABNORMALITY) FAILURE OF RENAL TUBULAR ABSORPTION OF MANY MOLECULES SMALLER THAN 50Da KIDNEYS LOSE CALCIUM,PHOSPHATE,MAGNESIUM, BICARBONATE,SODIUM,POTASSIUM,GLUCOSE, URIC ACID AND SMALL AMINOACIDS SHORT WITH RICKETS & DELAYED BONE AGE HYPOPHOSPHATEMIA,METABOLIC ACIDOSIS,RENAL OSTEODYSTROPHY(DECREASED CALCIUM AND PHOSPHATE REABSORPTION)

15. HYPOPHOSPHATASIA . ALP DEFICIENCY . 1 PER 1 LAKH POPULATION AUTOSOMAL RECESSIVE CONDITION MUTATION IN ALP GENE IN CHROMOSOME 1 ABNORMAL MINERALISATION OF BONE PATHOLOGICAL FRACTURES LOSS OF TEETH FAILURE TO THRIVE,RAISED INTRACRANIAL PRESSURE & CRANIOSYNOSTOSIS

16. PERINATAL LETHAL FORM CHILDHOOD FORM PRESENTS WITH RICKETS AT 2 OR 3 Yrs WITH REMISSION IN ADOLESCENCE ADULT FORM-MILD OSTEOMALACIA WITH PATHOLOGICAL FRACTURES

17. RENAL OSTEODYSTROPHY BONY CHANGES ACCOMPANYING ESRD RF HYPERPHOSPHATEMIA HYPOCALCEMIA SECONDARY HYPERPARATHYROIDISM SUBPERIOSTEAL EROSIONS & BROWN TUMORS RICKETS VARUS OR VALGUS DEFORMITY AT THE KNEE OR ANKLES

18. CLINICAL FEATURES OF RICKETS Delayed milestones Irritable child Lethargy & hypotonia Stunted growth

19. Rickets: signs Skull Craniotabes Frontal and parietal bossing, flat occiput Anterior fontanelle is large with delay in closure.

20. Chest Rosary Harrison’s sulcus Pigeon chest

21. Extremities : Widening of wrist, Bowing of legs, Knock knee

22. Others: Scoliosis Kyphosis lordosis

23. “POT BELLY “ due to hypotonia of abdominal muscles & intestine . Downward displacement of the liver & spleen .

24. Investigations X-RAYS The X-RAYS of the wrists is best for early diagnosis 1.The classic triad of rickets : Broadening Cupping (concave) Fraying ( irregular) 2.Increase distance between the distal ends of radius & ulna and the metacarpal bones .

25. 3.Demeniralization of the shaft “ hypodensity ” 4.Fractures & deformities may be present  LOOSER’S ZONE  pseudo # occuring at the site of stress.

26. SUBPERIOSTEAL EROSIONS & BROWN TUMOR IN RENALOSTEODYSTROPHY SUBPERIOSTEAL EROSIONS-LATERAL ASPECT OF DISTAL RADIUS & ULNA & MEDIAL ASPECT OF PROXIMAL TIBIA .

27. Biochemical findings NUTRITIONAL RICKETS S . Ca - low / normal S . Posphorus – low S . ALP - High PTH – Raised 25(OH)D - low

28. VDRR is suspected when rachitic patients fail to respond to Vit D & calcium. 1,25(OH)2D raised 3-30 FOLD

29. Hypophosphataemic rickets high ALP, low phosphorus normal 25(OH)D & 1,25(OH)D

30. 1 ALPHA HYDROXYLASE DEFICIENCY LOW CALCIUM AND PHOSPHORUS HIGH ALP & PTH NORMAL 25-HYDROXY VITAMIN D3 MARKEDLY DECREASED LEVEL OF 1,25(OH)2VITD3

31. Treatment of rickets NUTRITIONAL RICKETS Adequate exposure to sunlight. Supplementation of vit D in diet. Therapeutic doses of vit D 200-600 units/day or As single IM inj of 600000 IU induces rapid healing. If line of healing ( sclerosis on the metaphyseal side of growth plate) is not seen after 3-4 weeks , same dose is repeated.

32. GASTROINTESTINAL RICKETS RECTIFY THE UNDERLYING GI PROBLEM

33. HYPOPHOSPHATEMIC RICKETS phosphate supplements – 2-3 gm/day & active vit D metabolites .[1,25(OH)2D 0.25-1.5microgm daily]

34. 1 ALPHA HYDROXYLASE DEFICIENCY ORAL ADMINISTRATION OF ACTIVATED VITAMIN D3

35. END ORGAN INSENSITIVITY CANNOT BE COMPLETELY CURED VERY HIGH DOSES OF VITAMIN D IV HIGH DOSES OF CALCIUM FOLLOWED BY ORAL SUPPLEMENTATION

36. FANCONI SYNDROME SIMILAR TO X LINKED HYPOPHOSPHATEMIA-ORAL PHOSPHATE & VITAMIN D ELECTROLYTE IMBALANCE SHOULD BE TREATED

37. HYPOPHOSPHATASIA NO SATISFACTORY MEDICAL TREATMENT BONE MARROW TRANSPLANTATION

38. RENAL OSTEODYSTROPHY DIETARY PHOSPHATE RESTRICTION PHOSPHATE BINDING AGENTS CALCITRIOL RENAL TRANSPLANTATION

39. Orthopaedic treatment Conservative – deformities correct spontaneously as rickets heals & with splinting. Operative – after 6 months of medical treatment . Corrective osteotomies

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