Rickets

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Rickets

• Dr Rajesh
• 26/09/07

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Definition

• Rickets is defined as the failure of
  calcification of osteoid in the growing person

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Definition

• it is a general disorder of metabolism affecting
  chiefly the growing bones due to deficiency of
  the active form of vit.D 1,25 dihydroxy vit.D .
• The essential changes of the bones are
• Decalcification of the normal bones.
• Formation of imperfectly calcified bone
• ? widening enlargement of the epiphyseal end of
  the long bones.
• THE SKELETAL MUSCLES THE NERVOUS
• SYSTEM ARE SOMETIMETIMES AFFECTED.

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• THERE ARE 2 TYPES OF VIT. D
• 1.D3 "CHOLICALCIFEROLE" which is of animal origin
  and produced by action of the U/V on
  7-dehydochlesterol in the skin.
• 2. D2 "ERGOSTEROLE" which is of plant origin and
  produced by action of U/V on ergosterol in the
  plants.
• The both types are biologically inactive, so they
  HYDROXYLATED in the LIVER --gt25 HYDROXY vit.d
• then HYDROXYLATED in the KIDNEYS ---gt the final
  active form of vit.D ?1,25 HYDROXY VIT.D which
  called CALCITRIOLE.

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Vit D actions

1. Promotes ca p absorption in small gut .
2. Increase ca p reabsorption in the kidneys.
3. Direct effect of menirals metabolism of bones
   "depositioin resorption "

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Rickets Symptoms

• a. early symptoms "appear b/w 3-6 months "
• 1.head sweating.
• 2.irrit. by day sleepnessness by night.
• b. advanced rickets
• delayed motor development "sitting,
  standing walking "

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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 bere 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.

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• THE CHANGES IN INFANTILE RICKETS
• 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 tis.

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1. 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.
   and hence the irregularity of epiphseal line in
   the X-RAY.
2. the prov. calc. zone and newly formed ost. tis.
   will failed to calcified or will calcified
   irregularly...? wide irregular frayed zone of
   non rigid tis. " RACHITIC METAPHSIS " is
   produced? flaring of bone rachitic rosary.
3. in the shaft the preformed bone is replaced by
   uncalcified ost. tis. from the periosteom ...
   ? formation of shell surrounding the shaft
   ? soft rarified cortical bone ? bone
   deformities green stick fractures.

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Rickets signs

• Skull
• Craniotabes, Frontal and parietal bossing, flat
  occiput
• Chest
• Rosary, Harrisons sulcus, Pigeon chest
• Extremities
• Widening of wrist, Marphans sign at ankle,
  Bowing of legs, Knock knee

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Hypotonia and laxity of joints

• Delayed motor milestones as sitting walking.
  Flaccidity of the whole body ?
  hyperextinsibility of joints. Smooth kyphosis in
  the dorso-lumber region while sitting
• ? it is correctable if the pt. suspended from the
  shoulders.
• The abdomen is distended POT BELLY due to
• hypotonia of abd. Muscles intistine .
• downward displacement of the liver spleen due
  to
• 1. laxity of their lig. deformity of chest wall
  .
• 2.hypotonia of the abd. Muscles.

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X-Ray

• The X-RAYS of the wrists is best for early
  diagnosis an shows
• 1.The classic triad of rickets
• broadening cupping (concave) fraying (
  irregular) of lower ends of radius ulna .
• 2.Increase distance between the distal ends of
  radius ulna and the metacarpal bones .
• 3.Demeniralization of the shaft hypodensity
• 4.Fractures deformities may be present
• ? LOOSERS ZONE ? linear partial fractures
  of long bones which failed to calcify.

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X-Ray

• THE EVIDENCE OF HEALING WILL APPEAR IN X-RAY
  BTWEEN THE 2ND 3rd weeks ? the line preparatory
  calcification indicate start of healing

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Complications of rickets

• TETANY it is usually precipitated by inf. Due
  to failure of compensatory mechanism.
• RECURR. CHEST INF. due to
• a. chest wall deformity .
• b. ass. Vit.A deficiency which is essential for
  integrity of epith. Surface of the resp. mucosa.
• c. defective function of immunity system esp.
  T-lymph
• FRACTURES OF BONES.
• DEFORMITIES OF BONES the most important is
  RACHITIC PELVIS .

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Treatment of rickets

• Daily administration of 1000 4000 units ?
  produce healing in 2 4 weeks the healing
  complete in 6 8 weeks .
• alternative method of treatment oral or IM
  administration of massive dose of vit.D 600.000
  IU that should not repeated except if there is no
  evidence of healing in X-RAY.
• the prematures in addition to vit.D also ca. p(
  60mg elemental ca/day 30 mg elemental p / day
  ).

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Lab studies

• Calcium Early calcium (ionized fraction) will be
  low however, more often, normal at diagnosis.
• Phosphorus low for age unless recent partial
  treatment or recent exposure to sunlight has
  occurred.
• Alkaline phosphatase Elevated
• Calcidiol levels are low, and parathyroid hormone
  levels are elevated.
• Aminoaciduria Occurs from the parathyroid
  activity aminoaciduria does not occur in
  familial hypophosphatemia rickets (FHR).

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Lab

• Calcium Increased in Jansen type
• Phosphorus
• Increased in renal osteodystrophy
• Normal in metaphyseal dysostosis
• ALP
• Low in hypophospatasia
• Normal in metaphyseal dysostosis
• Aminoaciduria no in phosphate deficiency rickets
  except fanconi syndrome. No in metaphyseal
  dysostosis

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Rickets Classification

• 1 Calcium deficient
• Lack of vit D
• Lack of sunlight
• Dietary deficiency
• congenital
• Malabsorp of vit D
• Hepatic disease
• Anticonvulsants
• Renal osteodystrophy
• Vit D dependent type 1

• 2 Phosphate deficient
• Hypophosphatemia
• Fanconi syndrome
• RTA
• Oncogenic hypophosphetemia
• Phosphate deficiency

4 Conditions mimicking rickets Hypophospatasia
Metaphyseal dysostosis Jansen Schmid
3 End organ resistance to vit D VDDR type 2
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Rickets Classification

• Vitamin D dependent-caused by reduced activity of
  25 hydroxy alpha-hydroxylase(enzyme that
  activates vitamin D)
• Vitamin D deficiency- classical rickets caused
  by low endogenous vitamin D
• Vitamin D resistant- defect in tubular
  reabsorption of phosphate

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VITAMIN-DDEPENDENT RICKETS, TYPE 1

• Genetic deficiency (variable) in the enzyme to
  convert calcidiol to calcitriol in the kidney.
• Autosomal recessive, chromosome 12.
• Presentation as nutritional rickets with a more
  variable phosphate concentration.
• Medical therapy Treatment is calcitriol 0.5-1.5
  mcg/d.
• Also respond to pharmacologic doses of vitamin D
  (5000-10,000 u/d).

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RECEPTOR DEFECT RICKETS (FORMERLY
VITAMIN-DDEPENDENT RICKETS, TYPE II).

• Recessively inherited lack of calcitriol receptor
  sites
• Properly called vitamin-Dresistant.
• 50 have alopecia, which sometimes is complete.
• Hypocalcemic and usually normophosphatemic.
• Several mutant forms and a wide range of severity
  and of response to calcitriol therapy including
  some totally resistant to therapy.
• May respond to high oral calcium intake plus
  calcitriol.

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DEFECTIVE 25-HYDROXYLASE

• Two cases (a single family in the US and possibly
  1 in Germany) have been reported having
  deficiency of 25 hydroxylase.
• Inheritance probably is autosomal recessive.
• The clinical picture resembles nutritional
  rickets with a later age of onset.
• Treatment with calcidiol in physiologic amounts
  is sufficient. Calcidiol is a natural metabolite
  of vitamin D. It is hydroxylated once at the 25
  position and is the circulating form for vitamin
  D in plasma

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FANCONI SYNDROME AND ONCOGENOUS

• Fanconi syndrome
• E.g. cystinosis and tyrosinemia,
• Renal phosphate wasting along with aminoaciduria
  and glycosuria.
• Responsive to a combination of managing the
  underlying cause when possible and to either
  vitamin D or calcitriol therapy.
• Oncogenous
• Several mesenchymal tumors of bone or connective
  tissue (including those called nonossifying
  fibromas, fibroangioma, and giant cell tumors)
  secrete a phosphaturic substance (parathyroidlike
  protein) that results in rickets.

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Osteodystrophy (renal rickets)

• In end-stage renal disease, renal 1-hydroxylase
  is diminished or lost, and there is defective
  excretion of phosphate.
• This leads to hypocalcemia and to failure of
  osteoid calcification
• Only variety of rickets with a high serum
  phosphate.
• Management of these patients includes a low
  phosphate intake, calcitriol

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Hypophosphatasia

• This autosomal recessive
• Absence of alkaline phosphatase
• Causes rickets without disturbance of calcium and
  phosphate metabolism.
• There is a range of clinical expression from a
  severe, even lethal, form to mild disturbance.
  There is currently no useful treatment.

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METAPHYSEAL DYSPLASIA (SCHMID VARIETY)

• genetic disorder of collagen with the gene locus
  on chromosome 6.
• The appearance of the metaphyses on radiographs
  cannot be distinguished from changes seen in
  rickets
• Osteotomies, if needed, should be deferred until
  growth is complete.

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SUN EXPOSURE

• The AAP Committee on Environmental Health
  recommends that infants less than 6 months of age
  avoid all sunshine exposure (Pediatrics, 104328-
  333.1999)

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AAP Vit D Supplementation

• 2003 AAP Recommendation 200 IU/day of Vitamin D
  for all infants and children beginning in the
  first two months of life

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Knock Knees / Genu Valgum

• Legs are bowed inwards in the standing position.
  Bowing occurs at or around the knee. On standing
  with knees together, the feet are far apart.