Rickets

Definition: It is a metabolic disease of bone of infancy & childhood resulting from poor mineralisation of growing bones before epiphyses are fused & is caused by disturbance in Ca+2 & phosphate metabolism.

Classification of Rickets:  1)Nutritional Rickets (MC),   2)Renal Rickets ( 2nd MC), 3)Hypophosphatemic Rickets(Vit-D Resistant Rickets),   4)Vit-D dependent Rickets Type I (Liver),    5)Vit-D dependent Rickets Type II ( Receptor insensitivity)

NUTRITIONAL RICKETS

Pathophysiology: see the picture 

Clinical Features: 

1. HEAD:- Craniotabes ( earliest sign)- pingpong ball like sensation;
   Anterior fontenelle- larger & delayed closure
   Frontal & parietal bossing– Caput Quaratum, Hot-cross bun appearance
2. CHEST:- Rachitic Rosary,
   Harrison Sulcus,
   Pigeon Chest
3. ABDOMEN:- Potbelly(protuberent abdomen)
4. SPINE:- Kyphosis, Scoliosis, Lordosis
   
5. PELVIS:- Pelvic inlet & oulet-narrowed; Rachitic Pelvis- obstetric problem later on in female during child birth
6. EXTREMITIES:- Epiphyseal enlargement– wrist,knee, ankle.; Softened bone-bending; Knock knee(genu valgum), Bow leg(Genu varum), Coxa vara.
7. MUSCLES:- Lack of Tone, Poorly developed
8. OTHERS:- Rachitic Dwarfism, Delayed dentition, Deficient dental Enamel, Secondary Anaemia

RADIOLOGICAL FEATURES: (of lower end of Radius/Ulna (wrist), knee joint)

Lovette’s Radilogical Staging:

        I.            Stage I : Acute Stage (Early)
Epiphysis- cloudy appearance, poorly defined margin, ≥1 indistinct ossification centre
Metaphysis- Splaying, deficient in Ca
Periosteum- thickened
Frcature of long bones

      II.            Stage II : Established Stage
Epiphysis- Mottled, irregular, ill-defined
Metaphysis- Splaying & Cupping, Widening; Margin irregular & ragged- Fraying
Periosteum- Normal; if bowing of bone then thickened on concave side
Bowing of Long wt. bearing bones
Transverse trabeculae disappeared

    III.            Stage III : Stage of Repair(Healing stage)
Epiphysis- ossification centre—more dense, well defined; mottling
Dense line at epiphysio-metaphyseal junction→the newly formed calcified cartilage
Bending deformity gradually subsides with continued growth
Marked difference between end of shaft & epiphysis still there.
Appearance of transverse trabeculation.

    IV.Stage IV : Completely Repaired
-Broadened metaphysis- still there
–Bone clearly defined with normal Ca-content
-The stage marks the end of process
-Bone is now completely repaired.

LABORATORY INVESTIGATIONS:

• S. Ca-level  ̶  Normal/↓
• S. phosphorus- ↓↓
• S. Alkaline Phosphatase  ̶  ↑↑
• S. Vit-D level ̶   low
• Urine Ca  ̶  low

D/D:

1. Infantile Scurvy
2. Congenital Syphilis
3. Congenital Epiphyseal Dysplasia
4. Familial Bow leg

TREATMENT:

1. Medical Treatment
2. Prevention of Deformities
3. Treatment of existing deformities

1. Medical Treatment-
   –Adequate sunlight exposure; Milk & Cheese consumption
   –Severe Case: I/M injection of massive dose- 6 lac units ( 600,000 IU)
   –Milder Case: Oral Supplements of Vit-D
   # Ca- supplements along with Vit-D
   → 2-4 weeks period: X-ray evidence of healing to be evident.
2. Prevention of Deformities-
   -No pressure/strain over limb
   -movement control/Non-wt bearing
   -Splint use
3. T/t of Established deformity-
   a)Splinting
   b)Corrective Osteotomy- only after 3^rd stage of Rickets reached.

RENAL RICKETS

2 major types:

1)    Renal Disease with ‘Phosphate retention’

2)    Renal disease with excess ‘Phosphate loss’

1)    RENAL DISEASE WITH “PHOSPHATE RETENTION”:-  Glomerular Rickets

C/F–

• Pain in joints
• Leg deformities- genu valgus, slipping of upper femoral physis
• Renal dwarfism

X-Ray–

• Generalised rarefaction of bones
• Rachitic changes at epiphyseal ends of long bones
• Cystic lesion in the bones (Moth-eaten appearance)

Blood Investigation-

• S. Phosphate level ↑
• PTH ↑
• S. Ca²⁺ ↓/normal

2)    RENAL RICKETS WITH “EXCESS PHOSPHATE LOSS”:- Tubular Rickets

 a)     Defective phosphate reabsorption with defective excretion of H⁺-ion (Renal Tubular Acidosis)

b)    Defective reabsorption of phosphate, amino acids & glucose (Fanconi Syndrome)

 

a)     RENAL TUBULAR ACIDOSIS(RTA):  

–         A state of systemic “Hyperchloremic metabolic acidosis”

–         Impaired urinary acidification

–         Hypophosphataemia, phosphaturia

–         Bicarbonaturia(variable)

–         Hypercalciuria

–         Hyperkaluria

Alkaline urine→ Precipitation of Ca-salts in Renal tubules→ Nephrocalcinosis & Nephrolithiasis

C/F-

–         Bone pain

–         Growth retardation

–         Osteopenia

–         Pathological Fracture

–         Renal stone
X-ray-

• Rachitic changes in bones
• Calcification in renal tubules

Treatment-

–         Acidosis reversed by giving alkaline salts, e.g. Na-citrate & -lactate; Ca-gluconate

–         Administration of bicarbonate

–         Oral phosphate supplement (Joulie’s solution)
b)    FANCONI SYNDROME:

–         Proximal renal tubules fail to absorb Phosphate, Glucose, & Amino acids → Glycosuria, Phosphaturia, Aminoaciduria

–         Causes: 1)Inborn error of metabolism; 2)Acquired causes- Lead/Mercury poisoning, Drugs-tetracycline, gentamycin etc.

–         Lab Findings: a)Glycosuria, Phosphaturia, Aminoaciduria
b)Hyperchloremic metabolic acidosis
c)Hypokalemia, Hypophosphatemia, Hypouricemia

–         C/F:

• Vomiting, polydipsia, polyuria, dehydration
• Weakness, fever with dehydration
• Metabolic acidosis
• Clinical & radiological signs of Rickets

–         Diagnosis: Glycosuria & Aminoaciduria with stunted growth & rickets refractory to ordinary doses of Vit-D, Metabolic Acidosis & Hypokalemia

–         Treatment: Usually large dose of Vit-D, starting with 5000 IU/day increased to 2000-4000 IU/kg/day. Most patients need 25,000 IU/day to heal rickets.

Vit-D Resistant Rickets (Hypophosphatemic Rickets)/(Familial hypophosphatemia)

–         Non-nutritional

–         Most frequent cause of dwarfism

–         Fails to respond to usual dose of Vit-D but responds to massive dose of Vit-D

–         X-linked dominant (most common), Autosomal recessive & Sporadic

PATHOLOGY:

a)     Defect in proximal tubular reabsorption of phosphate;

b)    Defect in conversion of 25(OH)D₃ → 1,25(OH)D₃.
C/F:

–         Short stature

–         Pain

–         Deformity– bow leg, knock-knee, Tackle deformity(Wind-swept deformity)

–         Marked ligamentous instability

–         Waddling gait- due to Coxa vara

–         Usual findings of rickets
Lab Findings:

• S. Calcium level- ↓/N
• S. Phophate̶  ↓↓
• S. ALP- ↑↑↑
• S. PTH level- N
• Urine- Phosphate ↑↑↑
• No Amino acid/Glucose/Bicarbonate /Potassium in urine (differentiating features from Renal Rickets due to Fanconi syndrome)

Treatment:

1)    Phosphate supplementation (1-2 gm/day): Joulie’s solution 5-10 ml 4times a day (30.4 mg of phosphorus/ml); diet rich in phosphorus

2)    Large dose of Vitamin-D: 50,000 to 500,000 IU/day; Toxic side effects- Hypercalcemia, Renal injury
3)    Titration of dose by- a)Urine Sulkowitch Test: +1 or +2 maximum; b)S. Ca-level ≤ 12mg/dL; c)Urine excretion of Ca ˃200mg/day

4)    Vit-D supplementation:  until growth complete, after that →may be continued to prevent osteomalacia.

5)    Correction of deformities: A)SPLINTS– to prevent progression; B)SURGERY– after closure of epiphyses; – when X-ray shows healed stage of Rickets.

 

HEPATIC RICKETS (Vitamin-D dependent Rickets type I) 

Hepatobiliary conditions affect the vitamin-D metabolism by 2 ways:

1)    Failure of bile salts secretion due to abnormality in hepatobiliary system- ↓absorption of fat-soluble vitamins, e.g. extrabiliary atresia, cystic fibrosis

2)    Failure of hydroxylation of cholecalciferol in liver( by microsomal enzyme 25-hydroxylase) due to hepatocellular damage, e.g. hepatitis, heavy metal poisoning causing liver damage, prolonged anticonvulsant drugs use (Phenytoin, Phenobarbital etc.)

–         Clinical features/Radiological findings of rickets

–         Lab findings- s/o liver damage

Treatment:

–         t/t of underlying condition

–         Vitamin-D supplement: 100-250 μg vit-D or, 0.2 μg/kg 1,25(OH)-cholecalciferol

–         Ca & phosphorus supplementation.
CELIAC RICKETS

• Celiac ds has mal-absorptive defect causing loss of dietary fat & fat-soluble vitamin-D; usually due to Gluten-sensitive enteropathy
• Excess free fatty acids combine with Ca & precipitate as SOAP→ excreted in faeces.
• Rickets may develop in growing child
• Lab findings s/o fat in stool & +ve findings on biopsy of duodenal mucosa- diagnostic.
• Treatment: Gluten-free diet, parenteral administration of high potency Vit-D, I/M Ca-lactate injection & high protein diet.