Osteopetrosis: Bone Diseases

Fig: A 24 years old patient with infantile osteopetrosis with mandibular osteomyelitis and multiple draining fistulas
Other names:
1. Marble bone disease
2. Albers-Schonberg Disease
3. Osteosclerosis Fragilis Generalisata

Definition:
It is group of rare, hereditary bone disease in which there is defect in failure of osteoclasts to resorb bone, resulting in increased bone mass with poor mechanical properties.

It shows thickened or sclerotic bones, which are fragile due to the collagen fibres to augment bone matrix and defective remodelling of woven bone to compact bone.

Etiology: Genetic mutations

Clinical Features:
Three types: 
(A) Infantile osteopetrosis: 
- Autosomal recessive
- Malignant Osteopetrosis
1. Growth retardation
2. Bone fractures (due to widespread sclerosis)
3. Nasal stuffiness (due to mastoid and paranasal sinus malformation)
4. Macrocephaly, Frontal bossing, hypertelorism and a short nose
5. Sleep apnoea, blindness (due to retinal degeneration), deafness and facial paralysis → due to cranial nerve compression
6. Anemia and pancytopenia (due to sclerosis of trabecular bone replacing the medullary space often leads to deficiency of bone marrow tissue)
7.Bruising and bleedings (due to thrombocytopenia)
8. Recurrent infections (due to granulocytopenia)

Oral manifestations:
1. Failure or delay in eruption of teeth
2. Osteomyelitis?
3.  Fracture of jaw bone during normal extraction
4. Enamel hypoplasia, micro dentinal defects and arrested  root development

(B) Intermediate osteopetrosis:
- Autosomal recessive

(C) Adult osteopetrosis:
- Autosomal dominant
- Also called benign osteopetrosis
- Age: Late childhood or adults
Signs and Symptoms
Asymptomatic: 50% cases
1. Bone pain: Chief complaint
2. Scoliosis, osteoarthritis, Osteomyelitis of mandible (10%)
Note: Bone marrow function is not compromised.

Radiologic features:
1. Long bones: Sclerosis may be uniform or of alternating radiolucent-radiopaque bands at the end of bone

2. Skull bone: thickened and dense specially at the base of skull

3. Alternating focal sclerosis of skull base, pelvis, and vertebral end plate resulting in "Sandwich vertebrae" and "Rugger-jersey spine".

4. Thickening and defective bone remodeling results in funnel-like appearance (Erlenmeyer flask deformity) of the long bones and "Bone-in-bone" appearance of the vertebrae and phalanges.

5: If jaw involved: evidence of fractures and osteomyelitis

Laboratory findings: Markers
1. Creatinine kinase BB isoenzyme raised
2. Tartrate resistant acid phosphatase (TRAP) raised
Others:
3. Hypocalcemia
4. PTH level raised

Histologic features:
1. Endosteal production of the boone
2. Plenty osteoblasts, seldom osteoclasts
3. Residual fibrous marrow tissue

Treatment:

Infantile osteopetrosis if untreated → death in 1st decade of life due to severe anemia, bleeding or infections. Hence primary treatment is aimed to improve hematopoiesis and minimising neurologic problems.
- Hematopoietic stem cell transplantation (HSCT) before age of 3 months
- Calcitriol: Activates osteoclasts →bone resorption
- Erythropoietin and corticosteroids: To counter anemia and stimulate bone resorption
- IFN-Y1b with HSCT or alone
Prognosis: Poor

Adult osteopetrosis: No treatment required
Prognosis: Good