Osteopetrosis

Definition:
Osteopetrosis also known as marble bone disease and Albers-Schonberg disease is an extremely rare inherited disorder whereby the bones harden, becoming denser, in contrast to the more prevalent osteomalacia, in which the bones soften.

Variants:

1. Autosomal recessive (malignant type)
2. Autosomal dominant (benign type)
3. Carbonic anhydrase II deficiency (Type 3 Renal tubular acidosis)

Pathogenesis:


Pathologic alteration of osteoclastic bone resorption leads to thickening of cortical and lamellar bone.

Clinical Features:

• Brittle bones
• May have blindness, deafness and cranial nerve involvement if skull base involvement
• Osteopetrosis tarda
• Fractures related to brittle osteopetrotic bones or osteomyelitis
• Osteopetrosis congenita
• Failure to thrive
• Growth retardation
• Sshort stature
• Intracranial calcifications
• Sensorineural hearing loss
• Psychomotor retardation

Lab Investigations:

• X-rays

• Blood tests: anemia, elevated acid phosphatase level in some cases.
• Imaging studies: markedly increased density of skeleton, osteopetrosis tarda often detected as incidental finding, typical dense deformed sclerotic bones.

Differential Diagnosis:

• Hypervitaminosis D
• Hypoparathyroidism
• Paget's disease
• Diffuse bone metastasis of breast or prostate cancer .
• Intoxication with fluoride, lead or beryllium.
• Hematological disorders such as myelofibrosis, sickle cell disease and leukemia.

Complications:

• Multiple fractures
• Anemia (decreased marrow space)
• Hepatosplenomegaly
• Hypersplenism

Treatment:

1. Surgery

• Surgery useful if significant alterations of facial profile, recurrent fractures with subsequent deformity or severe related degenerative joint disease.
• Bone marrow transplant is only curative treatment for osteopetrosis congenita.
• Placental blood transplant (umbilical cord blood) as useful source of allogeneic hematopoietic stem cells for bone marrow reconstitution.

2. Medical

• Interferon gamma-1b
• 1,25-dihydroxyvitamin D

Prognosis:

• Good for osteopetrosis tarda, poor for other types.
• Osteopetrosis congenita usually results in death by 2 years from severe anemia, bleeding or infection.