Osteopetrosis

Question 1

What is the definition of osteoporosis?

Answer 1

A genetic disease characterised by abnormally dense thick bone.

Question 2

What are the two types of osteopetrosis?

Answer 2

Autosomal recessive osteopetrosis:
- caused by mutations on CA2 gene encoding carbon anhydrase
- deficiency of carbonic anhydrase - leads to inhibit on of proton pumping increasing pH so osteoclasts fail to resolve bone because acidic environments are required so there is an imbalance between bone formation and bone resorption = excess bone formation.

Autosomal dominant osteopetrosis:
- caused by mutation in chloride channel 7 gene; less severe type
- associated with renal tubular acidosis - deficiency of carbonic anhydrase in kidney.

Question 3

What is the presentation of autosomal recessive osteopetrosis?

Answer 3

Impaired growth
Osteomyelitis of mandible
Dental abnormalities
Visual/hearing impairment - sclerosis of skull bones and cranial nerve compression
Hydrocephalus - obstruction of foramen magnum Symptoms of anaemia, thrombocytopenia, leukopenia

Question 4

What is the presentation of autosomal dominant osteopetrosis?

Answer 4

Can be asymptomatic, most commonly affects spine, pelvis, base of skull.
Vision loss, hearing loss due to sclerosis of skull bones, cranial nerve compression.
Pathologic fractures
Osteoarthritis

Question 5

What is the pathology of osteopetrosis?

Answer 5

Rare genetic disorder characterises by osteoclasts dysfunction - hardening of the bone.
Osteoclasts failure to resorb bone - increased density, overgrowth of bone.
Despite increased density, bones have disordered architecture, lack flexibility, thus prone to fractures.

Question 6

What are the investigations for osteopetrosis?

Answer 6

X-ray: increased thickness, bone within bone appearance, sclerotic rings in iliac bones, widened costochondral junctions, radiolucent metaphyseal bands, sandwich vertebrae (peripheral bony sclerosis with central licence of vertebral body).
Hypocalcaemia due to decreased reabsorption of calcium ions.
Increased PTH - secondary hypoparathyroidism
Increased acid phosphatase
Creatinine kinase.

Question 7

What is the management of osteopetrosis?

Answer 7

Meds - calcium, phosphate, vit D, antibiotics to treat osteomyelitis, anaemia - erythropoietin, corticosteroids, leukopenia - gamma interferon.
Surgery - mend fractures, bone marrow transplant.
Other therapies - not curable, supportive treatment, fractures - braces, treat dental abnormalities.