Introduction: Osteopetrosis is a heterogeneous group of heritable disorders with a defect in osteoclast-mediated bone resorption. We present two cases which demonstrate the variability in phenotypes.
Cases: Case 1 is a 19-year-old man with a strong family history of osteopetrosis who was diagnosed at birth. He had sustained 10 upper and lower limb fractures, and has mild sensorineural hearing loss on audiometry. He was vitamin C and vitamin D deficient with a normocytic anaemia. He was given vitamin C and cautious vitamin D replacement.
Case 2 is a 54-year-old female who was diagnosed at six weeks of age. She has sustained >40 pathological fractures, is blind despite surgical optic nerve decompression at a young age, has pancytopenia and suffered from recurrent osteomyelitis and osteonecrosis of the jaw. She was managed with dexamethasone and interferon gamma.
Discussion: Osteopetrosis occurs as a result of a loss of function mutation, which impairs osteoclast acidification at the ruffled border through trafficking or fusion of lysosome-related organelles. Severe cases may have pancytopenia, hepato-splenomegaly, and cranial nerve dysfunction including blindness. Patients have high fracture risk. Radiologically, they often have characteristic ‘bone within bone’ appearance and ‘sandwich vertebrae’. Bone marrow transplant can be considered for osteoclast-intrinsic defects when diagnosed young (usually <1year). Corticosteroids are second line therapy and interferon gamma remains experimental, with case reports showing clinical improvement. A current randomised trial is running in adults.
Conclusions: While rare, osteopetrosis has a wide clinical spectrum. Less severe cases have normal life expectancy. Severe disease has high risk of fractures, pancytopenia, deafness and blindness and risk of recurrent osteomyelitis. While early diagnosis is important, there are still few management options available for these patients.