Human malignant osteopetrosis: pathophysiology, management and the role of bone marrow transplantation

Osteopetrosis is a heterogeneous group of diseases characterized by lack of osteoclast function. Osteopetrosis is found spontaneously in most mammalian species and many transgenic animals have been created, but so far no animal model has been found that genetically corresponds to human malignant autosomal recessive osteopetrosis. The only curative treatment for malignant osteopetrosis is bone marrow transplantation. A review of the literature and preliminary data from IBMTR shows that infants transplanted with marrow from an HLA-identical sibling or unrelated volunteer donor have an actuarian five-year survival with a functioning graft of 50-70%, while those transplanted with a T-cell-depleted mismatched marrow have a very poor survival of only about 10%.