Osteopetrosis.

Osteopetrosis is a rare skeletal condition characterized by skeletal sclerosis caused by aberrant osteoclast-mediated bone resorption. Three clinically distinct forms of osteopetrosis are recognized--the infantile malignant autosomal recessive form, the intermediate autosomal recessive form, and the adult benign autosomal dominant form. The disease represents a spectrum of clinical variants because of the heterogeneity of genetic defects resulting in osteoclast dysfunction. The pathogenic defects may be intrinsic to either the osteoclast-monocyte lineage or the mesenchymal cells that constitute the microenvironment that supports osteoclast ontogeny and activation. Implicated factors include specific proto-oncogenes, growth factors, and immune regulators. A subset of patients with the intermediate autosomal recessive form has been characterized with carbonic anhydrase II isoenzyme deficiency. Management of patients with osteopetrosis requires a comprehensive approach to characteristic clinical problems including hematologic and metabolic abnormalities, fractures, deformity, back pain, bone pain, osteomyelitis, and neurologic sequelae. Medical treatment of osteopetrosis is based on efforts to stimulate host osteoclasts or provide an alternative source of osteoclasts. Stimulation of host osteoclasts has been attempted with calcium restriction, calcitrol, steroids, parathyroid hormone, and interferon. Bone marrow transplant has been used with cure for infantile malignant osteopetrosis. As osteopetrosis likely represents a spectrum of underlying etiologies resulting in osteoclast dysfunction, effective therapies most likely need to be individualized.