CYTOKINES AND BONE-RESORPTION IN OSTEOPETROSIS

An understanding of the role of cytokines in the modulation of osteocl astic activity has provided new information on the pathophysiology and therapy of osteopetrosis. The following review will detail the theore tical basis for the use of macrophage colony stimulating factor (M-CSF ) and interferon gamma in treating patients with severe congenital ost eopetrosis. A case study of a representative patient treated with M-CS F and the results of a trial of interferon gamma will be reported. Unt reated, patients with severe congenital osteopetrosis have about a 90% chance of death by age three. The only accepted therapy has been bone marrow transplantation. In the absence of a marrow donor, supportive therapy has been the mainstay. Based upon observation in animal mutant s, studies with macrophage colony stimulating factor are showing promi sing results in improving the hematologic picture and restoring normal growth. Therapy with interferon gamma has been shown to be effective in treating some patients with osteopetrosis by stimulating superoxide generation in white cells and osteoclasts, resulting in an increase i n white cell function, bone resorption, hematopoietic status, and neur ologic function. These new therapeutic modalities promise hope for pat ients who, without successful bone marrow transplantation, have little opportunity for survival.