MALIGNANT OSTEOPETROSIS TREATED WITH GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR - ABSENCE OF BLOOD MONOCYTOSIS AND NO EFFECT ON BONE SCLEROSIS

Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates b oth osteoclasts and osteoblasts, and treatment with GM-CSF may cause o steoporosis. Malignant osteopetrosis is a disease of defective osteocl ast function. To study the possibility of an influence on bone scleros is, five children, aged 6 months to 2 years, with malignant osteopetro sis were entered into a phase I/II open study with recombinant human G M-CSF (rhGM-CSF). rhGM-CSF (2.5 mu g/kg) was given subcutaneously once daily for 3 months. No effect on bone sclerosis or marrow cellularity was observed. Serum alkaline phosphatase activity decreased successiv ely, which indicates an activation of osteoblasts. No peripheral blood monocytosis developed, although total white cell count, neutrophils, and eosinophils markedly increased. Dose-dependent side-effects includ ed respiratory symptoms with wheezing and dyspnea in four of five chil dren. We speculate that our results could suggest a more general defec t of the myeloid lineage, rather than only of the osteoclasts.