Skeletal changes during prolonged external irradiation: alterations in marrow, growth plate and osteoclast...

This report describes hematologic and skeletal changes in young mice subjected to continuous external whole body irradiation (45 rads/day) for 4 days to 12 weeks. Irradiation caused a rapid depletion of hematopoietic stem cells, marrow aplasia and pancytopenia, all of which persisted during the period of irradiation but resolved afterward. In spite of suppressed cellular proliferation and disarray of cartilage cell columns in metaphyseal plates, linear bone growth appeared to continue at physiologic rates. Histologic and morphometric studies provided no evidence of impaired osteoblast function, but the presence of thickended trabeculae beneath the growth plate and of cartilagenous islands within cortical shafts of long bones indicated that bone remodeling was deficient. Direct osteoclast counts demonstrated that marrow aplasia was followed by a progressive decline that could not be reversed by parathormone injections or infusions with mature macrophages and lymphocytes but that resolved once the bone marrow recovered following cessation of irradiation. Therefore, the altered bone remodeling probably resulted from radiation injury to osteoclast precursors in the hematopoietic compartment.