Effects of thymectomy on bone growth in the rat.

The effects of thymectomy (TMX) at 1 or 5 days of age on the subsequent growth of bone have been determined in male and female Holtzman rats. The rats were maintained under aseptic conditions to minimize any effects of infection or wasting disease on bone growth. Femur length and distal epiphyseal cross sectional area were significantly reduced in TMX female rats at 3 months of age. At 1 month of age, the width of the undifferentiated zone was increased and at all subsequent times the columnar zone and growth plate were narrower in TMX rats. The incorporation of 35S into the femur, particularly the proximal and distal growth plates, was uniformly reduced in TMX rats as determined by scintillation counting and autoradiography. Additionally, there was an obvious overall reduction in alcian blue stationing intensity in the growth plates of TMX rats when compared to sham-operated controls. These results suggest a significant reduction in detectable glycosaminoglycan (GAG) content and in bone growth in TMX rats. Although there were minor variations, there were no major differences attributable to sex or timing of thymectomy. At present the causes of this moderate reduction in bone growth in TMX rats are unknown. One explanation might be that the thymus supplies or is in some other way involved in the provision of a hormone and/or cells that are required for normal bone growth. Another possibility is that the thymus is normally a source of immune suppressor cells which are needed to limit auto-immune reactivity against GAG or other antigenic determinants associated with bone. Thymectomy would remove these suppressor cells, thus permitting an auto-immune response which interferes with bone growth. Finally, perhaps the most plausible explanation is that thymectomy reduces cell production in the bone marrow which, in particular, reduces the turnover of monocytes. This reduced output of monocytes in TMX rats might ultimately lead to a reduction in osteoclast activity necessary for normal remodelling and growth of bone. We currently favour this last explanation.