(Dichloromethylene)diphosphonate-induced impairment of T-lymphocyte function

The daily subcutaneous administration of (dichloromethylene)diphosphonate (clodronate) to 3-day-old normal inbred Wistar-Furth rats for 30 days produces osteopetrotic bone lesions resembling those of the osteopetrotic mutants. Furthermore, tooth eruption is prevented, growth slows down, and signs of runt disease appear. The weight of the thymus is decreased, and T cells from the thymus and spleen respond weakly to mitogens. These thymic disorders associated with defective bone resorption are very similar to those previously reported in the osteopetrotic mutant op rat and support the hypothesis of a link between the thymus and normal bone modeling and remodeling.