[The modification of fracture healing by the cytostatic agent cyclophosphamide - an experimental interdisciplinary...

The influence of the cytotoxic agent cyclophosphamide (Endoxan) on the course of fracture healing has been investigated in rats. -- In 200 rats the right femur was osteotomized and stabilized by intramedullar nailing. The rats were distributed to 4 groups (n = 50) and submitted to the following scheme of treatment: group I had no further treatment after operation, group II was injected intraperitoneally daily for 14 days with 10 mg cyclophosphamide per kg body-weight beginning at the 3rd day after operation, group III was treated the same dose as group II but until 2 days before operation, group IV was injected the same dose as group II but beginning 20 days after operation. Beside continuous check of body weight and white blood cells as well as x-ray of the hind-limbs, 10, 20, 30, 50 and 70 days after operation both femora were excised and investigated by means of radiologic, scintigraphic, biomechanic as well as histomorphologic methods. The results obtained indicate that cyclophosphamide significantly retards the course of fracture reparation. The degree of retardation was directly depended on the phase of fracture healing process during cyclophosphamide treatment. The retarding effect was supreme in case of coincidence of the beginning of fracture healing and cytotoxic treatment (group II) and diminished relatively in case of cyclophosphamide treatment before (group III) or after (group IV) operation.