The effects of cisplatin on the incorporation of fresh syngeneic and frozen allogeneic cortical bone grafts

Abstract

Allograft transplantation with concomitant chemotherapy has proven successful in the treatment of malignant bone tumors. However, these chemotherapeutic agents may delay tissue healing, resulting in clinical complications. To clarify the effects of cisplatin on the healing of bone grafts, we studied the incorporation of stably fixed massive diaphyseal femoral syngeneic and allogeneic grafts in rats treated with cisplatin. These data were compared with those of historical controls from animals that did not receive cisplatin. Rats that were to receive a fresh syngeneic graft or frozen allogeneic graft were given cisplatin every 4 weeks starting 9 weeks preoperatively and continuing until the time of death. The total bone area of the graft in animals that received cisplatin was smaller than that of the graft in untreated control rats that did not receive cisplatin. The area of the frozen allograft did not increase between 2 and 4 months. Revascularization was incomplete in cisplatin-treated groups at 2 months, but by 4 months, vessel ingrowth in fresh syngeneic grafts approached control values. Frozen allografts remained poorly revascularized at 4 months. Host-graft union was poor at 2 months in cisplatin-treated rats compared with controls. In cisplatin-treated rats, the host-graft union of the frozen allograft remained inferior at 4 months while that of the syngeneic graft improved. Allogeneic cortical bone grafts are incorporated more slowly and incompletely than syngeneic grafts, and this handicap is exacerbated by the administration of cisplatin.

Effect of cisplatin chemotherapy on extracortical tissue formation in canine diaphyseal segmental replacement

“…Zart et al (34) administered cisplatin to rats at 9,5, and 1 weeks before the surgical implantation of midfemoral allografts and continued every 4 weeks thereafter until the rats were killed at 2 or 4 months after surgery. Cisplatin caused a significant retardation of revascularization and of new bone growth of syngeneic cortical implants at 2 months, but the grafts were being well incorporated by 4 months (34). This shows that postoperative chemotherapy is more deleterious for bone formation than preoperative chemotherapy is, but some kind of cellular recovery is possible even during the active period of chemotherapy treatment.…”

“…The effects of different chemotherapeutic agents on bone formation have been studied in v i m and in small animals (8,15,29). Information about the effects of cisplatin on fracture healing (29), on bone turnover (2), and on allograft incorporation (34) has been reported, but there are no data concerning the formation of periprosthetic extracortical capsules, to our knowledge. One of the reasons for the failure of the techniques for allograft and prosthetic reconstruction is the effect of cytotoxic chemotherapy on the incorporation of bone graft and on the union of osteosynthesis sites.…”

Consolidation of massive bone allografts in limb-preserving operations for bone tumours

“…We found statistically sig-nificant differences between those who had intensive adjuvant chemotherapy for a year after the operation and those who had not. Experimental studies have also proved that chemotherapeutic agents impair bone healing and that allogenic cortical bone grafts incorporate more slowly when chemotherapy is given [27,52]. Radiological changes have been seen in the long bones of patients who have had chemotherapy without irradiation [44], and Shinohara found that all grafted bone in patients receiving chemotherapy failed to heal primarily [46].…”

Induction of bone by a demineralized bone matrix gel: A study in a rat femoral defect model

“…A model of a mid-diaphyseal segmental defect of critical size with internal fixation was used (52). Briefly, a lateral approach was made to the femur, with elevation of the muscles and periosteum.…”