The effect of multidrug chemotherapy on bone graft augmented prosthesis fixation

Abstract

Use of combination adjuvant chemotherapies have improved the disease free survival rate of tumor patients significantly. However, studies have shown that chemotherapeutic agents have negative effects on bone graft incorporation and fixation of porouscoated prostheses needed for reconstruction of bone defects after wide resection of malignant tumors. Unilateral resection of a 6-cm segment of the femoral diaphysis and reconstruction with a porous-coated segmental prosthesis was performed in eight mixed-breed dogs under perioperative chemotherapy with doxorubicin, cisplatin, and ifosfamide. Eight strips of autogenous cortical bone were evenly placed around the junctions between the femur and the prosthetic surface. Autogenous cancellous bone was placed under and between the strips of cortical bone. Two cycles of the chemotherapy were given preoperatively, and three cycles postoperatively. The animals were followed for 12 weeks, with sequential assessments of weight-bearing and radiographic evaluation. Biomechanical, histological, and microradiographic analyses of the retrieved specimens were performed. Doxorubicin, cisplatin, and ifosfamide combination chemotherapy showed a significant effect on new bone formation as seen in reduced callus size and lower ultimate strength of extracortical fixation. However, the onlay corticocancellous grafting method provided better biologic fixation of the prosthesis compared with fixation without any bone grafting under non-chemotherapy condition in a previous study. Extracortical bone grafting is an effective modality for implant fixation even under intensive chemotherapy.

Experience with Cemented Large Segment Endoprostheses for Tumors

“…For those with a good prognosis, ensuring adjuvant treatment does not interfere with the fixation of the reconstruction could ensure a better outcome, as chemotherapy and radiotherapy may interfere with osteointegration. 7,28,31,32 This theoretical concern, however, has not been documented clinically.…”

“…[1][2][3]6,7,9,14,[16][17][18]21,[23][24][25][26][27][28][29] Furthermore, the literature does not demonstrate a clear advantage in implant survival when comparing cemented and cementless constructs. Published prosthetic 10-year survival for cemented prosthesis ranges from 30% to 90%, 6,12,19,21,23,33 while 10-year survival for cementless constructs ranges from 25% to 85%.…”

Multidrug chemotherapy causes early radiological signs of loosening in distal femoral replacements

“…Evidence also exists which has conversely shown bone turnover to be clearly affected by the use of chemotherapy. 6 Avedian et al 14 found chemotherapy to temporarily adversely affect bone growth at the bone-implant interface, however after one year they observed no differences between the two groups. Either chemotherapy has no true effect on extracortical bone growth, or the three-year follow-up period in our study is not long enough to detect the difference in ECBB between the two groups.…”

“…Literature has shown the substantial effects of doxorubicin, cisplatin, and ifosfamide on osteotomy healing and incorporation of cortical autografts, with histological evidence of poor new bone formation and decreased strength of healed osteotomies. 6 A study evaluating cortical hypertrophy around the Compress distal femoral endoprosthesis (Biomet, Warsaw, Indiana, USA) showed greater hypertrophy around the implant in patients not receiving chemotherapy in the first postoperative year. 14 In contrast, Muscolo et al 15 found that the use of chemotherapy did not have a significant effect on the overall allograft survival rates in patients undergoing reconstruction using osteoarticular allografts for musculoskeletal sarcomas.…”

“…Literature has shown there to be substantial effects of doxorubicin, cisplatin, and ifosfamide on osteotomy healing and incorporation of cortical autografts. 6 For bone tumour implants, extracortical bony-bridging (ECBB) where bone forms over the implant shaft and stabilizes the fixation has been shown to reduce loosening. 7 Coathup et al 8 showed that 98% of distal femoral arthroplasties (DFRs) survive to ten years if their hydroxyapatite (HA) collar had osseointegrated compared to 75% if they had not.…”