title: Bone allograft and implant fixation tested under influence of bio-burden reduction, periosteal augmentation and topical antibiotics. Animal experimental studies.
abstract: Loosening of an artificial joint prosthesis is a painful and debilitating condition that can be treated only by re-operation. Re-operations accounted for approximately 15% of all hip replacement operations performed in Denmark between the year 1995 and 2010. The process of loosening is often accompanied by destructive inflammation and osteolysis, which leads to insufficient bone stock that often requires extensive bone grafting. Impacted morselized bone graft is a well-established method for improving the amount and quality of bone stock that ensures sufficient stability and anchorage of the revision implants. Among bone graft options, the autologous bone graft is considered the gold standard. It is naturally biocompatible, but its use in revision surgery is curtailed by its limited volume and by considerable donor site morbidity. Allograft bone is readily available and is the most commonly used graft material. However, it has been shown that the incorporation of allograft bone into the host bone is not always complete, and substantial fibrous tissue formation has been described. A reason for this may be that allograft bone is a foreign tissue, which, contrary to autogenic bone, may induce an immunogenic response that leads to increased fibrous tissue formation. Furthermore, the fresh-frozen allograft has minimal osteoinductive and no osteogenic capacity. The studies in this thesis have investigated ways of improving the incorporation of allograft bone by adding osteoinductive cells from the periosteum and reducing the immunogenic load of the allograft bone by rinsing. Furthermore, the impact of antibiotic protection of the bone graft has been evaluated. The same experimental implant model was used in all three studies. This model enables evaluation of early implant fixation and osseointegration of an uncemented implant surrounded by impacted morselized bone graft. Unloaded gap implants were inserted into the metaphysis of the proximal tibia (Study I) and distal femur (Study II and III) in dogs. The observation period was four weeks and the bone-implant specimens were evaluated by mechanical tests and histomorphometry. Study I compared the fixation of grafted implants where the morselized allograft bone was either rinsed in saline or not. Since the majority of immunogenic factors in allograft bone are present in the blood, the marrow and fat, the objective of this study was to investigate whether rinsing of the allograft bone would lower the immunogenic load and thereby improve osseointegration and bone graft incorporation. We found no statistically significant difference in the histomorphometric or the mechanical evaluations between the two groups. Study II investigated the addition of minced periosteal tissue to the allograft bone. The objective of this study was to investigate whether adding autologous tissue containing bone-forming cells could augment the bioactivity of allograft bone and thereby improve bone graft incorporation. Contrary to our hypothesis, we found no benefit of adding autologous periosteum to the allograft bone. No differences in mechanical fixation were observed, and the periosteum-treated implants had reduced new-bone ongrowth and increased amounts of fibrous tissue. Study III evaluated the impact of antibiotic impregnation of the allograft bone prior to impaction. Antibiotic-impregnated bone graft has been used in one-stage septic revisions and in cases where potential infection is suspected, but its potentially harmful effect on bone graft incorporation has not been studied. The aim of this study was to evaluate the impact of Tobramycin impregnation of bone-grafted implants by mechanical testing and histomorphometric assessment. We hypothesized that Tobramycin impregnation would impair implant fixation. Under the conditions of the present study, Tobramycin impregnation of allograft bone did not appear to impair implant fixation or tissue in-growth. In conclusion, under the premises of the present studies, no benefits of periosteal augmentation or rinsing of the bone graft prior to impaction were found. Antibiotic impregnation seems safe in terms of osseointegration, but surgeons should weigh the potentially cytotoxic effect of Tobramycin against its beneficial anti-microbial effect in joint arthroplasty revisions until further basic data on toxicity are available.
authors.affiliation: Department of Orthopaedic Surgery, Aarhus University Hospital, Nørrebrogade 44, Build. 1A, 8000 Aarhus C, Denmark. jeppebarckman@dadlnet.dk.
authors.forename: Jeppe
authors.initials: J
authors.lastname: Barckman
mesh_terms: D000287:Administration, Topical; D064591:Allografts / Q000276:immunology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use; D019072:Antibiotic Prophylaxis / Q000009:adverse effects / Q000379:methods*; D019644:Arthroplasty, Replacement, Hip / Q000295:instrumentation / Q000379:methods*; D001696:Biomechanical Phenomena; D016025:Bone Transplantation / Q000379:methods*; D004285:Dogs; D006622:Hip Prosthesis; D010521:Periosteum / Q000637:transplantation*; D011475:Prosthesis Failure; D016459:Prosthesis-Related Infections / Q000517:prevention & control*; D012086:Reoperation; D014031:Tobramycin / Q000009:adverse effects / Q000627:therapeutic use; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous / Q000379:methods
chemical_list: D000900:Anti-Bacterial Agents; D014031:Tobramycin