New and innovative approaches to comprehensive cancer care include limb-sparing en bloc tumor resections followed by reconstruction of the skeletal deficit with a preserved bone allograft. In order to provide predictably useful osteochondral tissues for this purpose, immunological, biological, and biomechanical parameters must be documented and correlated over time. Furthermore, effects of various methods of long-term preservation (especially deep-freezing and freeze-drying) and the effects of other cancer treatment modalities on bone must also be evaluated in order to extend safely the application of this reconstructive approach. Using rat models, immune responses to cell surface transplantation antigens have been demonstrated by chromium-release assays following transplantation of disparate fresh osseous grafts. The response is greatly diminished by freezing bone to -80~C prior to use. Rats have received therapeutic doses of adriamycin or methotrexate over a 16-week period, and intact tail vertebrae were analyzed histomorphometrically at intervals. Both drugs significantly and profoundly decrease bone formation rates as well as fracture repair as judged histologically and biomechanically. Adriamycin also adversely affects resorption to a similar magnitude as formation and also results in little change in bone mass. Methotrexate is initially less toxic to osteoclastic activity such that cancellous bone volume is reduced by approximately 25 to 30%. The effects of these drugs on allograft incorporation is being evaluated. Radiation therapy (2500 rads) profoundly, but temporarily, decreases bone turnover and seriously interferes with fracture repair. Cyclosporin-A demonstrates severe suppression to the bone remodeling process. This mechanism is being explored. (IP)
