Etiology and Prevention of Loss of Fixation in Cemented Knee Replacements

项目总结/文摘

Project Summary/Abstract Over 750,000 total knee arthroplasties (TKA) are performed annually in the US and demand is expected to grow to over 3 million annually by 2030. Despite the success with these devices, revision rates remain unacceptably high; the lifetime risk of revision has been estimated to be 14.9% for males and 17.4% for females. During the current funding cycle, we found that there was loss of mechanical interlock between the cement and bone that increased with time in service and was more extensive in older TKA donors. The loss of interlock was associated with weaker interfaces, and the constructs were more likely to be damaged in the case of a mechanical overload. Recent clinical retrospective studies have indicated that administration of bisphosphonates after TKA surgery may reduce revision rates. However, the mechanism by which this treatment may be affecting the interfaces and peri-implant bone is not known. The overall goal of this study is to provide a mechanistic and functional understanding of the role of mechanical interlock between cement and bone in TKA fixation, and determine if implant fixation can be improved by mitigating the loss of interlock through use of an established drug therapy. In this competitive renewal, we will develop a cemented tibial replacement model in the rat that recapitulates the cement-bone interlock that occurs in human arthroplasty. We will: 1) investigate alterations in the morphology and micro-mechanics of TKA cement-bone interlock as a function of time with in vivo service, 2) investigate dynamic bone remodeling and cellular response as a function of position in the interlocked construct, 3) determine the longitudinal effect aging/osteoporosis on morphology, micro-mechanics, and cellular changes of cement-bone interlock for TKA using an ovariectomy (OVX) model, 4) determine if systemic dosing of an antiresorptive agent (zoledronic acid) can prevent loss of TKA interlock in normal and OVX cases, and 5) determine if local dosing of zoledronic acid from PMMA cement in TKA can confer a positive effect as similar to systemic dosing. In summary, this work will provide a mechanistic understanding of the processes leading to loss of TKA micro- interlock and fixation. The work will also produce (or refute) a scientific rationale for the use of local or systemic anti-resorptive agents to prevent clinical loosening due to loss of implant fixation.