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Etiology and Prevention of Loss of Fixation in Cemented Knee Replacements

骨水泥膝关节置换术中失去固定的原因和预防

基本信息

批准号：
10222568
负责人：
KENNETH A. MANN
金额：
$ 34.57万
依托单位：
UPSTATE MEDICAL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-07-15 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10222568
关键词：
Affect Age-Related Bone Loss Aging Area Autopsy Beds Bone remodeling Cell physiology Clinical Clinical Research Databases Devices Dose Etiology Failure Female Formulation Funding Goals Human Implant Intervention Knee Liquid substance Longevity Marrow Mechanics Modeling Morphology Operative Surgical Procedures Osteoclasts Osteocytes Osteogenesis Osteoporosis Ovariectomy Patients Pharmacotherapy Polyethylenes Polymethyl Methacrylate Positioning Attribute Prevention Procedures Process Quality of life Rattus Registries Replacement Arthroplasty Retrospective Studies Role Services Testing Time United States Work Zoledronic Acid age effect base bisphosphonate bone bone loss clinical risk functional status improved in vivo kinematics knee replacement arthroplasty lifetime risk male mechanical load placebo group prevent protective effect response sample fixation shear stress solute substantia spongiosa success technique development

项目摘要

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.

项目总结/摘要美国每年进行超过750，000例全膝关节置换术（TKA），预计需求将到2030年将增长到每年300多万。尽管这些器械取得了成功，高得不可接受;据估计，男性的终身翻修风险为14.9%，女性为17.4% 女性在本供资周期，我们发现，骨水泥和骨密度随着使用时间的增加而增加，并且在老年TKA供体中更广泛。的损失互锁与较弱的界面相关，并且结构更可能在机械过载的情况下。最近的临床回顾性研究表明，TKA手术后给予双膦酸盐可以降低翻修率。然而，这种处理可能影响界面的机制并且植入物周围的骨是未知的。本研究的总体目标是提供一个机制和功能了解骨水泥和骨之间的机械互锁在TKA固定中的作用，并确定植入物固定可以通过使用已建立的药物治疗减轻互锁的损失来改善。在这次竞争性更新中，我们将在大鼠中开发一种骨水泥胫骨置换模型，在人类关节成形术中出现的骨水泥-骨互锁。我们将：1）调查 TKA骨水泥-骨互锁的形态学和微观力学随时间变化的体内服务，2）研究动态骨重建和细胞反应作为位置的功能，在联锁结构，3）确定老化/骨质疏松对形态学、微观力学和使用卵巢切除术（OVX）模型进行TKA的骨水泥-骨互锁的细胞变化，4）确定系统性抗吸收剂（唑来膦酸）的剂量可以防止正常和OVX病例中TKA联锁的丧失，和5）确定在TKA中从PMMA骨水泥中局部给药唑来膦酸是否可以赋予积极作用，类似于全身给药。总之，这项工作将提供一个机制的理解，导致损失的TKA微，互锁和固定。这项工作还将产生（或反驳）一个科学的理由，使用当地或系统的抗再吸收剂，以防止由于植入物固定丧失而导致的临床松动。