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.

项目摘要/摘要每年在美国进行超过750,000次总膝关节碎裂（TKA），预计需求将到2030年，每年增长到每年超过300万。尽管这些设备取得了成功，但修订率仍然高度高；估计，男性的终身风险估计为14.9％，17.4％为17.4％女性。在当前的融资周期中，我们发现水泥和骨骼随着服务时间而增加，在老年TKA供体中更为广泛。损失互锁与较弱的接口有关，构造更有可能在机械超负荷的情况。最近的临床回顾性研究表明，TKA手术后的双膦酸盐给药可能会降低修订率。但是，这种处理可能影响界面的机制尚不清楚植入植物的骨骼骨外骨。这项研究的总体目标是提供机械和功能了解水泥和骨头在TKA固定中的机械互锁的作用，并确定是否通过使用已建立的药物治疗，可以通过减轻互锁的损失来改善植入物固定。在这种竞争性更新中，我们将在大鼠中开发一个胶结的胫骨替代模型，以概括为在人类关节置换术中发生的水泥骨互锁。我们将：1）调查在 TKA水泥骨互锁的形态和微力学与体内服务的时间有关，2）研究动态骨重塑和细胞反应，与互锁中的位置的函数构造，3）确定纵向效应衰老/骨质疏松症对形态学，微力学和使用卵巢切除术（OVX）模型的TKA水泥骨互锁的细胞变化，4）确定是否系统剂量的抗吸收剂（唑来膦酸）可以防止在正常和OVX病例中损失TKA互锁的损失， 5）确定从TKA中PMMA水泥中唑来膦酸的局部剂量是否可以赋予积极作用为类似于系统性剂量。总而言之，这项工作将提供对导致TKA微型损失的过程的机械理解互锁和固定。这项工作还将产生（或驳斥）使用本地或系统的科学原理抗敏化剂，以防止由于植入物丢失而导致临床松动。