# Etiology and Prevention of Loss of Fixation in Cemented Knee Replacements

> **NIH NIH R01** · UPSTATE MEDICAL UNIVERSITY · 2020 · $356,400

## Abstract

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.

## Key facts

- **NIH application ID:** 9984854
- **Project number:** 5R01AR042017-23
- **Recipient organization:** UPSTATE MEDICAL UNIVERSITY
- **Principal Investigator:** KENNETH A. MANN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $356,400
- **Award type:** 5
- **Project period:** 1996-07-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984854

## Citation

> US National Institutes of Health, RePORTER application 9984854, Etiology and Prevention of Loss of Fixation in Cemented Knee Replacements (5R01AR042017-23). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9984854. Licensed CC0.

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