Peri-operative zoledronic acid attenuates peri-prosthetic osteolysis in a rat model of cemented knee replacement.

Progressive osteolysis can occur at the cement-bone interface of joint replacements and the associated loss of fixation can lead to clinical loosening. We previously developed a rat hemiarthroplasty model that exhibited progressive loss of fixation with the development of cement-bone gaps under the tibial tray that mimicked patterns found in human arthroplasty retrievals. Here we explored the ability of a bisphosphonate (zoledronic acid, ZA) to attenuate cement-bone osteolysis and maintain implant stability. Sprague-Dawley rats (n = 59) received a poly(methylmethacrylate) cemented tibial component and were followed for up to 12 weeks. Treatment groups included peri-operative administration of ZA (ZA group), administration of ZA at 6 weeks postop (late ZA group), or vehicle (Veh group). There was a 60% reduction in the rate of cement-bone gap formation for the ZA group (0.15 mm3/week) compared to Veh group (0.38 mm3/week, p = 0.016). Late ZA prevented further progression of gap formation but did not reverse bone loss to the level achieved in the ZA group. Micromotion from five times body weight toggle loading was positively correlated with cement-bone gap volume (p = 0.009) and negatively correlated with the amount of cement in the metaphysis (p = 0.005). Reduced new bone formation and enduring nonviable bone in the epiphysis for the ZA group were found. This suggests that low bone turnover in the epiphysis may suppress the early catabolic response due to implantation, thereby maintaining better fixation in the epiphysis. This preclinical model presents compelling supporting data documenting improved maintenance of the cement-bone fixation with the use of peri-operative bisphosphonates.

Progressive loss of implant fixation in a preclinical rat model of cemented knee arthroplasty.

Aseptic loosening of total knee arthroplasty continues to be a challenging clinical problem. The progression of the loosening process, from the initial well-fixed component, is not fully understood. In this study, loss of fixation of cemented hemiarthroplasty was explored using 9-month-old Sprague-Dawley rats with 0, 2, 6, 12, 26 week end points. Morphological and cellular changes of cement-bone fixation were determined for regions directly below the tibial tray (epiphysis) and distal to the tray (metaphysis). Loss of fixation, with a progressive increase in cement-bone gap volume was found in the epiphysis (0.162 mm3 /week), but did not progress appreciably in the metaphysis (0.007 mm3 /week). In the epiphysis, there was an early and sustained elevation of osteoclasts adjacent to the cement border and development of a fibrous tissue layer between the cement and bone. There was early formation of bone around the cement in the metaphysis, resulting in a condensed bone layer without osteoclastic bone resorption or development of a fibrous tissue layer. Implant positioning was also an important factor in the cement-bone gap formation, with greater gap formation for implants that were placed medially on the tibial articular surface. Loss of fixation in the rat model mimicked patterns found in human arthroplasty where cement-bone gaps initiate under the tibial tray, at the periphery of the implant. This preclinical model could be used to study early biological response to cemented fixation and associated contributions of mechanical instability, component alignment, and periprosthetic inflammation.

Similitude of cement-bone micromechanics in cemented rat and human knee replacement.

A preclinical rat knee replacement model was recently developed to explore the biological and mechanobiological changes of trabecular resorption for cement-bone interdigitated regions. The goal here was to evaluate the relevance of this model compared with human knee replacement with regards to functional micromechanics. Eight nonsurvival, cemented knee replacement surgeries were performed, the interdigitated gap morphology was quantified, and interface micromotion between cement and bone was measured for 1 to 5 bodyweight loading. Computational fluid dynamics modeling of unit cell geometries with small gaps between trabeculae and cement was used to estimate fluid flow. Gap width (3.6 µm) was substantially smaller compared with cement-bone gaps reported in human knee replacement (11.8 µm). Micromotion at the cement-bone border was also decreased for the rat knee replacement (0.48 µm), compared with human (1.97 µm), for 1 bodyweight loading. However, the micromotion-to-gap width ratio (0.19 and 0.22 for, rat and human), and estimated fluid shear stress (6.47 and 7.13 Pa, for rat and human) were similar. Replicating the fluid dynamic characteristics of cement-bone interdigitated regions in human knee replacements using preclinical models may be important to recapitulate trabecular resorption mechanisms due to proposed supraphysiologic fluid shear stress. Statement of clinical significance: local cement-bone micromotion due to joint loading may contribute to the process of clinical loosening in total joint replacements. This work shows that while micromotion and gap morphology are diminished for the rat knee model compared to human, the motion-to-gap ratio, and corresponding fluid shear stress are of similar magnitudes.