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

• Published in: Journal of orthopaedic research Vol. 42; no. 12; pp. 2693 - 2704
• Main Authors: Mann, Kenneth A., Miller, Mark A., Gandhi, Sachin A., Kusler, Jace E., Tatusko, Megan E., Biggs, Amy E., Oest, Megan E.
• Format: Journal Article
• Language: English
• Published: United States 01.12.2024
• Subjects: Animals; Arthroplasty, Replacement, Knee - adverse effects; Bone Cements; Bone Density Conservation Agents - administration & dosage; Bone Density Conservation Agents - therapeutic use; cement; Diphosphonates - administration & dosage; Diphosphonates - pharmacology; Diphosphonates - therapeutic use; Disease Models, Animal; fixation; Imidazoles - administration & dosage; Imidazoles - therapeutic use; knee arthroplasty; Male; morphology; osteolysis; Osteolysis - drug therapy; Osteolysis - etiology; Osteolysis - prevention & control; Rats; Rats, Sprague-Dawley; Zoledronic Acid - administration & dosage; Zoledronic Acid - therapeutic use; fixation; knee arthroplasty; cement; morphology; osteolysis
• ISSN: 0736-0266; 1554-527X; 1554-527X
• DOI: 10.1002/jor.25941

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. The ability of bisphosphonate (zoledronic acid, ZA) to attenuate cement–bone osteolysis and maintain implant stability was studied using a rat hemiarthroplasty model. There was a 60% reduction in the rate of cement–bone gap formation for the ZA group (0.15 mm3/week) compared to the Veh group (0.38 mm3/week, p = 0.016) over a 12‐week period. Late administration of ZA at 6 weeks prevented further progression of gap formation but did not reverse bone loss to the level achieved in the ZA group.