• Mechanisms of aseptic loosening in total knee arthroplasty

      Cyndari, Karen (2017)
      Introduction: Cemented Total Knee Arthroplasty (TKA) is the gold standard of care for end-stage, multi-etiologic arthritis. While the longevity of these devices may now reach or even surpass 15 years in service, a minority (~10%) will fail prematurely due to a process called aseptic loosening. Historically, this process has been attributed to an inflammatory reaction against wear debris from the TKA polyethylene (PE) insert. However, we have previously estimated supraphysiologic fluid shear stress (FSS) (exceeding 900 Pa) at the cement-bone interface of cemented joint replacements, and examined this as a possible alternative cause of increased osteoclast activity. Methods: We analyzed the cement-bone interlock of tibial and femoral components from en-bloc, postmortem-retrieved, non-revised TKAs to explore the process of loss of fixation, prior to any clinical loosening. For the tibial components, we used a novel protocol wherein whole undecalcified bone+PMMA cement segments from the proximal tibia were embedded in Spurr’s resin and thinly sectioned. Polarized light microscopy was used to identify and quantify co-located PE debris. Using a novel bioreactor developed by our lab called the Multi-Well Fluid Loading (MFL) System, we examined static, subphysiologic, physiologic, and supraphysiologic FSS on RAW 264.7 osteoclast activity and morphology, with and without PE particle treatment. Results: We found no association been the amount or presence of PE debris and the amount or location of loss of interlock in retrieved TKAs. FSS up to 17 Pa increased the ability of osteoclasts to resorb mineral, and FSS up to 4.4 Pa induced the formation of larger osteoclasts. FSS and fluid shear rate interacted together to increase the area of actin rings, while PE treatment increased the number of actin rings and TRAP production. FSS up to 4.4 Pa decreased expression of Ctsk and Il1a, but PE co-treatment abolished this effect. Conclusions: These results indicate there may be alternative factors leading to aseptic loosening apart from PE debris. We demonstrated that osteoclasts are mechanosensitive and able to adjust activity, morphology, and gene expression based on FSS. Further, PE interferes with osteoclast gene downregulation in response to FSS, indicating PE could be a potentiator of osteoclast activity or differentiation.