Rapid repair of titanium particle‐induced osteolysis is dramatically reduced in aged mice

Abstract

Aseptic loosening is the most common cause of ortliopaedic implant failure. This process is thought to be due to osteolysis induced by implant-derived wear particles. Teitelbaum and colleagues have recently developed a promising murine calvarial model of wear particle-induced osteolysis. However, prior to this study, this model had only been assessed qualitatively. We now report a reproducible, quantitative version of the calvarial model of wear particle-induced osteolysis, in which the extent of osteolysis (and repair) of entire parietal bones is assessed by histomorphometry of contact microradiographs. Using this model, we found that the osteolytic response is transient and rapidly repaired in one month old mice. The extent of osteolysis peaks 7 days after particle implantation and returns to baseline levels by 13 days. A similar amount of osteolysis and even more extensive repair is observed when particles are implanted repeatedly. In contrast, aged mice develop progressive osteolysis with no detectable repair. As a result. 26 month old mice have approximately 17-fold more osteolysis than one month old mice 21 days after particle implantation.Skeletally mature, adult mice (4-16 months old) show an intermediate pattern of response. Osteolysis in these mice peaks at 7 days after particle implantation but it is repaired more slowly than in the one month old mice. Taken together, these results underscore the role of an imbalance between bone resorption and bone formation in the development of aseptic loosening and suggest that agents that stimulate bone formation maybe useful in prevention or treatment of aseptic loosening.

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

“…Consistent with that possibility, antibodies that neutralize sclerostin, an inhibitor of wnt signaling, block the negative effect of polyethylene particles on implant fixation in rats by increasing bone formation and decreasing bone resorption [60]. Also consistent with that possibility, the number of osteoblasts is reduced on bone surfaces surrounding loose implants [49]; patients with high rates of bone formation have lower rates of aseptic loosening [55]; wear particles can reduce osteogenesis in vitro and in animal models [17,108]; and osteoblasts rapidly repair osteolysis induced by wear particles in young mice [48]. Another possibility is that altered wnt signaling results in skeletal anatomy that predisposes the patient to loosening.…”

Adherent endotoxin mediates biological responses of titanium particles without stimulating their phagocytosis

“…Phagocytosis of wear particles has been observed in patients with loose implants [12] and in aninial experiments [15,23]. It is thought that phagocytosis of wear particles leads to activation of cells to produce inflammatory mediators since both phagocytosis and cytokine production occur when wear particles are incubated with macrophages [9,19,22,26,28,38].…”

The role of p105 protein in NFκB activation in ANA‐1 murine macrophages following stimulation with titanium particles

“…Finally, our findings also suggest independent mechanisms of macrophage activation since LPS stimulated IKBU catabolism, while titanium particles had minimal, if any activation. Thus, the particles used in these studies are a valuable method of to assess inflammatory effects in vitro and in vivo and are and well-accepted model commonly used by us and others [5,13,25,37,44,45].…”