Elsevier

The Journal of Arthroplasty

Volume 19, Issue 8, December 2004, Pages 1028-1038
The Journal of Arthroplasty

Review article
Particle bioreactivity and wear-mediated osteolysis

https://doi.org/10.1016/j.arth.2004.03.024Get rights and content

Abstract

This review focuses on wear debris-mediated osteolysis, a major factor compromising the long-term success of total joint arthroplasty. Studies on retrieved implants and animal models, as well as in vitro studies on particle bioreactivity, suggest that wear-mediated periprosthetic osteolysis is unlikely to be caused solely by 1 particular cell type or particulate species, but is rather the cumulative consequence of a number of biological reactions. Our recent findings suggest 3 novel mechanisms of particle bioreactivity that may contribute to osteolysis: 1) exacerbated inflammation caused by elevated reactive oxygen species production by activated macrophages and osteoclasts, (2) impaired periprosthetic bone formation secondary to disrupted osteogenesis, and (3) compromised bone regeneration resulting from increased cytotoxic response of mesenchymal osteoprogenitor cells. Understanding the pathogenesis of wear-mediated osteolysis is needed to improve orthopedic implant biocompatibility and wear reduction, and to develop effective pharmacotherapies.

Section snippets

Clinical findings

Wear-mediated osteolysis was first described by Sir John Charnley in 1975 as a “cystic erosion of bone” [12]. While investigating fractured femoral stems, Charnley reported fragments of polymethylmethacrylate (PMMA) bone cement within the surrounding tissue and nonlinear erosion of periprosthetic bone [12]. Later, in 1976, Harris et al [13] reported osteolysis at the proximal femur surrounding loose hip implants and characterized periprosthetic tissue histologically as “sheets of macrophages, a

Particle bioreactivity

Established cell-culture systems have allowed investigators to study the relationship between well-characterized biomaterials and the biological reactions suspected of playing a role in wear-mediated loosening. The complexity of wear-mediated osteolysis can be appreciated by the numerous in vitro studies on particle bioreactivity that have investigated diverse populations of cell types found in the periprosthetic environment, particles differing in size and material composition relevant to the

The current model of wear-mediated osteolysis

The current model of wear-mediated osteolysis hypothesizes that the phagocytosis of wear particles by macrophages and foreign-body giant cells (arising from macrophages) initiates the release of cytokines and other inflammatory mediators, which stimulate increased osteoclastic activity and focal bone resorption at the bone-implant interface. Additionally, osteoblasts and fibroblasts are also believed to play a significant role in aseptic implant loosening, responding to particle exposure with

Anti-inflammatory agents

Ultimately, the goal of wear-particle research is to identify or develop suitable therapeutic agents to treat and eventually reverse or abolish the adverse biological responses to wear particles. Cytokines are generally considered the principal mediators of the initial foreign-body response to orthopedic wear particles. The modulation of proinflammatory cytokines, such as TNF-α, IL-1, and IL-6, may prove useful in ameliorating early aseptic inflammation. As a result, there are an increasing

Conclusion

Until the utopian goal of joint reconstruction via tissue engineering is reached, arthroplasty will continue to be the most efficacious means to restore function of the degenerated joint. Wear-mediated osteolysis, an inherent complication of arthroplasty, is a multidisciplinary problem requiring the coordinated expertise of diverse fields, including orthopedic surgery, cell and molecular biology, clinical pharmacology, and bioengineering, for a solution. Successfully meeting the challenge of

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