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Mediators of the inflammatory response to joint replacement devices

Nature Reviews Rheumatology volume 7, pages 600–608 (2011)Cite this article

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Abstract

Joint replacement surgery is one of the success stories of modern medicine, restoring mobility, diminishing pain and improving the overall quality of life for millions of people. Unfortunately, wear of these prostheses over time generates debris, which activates an innate immune response that can ultimately lead to periprosthetic resorption of bone (osteolysis) and failure of the implant. Over the past decade, the biological interactions between the particulate debris from various implant materials and the immune system have begun to be better understood. The wear debris induces a multifaceted immune response encompassing the generation of reactive oxygen species and damage-associated molecular patterns, Toll-like receptor signaling and NALP3 inflammasome activation. Acting alone or in concert, these events generate chronic inflammation, periprosthetic bone loss and decreased osteointegration that ultimately leads to implant failure.

Key Points

  • Wear debris is generated by the movements of the articulating surfaces of a joint replacement under load

  • Microparticle wear debris induces “frustrated phagocytosis” and multinucleated giant cell fusion

  • Nanoparticle wear debris induces endosomal destabilization and NALP3 inflammasome activation

  • Ultra-high-molecular-weight polyethylene polymeric wear debris and damage-associated molecular patterns induce activation of Toll-like receptors 2 and 4

  • Metal wear debris and metal ions can induce a type IV hypersensitivity reaction

  • The multifaceted myelomonocytic inflammatory response induced by wear debris increases osteoclastogenesis and promotes periprosthetic osteolysis

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Figure 1: Schematics of typical joint implant devices.
Figure 2: Radiography of a total knee replacement complicated by osteolysis.
Figure 3: Schematic of periprosthetic inflammation and aseptic osteolysis.
Figure 4: Infiltration of macrophages and dendritic cells in periprosthetic tissue.
Figure 5: UHMWPE wear debris are phagocytosed by infiltrating cells.
Figure 6: Schematic of the multifaceted immune response to wear debris.

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Acknowledgements

This work was supported by the generous donation of Arnold Penner and the Jabez and Helen Hardin Foundation. We would like to thank Paolo Verzani for assistance with Figure 1 and Figure 2.

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Montefiore Medical Center, 1250 Waters Place, New York, 10461, NY, USA

    Neil Cobelli

  2. Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, 10461, NY, USA

    Brian Scharf & Laura Santambrogio

  3. Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, 10461, NY, USA

    John Hardin

  4. Department of Pathology, Baystate Medical Center, 759 Chestnut Street, Springfield, 01199, MA, USA

    Giovanna M. Crisi

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Contributions

N. Cobelli, B. Scharf, G. M. Crisi and L. Santambrogio researched data for the article. G. M. Crisi and J. Hardin made substantial contributions to the discussion of content. N. Cobelli, B. Scharf and L. Santambrogio wrote the article. N. Cobelli and L. Santambrogio performed review/editing of the manuscript before submission.

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Correspondence to Laura Santambrogio.

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Cobelli, N., Scharf, B., Crisi, G. et al. Mediators of the inflammatory response to joint replacement devices. Nat Rev Rheumatol 7, 600–608 (2011). https://doi.org/10.1038/nrrheum.2011.128

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