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Are Biologic Treatments a Potential Approach to Wear- and Corrosion-related Problems?

  • Symposium: ABJS Carl T. Brighton Workshop on Implant Wear and Tribocorrosion of Total Joint Replacements
  • Published:
Clinical Orthopaedics and Related Research®

Abstract

Where Are We Now?

Biological treatments, defined as any nonsurgical intervention whose primary mechanism of action is reducing the host response to wear and/or corrosion products, have long been postulated as solutions for osteolysis and aseptic loosening of total joint arthroplasties. Despite extensive research on drugs that target the inflammatory, osteoclastic, and osteogenic responses to wear debris, no biological treatment has emerged as an approved therapy. We review the extensive preclinical research and modest clinical research to date, which has led to the central conclusion that the osteoclast is the primary target. We also allude to the significant changes in health care, unabated safety concerns about chronic immunosuppressive/antiinflammatory therapies, industry’s complete lack of interest in developing an intervention for this condition, and the practical issues that have narrowly focused the possibilities for a biologic treatment for wear debris-induced osteolysis.

Where Do We Need to Go?

Based on the conclusions from research, and the economic, regulatory, and practical issues that limit the future directions toward the development of a biologic treatment, there are a few rational approaches that warrant investigation. These largely focus on FDA-approved osteoporosis therapies that target the osteoclast (bisphosphonates and anti-RANK ligand) and recombinant parathyroid hormone (teriparatide) prophylactic treatment to increase osseous integration of the prosthesis to overcome high-risk susceptibility to aseptic loosening. The other roadblock that must be overcome if there is to be an approved biologic therapy to prevent the progression of periprosthetic osteolysis and aseptic loosening is the development of radiological measures that can quantify a significant drug effect in a randomized, placebo-controlled clinical trial. We review the progress of volumetric quantification of osteolysis in animal studies and clinical pilots.

How Do We Get There?

Accepting the aforementioned rigid boundaries, we describe the emergence of repurposing FDA-approved drugs for new indications and public (National Institutes of Health, FDA, Centers for Disease Control and Prevention) and private (universities and drug and device manufactures) partnerships as the future roadmap for clinical translation. In the case of biologic treatments for wear debris-induced osteolysis, this will involve combined federal and industry funding of multicenter clinical trials that will be run by thought leaders at large medical centers.

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Acknowledgments

We thank Drs. Timothy Wright and Stuart Goodman and our colleagues who participated in the ABKS CT Brighton Workshop on Wear and Tribocorrosion and provided critical insights that were incorporated into this review.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Stanford University, Redwood City, CA, USA

    R. Lane Smith PhD

  2. Department of Orthopaedics, University of Rochester, Rochester, NY, USA

    Edward M. Schwarz PhD

  3. The Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Box 665, Rochester, NY, 14642, USA

    Edward M. Schwarz PhD

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Correspondence to Edward M. Schwarz PhD.

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One of the authors (EMS) certifies that he or she, or a member of his or her immediate family, has received or may receive payments or benefits, during the study period, an amount of USD (note less than USD 10,000), from Amgen Inc (Thousand Oaks, CA, USA), and an amount of USD (USD 10,000 to USD 100,000) from Lilly Inc (Indianapolis, IN, USA).

All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research ® editors and board members are on file with the publication and can be viewed on request.

This work was performed at Stanford University, Stanford, CA, USA, and University of Rochester, Rochester, NY, USA.

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Smith, R.L., Schwarz, E.M. Are Biologic Treatments a Potential Approach to Wear- and Corrosion-related Problems?. Clin Orthop Relat Res 472, 3740–3746 (2014). https://doi.org/10.1007/s11999-014-3765-9

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  • DOI: https://doi.org/10.1007/s11999-014-3765-9

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