Serendipity of Erythromycin in the Management of Periprosthetic Inflammation

Weiping      Ren; Ralph      Blasier; David      C. Markel

Abstract

The formation of an inflammatory periprosthetic membrane at the interface of the bone and the prosthesis constitutes a major component of periprosthetic osteolysis and aseptic loosening (AL). Prevention and treatment of periprosthetic membrane inflammation represent a logical approach to prevent this complication of total joint replacement (TJR). Delivering adequate levels of cell-specific therapy to the site of periprosthetic inflammation, without undesirable systemic side effects, present a considerable challenge. Erythromycin (EM), a 14-member lactone ring macrolide antibiotic, has novel anti-inflammatory effects at sub-antimicrobial doses through targeting to the NFκB signaling pathway. This manuscript describes a unique line of research that investigated the conceptual application of EM to AL/osteolysis from the benchtop to a clinical trial. Our previous studies indicated that EM inhibits wear debris- induced inflammation and osteolysis (both in vitro and in vivo). In addition, we found that oral EM treatment (600 mg/day) improved periprosthetic tissue inflammation in a group of AL patients. EM represents a promising drug candidate for AL, because it is immunomodulatory, anabolic, and inhibits osteoclastogenesis. Additional efforts are needed to address some practical issues, including development of quantitative outcome measure(s) for the evaluation of drug efficacy and creation of periprosthetic EM delivery devices. If achievable, EM therapy, because of its clinical safety, efficacy, simplicity and good compliance, will be a novel option to provide solutions for extending the implant life for those patients who are at a high risk of AL development.

Keywords: Erythromycin, macrolide, inflammation, osteoclast, osteolysis, aseptic loosenin, Periprosthetic Inflammation, Total joint replacement, mRNA gene copies, anti-inflammation drug