EMERGING IDEAS Emerging Ideas Can Erythromycin Reduce the Risk of Aseptic Loosening? Weiping Ren MD, PhD, David C. Markel MD Received: 15 March 2010 / Accepted: 4 May 2011 / Published online: 17 May 2011 Ó The Association of Bone and Joint Surgeons1 2011 Abstract Background Persistent inflammatory reaction to wear debris causes periprosthetic osteolysis and loosening. Some authors have advocated pharmaceutical approaches to reduce the inflammatory reaction. Erythromycin has anti- inflammatory effects independent of its antimicrobial properties. Although oral erythromycin reportedly inhibits periprosthetic tissue inflammation in patients with aseptic loosening, long-term systematic erythromycin treatment is not recommended owing to its side effects. Therefore, it would be advantageous to restrict erythromycin delivery to the inflammatory periprosthetic tissue without causing side effects. Questions/hypotheses Erythromycin eluted from hydroxy- apatite-coated titanium (Ti) pins inhibits periprosthetic tissue inflammation and osteolysis. Method of study We propose restricting erythromycin delivery to the inflammatory periprosthetic site. A previ- ously described rat model of ultrahigh molecular weight polyethylene (UHMWPE) particle-induced periprosthetic tissue inflammation and osteolysis will be used to test the effect of local delivery of erythromycin via Peri-Apatite TM - coated Ti implants. The outcome measures will include bone ingrowth (lCT), implant stability (pullout test), and histologic analysis of periprosthetic tissues. Significance Pharmacologic intervention aimed at slow- ing, preventing, or reversing the aseptic loosening process would represent an advance in the management of joint replacement. Erythromycin may be appropriate for pro- phylactically treating patients who have repeated revision surgery and/or show early signs of progressive osteolysis after arthroplasty. Questions/Hypotheses Erythromycin eluted from PA-coated titanium pins inhibits periprosthetic tissue inflammation and osteolysis in a rat model of revision arthroplasty. Background Aseptic loosening of joint implants occurs for many rea- sons [40]. There is compelling evidence that the most important factor in late periprosthetic osteolysis is a per- sistent inflammatory reaction to wear debris [47]. Inhibiting periprosthetic inflammation through pharma- ceutical intervention is one approach to limiting osteolysis [5, 27, 35]. There are numerous commercially available antiinflammatory drugs, such as NSAIDs, cyclooxygenase (COX) inhibitors [11, 20, 24, 43, 46], antagonists of TNF and IL-1 (eg, etanercept, infliximab, and anakinra) [5, 34, 36], and RANKL inhibitor [6, 39]. However, for long-term use, all of these drugs have major side effects, most notably One of the authors (WR) was supported by a grant from the Orthopaedic Research and Education Foundation (#04-027). One of the authors (DCM) has received funding from the Orthopaedic Research and Education Foundation. Each author certifies that his institution has approved the human investigation protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research. W. Ren (&) Department of Biomedical Engineering, Wayne State University, 818 West Hancock, Detroit, MI 48201, USA e-mail: as7606@wayne.edu; weipingren@yahoo.com D. C. Markel Department of Orthopaedic Surgery, Wayne State University School of Medicine, Southfield, MI, USA 123 Clin Orthop Relat Res (2011) 469:2399–2403 DOI 10.1007/s11999-011-1918-7