Particle disease really does exist

© 2017 The Author(s). Published by Taylor & Francis on behalf of the Nordic Orthopedic Federation. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (https://creativecommons.org/licenses/by-nc/3.0) DOI 10.1080/17453674.2017.1402463 Sir,—In a recent correspondence, Dr. Mjöberg questions the role of wear particles in the pathogenesis of periprosthetic osteolysis (Mjöberg et al. 2017). In Dr. Mjöberg’s view, implant wear and wear particles are innocent bystanders in a process that is driven by micromotion of poorly fi xed implants, and subsequently, increased fl uid pressure at the bone / implant interface. Indeed, as summarized by Dr. Mjöberg, increased fl uid pressure has been reported from the tissues surrounding loose implants, and increased pressure can induce osteolysis in certain animal models. Nevertheless, we feel that Dr. Mjöberg’s strong conclusion that particle disease does not exist is not supported by the vast body of existing scientifi c literature. The particle disease paradigm states that periprosthetic osteolysis is driven by wear particles continuously released from the implant, or from the interface between the implant and the surrounding bone (Willert and Semlitsch 1977 Purdue et al. 2007, Gallo et al. 2013, Landgraeber et al. 2014). These biomaterial particles cause acute/chronic infl ammation that culminates in local bone resorption with foreign body granuloma and periprosthetic connective tissue weakening, and ultimately, to the loss of implant fi xation. Macrophages play a central role in the pathogenesis of the condition by secreting multiple pro-infl ammatory meditators upon contact with implant debris (Ingham and Fisher 2005, Nich et al. 2013). Macrophage derived pro-infl ammatory meditators stimulate the recruitment and formation of osteoclasts and bone resorption. At the same time, particles directly suppress the differentiation and function of osteoblasts and their progenitors (O’Neill et al. 2013, Pajarinen et al. 2017a). Thus, wear particles both increase bone resorption and suppress formation, resulting in net loss of bone in the periprosthetic tissues. In the following paragraphs we summarize the evidence supporting this sequence of events. 1) Osteolytic lesions with clearly infl ammatory characteristics often appear many years after the initial surgery, and develop around mechanically stable implants. There is strong evidence that clinically sound implants often require reoperation for aseptic loosening 15 to 20 years after the primary procedure (Garellick et al. 2014, Bedard et al. 2015, Junnila et al. 2016). Therefore, the pathological process had to start much later than the immediate postoperative period, and be driven by factors other than poor initial fi xation of the implant. Otherwise, the loosening process would have appeared much earlier, as is described by Dr. Mjöberg, but usually this is not the case. Furthermore, numerous researchers have documented the wear particle-induced activation of infl ammatory pathways in retrieved tissue samples from aseptically loose implants (Gallo et al. 2014). 2) There exists a strong correlation between implant wear and periprosthetic osteolysis, even in mechanically stable implants. Clinical studies have exhaustively documented this positive correlation between implant wear and the risk for periprosthetic osteolysis and aseptic loosening (Dumbleton et al. 2002, Gallo et al. 2010) Dr. Mjöberg argues that the accelerated wear is a consequence of progressive implant loosening rather than its cause. However, recent observations from implants with hard-on-hard bearings and those that use highly cross-linked polyethylene show minimal wear and a corresponding reduction in wear related complications including loosening and osteolysis (Paxton et al. 2015, Hanna et al. 2016, Tsukamoto et al. 2017). Together these observations strongly implicate wear as a causative agent in so called “particle disease”. 3) Wear particles activate infl ammatory pathways in cell culture, and cause bone loss in different animal models. Macrophages exposed to wear debris in cell culture respond by secreting the same pro-infl ammatory and chemotactic mediators that have been detected in the tissues surrounding loose implants (Ingham and Fisher 2005, Nich et al. 2013, Pajarinen et al. 2013, Lin et al. 2014). Similarly, mesenchymal stem cells lose their ability to differentiate to osteoblasts, and osteoblasts lose their ability to produce bone, if exposed to particle debris (Goodman et al. 2006, O’Neill et al. 2013, Lin et al. 2015, Pajarinen et al. 2017a). Most importantly, animal models have repeatedly demonstrated the infl ammatory and osteolytic nature of wear particles following either an acute or chronic particle exposure (Shanbhag et al. 1997, Merkel et al. 1999, Wooley et al. 2002, Ma et al. 2008, Greenfi eld et al. 2010, Ren et al. 2011, Gibon et al. 2012, Bechtel et al. 2016, Nabeshima et al. 2017, Samelko et al. 2017). For example, wear particles implanted on mouse calvaria cause rapid infl ammation and osteolysis (Merkel et al. 1999, Bechtel. et