Low dose metal particles can induce monocyte/macrophage survival

Aseptic loosening results in pain, loss of function, and ultimately prosthetic joint failure and revision surgery. The generation of wear particles from the prosthesis is a major factor in local osteolysis. We investigated the effects of such wear particles on the survival of monocytes and macrophages, populations implicated in wear particle‐driven pathology. Particles from titanium aluminum vanadium (TiAlV) and cobalt chromium (CoCr) alloys were generated in‐house and were equivalent in size (0.5–3 µm) to those seen in patients. Human CD14⁺ monocytes and murine bone marrow‐derived macrophages (BMM) were treated with TiAlV and CoCr particles in vitro, and cell survival was assayed. Both particles increased monocyte and macrophage survival in a dose‐dependent manner, with an optimal concentration of around 10⁷ particles/mL. Conditioned media from particle‐treated BMM also increased macrophage survival. Studies with antibody blockade and gene‐deficient mice suggest that particle‐induced BMM survival is independent of endogenous CSF‐1 (M‐CSF), GM‐CSF, and TNFα. These data indicate that wear particles can promote monocyte/macrophage survival in vitro possibly via an endogenous mediator. If this phenomenon occurs in vivo, it could mean that increased numbers of macrophages (and osteoclasts) would be found at a site of joint implant failure, which could contribute to the local inflammatory reaction and osteolysis.