MOM WEAR PRODUCTS PROMOTE PERIPROSTHETIC OSTEOLYSIS

INTRODUCTION The uncertainty of the biological effects of wear and corrosion from Metal-on-metal (MoM) implants has initiated a debate on their safety and use. Generally, the release of wear particles from MoM hip implants can clinically manifest in aseptic osteolysis. In our study, the effect of MoM-wear particles and particle originated Co and Cr ions on mesenchymal stromal cells (MSCs) was investigated [1]. The lead hypotheses were that (1) dissociated Co and Cr, originated from MoM-wear particles, accumulate in the bone marrow and (2) apparently impair the osteogenic function of local MSCs. This impairment could be one element contributing to the manifestation of periprosthetic osteolyses. METHODS The study was approved by the local ethical committee (EA1/194/13); all donors gave written informed consent. Blood (B), Synovial fluid (SF) periprosthetic tissue (PT) and bone marrow (BM) were collected from patients with at least one osteolytic lesion, undergoing a revision of a MoM hip implant. Patients undergoing primary THA served as controls. Metal wear particles were isolated from PT by enzymatic digestion and their size and shape characterized by transmission electron microscopy (TEM). Local and systemic levels of Co and Cr were analyzed by graphite furnace atomic absorption spectroscopy. MoM-MSCs and control-MSCs were isolated from BM for in vitro assessment of their viability, proliferation, migration and multilineage differentiation. In addition, control-MSCs were in vitro exposed to Co and Cr ions and assessed for their viability, proliferation and osteogenic differentiation. RESULTS We confirmed the presence of nanoscaled particles that appeared heterogeneous in size and shape (mean diameter: 34.7 ± 16.2 nm; n = 64 ). Second, we confirmed the exposure to Co and Cr and quantified its particulate and dissociated amounts. Local metal levels exceed systemic ones by several magnitudes and dissociated Co and Cr was found in periprosthetic compartments including BM (peak BM Co concentration: 977 µg/L, peak BM Cr concentration: 2,875 µg/L; n = 10 ). While in vivo exposure to MoM-wear did not influence MSCs9 viability, proliferation, migration capacity, adipogenic- and chondogenic differentiation, it decreased osteogenic matrix mineralization and cellular ALP activity (FIGURE 1). In vitro exposure of control-MSCs to Co(II) and Cr(III) ions, at concentrations detected in BM, confirmed the decrease in osteogenic matrix mineralization and ALP activity (FIGURE 2). DISCUSSION We found that extensive amounts of Co and Cr occurred in their dissociated state within the periprosthetic region (SF, PT, BM), indicating that vast amounts of particulate wear in degraded. Our work represents an important piece in the puzzle of the clinical manifestation of periprosthetic osteolysis: dissociated Co and Cr at clinically relevant concentrations impair the bone forming function of MSCs. The study9s data indicate an influence of MoM-wear on BM residing MSCs9 osteogenic differentiation that is relevant for maintaining vital bone structure, thus confirming the lead hypothesis. The use of CoCrMo alloys for articulating surfaces in hip implants needs critical reconsideration. For figures/tables, please contact authors directly.