EFFECT OF COBALT AND CHROMIUM IONS ON THE FORMATION AND FUNCTION OF HUMAN PERIPHERAL BLOOD DERIVED OSTEOCLASTS IN-VITRO

Abstract

One possible mechanism by which metal-on-metal hip resurfacing (MOMHR) may be associated with prosthesis loosening, periprosthetic fracture, and femoral neck narrowing is through an increase in bone resorption by osteoclast cells. Whilst it is known that metal ions such as cobalt (Co) and chromium (Cr) ions (that are elevated locally and systemically after MOMHR), may affect osteoblast and macrophage activity in-vitro, little is known about the effect of these ions on osteoclasts. We examined whether these ions have an adverse effect on human peripheral blood derived osteoclasts at levels that are clinically relevant after MOMHR. Peripheral blood mononuclear cells from healthy donors were seeded onto dentine wafers, and treated to transform them into osteoclasts using standard techniques in the presence of various clinically relevant concentrations of Co2+, Cr3+, and Cr6+. After 3 weeks of culture osteoclast number and resorption pit formation was quantified using histological techniques. All 3 metal ions had a dose-dependent effect on both osteoclast formation and resorption activity. At ion levels found in serum after MOMHR, an increase in osteoclast formation and bone resorption was found, but at higher levels found in synovial fluid, osteoclast cell proliferation and resorption activity was decreased, likely due to a direct toxic effect of the ions on the cells (Figure 1). Cr6+ was more toxic than the other ions at higher concentrations. Our data suggest that metal ion release following MOMHR may increase osteoclast activity systemically that might have a deleterious effect on general and local bone health, and may contribute to the observed bone related complications of MOMHR.