Effects of soluble cobalt and cobalt incorporated into calcium phosphate layers on osteoclast differentiation and activation.

Metal ions originating from mechanical debris and corrosive wear of prosthetic implant alloys accumulate in peri-implant soft tissues, bone mineral, and body fluids. Eventually, metal ions such as cobalt (II) (Co(2+)), which is a major component of cobalt-chromium-based implant alloys and a known activator of osteolysis, are incorporated into the mineral phase of bone. We hypothesize that the accumulation of Co(2+) in the mineral could directly activate osteolysis by targeting osteoclasts. To test this hypothesis, we coated tissue culture plastic with a thin layer of calcium phosphate (CaP) containing added traces of Co(2+), thereby mimicking the bone mineral accumulation of Co(2+). Murine bone marrow osteoclasts formed in the presence of M-CSF and RANKL were cultured on these surfaces to examine the effects of Co(2+) on osteoclast formation and resorptive activity. Treatment conditions with Co(2+) involved incorporation into the CaP layer, adsorption to the mineral surface, or addition to culture media. Micromolar concentrations of Co(2+) delivered to developing osteoclast precursors by all 3 routes increased both osteoclast differentiation and resorptive function. Compared to CaP layers without Co(2+), we observed a maximal 75% increase in osteoclast numbers and a 2.3- to 2.7-fold increase in mineral resorption from the tissue culture wells containing 0.1 microM Co(2+) and 0.1-10 microM Co(2+), respectively. These concentrations are well within the range found in peri-implant tissues in vivo. This direct effect of Co(2+) on osteoclasts appears to act independently of the particulate phagocytosis/inflammation-mediated pathways, thus enhancing osteolysis and aseptic implant loosening.