Effects of cobalt and chromium ions at clinically equivalent concentrations after metal-on-metal hip replacement on human osteoblasts and osteoclasts: Implications for skeletal health

Metal-on-metal hip replacement (MOMHR) using large diameter bearings has become a popular alternative to conventional total hip arthroplasty, but is associated with elevated local tissue and circulating levels of chromium (Cr) and cobalt (Co) ions that may affect bone health. We examined the effects of acute and chronic exposure to these metals on human osteoblast and osteoclast formation and function over a clinically relevant concentration range previously reported in serum and within hip synovial fluid in patients after MOMHR. SaOS-2 cells were cultured with Co2+, Cr3+ and Cr6+ for 3 days after which an MTS assay was used to assess cell viability, for 13 days after which alkaline phosphatase and cell viability were assessed and for 21 days after which nodule formation was assessed. Monocytes were isolated from human peripheral blood and settled onto dentine disks then cultured with M-CSF and RANKL plus either Co2+, Cr3+ or Cr6+ ions for 21 days from day 0 or between days 14 and 21. Cells were fixed and stained for TRAP and osteoclast number and amount of resorption per dentine disk determined. Co2+ and Cr3+ did not affect osteoblast survival or function over the clinically equivalent concentration range, whilst Cr6+ reduced osteoblast survival and function at concentrations within the clinically equivalent serum range after MOMHR (IC50 = 2.2 μM). In contrast, osteoclasts were more sensitive to metal ions exposure. At serum levels a mild stimulatory effect on resorption in forming osteoclasts was found for Co2+ and Cr3+, whilst at higher serum and synovial equivalent concentrations, and with Cr6+, a reduction in cell number and resorption was observed. Co2+ and Cr6+ within the clinical range reduced cell number and resorption in mature osteoclasts. Our data suggest that metal ions at equivalent concentrations to those found in MOMHR affect bone cell health and may contribute to the observed bone-related complications of these prostheses.

Research highlights► Cr6+, but not Co2+ or Cr3+ reduced osteoblast survival and function at clinically equivalent serum concentrations after MOMHR. ► At serum levels a mild stimulatory effect on resorption in forming osteoclasts was found for Co2+ and Cr3+. ► Cr6+ at higher serum and synovial equivalent concentrations reduced osteoclast cell number and resorption. ► Co2+ and Cr6+ within the clinical range reduced mature osteoclast cell number and resorption.