title: 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.
abstract: 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 Co(2+), Cr(3+) and Cr(6+) 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 Co(2+), Cr(3+) or Cr(6+) 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. Co(2+) and Cr(3+) did not affect osteoblast survival or function over the clinically equivalent concentration range, whilst Cr(6+) reduced osteoblast survival and function at concentrations within the clinically equivalent serum range after MOMHR (IC(50) =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 Co(2+) and Cr(3+), whilst at higher serum and synovial equivalent concentrations, and with Cr(6+), a reduction in cell number and resorption was observed. Co(2+) and Cr(6+) 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.
authors.affiliation: The Mellanby Centre for Bone Research, Department of Human Metabolism, The University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Andrews
authors.forename: Karan M
authors.initials: KM
authors.lastname: Shah
authors.forename: J Mark
authors.initials: JM
authors.lastname: Wilkinson
authors.forename: Alison
authors.initials: A
authors.lastname: Gartland
mesh_terms: D019644:Arthroplasty, Replacement, Hip; D001862:Bone Resorption / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002857:Chromium / Q000494:pharmacology*; D003035:Cobalt / Q000494:pharmacology*; D003804:Dentin / Q000378:metabolism; D006262:Health; D006801:Humans; D007477:Ions; D010006:Osteoblasts / Q000187:drug effects* / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects* / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D013997:Time Factors
chemical_list: D007477:Ions; D002857:Chromium; D003035:Cobalt