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.

The effects on bone cells of metal ions released from orthopaedic implants. A review

“…In vivo data suggest that the concentrations of Co and Cr ions reported in serum and hip synovial fluid of patients with MoM implants have an effect on human osteoclasts. These ions have a mild stimulatory effect on developing osteoclasts, but have an inhibitory effect on mature osteoclasts at higher concentrations (equivalent to the levels found in synovial fluid) (65). The reason for this difference might be explained by the substrate resorbing activity of the cells and the dose-related toxicity of metal ions.…”

Biological Response of Osteoblasts and Osteoprogenitors to Orthopaedic Wear Debris

“…A study evaluating the comparative cytotoxicity of cobalt, chromium, and cobalt-chromium alloy particles on MG-63 and SaOS-2 cells has shown that all three particle types inhibit alkaline phosphatase and osteocalcin expression, but cobalt particles inhibit these parameters to a much greater extent and are the only particles toxic enough to impair cell viability and type I collagen synthesis (Allen et al, 1997). Another study has shown that cobalt (Co 2+ , 0-10 ppm) and chromium (Cr 3+ , 0-150 ppm) ions generated from CoCl 2 and CrCl 3 are cytotoxic to MG-63 cells in a dose-and time-dependent manner over 72 hours, as (Andrews et al, 2011). All three ion types have reduced alkaline phosphatase production and mineralization, but only at doses > 100 M.…”

Osteocyte physiology and response to fluid shear stress are impaired following exposure to cobalt and chromium: Implications for bone health following joint replacement

“…Working concentrations of each metal ion were prepared, as previously described 20. The stability of these metal ions in culture media has been confirmed previously using flame‐atomic absorption spectroscopy 20. Control treatment contained equivalent volume of sterile distilled water to maintain conditions, and referred to as 0 µg/L treatments.…”

“…Periprosthetic concentrations are several fold higher (median Co, 113 μg/L; median Cr, 54 μg/L),18 while patients with failing prosthesis have reported Co and Cr concentrations as high as 528 μg/L (range: 0–13,000 μg/L) and 1,844 μg/L (range: 0–38,600 μg/L), respectively 19. We recently demonstrated that exposure to Co 2+ and Cr 3+ adversely affects both osteoclast and osteoblast survival and function, including the mineralization of prosthesis surfaces in vitro, at concentrations equivalent to those found clinically 20, 21, 22…”