Cobalt and chromium exposure affects osteoblast function and impairs the mineralization of prosthesis surfaces in vitro

Abstract

Cobalt (Co) and chromium (Cr) ions and nanoparticles equivalent to those released through tribo-corrosion of prosthetic metal-on-metal (MOM) bearings and taper junctions are detrimental to osteoblast activity and function in vitro when examined as individual species. Here we examined the effects of Co 2þ :Cr 3þ and Co 2þ :Cr 6þ combinations on osteoblast-like SaOS-2 cellular activity, alkaline phosphatase (ALP) activity and mineralization to better reflect clinical exposure conditions in vivo. We also assessed the effect of Co 2þ :Cr 3þ combinations and Co:Cr nanoparticles on SaOS-2 cell osteogenic responses on grit-blasted, plasma-sprayed titaniumcoated, and hydroxyapatite-coated prosthesis surfaces. Cellular activity and ALP activity were reduced to a greater extent with combination treatments compared to individual ions. Co 2þ and Cr 3þ interacted additively and synergistically to reduce cellular activity and ALP activity, respectively, while the Co 2þ with Cr 6þ combination was dominated by the effect of Cr 6þ alone. Mineralization by osteoblasts was greater on hydroxyapatite-coated surfaces compared to grit-blasted and plasma-sprayed titanium-coated surfaces. Treatments with Co Keywords: hip replacement; cobalt; chromium; osteoblasts; prosthesis wear; prosthesis surfacesThe early failure of metal-on-metal prostheses, in part due to failures of osseointegration of cementless components, has highlighted the adverse effects of wear and corrosion mediated release of cobalt (Co) and chromium (Cr) on the periprosthetic environment.

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

“…The lack of any effect of Cr 3+ alone is consistent with the observations of Kanaji and coworkers and the previously held dogma of the relative inability of Cr 3+ to cross cell‐membranes 34. In contrast to this dogma, we have previously shown the intracellular localization of Cr 3+ in osteoblasts,21 as well as an additive effect of Co 2+ and Cr 3+ treatment 22. Thus the increased effect of combined ions at 500 μg/L over the effect of Co 2+ alone observed in this study suggests for the first time potential facilitation of Cr 3+ entry into osteocytes, as well as common downstream signaling.…”

“…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…”

“…19 We recently demonstrated that exposure to Co 2þ and Cr 3þ 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] Previous studies have suggested that exposure to Co 2þ in vitro has a cytotoxic and pro-inflammatory effect on osteocytes. [23][24][25][26] Here, we develop understanding in this area by examining the effects of exposure to both Co 2þ and Cr 3þ at clinically relevant concentrations on osteocyte physiology-in particular their survival, dendritic morphology, response to fluid shear stress (FSS), and mineralization.…”

Effects of chronic cobalt and chromium exposure after metal‐on‐metal hip resurfacing: An epigenome‐wide association pilot study

“…The adverse effects of elevated levels of metal exposure have been highlighted by the high failure rates of MOM prostheses, and by case reports of cardiac, neurological, and endocrine disorders, resulting in their recent recall from many markets . Several investigators have described the detrimental effects of metal exposure on survival and function of cell types including bone cells, monocytes, and macrophages in vitro . The mechanism by which metal debris exerts these effects is still unclear, although some investigators have studied changes in gene expression of candidate genes in cell and animal models …”

“…11 Several investigators have described the detrimental effects of metal exposure on survival and function of cell types including bone cells, monocytes, and macrophages in vitro. [12][13][14][15] The mechanism by which metal debris exerts these effects is still unclear, although some investigators have studied changes in gene expression of candidate genes in cell and animal models. [16][17][18] Several studies have reported metal-induced changes in DNA methylation, alteration in gene expression and cell physiology in the setting of cancer.…”