Toxicology‐based cancer causation analysis of CoCr‐containing hip implants: a quantitative assessment of genotoxicity and tumorigenicity studies

Abstract

In this paper, quantitative methods were used to evaluate the weight of evidence regarding a causative relationship between cobalt-chromium (CoCr)-containing hip implants and increased cancer risk. We reviewed approximately 80 published papers and identified no-observed-adverse-effect level (NOAEL) and/or lowest-observed-adverse-effect level (LOAEL) values for specific endpoints of interest: genotoxic effects from in vitro studies with human cell lines as well as genotoxicity and tumor formation in animal bioassays. Test articles included Co particles and ions, Cr particles and ions, and CoCr alloy particles as well as CoCr alloy implants. The NOAEL/LOAEL values were compared with body burdens of Co/Cr particles and ions we calculated to exist in systemic tissues of hip implant patients under normal and excessive wear conditions. We found that approximately 40 tumor bioassays have been conducted with CoCr alloy implants or Co/Cr particles and ions at levels hundreds to thousands of times higher than those present in hip implant patients, and none reported a statistically significant increased incidence of systemic tumors. Results from in vitro and in vivo genotoxicity assays, which are relatively less informative owing to false positives and other factors, also indicated that DNA effects would be highly unlikely to occur as a result of wear debris from a CoCr implant. Hence, the toxicological weight of evidence suggests that CoCr-containing hip implants are unlikely to be associated with an increased risk of systemic cancers, which is consistent with published and ongoing cancer epidemiology studies involving patients with CoCr hip implants.

Role of implants surface modification in osseointegration: A systematic review

“…It is also found to have an excellent combination of material toughness and yield strength, ductility, and hardness (Navarro, Michiardi, Castaño, & Planell, 2008). However, adding more than 30% chromium makes this alloy hard to cast and results in a brittle phase (Christian, Oliver, Paustenbach, Kreider, & Finley, 2014). However, adding more than 30% chromium makes this alloy hard to cast and results in a brittle phase (Christian, Oliver, Paustenbach, Kreider, & Finley, 2014).…”

“…vance between particles and complications has not been thoroughly evaluated and Christian et al suggested that the Co/Cr concentrations in the blood and tissue of MoM implant patients are too low to increase the risk of systemic disease(Christian et al, 2014).…”

The biological response to orthopaedic implants for joint replacement: Part I: Metals

“…One study analyzed over 80 published papers to determine if there is a relationship between CoCr implants and an increase in cancer. They found that the Co and Cr ion concentration in the bodies of those with meal‐on‐metal articulations were far too small to substantially increase the risk of developing systemic cancer . In vitro and in vivo assays showed that DNA defects would be very unlikely to occur due to the increase in Co or Cr ion concentration as a result of a MOM articulation .…”

“…They found that the Co and Cr ion concentration in the bodies of those with meal‐on‐metal articulations were far too small to substantially increase the risk of developing systemic cancer . In vitro and in vivo assays showed that DNA defects would be very unlikely to occur due to the increase in Co or Cr ion concentration as a result of a MOM articulation . Moreover, in 40 tumor bioassays where Co and Cr ion concentrations were significantly higher than those in hip implants, none reported a significant increase in systemic cancer .…”

Les prothèses de hanche au cobalt sont-elles dangereuses ?

“…Après le retrait de la prothèse chez les patients intoxiqués par le cobalt, l'état clinique s'améliore même si certains symptômes peuvent persister [22,24]. Plusieurs études ont démontré que le risque cancérogène n'est pas significativement différent de celui de la population générale [7,26]. En raison du passage transplacentaire du cobalt au cours de la grossesse, le risque pour la descendance est suspecté même s'il n'est pas prouvé.…”