title: Does chronic raise of metal ion levels induce oxidative DNA damage and hypoxia-like response in patients with metal-on-metal hip resurfacing?
abstract: Metal-on-metal hip resurfacing (MOM-HR) represents a viable alternative to traditional arthroplasty. Nevertheless, in MOM coupling both metal nanoparticles and ions are released, whose toxicity remains a matter of concern. We investigated whether 'endogenous' chronic exposure to cobalt and chromium induced a state of oxidative stress, DNA damage and a hypoxia-like response in patients with well-functioning MOM-HR. Twenty-two patients with unilateral MOM-HR were recruited at long-term. Twenty-one osteoarthritic subjects were enrolled for comparison. Serum ion levels were measured and correlated with 8-hydroxydeoxyguanosine and circulating-free-DNA, as markers of oxidative DNA damage. Moreover, the hypoxia-inducible factor-1α, marker of hypoxic state, was evaluated. Ion concentrations were found to be 5-to-15 times higher in MOM-HR patients than in presurgery subjects (p < 0.001); circulating-free-DNA, 8-hydroxydeoxyguanosine, and hypoxia-inducible factor-1α levels were not significantly different between groups and did not correlate with ion levels. Analyzing the results according to gender, MOM-HR males had higher 8-hydroxydeoxyguanosine levels (p = 0.01) compared with MOM-HR females. Similarly, circulating-free-DNA values were higher in males than females, even if this difference did not reach statistical significance. This research is the first that attempted to investigate the long-term effects of ion dissemination in subjects with well-fixed MOM implants. A significant correlation between biomarkers increase and ion levels was not demonstrated. Nevertheless, both circulating-free-DNA and 8-hydroxydeoxyguanosine showed a tendency to increase in MOM-HR males. Further studies with a larger sample size should be performed to detect the clinical relevance of biomarkers increase especially in younger subjects, where a chronic moderately elevated exposure has to be faced. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 460-466, 2017.
authors.affiliation: Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Savarino
authors.affiliation: Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Fotia
authors.affiliation: Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Roncuzzi
authors.affiliation: Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: Michelina
authors.initials: M
authors.lastname: Greco
authors.affiliation: Department I of Orthopaedics and Traumatology, Rizzoli Orthopedic Institute, Bologna, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Cadossi
authors.affiliation: Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Rizzoli Orthopaedic Institute, Bologna, Italy.|Department of Biomedical and Neuromotor Sciences, Bologna University, Bologna, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Baldini
authors.affiliation: Department I of Orthopaedics and Traumatology, Rizzoli Orthopedic Institute, Bologna, Italy.|Department of Biomedical and Neuromotor Sciences, Bologna University, Bologna, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Giannini
mesh_terms: D000328:Adult; D000368:Aged; D019644:Arthroplasty, Replacement, Hip; D004247:DNA / Q000097:blood*; D004249:DNA Damage; D005260:Female; D005500:Follow-Up Studies; D006622:Hip Prosthesis / Q000009:adverse effects*; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000209:etiology; D008297:Male; D008670:Metals / Q000097:blood*; D008875:Middle Aged; D010003:Osteoarthritis / Q000097:blood; D013499:Surface Properties
chemical_list: D008670:Metals; D004247:DNA
keywords: hip prosthesis; metal ions; metal-on-metal bearing; toxicity; wear