title: Chromosomal aberrations in the peripheral blood of patients with metal-on-metal hip bearings.
abstract: BACKGROUND
  Approximately one-third of patients undergoing joint replacement are under sixty years of age. Many of these patients may be exposed to wear debris from the orthopaedic implant for several decades. Clinical follow-up of this group of patients has been short compared with the lifetimes of the patients, and the long-term effects of this chronic exposure are unknown.
  
  
  METHODS
  By using cytogenetic biomarkers (twenty-four-color fluorescent in situ hybridization [FISH]), we analyzed the peripheral blood leukocytes for chromosomal aberrations in three groups of subjects: (1) six age and sex-matched control subjects who had no implant and did not smoke (control group), (2) five subjects in whom an implant with a metal-on-metal articulation had been in situ for an average of thirty-five years (metal-on-metal group), and (3) four subjects in whom a metal-on-metal implant had been revised to a metal-on-polyethylene articulation at an average of twenty-two years (revised group).
  
  
  RESULTS
  The number of chromosomal aberrations in the metal-on-metal group was greater than that in the control group. Specifically, the percentage of aneuploidy gain was three times greater (p = 0.01) in the metal-on-metal group. Structural aberrations were not seen in the control group, and this difference was highly significant (p = 0.003). Also, the number of chromosomal aberrations in the metal-on-metal group was greater than that in the revised group. Specifically, the percentage of structural aberrations was thirty-one-fold higher (p = 0.013). The percentage of aneuploidy gain in the metal-on-metal group was about twice that in the revised group, although this difference was not significant (p = 0.37). The percentage of aneuploidy gain in the revised group was about double that in the control group, although this difference was also not significant (p = 0.41). Translocations were seen only in subjects with a metal-on-metal articulation.
  
  
  CONCLUSIONS
  The clinical consequences of the chromosomal changes seen in this study are unknown, and it is unknown if the changes are present in other cells in the body. The results emphasize the need for additional investigations into the effect of chronic exposure to elevated levels of metal ions produced by orthopaedic implants.
authors.affiliation: Royal National Orthopaedic Hospital, Brockley Hill, Stanmore, Middlesex HA7 4LP, England. erdunstan@aol.com
authors.forename: E
authors.initials: E
authors.lastname: Dunstan
authors.forename: D
authors.initials: D
authors.lastname: Ladon
authors.forename: P
authors.initials: P
authors.lastname: Whittingham-Jones
authors.forename: R
authors.initials: R
authors.lastname: Carrington
authors.forename: T W R
authors.initials: TW
authors.lastname: Briggs
mesh_terms: D000293:Adolescent; D000328:Adult; D002869:Chromosome Aberrations / Q000139:chemically induced*; D005260:Female; D005266:Femoral Neoplasms / Q000601:surgery; D006622:Hip Prosthesis; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007962:Leukocytes; D008297:Male; D008670:Metals / Q000009:adverse effects*; D008875:Middle Aged; D011474:Prosthesis Design; D011475:Prosthesis Failure; D012086:Reoperation; D013997:Time Factors
chemical_list: D008670:Metals