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Chromosomal Aberrations in the Peripheral Blood of Patients with Metal-on-Metal Hip Bearings
E. Dunstan, FRCS(Orth)1; D. Ladon, PhD2; P. Whittingham-Jones, MRCS1; R. Carrington, FRCS(Orth)1; T.W.R. Briggs, FRCS1
1 Royal National Orthopaedic Hospital, Brockley Hill, Stanmore, Middlesex HA7 4LP, England. E-mail address for E. Dunstan: erdunstan@aol.com
2 Bristol Implants Research Center, Southmead Hospital, University of Bristol, Bristol BS10 5NB, England
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Disclosure: The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.
Investigation performed at the Bristol Implants Research Center, Bristol, England

The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2008 Mar 01;90(3):517-522. doi: 10.2106/JBJS.F.01435
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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.

Level of Evidence: Therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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