Women More Sensitized than Men to Metal Used in TJA

    Why are women at higher risk of complications after total hip or knee replacement surgery? An increased rate of hypersensitivity to the metals contained in joint implants might be a contributing factor, suggests a study published in The Journal of Bone & Joint Surgery.

    Among patients who experienced unexplained pain after total joint arthroplasty (TJA) with metal-containing components, women are more likely than men to test positive for metal sensitization, according to the report by Nadim J. Hallab, PhD, and colleagues from Rush University Medical Center, Chicago.

    “These findings may explain, at least in part, the sex disparity in the outcomes of certain TJA implant designs,” Dr. Hallab and his co-authors write in the article.

    Lymphocyte Transformation Test Results

    The researchers reviewed data on 2,613 patients who were evaluated for unexplained joint pain after total hip arthroplasty (THA) and/or total knee arthroplasty (TKA). All had metal-containing joint replacement components, and none had signs of infection, inflammation, or other findings that would explain their pain.

    The patients’ average age was 62 years; 60% of the patients were women. The average time since TJA was about 3 years, and in most cases, less than 2 years. Women had higher average pain scores than men: 6.8 versus 6.1 on a scale of 0 to 10, with 0 being no pain and 10 being the worst pain ever experienced.

    All patients underwent a lymphocyte transformation test (LTT) to evaluate immune cell sensitization to metals. The LTT can assess whether the patient has developed hypersensitivity to 1 or more of the metals contained in the implant components, such as cobalt, chromium, or nickel.

    The LTT results suggested immune sensitization to implant metals in 49% of women and 38% of men. The difference persisted when researchers used a more stringent definition of sensitization: 25% versus 18%. In addition, among patients with positive LTT results, the severity of metal sensitivity was greater in women.

    Prior to blood testing, 29% of women with pain after TJA said they had experienced an allergic skin reactions to metals, compared with 4% of men.

    The results show a “remarkable and significant” increase in immune cell sensitivity to metals in women compared with men who reported unexplained pain after THA or TKA. “This supports both our hypothesis and previous reports that females may have a higher risk of adverse responses to implant metals,” Dr. Hallab and co-authors write in the article.

    More Questions to Be Answered

    The findings support the possibility that the higher rate of complications after TJA in women may have an “adaptive immunological basis.” But it is still unclear whether the sex-related difference in immune sensitization is related to intrinsic biologic factors, such as hormones, or to environmental factors, such as exposure to metals in jewelry or cosmetics.

    In addition, the study could not determine whether sensitization to metals is a pre-existing condition or is induced by the metal-containing joint implants, or whether it is a combination of these 2 possible causes. The researchers call for more targeted studies to assess the clinical outcomes of patients who test positive for metal sensitization.

    “We feel these results add credence to the utility of metal allergy LTT testing for diagnosing orthopaedic patients who demonstrate a history of dermal metal allergy or have an implant with idiopathic pain and/or peri-implant inflammation,” Dr. Hallab said.


    Caicedo MS, Solver E, Coleman L, Jacobs JJ, Hallab NJ. Females with unexplained joint pain following total joint arthroplasty exhibit a higher rate and severity of hypersensitivity to implant metals compared with males: implications of sex-based bioreactivity differences. J Bone Joitn Surg Am. 2017 Apr 19;99(8):621-628. doi: 10.2106/JBJS.16.00720.