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Biological Responses to Spinal Implant Debris

Hallab, Nadim J., PhD

doi: 10.1097/BRS.0000000000002020

Rush University Medical Center, Chicago, IL.

Address correspondence and reprint requests to Nadim J. Hallab, PhD, Rush University Medical Center, 1653 W. Congress Pkwy, Chicago, IL 60612; E-mail:

Received 6 December, 2016

Accepted 6 December, 2016

The manuscript submitted does not contain information about medical device(s)/drug(s).

No funds were received in support of this work.

No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

To identify the role of adaptive immune responses in the long-term performance of spine implants (i.e., spinal implant debris), the contributions of both the innate and the adaptive immune system to implant debris bioreactivity need to be evaluated. Clinical evidence points to implant wear debris as the main reason for implant failure. However, most data pertain to polymeric wear debris from articular surfaces, not to metal debris. Some cases are the result of adaptive immune reactivity to metal debris, also termed metal sensitivity, metal allergy, or delayed-type hypersensitivity (DTH) responses.1,2 Most often, aseptic implant failure over time is due to slow, subtle innate macrophage reactivity to particulate debris. This innate immune response controlled by macrophages elicits an immediate maximal response, is not antigen specific, and results in no (little) immunologic memory following exposure. Innate immune macrophage-dominated granulomas over time typically invade the implant/bone interface, causing pain and implant loosening. In contrast, adaptive immunity in orthopedics generally is controlled by lymphocytes, is antigen dependent, involves lag time (weeks to years) between immediate or accumulated exposure and maximal response, is antigen specific, and results in immunologic memory following exposure. A total joint arthroplasty implant may produce adaptive immune responses to implant debris that can cause premature implant failure and generally are correlated with aseptic long-term failure (Figure 1).1,2 Through DTH responses, lymphocytes can become activated to the metal-protein complexes formed from implant corrosion and wear. Diagnostic tests of hypersensitivity include dermal patch testing and lymphocyte transformation testing (LTT; Figure 1). Cohort studies over 30+ years have suggested a strong connection between the amount of metal implant debris and the development of metal sensitivity.1,3 DTH responses are clinically important for spinal implants, but it remains unknown how prevalent or severe this problem is. Very few case reports of spinal implant–related pain/poor implant performance and osteolysis have shown any evidence of pathogenic adaptive immune responses such as histologically identifiable local lymphocyte accumulations.4–6 Cohort studies of quantitative diagnostic techniques such as metal-LTT are required to identify metal-induced DTH responses to spinal implants. Metal allergy diagnostic testing (LTT) may be beneficial for optimizing biocompatibility and/or planning revision surgery with patient-specific nonreactive implant materials.

Figure 1

Figure 1

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1. Hallab NJ, Caicedo M, McAllister K, et al. Asymptomatic prospective and retrospective cohorts with metal-on-metal hip arthroplasty indicate acquired lymphocyte reactivity varies with metal ion levels on a group basis. J Orthop Res 2013; 31:173–182.
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6. Cavanaugh DA, Nunley PD, Kerr EJ III, et al. Delayed hyper-reactivity to metal ions after cervical disc arthroplasty: a case report and literature review. Spine (Phila Pa 1976) 2009; 34:E262–E265.

adaptive immune response; metal hypersensitivity; spine implant

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