Advertisement

James A. Rand Young Investigator's Award: Questioning the “Nickel Free” Total Knee Arthroplasty

Published:April 01, 2022DOI:https://doi.org/10.1016/j.arth.2022.03.058

      Abstract

      Background

      A study was performed to measure metal ions present in the knee joint after performing a total knee arthroplasty (TKA) with standard cobalt chromium (CoCr) components as well as with “nickel-free” oxidized zirconium femoral and titanium tibial (OxZr/Ti) components.

      Methods

      Knee joint fluid was collected prior to arthrotomy, and on postoperative day one to determine the amount of metal debris generated when performing a TKA with standard instrumentation from consecutive cases with CoCr components (n = 24) and OxZr/Ti components (n = 16).

      Results

      CoCr implant patients had statistically higher levels of nickel (Ni) (29.7%, P = .033), cobalt (Co), (1,100.7%, P < .0001) and chromium (Cr) (118.9%, P < .0001) postoperatively. The cutting blocks and sawblades do not contain Co, which therefore must have come from the components. The metal ions generated from the sawblades and cutting blocks, therefore, could be discerned from the OxZr/Ti whose components don’t contain Co, Cr, or Ni. The OxZr patients had significantly higher Cr (9.5×, P < .001) and Ni (5.1×, P < .001) post-TKA vs pre-TKA; Co levels were not significantly different as expected with the absence of Co in the components (P = .60). The Ni levels generated in performing an Oxinium TKA was 3.3 times higher than when performing a CoCr TKA (1.37 vs. 41 ppb, P < .001).

      Conclusions

      The substantial degree of Ni generation resulting from performing a hypoallergenic “nickel-free” TKA calls into questions the rationale of utilizing more expensive lower Ni components on the basis of known or suspected Ni or Cr allergy.

      Keywords

      The contribution of metal allergy or hypersensitivity reaction to residual symptoms and early failure in total knee arthroplasty (TKA) remains controversial. Several studies implicate a link between metal ion allergy, especially nickel, and persistent pain, recurrent effusions and aseptic failure after TKA [
      • Mitchelson A.J.
      • Wilson C.J.
      • Mihalko W.M.
      • Grupp T.M.
      • Manning B.T.
      • Dennis D.A.
      • et al.
      Biomaterial hypersensitivity: is it real? Supportive evidence and approach considerations for metal allergic patients following total knee arthroplasty.
      ]. Evidence to the contrary, refuting metal allergy or hypersensitivity as a mechanism of persistent symptoms or failure of TKA, is equally compelling [
      • Middleton S.
      • Toms A.
      Allergy in total knee arthroplasty: a review of the facts.
      ]. Similarly, the use of “hypoallergenic” or “metal-sensitive” implants has been reported with mixed success in improving outcomes in patients with known or suspected metal allergy or hypersensitivity [
      • Hallab N.
      • Merritt K.
      • Jacobs J.J.
      Metal sensitivity in patients with orthopaedic implants.
      ,
      • Graves C.M.
      • Otero J.E.
      • Gao Y.
      • Goetz D.D.
      • Willenborg M.D.
      • Callaghan J.J.
      Patient reported allergies are a risk factor for poor outcomes in total hip and knee arthroplasty.
      ,
      • Bravo D.
      • Wagner E.R.
      • Larson D.R.
      • Davis M.P.
      • Pagnano M.W.
      • Sierra R.J.
      No increased risk of knee arthroplasty failure in patients with positive skin patch testing for metal hypersensitivity: a matched cohort study.
      ,
      • Nam D.
      • Li K.
      • Riegler V.
      • Barrack R.L.
      Patient-reported metal allergy: a risk factor for poor outcomes after total joint arthroplasty?.
      ].
      In spite of the conflicting evidence on the topic, the development and use of “hypoallergenic” or “- sensitive” implants have continued to grow, with most major implant manufacturers offering such a model of their TKA at an increased cost [
      ,
      ,
      ,
      ]. However, little recent attention has been paid to the fact that the instruments used to perform TKA, including sawblades and traditional cutting blocks, may generate a large amount of intraarticular metal ions when performing TKA [
      • Sunderman Jr., F.W.
      • Hopfer S.M.
      • Swift T.
      • Rezuke W.N.
      • Ziebka L.
      • Highman P.
      • et al.
      Cobalt, chromium, and nickel concentrations in body fluids of patients with porous-coated knee or hip prostheses.
      ]. This metal debris from sawblade and cutting block damage and wear may lead to high postoperative levels of metal ions in the knee joint even if a “hypoallergenic” or “metal-sensitive” implant is used, calling into question the value of these more expensive specialized implants.
      Previous studies with in vitro and animal models have demonstrated that metal particles are generated using sawblades through captured cutting blocks in TKA [
      • Gotterson P.R.
      • Nusem I.
      • Pearcy M.J.
      • Crawford R.W.
      Metal debris from bony resection in knee arthroplasty–is it an issue?.
      ,
      • Sydney S.E.
      • Pickering S.A.
      • Bell C.G.
      • Crawford R.
      Reducing metal debris generation during total knee arthroplasty.
      ]. To our knowledge, the intraarticular levels of metal ions after TKA has not been reported on. The purpose of this study is to determine postoperative intraarticular levels of nickel, cobalt and chromium generated during the primary TKA performed with standard instrumentation with “metal sensitive”/”hypoallergenic” implants and standard cobalt chromium implants.

      Methods

      A prospective two cohort study was performed. Institutional review board approval was obtained prior to initiation of the study. All patients undergoing primary unilateral cemented TKA for a diagnosis of primary knee osteoarthritis with one of four surgeons (R.L.B., C.M.L., R.M.N., R.W.W.) at a single institution during the study period were considered for the study. Patients were excluded if they were unwilling to participate in the study or had a diagnosis of stage III or IV chronic kidney disease. An Informed Consent was signed by all participants enrolled in the study.
      All patients underwent standard perioperative procedures per institutional protocol. Patients with self-reported or known nickel allergies had TKA performed with a nickel-sensitive implant: Legion Primary Knee System with a cruciate retaining Oxinium femoral component, titanium tibial baseplate and cruciate retaining polyethylene tibial bearing (Smith and Nephew, Memphis, TN). Patients without a known or reported nickel allergy had TKA performed with a standard, non-hypoallergenic implant: Evolution Primary Knee System with cobalt chromium femoral and tibial components and a cruciate sacrificing medial pivot tibial polyethylene bearing (MicroPort, Memphis, TN).
      Joint aspiration was performed after skin incision, but prior to arthrotomy to establish baseline synovial fluid metal levels. An oscillating dual-cut sawblade made of Sandovik 7C27Mo2 Strip Steel (Stryker, Malwah, NJ) was used through 17-4 stainless steel cutting blocks for all bone preparation. Three liters of normal saline were used for irrigation via low pressure pulse lavage throughout the procedure. A single, medium hemovac drain was placed in the suprapatellar pouch and attached to self-suction after skin closure. All patients underwent standard post-operative procedures per institution protocol. All drains were removed at 6:00 AM on post-operative day one and post-operative synovial fluid was collected at that time. Pre-operative and post-operative synovial fluid levels of cobalt, chromium and nickel were measured using standard laboratory procedures. All metal ion levels are reported in parts per billion (ppb). Material composition of the knee arthroplasty components, cutting blocks and sawblades are shown in Table 1.
      Table 1Composition of Metallic Materials Used During TKA Procedure.
      Component/InstrumentMaterialCobaltChromiumNickel
      MicroPort Evolution Femoral and Tibial componentsCobalt Chromium58%30%<0.5%
      Smith and Nephew Legion Femoral componentOxidized Zirconium<0.002%<0.02%<0.0035%
      Smith and Nephew Legion Tibial componentTitanium (Ti6Al4V)0%0%0%
      Captured cutting guides17-4 Stainless Steel0%17.5%4%
      Saw bladeStrip Steel (7C27Mo2)0%13.5%<0.01%
      A representative sample of 6 saw blades underwent wear analysis using scanning electron microscopy and profilometry. They were cleaned with isopropanol for 5 minutes in an ultrasonic bath and then examined in a scanning electron microscope (IT500HR, JEOL). Secondary electron images were acquired at 10 kV with magnifications ranging from 500× to 2000× to visualize surface damage and morphology. We used an energy dispersive x-ray spectroscopy detector (Ultim-Max detector, Oxford Instruments, UK) at 20 kV to verify the local and overall chemical distribution of the alloying elements and potential chemical alterations at the worn surfaces. Material loss was assessed with an optical 3D surface profiler (OrthoLux, RedLux, UK). Sawblades were placed in a custom-made fixture and rotated in front of a white light confocal sensor for data acquisition. The original surface was digitally reconstructed based on unworn areas. Volume loss was then computed using the RedLux studio software. In addition, heat maps and light intensity maps where generated of each saw blade surface.
      Data collection, organization and statistical analysis were all performed in Microsoft Excel 365 (Microsoft, USA). Paired Student’s t-test was used to compare preoperative to postoperative metal ion values. Unpaired Student’s t-test was used to compare continuous variables between CoCr and OxZr/Ti groups. Chi-square test was used to compare categorical demographic values between groups.

      Results

      Fourty patients who met inclusion and exclusion criteria were enrolled. Twenty four patients who were enrolled underwent TKA with the standard, non-hypoallergenic CoCr implants. Sixteen patients enrolled underwent TKA with nickel-sensitive OxZr/Ti implants. There was no statistically significant difference in demographic data, time to collection of drain fluid and amount of drain fluid between the CoCr and OxZr/Ti groups (Table 2).
      Table 2Demographic Data of the Two Patient Groups.
      VariableCobalt Chromium GroupOxidized Zirconium GroupP-Value
      Sex (#)
       Male146.259
       Female1110
      Age, y (mean ± SD)62.6 ± 10.0266.75 ± 7.92.170
      BMI, kg/mm2 (mean ± SD)31.97 ± 4.6032.4 ± 6.61.808
      Drain Collection Time, hours postoperatively (median (range))17.8 (12-21)17.3 (13.5-19.5).569
      Drain Output, cc (median (range))215 (45-540)240 (20-400).849
      Table 3Preoperative and Postoperative Chromium, Cobalt and Nickel Converted to Part per Billion for TKAs Performed With CoCr Implants (N = 24).
      Metal IonPre-OpPost-OpP-Value
      Chromium0.127 ± 0.1260.278 ± 0.191<.001
      Median (range)(0.028-0.554)(0.067-0.807)
      Cobalt0.115 ± 0.0791.382 ± 1.802.002
      Median (range)(0.010-0.363)(0.007-8.209)
      Nickel0.316 ± 0.1960.410 ± 0.158.033
      Median (range)(0.058-0.866)(0.116-0.700)
      Table 4Preoperative and Postoperative Chromium, Cobalt and Nickel Converted to Part per Billion for TKAs Performed With OxZr/Ti Implants (N = 17).
      ScoresPre-OpPost-OpP-Value
      Chromium0.054 ± 0.0210.502 ± 0.209<.001
      (range)(0.020-0.090)(0.170-0.840)
      Cobalt0.071 ± 0.0340.124 ± 0.421.601
      (range)(0.120-0.030)(0.010-1.750)
      Nickel0.267 ± 0.1671.37 ± 0.707<.001
      (range)(0.140-0.810)(0.550-2.99)
      The metal ions measured in the joint fluid recovered on postoperative day one are summarized in Table 3 for the CoCr implant group and Table 4 for the OxZr/Ti implant group. The CoCr implant group had statistically higher levels of cobalt (1,100.7%, P < .001), chromium (118.9%, P < .001) and nickel (29.7%, P = .033) postoperatively compared to preoperative levels. The cutting blocks and sawblades do not contain cobalt, which therefore must have come from the femoral and tibial components during or after implantation. The debris generation purely from the sawblades and cutting blocks, therefore, could be discerned from the OxZr/Ti implant group as these components don’t contain Co, Cr, or Ni. The OxZr/Ti patients had 9.5× significantly higher chromium (0.502 vs. 0.053, P < .001) and 5.1× higher nickel (1.370 vs. 0.267, P < .001) postoperative vs preoperatively while the cobalt level was not significantly different after TKA, as expected with the absence of cobalt in the components (0.124 vs. 0.071, P = .60). The nickel levels generated in performing an Oxinium TKA was 3.3 times higher than when performing a Co-Cr TKA (1.37 vs. 41, P < .001).
      Representative scanning electronic microscopy demonstrated significant sawblade surface fatigue wear, abrasive wear, adhesive wear and plastic deformation (Fig. 1). Representative profilometry of the 6 sawblades demonstrated the median material loss of 0.26 mm3 (range: 0.0162 to 1.015 mm3). The greatest material loss from the sawblades were observed on the outside edges of the blades.
      Figure thumbnail gr1
      Fig. 1Profilometry (A) and scanning electron micrography (B) of a representative portion of a sawblade used for TKA bone cuts through captured femoral and tibial cutting blocks.

      Discussion

      This study describes the levels of intraarticular cobalt, chromium and nickel present after primary TKA performed with standard manual instrumentation. The interference between the sawblades and cut blocks seems to be the major source of nickel and chromium ions. Specifically, the captured cutting blocks seem to be a major source of nickel during performance of TKA. While impaction of the final implants seems to have caused release of cobalt into the joint, as they are the only possible source of cobalt, the implants do not appear to have been a major source of nickel in the joint on postoperative day one. In fact, performing a hypoallergenic, “nickel-free” TKA with the specific knee system we used in this study resulted in substantially greater levels of intraarticular nickel levels than conventional cobalt chromium containing implants. Our results demonstrate nickel and chromium levels in the joint are elevated by the actual performance of TKA, calling into question the rationale of utilizing more expensive hypoallergenic lower nickel content components on the basis of suspected nickel or chromium allergy.
      Despite controversy regarding the role of metal hypersensitivity in persistent symptoms or failure of TKA, hypoallergenic implants are routinely used for TKA in patients with reported allergies to nickel, cobalt or chromium. The self-reported incidence of dermal hypersensitivity to metal is 10%-15% in the general population [
      • Hallab N.
      • Merritt K.
      • Jacobs J.J.
      Metal sensitivity in patients with orthopaedic implants.
      ,
      • Bloemke A.D.
      • Clarke H.D.
      Prevalence of self-reported metal allergy in patients undergoing primary total knee arthroplasty.
      ]. However, the correlation between dermal hypersensitivity and synovial hypersensitivity resulting in implant failure is unclear [
      • Bravo D.
      • Wagner E.R.
      • Larson D.R.
      • Davis M.P.
      • Pagnano M.W.
      • Sierra R.J.
      No increased risk of knee arthroplasty failure in patients with positive skin patch testing for metal hypersensitivity: a matched cohort study.
      ]. Furthermore, patients with reported allergy to nickel, cobalt or chromium have poorer outcomes as compared to patients without these allergies, regardless of implant choice [
      • Graves C.M.
      • Otero J.E.
      • Gao Y.
      • Goetz D.D.
      • Willenborg M.D.
      • Callaghan J.J.
      Patient reported allergies are a risk factor for poor outcomes in total hip and knee arthroplasty.
      ,
      • Nam D.
      • Li K.
      • Riegler V.
      • Barrack R.L.
      Patient-reported metal allergy: a risk factor for poor outcomes after total joint arthroplasty?.
      ,
      • McLawhorn A.S.
      • Bjerke-Kroll B.T.
      • Blevins J.L.
      • Sculco P.K.
      • Lee Y.Y.
      • Jerabek S.A.
      Patient-reported allergies are associated with poorer patient satisfaction and outcomes after lower extremity arthroplasty: a retrospective cohort study.
      ]. Psychosocial and emotional factors have been implicated in the link between metal allergy and poor outcomes after TKA [
      • Ferrer T.
      • Hinarejos P.
      • Goicoechea N.
      • Leal-Blanquet J.
      • Sanchez-Soler J.
      • Torres-Claramunt R.
      • et al.
      Anxiety is the cause of the worse outcomes of allergic patients after total knee arthroplasty.
      ,
      • Pena P.
      • Ortega M.A.
      • Bujan J.
      • De la Torre B.
      Decrease of quality of life, functional assessment and associated psychological distress in patients with hypoallergenic total knee arthroplasty.
      ].
      Prior studies have demonstrated significant metal debris generation occurs during performance of TKA. Gotterson et al. performed bony resections simulating TKA in a pig model and collected metal debris from sawblades, cutting blocks and bone surfaces in attempt to characterize this phenomenon. On an average, 1.13 mg of metal was lost from the sawblades alone. Based on material composition, they determined that cutting blocks were the major source of this debris, followed by the sawblades, with an estimate that millions of metal particles are generated during standard TKA resections [
      • Gotterson P.R.
      • Nusem I.
      • Pearcy M.J.
      • Crawford R.W.
      Metal debris from bony resection in knee arthroplasty–is it an issue?.
      ]. Interestingly, they also found that uncaptured cutting blocks led to increased metal debris generation, which the authors hypothesized was from surgeons pushing harder on the cutting block in attempt to maintain an accurate cut [
      • Gotterson P.R.
      • Nusem I.
      • Pearcy M.J.
      • Crawford R.W.
      Metal debris from bony resection in knee arthroplasty–is it an issue?.
      ]. In another in vitro study, the metal ion generation using an end-only oscillating sawblade (Precision SawBlade, Stryker) significantly decreased metal ion generation as compared to a conventional sawblade [
      • Sydney S.E.
      • Pickering S.A.
      • Bell C.G.
      • Crawford R.
      Reducing metal debris generation during total knee arthroplasty.
      ]. The same study found that the majority of material loss with performance of TKA was from the cutting blocks, not the saw blades, as a result of the blades having a higher hardness value than the 4-in-1 cutting blocks [
      • Sydney S.E.
      • Pickering S.A.
      • Bell C.G.
      • Crawford R.
      Reducing metal debris generation during total knee arthroplasty.
      ]. Similarly, the profilometry we performed in our study demonstrated little overall material loss form the saw blades, and substantial material deposition on the surface of the blades. De Baets et al. performed a similar study in vivo, recovering all pulsed irrigation fluid at the conclusion of TKAs performed in live patients to look at potential sources of wear debris generated during TKA. They found that on an average 134.9 mg of debris was present in the lavage fluid, including 1.96 mg of metal particles [
      • De Baets T.
      • Waelput W.
      • Bellemans J.
      Analysis of third body particles generated during total knee arthroplasty: is metal debris an issue?.
      ].
      These findings support our hypothesis that the interference between the sawblade and cutting blocks is a major source of metal wear debris generation intraarticularly while performing TKA. This hypothesis is further supported by our the representative profilometry which demonstrated the wear on the sawblades concentrated at the peripheral edges, presumably from interference with the captured cutting blocks. Despite irrigation of the wound prior to closure that would remove some of the debris as reported by De Baets et al., a significant amount of cobalt, chromium and nickel remained intraarticularly as demonstrated by high levels in the drain fluid collected on postoperative day one. Sunderman et al. found levels of serum and urine nickel after TKA performed with titanium alloy implants containing <0.2% nickel content remained elevated up to 2 weeks postoperatively; they concluded the source of these ions was from instrumentation used during performance of the TKA [
      • Sunderman Jr., F.W.
      • Hopfer S.M.
      • Swift T.
      • Rezuke W.N.
      • Ziebka L.
      • Highman P.
      • et al.
      Cobalt, chromium, and nickel concentrations in body fluids of patients with porous-coated knee or hip prostheses.
      ]. At a minimum of one year postoperatively, serum nickel levels are not significantly different than preoperative values, and are not affected by the use of “hypoallergenic”, “nickel-free” or “coated” implants [
      • Postler A.
      • Beyer F.
      • Lutzner C.
      • Tille E.
      • Lutzner J.
      Similar outcome during short-term follow-up after coated and uncoated total knee arthroplasty: a randomized controlled study.
      ]. Of further concern is that the majority of the metal particulate debris generated during TKA has been measured to be in the 1 to 2 micrometers [
      • Gotterson P.R.
      • Nusem I.
      • Pearcy M.J.
      • Crawford R.W.
      Metal debris from bony resection in knee arthroplasty–is it an issue?.
      ,
      • Sydney S.E.
      • Pickering S.A.
      • Bell C.G.
      • Crawford R.
      Reducing metal debris generation during total knee arthroplasty.
      ]. Particles in this size range are well established to activate inflammatory macrophages, resulting in synovitis and osteolysis [
      • Schwarz E.M.
      • Lu A.P.
      • Goater J.J.
      • Benz E.B.
      • Kollias G.
      • Rosier R.N.
      • et al.
      Tumor necrosis factor-alpha/nuclear transcription factor-kappaB signaling in periprosthetic osteolysis.
      ].
      This study is not without limitations. The cutting guides had variable prior use before being used in the study, and were not able to be removed from clinical use for wear analysis. Furthermore, the amount of metal ions released from the cutting blocks and sawblades is likely dependent on the design of the cutting blocks, with some designs with tighter tolerances for the sawblade, central posts or peripheral pins that may increase the contact with the sawblade and therefore, increase the amount of metal deposition in the joint. Several other potential sources of metallic ions including surgical instruments, scalpels, fixation pins for cutting jigs, suture needles and drain trochars cannot be ignored; however the use of these other potential metal sources were uniform during the TKAs performed. Lastly, the ion levels on post-operative day one may not be indicative of the ion levels weeks to months post-operatively and thus may not be the most important measure for risk of metal hypersensitivity.
      In conclusion, this study shows significant levels of chromium and nickel ions are generated by performance of TKA with standard instrumentation. Cutting blocks, and to a lesser extent saw blades, appear to be the major sources of these metal ions, and therefore the, use of hypoallergenic implants does not mitigate this generation of metal debris into the knee joint. Furthermore, standard TKA implants contain less than 0.5% nickel, are polished and hardened, and articulate against plastic, and are therefore unlikely to represent a significant source of intraarticular nickel ions in the long term. Indeed, studies have failed to demonstrate elevated serum nickel levels in well-functioning TKA at greater than one year postoperatively, although data on intraarticular metal ion concentrations beyond the early postoperative period are lacking [
      • Postler A.
      • Beyer F.
      • Lutzner C.
      • Tille E.
      • Lutzner J.
      Similar outcome during short-term follow-up after coated and uncoated total knee arthroplasty: a randomized controlled study.
      ]. Standard cutting blocks contain 8-10× as much nickel as the standard TKA implants and liberate substantial micron and submicron size debris from abrasion by the harder saw blade. Our results indicate that the generation of metal ions, specifically nickel, during performance of TKA may be more significant than the nickel generated by a well-functioning TKA over time. This calls into question the rationale of using hypoallergenic implants, as the level of intraarticular metal ions on postoperative day one are elevated even with these implants.

      Acknowledgments

      Jackie King, Elizabeth Carnaghi and Alyssa Bjerk, nurse practitioners, for their work in assisting with drain fluid specimen collection.Venessa Riegler and Rondek Saleh, senior research coordinators for their work enrolling, consenting, collecting and organizing the data for analysis. Robin Pourzal for his assistance with profilometry.

      Appendix A. Supplementary Data

      References

        • Mitchelson A.J.
        • Wilson C.J.
        • Mihalko W.M.
        • Grupp T.M.
        • Manning B.T.
        • Dennis D.A.
        • et al.
        Biomaterial hypersensitivity: is it real? Supportive evidence and approach considerations for metal allergic patients following total knee arthroplasty.
        Biomed Res Int. 2015; 2015: 137287
        • Middleton S.
        • Toms A.
        Allergy in total knee arthroplasty: a review of the facts.
        Bone Joint J. 2016; 98-B: 437-441
        • Hallab N.
        • Merritt K.
        • Jacobs J.J.
        Metal sensitivity in patients with orthopaedic implants.
        J Bone Joint Surg Am. 2001; 83: 428-436
        • Graves C.M.
        • Otero J.E.
        • Gao Y.
        • Goetz D.D.
        • Willenborg M.D.
        • Callaghan J.J.
        Patient reported allergies are a risk factor for poor outcomes in total hip and knee arthroplasty.
        J Arthroplasty. 2014; 29: 147-149
        • Bravo D.
        • Wagner E.R.
        • Larson D.R.
        • Davis M.P.
        • Pagnano M.W.
        • Sierra R.J.
        No increased risk of knee arthroplasty failure in patients with positive skin patch testing for metal hypersensitivity: a matched cohort study.
        J Arthroplasty. 2016; 31: 1717-1721
        • Nam D.
        • Li K.
        • Riegler V.
        • Barrack R.L.
        Patient-reported metal allergy: a risk factor for poor outcomes after total joint arthroplasty?.
        J Arthroplasty. 2016; 31: 1910-1915
      1. Persona the personalized knee Ti-Nidium knee. Zimmer Biomet, Warsaw, IN2021
      2. Evolution Nitrx knee system. MicroPort Orthopedics, Memphis, TN2021
      3. Vega system knee implant. Aesculap Implant Systems, Center Valley, PA2020
      4. Oxinium Oxidized Zirconium for hip and knee replacement. Smith and Nephew, Memphis, TN2021
        • Sunderman Jr., F.W.
        • Hopfer S.M.
        • Swift T.
        • Rezuke W.N.
        • Ziebka L.
        • Highman P.
        • et al.
        Cobalt, chromium, and nickel concentrations in body fluids of patients with porous-coated knee or hip prostheses.
        J Orthop Res. 1989; 7: 307-315
        • Gotterson P.R.
        • Nusem I.
        • Pearcy M.J.
        • Crawford R.W.
        Metal debris from bony resection in knee arthroplasty–is it an issue?.
        Acta Orthop. 2005; 76: 475-480
        • Sydney S.E.
        • Pickering S.A.
        • Bell C.G.
        • Crawford R.
        Reducing metal debris generation during total knee arthroplasty.
        Orthopedics. 2007; 30: 999-1000
        • Bloemke A.D.
        • Clarke H.D.
        Prevalence of self-reported metal allergy in patients undergoing primary total knee arthroplasty.
        J Knee Surg. 2015; 28: 243-246
        • McLawhorn A.S.
        • Bjerke-Kroll B.T.
        • Blevins J.L.
        • Sculco P.K.
        • Lee Y.Y.
        • Jerabek S.A.
        Patient-reported allergies are associated with poorer patient satisfaction and outcomes after lower extremity arthroplasty: a retrospective cohort study.
        J Arthroplasty. 2015; 30: 1132-1136
        • Ferrer T.
        • Hinarejos P.
        • Goicoechea N.
        • Leal-Blanquet J.
        • Sanchez-Soler J.
        • Torres-Claramunt R.
        • et al.
        Anxiety is the cause of the worse outcomes of allergic patients after total knee arthroplasty.
        Knee Surg Sports Traumatol Arthrosc. 2020; 28: 3135-3141
        • Pena P.
        • Ortega M.A.
        • Bujan J.
        • De la Torre B.
        Decrease of quality of life, functional assessment and associated psychological distress in patients with hypoallergenic total knee arthroplasty.
        J Clin Med. 2020; 9: 3270
        • De Baets T.
        • Waelput W.
        • Bellemans J.
        Analysis of third body particles generated during total knee arthroplasty: is metal debris an issue?.
        Knee. 2008; 15: 95-97
        • Postler A.
        • Beyer F.
        • Lutzner C.
        • Tille E.
        • Lutzner J.
        Similar outcome during short-term follow-up after coated and uncoated total knee arthroplasty: a randomized controlled study.
        Knee Surg Sports Traumatol Arthrosc. 2018; 26: 3459-3467
        • Schwarz E.M.
        • Lu A.P.
        • Goater J.J.
        • Benz E.B.
        • Kollias G.
        • Rosier R.N.
        • et al.
        Tumor necrosis factor-alpha/nuclear transcription factor-kappaB signaling in periprosthetic osteolysis.
        J Orthop Res. 2000; 18: 472-480