title: Do retrieval analysis and blood metal measurements contribute to our understanding of adverse local tissue reactions?
abstract: BACKGROUND
  Metal-on-metal (MoM) total hip arthroplasties (THAs) and the head-neck and neck-body junctions in modular THA are associated with a variety of local and systemic reactions to their related wear and corrosion products. Although laboratory testing is available, the relationship between laboratory values--including serum metal ion levels--and adverse local tissue reactions (ALTRs) remains controversial and incompletely characterized.
  
  
  OBJECTIVE
  (1) What is the range of serum metal levels associated with ALTR in patients who have MoM THAs or corrosion at the head-neck and neck-body junctions in metal-on-polyethylene (or ceramic-on-polyethylene) THAs? (2) How much wear occurs in patients with MoM total hips? (3) Is there evidence of a dose-response relationship between wear and ALTR?
  
  
  METHODS
  PubMed and Embase databases were reviewed for English-language studies assessing serum metal levels in the presence of ALTR and papers describing the results of wear measurements from revised MoM implants and ALTR histopathology were systematically reviewed. Reported linear wear data were separated into groups with ALTR and without ALTR as listed in individual papers and graphed to determine whether a dose-response relationship was present between wear and ALTR. Overall, 15 studies including 338 hips with ALTR with corresponding serum metal levels were identified and analyzed. Twelve studies reported the wear depth or volume of MoM components from patients with a variety of local reactions. Two studies investigated corrosion at the head-neck and neck-body junctions in metal-on-polyethylene THA. There was a high level of variability and study heterogeneity, and so data pooling (meta-analysis) could not be performed.
  
  
  RESULTS
  Average reported metal concentrations were elevated above established normal values in patients with ALTR (cobalt concentrations ranged from 5 to 40 ppb, and chromium levels ranged from 5 to 54 ppb). Whereas several studies demonstrated that patients with ALTR had higher average linear wear of the bearing surfaces, this finding was not made in all studies that we identified in this systematic review. Because of this high degree of variability, no clear dose-response relationship between wear and ALTR could be established.
  
  
  CONCLUSIONS
  Serum metal level analysis and implant retrieval analysis both contribute to the understanding of ALTR. Serum metal levels generally are elevated in the presence of ALTR but should not be used in isolation for clinical decision-making. Many but not all patients with ALTR, including those with pseudotumors, demonstrate high wear, but more data and more systematic descriptions of the histopathology are needed to define the amount of wear that induces adverse reactions.
authors.affiliation: Orthopaedic Institute for Children, Los Angeles/UCLA Department of Orthopaedic Surgery, Los Angeles, CA, USA, pcampbell@mednet.ucla.edu.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Campbell
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kung
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Hsu
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Jacobs
mesh_terms: D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects / Q000295:instrumentation*; D015415:Biomarkers / Q000097:blood; D001696:Biomechanical Phenomena; D002516:Ceramics; D020878:Device Removal; D005549:Foreign-Body Reaction / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000601:surgery; D006621:Hip Joint / Q000503:physiopathology / Q000601:surgery*; D006622:Hip Prosthesis; D006801:Humans; D061825:Metal-on-Metal Joint Prostheses; D008670:Metals / Q000097:blood*; D020959:Polyethylene; D011237:Predictive Value of Tests; D011474:Prosthesis Design; D011475:Prosthesis Failure; D012086:Reoperation; D012307:Risk Factors; D013314:Stress, Mechanical; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D008670:Metals; D020959:Polyethylene