There is an increasing recognition that, in the long-term, total joint replacement (TJR) may be associated with adverse local and remote tissue responses that are mediated by the degradation products of prosthetic materials. There has been particular interest in the metallic degradation products of TJR because of the known toxicities of the metallic elements that comprise implant alloys. In this long-term study, metal release, transport, storage and excretion in patients with TJRs habs been investigated. In the current grant period, it has been demonstrated that (1) elevations in serum Ti, Co and Cr can be detected in individuals with well functioning total hip and knee replacements up to 84 months postoperative;(2) the highest Cr and Co levels have been observed in patients with metal-on-metal bearings;(3) passive dissolution from extensively porous coated Co-base alloy femoral stems is not a dominant mode of metal release;rather, fretting corrosion of femoral components at modular junctions is more closely associated with elevations in serum Cr;(4) in patients with TJR and elevated serum metal concentrations, two molecular weight ranges were found to bind Cr (at approximately 70 kD and approximately 180 kD) whereas a single molecular weight range (at approximately 70 kD) was found to bind Ti;(5) following revision surgery for a failed total hip replacement, circulating metal levels diminish, but remain chronically elevated up to 60 months post-revision;(6) Co- and Ti-alloy particulate degradation products, usually from sources other than the bearing surface, commonly disseminate to paraaortic lymph nodes, liver and spleen, particularly in individuals who have had a failed TJR;and (7) the bioreactivity of metal degradation products is governed by its'physiochemical nature and protein adducts: a Cr-containing 180 kD metal-protein complex was the most stimulatory in these studies. This proposal expands on these findings by addressing the following Specific Aims: (1) to quantify metal release in the prospective primary THR study groups which will be 10 to 15 years postoperative, an interval in which complications related to the implant are more prevalent;(2) to prospectively follow patients with Co-alloy metal-on-metal hip replacements to determine the prevalence of metal hypersensitivity in correlation with the serum and urine metal content;(3) to expand the autopsy retrieval program to characterize not: only the systemic distribution of particulate wear debris but also the tissue metal levels and the cellular localization;and (4) to conduct bioavailability and bioreactivity studies of circulating metal-protein complexes which result from corrosion and wear of joint replacement components.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
Project #
Application #
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Panagis, James S
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Rush University Medical Center
Schools of Medicine
United States
Zip Code
Lachiewicz, Paul F; Watters, Tyler Steven; Jacobs, Joshua J (2016) Metal Hypersensitivity and Total Knee Arthroplasty. J Am Acad Orthop Surg 24:106-12
Levine, Brett R; Hsu, Andrew R; Skipor, Anastasia K et al. (2013) Ten-year outcome of serum metal ion levels after primary total hip arthroplasty: a concise follow-up of a previous report*. J Bone Joint Surg Am 95:512-8
Hallab, Nadim J; Caicedo, Marco; McAllister, Kyron et al. (2013) 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 31:173-82
Hsu, Andrew R; Levine, Brett R; Skipor, Anastasia K et al. (2013) Effect of a second joint arthroplasty on metal ion levels after primary total hip arthroplasty. Am J Orthop (Belle Mead NJ) 42:E84-7
Cooper, H John; Della Valle, Craig J; Berger, Richard A et al. (2012) Corrosion at the head-neck taper as a cause for adverse local tissue reactions after total hip arthroplasty. J Bone Joint Surg Am 94:1655-61
Mathew, Mathew T; Jacobs, Joshua J; Wimmer, Markus A (2012) Wear-corrosion synergism in a CoCrMo hip bearing alloy is influenced by proteins. Clin Orthop Relat Res 470:3109-17
Urban, Robert M; Hall, Deborah J; Della Valle, Craig et al. (2012) Successful long-term fixation and progression of osteolysis associated with first-generation cementless acetabular components retrieved post mortem. J Bone Joint Surg Am 94:1877-85
Laurent, Michel P; Pourzal, Robin; Fischer, Alfons et al. (2011) In vivo wear of a squeaky alumina-on-alumina hip prosthesis: a case report. J Bone Joint Surg Am 93:e27
Guyer, Richard D; Shellock, Jessica; MacLennan, Benjamin et al. (2011) Early failure of metal-on-metal artificial disc prostheses associated with lymphocytic reaction: diagnosis and treatment experience in four cases. Spine (Phila Pa 1976) 36:E492-7
Wright, Geoffrey; Sporer, Scott; Urban, Robert et al. (2010) Fracture of a modular femoral neck after total hip arthroplasty: a case report. J Bone Joint Surg Am 92:1518-21

Showing the most recent 10 out of 54 publications