CC BY-NC-ND 4.0 · Revista Chilena de Ortopedia y Traumatología 2023; 64(01): e50-e57
DOI: 10.1055/s-0043-1760860
Artículo de Revisión | Review Article

Hipoxia e hipersensibilidad de tipo IV: patogenia dual en reacciones a implantes de cadera

Article in several languages: español | English
Mauricio Quezada
1   Facultad de Medicina, Universidad Finis Terrae, Santiago, Chile
2   Vancouver Prostate Centre, Vancouver, Canada
3   Facultad de Ingeniería Biomédica, University of British Columbia, Vancouver, Canada
› Author Affiliations


Antecedentes Las reacciones tisulares adversas (RTAs) a implantes de cadera afectan a una alta proporción de pacientes. Si bien fueron inicialmente descritas en articulaciones de metal sobre metal, un creciente número de estudios señala su presencia en otros tipos de implante. El gran número de pacientes con prótesis de cadera en el mundo señala la urgencia de comprender cabalmente los mecanismos que dan origen a RTAs para el desarrollo de alternativas de monitoreo, diagnóstico y terapéuticas eficientes.

Ámbito de revisión y público objetivo En la siguiente revisión bibliográfica, abarcamos desde la corrosión y el desgaste de los materiales utilizados en implantes de cadera hasta los mecanismos celulares e inmunológicos involucrados, con el fin de ofrecer una visión actualizada de antecedentes clínicos y científicos a estudiantes, cirujanos ortopédicos e investigadores.

Publication History

Received: 04 February 2020

Accepted: 28 September 2022

Article published online:
18 May 2023

© 2023. Sociedad Chilena de Ortopedia y Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

  • Referencias

  • 1 RIPO. Regional Register of Orthopedic Prosthetic Implantology, annual report. Bologna: 2014
  • 2 The Canadian Joint Replacement Registry. Hip and Knee Replacements in Canada: Canadian Joint Replacement Registry. 2015 Annual Report.
  • 3 Erivan R, Villatte G, Millerioux S, Mulliez A, Descamps S, Boisgard S. Survival at 11 to 21 years for 779 Metasul® metal-on-metal total hip arthroplasties. J Orthop Surg (Hong Kong) 2020; 28 (02) 23 09499020926265
  • 4 Whitehouse MR, Endo M, Zachara S. et al. Adverse local tissue reactions in metal-on-polyethylene total hip arthroplasty due to trunnion corrosion: the risk of misdiagnosis. Bone Joint J 2015; 97-B (08) 1024-1030
  • 5 Eltit F, Assiri A, Garbuz D. et al. Adverse reactions to metal on polyethylene implants: Highly destructive lesions related to elevated concentration of cobalt and chromium in synovial fluid. J Biomed Mater Res A 2017; 105 (07) 1876-1886
  • 6 National Joint Registry for England. , Wales NI and the I of M. 14th Annual Report; 2017
  • 7 Almousa SA, Greidanus NV, Masri BA, Duncan CP, Garbuz DS. The natural history of inflammatory pseudotumors in asymptomatic patients after metal-on-metal hip arthroplasty. Clin Orthop Relat Res 2013; 471 (12) 3814-3821
  • 8 Williams DH, Greidanus NV, Masri BA, Duncan CP, Garbuz DS. Prevalence of pseudotumor in asymptomatic patients after metal-on-metal hip arthroplasty. J Bone Joint Surg Am 2011; 93 (23) 2164-2171
  • 9 Cooper HJ, Urban RM, Wixson RL, Meneghini RM, Jacobs JJ. Adverse local tissue reaction arising from corrosion at the femoral neck-body junction in a dual-taper stem with a cobalt-chromium modular neck. J Bone Joint Surg Am 2013; 95 (10) 865-872
  • 10 Ardaugh BM, Graves SE, Redberg RF. The 510(k) ancestry of a metal-on-metal hip implant. N Engl J Med 2013; 368 (02) 97-100
  • 11 Zuckerman D, Brown P, Das A. Lack of publicly available scientific evidence on the safety and effectiveness of implanted medical devices. JAMA Intern Med 2014; 174 (11) 1781-1787
  • 12 Eltit F, Wang Q, Wang R. Mechanisms of adverse local tissue reactions to hip implants. Front Bioeng Biotechnol 2019; 7: 176
  • 13 August AC, Aldam CH, Pynsent PB. The McKee-Farrar hip arthroplasty. A long-term study. J Bone Joint Surg Br 1986; 68 (04) 520-527
  • 14 Charnley J. Total hip replacement by low-friction arthroplasty. Clin Orthop Relat Res 1970; 72 (72) 7-21
  • 15 Brånemark PI. Osseointegration and its experimental background. J Prosthet Dent 1983; 50 (03) 399-410
  • 16 Ormsby RT, Solomon LB, Yang D. et al. Osteocytes respond to particles of clinically-relevant conventional and cross-linked polyethylene and metal alloys by up-regulation of resorptive and inflammatory pathways. Acta Biomater 2019; 87: 296-306
  • 17 Schmidt M, Weber H, Schön R. Cobalt chromium molybdenum metal combination for modular hip prostheses. Clin Orthop Relat Res 1996; (329, Suppl) S35-S47
  • 18 Anissian HL, Stark A, Gustafson A, Good V, Clarke IC. Metal-on-metal bearing in hip prosthesis generates 100-fold less wear debris than metal-on-polyethylene. Acta Orthop Scand 1999; 70 (06) 578-582
  • 19 Clarke IC, Good V, Williams P. et al. Ultra-low wear rates for rigid-on-rigid bearings in total hip replacements. Proc Inst Mech Eng H 2000; 214 (04) 331-347
  • 20 Kostensalo I, Seppänen M, Mäkelä K, Mokka J, Virolainen P, Hirviniemi J. Early results of large head metal-on-metal hip arthroplasties. Scand J Surg 2012; 101 (01) 62-65
  • 21 Dargel J, Oppermann J, Brüggemann G-P, Eysel P. Dislocation following total hip replacement. Dtsch Arztebl Int 2014; 111 (51-52): 884-890
  • 22 Rieker CB, Schön R, Konrad R. et al. Influence of the clearance on in-vitro tribology of large diameter metal-on-metal articulations pertaining to resurfacing hip implants. Orthop Clin North Am 2005; 36 (02) 135-142 , vii
  • 23 Dowson D. Tribological principles in metal-on-metal hip joint design. Proc Inst Mech Eng H 2006; 220 (02) 161-171
  • 24 Jameson SS, Kyle J, Baker PN. et al. Patient and implant survival following 4323 total hip replacements for acute femoral neck fracture: a retrospective cohort study using National Joint Registry data. J Bone Joint Surg Br 2012; 94 (11) 1557-1566
  • 25 Ward WG, Carter CJ, Barone M, Jinnah R. Primary total hip replacement versus hip resurfacing - hospital considerations. Bull NYU Hosp Jt Dis 2011; 69 (Suppl. 01) S95-S97
  • 26 Mäkelä KT, Visuri T, Pulkkinen P. et al. Risk of cancer with metal-on-metal hip replacements: population based study. BMJ 2012; 345: e4646-e4646
  • 27 Keegan GM, Learmonth ID, Case CP. A systematic comparison of the actual, potential, and theoretical health effects of cobalt and chromium exposures from industry and surgical implants. Crit Rev Toxicol 2008; 38 (08) 645-674
  • 28 Mathiesen EB, Ahlbom A, Bermann G, Lindgren JU. Total hip replacement and cancer. A cohort study. J Bone Joint Surg Br 1995; 77 (03) 345-350
  • 29 Lalmohamed A, MacGregor AJ, de Vries F, Leufkens HGM, van Staa TP. Patterns of risk of cancer in patients with metal-on-metal hip replacements versus other bearing surface types: a record linkage study between a prospective joint registry and general practice electronic health records in England. PLoS One 2013; 8 (07) e65891
  • 30 Fritzsche J, Borisch C, Schaefer C. Case report: High chromium and cobalt levels in a pregnant patient with bilateral metal-on-metal hip arthroplasties. Clin Orthop Relat Res 2012; 470 (08) 2325-2331
  • 31 Meier B. Concerns Over ‘Metal on Metal’ Hip Implants. New York Times. Mar
  • 32 Liao Y, Hoffman E, Wimmer M, Fischer A, Jacobs J, Marks L. CoCrMo metal-on-metal hip replacements. Phys Chem Chem Phys 2013; 15 (03) 746-756
  • 33 Pandit H, Glyn-Jones S, McLardy-Smith P. et al. Pseudotumours associated with metal-on-metal hip resurfacings. J Bone Joint Surg Br 2008; 90 (07) 847-851
  • 34 Mahendra G, Pandit H, Kliskey K, Murray D, Gill HS, Athanasou N. Necrotic and inflammatory changes in metal-on-metal resurfacing hip arthroplasties. Acta Orthop 2009; 80 (06) 653-659
  • 35 Cohen D. Out of joint: the story of the ASR. BMJ 2011; 342 (may13 2): d2905-d2905
  • 36 Wang Q, Eltit F, Garbuz D. et al. CoCrMo metal release in metal-on-highly crosslinked polyethylene hip implants. J Biomed Mater Res B Appl Biomater 2020; 108 (04) 1213-1228
  • 37 Wang Q, Parry M, Masri BA, Duncan C, Wang R. Failure mechanisms in CoCrMo modular femoral stems for revision total hip arthroplasty. J Biomed Mater Res B Appl Biomater 2017; 105 (06) 1525-1535
  • 38 Kop AM, Keogh C, Swarts E, Kjop A, Keogh C, Swarts E. Proximal component modularity in THA–at what cost? An implant retrieval study. Clin Orthop Relat Res 2012; 470 (07) 1885-1894
  • 39 Natu S, Sidaginamale RP, Gandhi J, Langton DJ, Nargol AVF. Adverse reactions to metal debris: histopathological features of periprosthetic soft tissue reactions seen in association with failed metal on metal hip arthroplasties. J Clin Pathol 2012; 65 (05) 409-418
  • 40 Matharu GS, Pandit HG, Murray DW, Judge A. Adverse reactions to metal debris occur with all types of hip replacement not just metal-on-metal hips: a retrospective observational study of 3340 revisions for adverse reactions to metal debris from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man. BMC Musculoskelet Disord 2016; 17 (01) 495
  • 41 Davies AP, Willert HG, Campbell PA, Learmonth ID, Case CP. An unusual lymphocytic perivascular infiltration in tissues around contemporary metal-on-metal joint replacements. J Bone Joint Surg Am 2005; 87 (01) 18-27
  • 42 Doorn PF, Mirra JM, Campbell PA, Amstutz HC. Tissue reaction to metal on metal total hip prostheses. Clin Orthop Relat Res 1996; (329, Suppl) S187-S205
  • 43 Konan S, Duncan CP, Masri BS, Garbuz DS. What Is the Natural History of Asymptomatic Pseudotumors in Metal-on-metal THAs at Mid-term Followup?. Clin Orthop Relat Res 2017; 475 (02) 433-441
  • 44 Maurer-Ertl W, Friesenbichler J, Liegl-Atzwanger B, Kuerzl G, Windhager R, Leithner A. Noninflammatory pseudotumor simulating venous thrombosis after metal-on-metal hip resurfacing. Orthopedics 2011; 34 (10) e678-e681
  • 45 Perino G, Ricciardi BF, Jerabek SA. et al. Implant based differences in adverse local tissue reaction in failed total hip arthroplasties: a morphological and immunohistochemical study. BMC Clin Pathol 2014; 14 (01) 39
  • 46 Langton DJ, Jameson SS, Joyce TJ. et al. Accelerating failure rate of the ASR total hip replacement. J Bone Joint Surg Br 2011; 93 (08) 1011-1016
  • 47 Wang Q, Eltit F, Wang R. Corrosion of Orthopedic Implants. In: Narayan R. editor. Encyclopedia of Biomedical Engineering. Amsterdam, The Netherlands: Elsevier; 2019: 65-85
  • 48 Ricciardi BF, Nocon AA, Jerabek SA. et al. Histopathological characterization of corrosion product associated adverse local tissue reaction in hip implants: a study of 285 cases. BMC Clin Pathol 2016; 16: 3
  • 49 Garbuz DS, Tanzer M, Greidanus NV, Masri BA, Duncan CP. The John Charnley Award: Metal-on-metal hip resurfacing versus large-diameter head metal-on-metal total hip arthroplasty: a randomized clinical trial. Clin Orthop Relat Res 2010; 468 (02) 318-325
  • 50 Medicines and Healthcare products Regulatory Agency. Metal-on-metal (MoM) hip replacements - guidance on implantation and patient management Medical safety alert - GOV.UK. 2015
  • 51 Schmalzried TP. Metal-metal bearing surfaces in hip arthroplasty. Orthopedics 2009;32(09)
  • 52 Willert HG, Buchhorn GH, Fayyazi A. et al. Metal-on-metal bearings and hypersensitivity in patients with artificial hip joints. A clinical and histomorphological study. J Bone Joint Surg Am 2005; 87 (01) 28-36 , 54
  • 53 Huber M, Reinisch G, Trettenhahn G, Zweymüller K, Lintner F. Presence of corrosion products and hypersensitivity-associated reactions in periprosthetic tissue after aseptic loosening of total hip replacements with metal bearing surfaces. Acta Biomater 2009; 5 (01) 172-180
  • 54 Thomas P. Patch testing and hypersensitivity reactions to metallic implants: still many open questions. Dermatitis 2013; 24 (03) 106-107
  • 55 Granchi D, Cenni E, Giunti A, Baldini N. Metal hypersensitivity testing in patients undergoing joint replacement: a systematic review. J Bone Joint Surg Br 2012; 94 (08) 1126-1134
  • 56 Eltit F, Noble J, Sharma M. et al. Cobalt ions induce metabolic stress in synovial fibroblasts and secretion of cytokines/chemokines that may be diagnostic markers for adverse local tissue reactions to hip implants. Acta Biomater 2021; 131: 581-594
  • 57 Salloum Z, Lehoux EA, Harper M-E, Catelas I. Effects of cobalt and chromium ions on oxidative stress and energy metabolism in macrophages in vitro. J Orthop Res 2018; 36 (12) 3178-3187
  • 58 Battaglia V, Compagnone A, Bandino A. et al. Cobalt induces oxidative stress in isolated liver mitochondria responsible for permeability transition and intrinsic apoptosis in hepatocyte primary cultures. Int J Biochem Cell Biol 2009; 41 (03) 586-594
  • 59 Granchi D, Cenni E, Ciapetti G. et al. Cell death induced by metal ions: necrosis or apoptosis?. J Mater Sci Mater Med 1998; 9 (01) 31-37
  • 60 Huk OL, Catelas I, Mwale F, Antoniou J, Zukor DJ, Petit A. Induction of apoptosis and necrosis by metal ions in vitro. J Arthroplasty 2004; 19 (8, suppl 3) 84-87
  • 61 Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 535 p.
  • 62 Campbell P, Ebramzadeh E, Nelson S, Takamura K, De Smet K, Amstutz HC. Histological features of pseudotumor-like tissues from metal-on-metal hips. Clin Orthop Relat Res 2010; 468 (09) 2321-2327
  • 63 Mittal S, Revell M, Barone F. et al. Lymphoid aggregates that resemble tertiary lymphoid organs define a specific pathological subset in metal-on-metal hip replacements. PLoS One 2013; 8 (05) e63470
  • 64 Eltit F, Mohammad N, Medina I. et al. Perivascular lymphocytic aggregates in hip prosthesis-associated adverse local tissue reactions demonstrate Th1 and Th2 activity and exhausted CD8+ cell responses. J Orthop Res 2021; 39 (12) 2581-2594
  • 65 Catelas I, Lehoux EA, Hurda I. et al. Do patients with a failed metal-on-metal hip implant with a pseudotumor present differences in their peripheral blood lymphocyte subpopulations?. Clin Orthop Relat Res 2015; 473 (12) 3903-3914
  • 66 Kilb BKJ, Kurmis AP, Parry M. et al. Frank Stinchfield Award: Identification of the At-risk Genotype for Development of Pseudotumors Around Metal-on-metal THAs. Clin Orthop Relat Res 2018; 476 (02) 230-241
  • 67 Thierse H-J, Gamerdinger K, Junkes C, Guerreiro N, Weltzien HU. T cell receptor (TCR) interaction with haptens: metal ions as non-classical haptens. Toxicology 2005; 209 (02) 101-107
  • 68 Kwon YM, Thomas P, Summer B. et al. Lymphocyte proliferation responses in patients with pseudotumors following metal-on-metal hip resurfacing arthroplasty. J Orthop Res 2010; 28 (04) 444-450
  • 69 Gill HS, Grammatopoulos G, Adshead S, Tsialogiannis E, Tsiridis E. Molecular and immune toxicity of CoCr nanoparticles in MoM hip arthroplasty. Trends Mol Med 2012; 18 (03) 145-155
  • 70 Reito A, Lehtovirta L, Parkkinen J, Eskelinen A. Histopathological patterns seen around failed metal-on-metal hip replacements: Cluster and latent class analysis of patterns of failure. J Biomed Mater Res B Appl Biomater 2020; 108 (03) 1085-1096