Orthopaedic implant failure: Aseptic implant loosening - the contribution and future challenges of mouse models in translational research

Clinical Science

Volumn 127, Issue 5, 2014, Pages 277-293

  Cordova, Luis Alberto ^a,b,c   Stresing, Verena ^a,b   Gobin, Bérengère ^a,b   Rosset, Philippe ^a,b,d   Passuti, Norbert ^a,b,e   Gouin, François ^a,b,e   Trichet, Valérie ^a,b   Layrolle, Pierre ^a,b   Heymann, Dominique ^a,b,e  

^a INSERM   (France)

^b UNIVERSITÉ DE NANTES   (France)

^c UNIVERSITY OF CHILE   (Chile)

^d UNIVERSITÉ DE TOURS   (France)

^e NANTES UNIVERSITY HOSPITAL   (France)

Author keywords

Mouse model; Orthopaedic implant; Particle; Periprosthetic osteolysis; Polyethylene; Wear debris

Indexed keywords

AIR POUCHES; BIOMATERIAL; METAL; ULTRA HIGH MOLECULAR WEIGHT POLYETHYLENE; UNCLASSIFIED DRUG; CERAMICS; NANOPARTICLE; POLY(METHYL METHACRYLATE); POLYETHYLENE DERIVATIVE; ULTRA-HIGH MOLECULAR WEIGHT POLYETHYLENE;

ARTHROPLASTY; ARTICLE; CALVARIA; CERAMICS; HIP PROSTHESIS; IMPLANT; IN VITRO STUDY; IN VIVO STUDY; INTRAMEDULLARY IMPLANT; JOINT PROSTHESIS; MACROPHAGE; MECHANICAL STRESS; MOUSE MODEL; NONHUMAN; ORTHOPEDIC IMPLANT; OSTEOBLAST; OSTEOCLAST; OSTEOLYSIS; PRIORITY JOURNAL; PROSTHESIS LOOSENING; REGISTER; TIBIA; TRANSLATIONAL RESEARCH; ANIMAL; BIOMECHANICS; CHEMISTRY; CLINICAL TRIAL (TOPIC); DEVICE FAILURE; DISEASE MODEL; ETIOLOGY; HUMAN; INFLAMMATION; MOUSE; PARTICLE SIZE; PATHOPHYSIOLOGY; PHYSIOLOGY; REOPERATION;

ANIMALS; ARTHROPLASTY, REPLACEMENT; BIOMECHANICAL PHENOMENA; CERAMICS; CLINICAL TRIALS AS TOPIC; DISEASE MODELS, ANIMAL; EQUIPMENT FAILURE; HUMANS; INFLAMMATION; MACROPHAGES; MICE; NANOPARTICLES; OSTEOLYSIS; PARTICLE SIZE; POLYETHYLENES; POLYMETHYL METHACRYLATE; REOPERATION; TRANSLATIONAL MEDICAL RESEARCH;

EID: 84899839414     PISSN: 01435221     EISSN: None     Source Type: Journal    
DOI: 10.1042/CS20130338     Document Type: Article

References (149)

1. Affatato, S., Spinelli, M., Zavalloni, M., Mazzega-Fabbro, C. and Viceconti, M. (2008) Tribology and total hip joint replacement: current concepts in mechanical simulation. Med. Eng. Phys. 30, 1305-1317
2. Bozic, K. J., Kurtz, S., Lau, E., Ong, K., Chiu, V., Vail, T. P., Rubash, H. E. and Berry, D. J. (2009) The epidemiology of bearing surface usage in total hip arthroplasty in the United States. J. Bone Joint Surg. Am. 91, 1614-1620
3. Marshall, A., Ries, M. D. and Paprosky, W. (2008) How prevalent are implant wear and osteolysis, and how has the scope of osteolysis changed since 2000? J. Am. Acad. Ortho. Surg. 16, S1-S6
4. Purdue, P. E., Koulouvaris, P., Nestor, B. J. and Sculco, T. P. (2006) The central role of wear debris in periprosthetic osteolysis. HSS J. 2, 102-113
5. Kurtz, S. M., Lau, E., Ong, K., Zhao, K., Kelly, M. and Bozic, K. J. (2009) Future young patient demand for primary and revision joint replacement: national projections from 2010 to 2030. Clin. Orthop. Relat. Res. 467, 2606-2612
6. Coathup, M. J., Blackburn, J., Goodship, A. E., Cunningham, J. L., Smith, T. and Blunn, G. W. (2005) Role of hydroxyapatite coating in resisting wear particle migration and osteolysis around acetabular components. Biomaterials 26, 4161-4169
7. Goodman, S. B., Song, Y., Yoo, J. Y., Fox, N., Trindade, M. C. D., Kajiyama, G., Ma, T., Regula, D., Brown, J. and Smith, R. L. (2003) Local infusion of FGF-2 enhances bone ingrowth in rabbit chambers in the presence of polyethylene particles. J. Biomed. Mater. Res. A 65, 454-461
8. Bragg, B., Epstein, N. J., Ma, T., Goodman, S. and Smith, R. L. (2008) Histomorphometric analysis of the intramedullary bone response to titanium particles in wild-type and IL-1R1 knock-out mice: a preliminary study. J. Biomed. Mater. Res. B Appl. Biomater. 84, 559-570
9. Ma, T., Huang, Z., Ren, P.-G., McCally, R., Lindsey, D., Smith, R. L. and Goodman, S. B. (2008) An in vivo murine model of continuous intramedullary infusion of polyethylene particles. Biomaterials 29, 3738-3742
10. Shetty, N., Hamer, A. J., Stockley, I., Eastell, R. and Willkinson, J. M. (2006) Clinical and radiological outcome of total hip replacement five years after pamidronate therapy. A trail extension. . J. Bone Joint Surg. Br. 88, 1309-1315
11. Judman, K. P. and Reinisch, G. (2001) Tribological aspects of total hip arthroplasty. Europ. Cells Mater. 1 (Suppl. 2), 46
12. Konttinen, Y. T. and Pajarinen, J. (2013) Surgery: adverse reactions to metal-on-metal implants. Nat. Rev. Rheumatol. 9, 5-6
13. Ingham, E. and Fisher, J. (2005) The role of macrophages in osteolysis of total joint replacement. Biomaterials 26, 1271-1286
14. Charnley, J. (1972) The long-term results of low-friction arthroplasty of the hip performed as a primary intervention. J. Bone Joint Surg. Br. 54, 61-76
15. Gomez-Barrena, E., Puertolas, J.-A., Munuera, L. and Konttinen, Y. T. (2008) Update on UHMWPE research from the bench to the bedside, Acta Orthop. 79, 832-840
16. Atkins, G. J., Haynes, D. R., Howie, D. W. and Findlay, D. M. (2011) Role of polyethylene particles in peri-prosthetic osteolysis: a review. World J. Orthop. 2, 93-101
17. Thomas, G. E. R., Simpson, D. J., Mehmood, S., Taylor, A., McLardy-Smith, P., Gill, H. S., Murray, D. W. and Glyn-Jones, S. (2011) The seven-year wear of highly cross-linked polyethylene in total hip arthroplasty: a double-blind, randomized controlled trial using radiostereometric analysis. J. Bone Joint Surg. Am. 93, 716-722
18. Kuzyk, P. R. T., Saccone, M., Sprague, S., Simunovic, N., Bhandari, M. and Schemitsch, E. H. (2011) Cross-linked versus conventional polyethylene for total hip replacement: a meta-analysis of randomised controlled trials. J. Bone Joint Surg. Br. 93, 593-600
19. Bragdon, C. R., Doerner, M., Martell, J., Jarrett, B., Palm, H. and Malchau, H. (2013) The 2012 John Charnley Award: clinical multicenter studies of the wear performance of highly crosslinked remelted polyethylene in THA. Clin. Orthop. Relat. Res. 471, 393-402
20. Jacobs, J. J., Roebuck, K. A., Archibeck, M., Hallab, N. J. and Glant, T. T. (2001) Osteolysis: basic science. Clin. Orthop. Relat. Res. 71-77
21. Goodman, S. B. (2007) Wear particles, periprosthetic osteolysis and the immune system. Biomaterials 28, 5044-5048
22. Keegan, G. M., Learmonth, I. D. and Case, C. P. (2008) A systematic comparison of the actual, potential, and theoretical health effects of cobalt and chromium exposures from industry and surgical implants. Crit. Rev. Toxicol. 38, 645-674
23. Helm, C. S. and Greenwald, A. S. (2005) The rationale and performance of modularity in total hip arthroplasty. Orthopedics 28, s1113-s1115
24. Hasegawa, M., Yoshida, K., Wakabayashi, H. and Sudo, A. (2013) Prevalence of adverse reactions to metal debris following metal-on-metal THA. Orthopedics 36, e606-e612
25. Cuckler, J. M. (2005) The rationale for metal-on-metal total hip arthroplasty. Clin. Orthop. Relat. Res. 441, 132-136
26. Hartmann, A., Hannemann, F., Lützner, J., Seidler, A., Drexler, H., Günther, K.-P. and Schmitt, J. (2013) Metal ion concentrations in body fluids after implantation of hip replacements with metal-on-metal bearing: systematic review of clinical and epidemiological studies. PLoS ONE 8, e70359
27. Hart, A. J., Satchithananda, K., Liddle, A. D., Sabah, S. A., McRobbie, D., Henckel, J., Cobb, J. P., Skinner, J. A. and Mitchell, A. W. (2012) Pseudotumors in association with well-functioning metal-on-metal hip prostheses: a case-control study using three-dimensional computed tomography and magnetic resonance imaging. J. Bone Joint Surg. Am. 94, 317-325
28. Whitehouse, M. R., Endo, M. and Masri, B. A. (2013) Adverse local tissue reaction associated with a modular hip hemiarthroplasty. Clin. Orthop. Relat. Res. 471, 4082-4086
29. Langton, D. J., Sidaginamale, R. P., Joyce, T. J., Natu, S., Blain, P., Jefferson, R. D., Rushton, S. and Nargol, A. V. F. (2013) The clinical implications of elevated blood metal ion concentrations in asymptomatic patients with MoM hip resurfacings: a cohort study. BMJ Open 3, e001541
30. Billi, F. and Campbell, P. (2010) Nanotoxicology of metal wear particles in total joint arthroplasty: a review of current concepts. J. Appl. Biomater. Biomech. 8, 1-6
31. Caicedo, M. S., Desai, R., McAllister, K., Reddy, A., Jacobs, J. J. and Hallab, N. J. (2009) Soluble and particulate Co-Cr-Mo alloy implant metals activate the inflammasome danger signaling pathway in human macrophages: a novel mechanism for implant debris reactivity. J. Orthop. Res. 27, 847-854
32. Solarino, G., Piazzolla, A., Notarnicola, A., Moretti, L., Tafuri, S., De Giorgi, S. and Moretti, B. (2012) Long-term results of 32-mm alumina-on-alumina THA for avascular necrosis of the femoral head. J. Orthop. Traumatol. 13, 21-27
33. Sugano, N., Takao, M., Sakai, T., Nishii, T., Miki, H. and Ohzono, K. (2012) Eleven- to 14-year follow-up results of cementless total hip arthroplasty using a third-generation alumina ceramic-on-ceramic bearing. J. Arthroplasty 27, 736-74
34. Kim, Y. H., Kim, J. S. and Cho, S. H. (2001) A comparison of polyethylene wear in hips with cobalt-chrome or zirconia heads. A prospective, randomised study. J. Bone Joint Surg. Br. 83, 742-750
35. Wang, S., Zhang, S. and Zhao, Y. (2013) A comparison of polyethylene wear between cobalt-chrome ball heads and alumina ball heads after total hip arthroplasty: a 10-year follow-up. J. Orthop. Surg. Res. 8, 20
36. Dahl, J., Snorrason, F., Nordsletten, L. and Röhrl, S. M. (2013) More than 50% reduction of wear in polyethylene liners with alumina heads compared to cobalt-chrome heads in hip replacements. Acta Orthop. 84, 360-364
37. Van der Veen, H. C., van Jonbergen, H.-P. W., Poolman, R. W., Bulstra, S. K. and van Raay, J. J. A. M. (2013) Is there evidence for accelerated polyethylene wear in uncemented compared to cemented acetabular components? A systematic review of the literature. Int. Orthop. 37, 9-14
38. Toossi, N., Adeli, B., Timperley, A. J., Haddad, F. S., Maltenfort, M. and Parvizi, J. (2013) Acetabular components in total hip arthroplasty: is there evidence that cementless fixation is better? J. Bone Joint Surg. Am. 95, 168-174
39. Zhang, H.-Y., Blunt, L., Jiang, X.-Q., Brown, L., Barrans, S. and Zhao, Y. (2008) Femoral stem wear in cemented total hip replacement. Proc. Inst. Mech. Eng. H 222, 583-592
40. Zhang, H. Y., Brown, L., Barrans, S., Blunt, L. and Jiang, X. Q. (2009) Investigation of relative micromotion at the stem-cement interface in total hip replacement. Proc. Inst. Mech. Eng. H 223, 955-964
41. Shearwood-Porter, N., Browne, M. and Sinclair, I. (2012) Micromechanical characterisation of failure in acrylic bone cement: the effect of barium sulphate agglomerates. J. Mech. Behav. Biomed. Mater. 13, 85-92
42. Stoffel, K. A., Yang, D. T. and Arola, D. (2008) The influence of surface topography on wear debris generation at the cement/bone interface under cyclic loading. J. Mater. Sci. Mater. Med. 19, 1935-1943
43. Bourne, R. B. and Corten, K. (2010) Cemented versus cementless stems: a verdict is in. Orthopedics 33, 638
44. Corten, K., Bourne, R. B., Charron, K. D., Au, K. and Rorabeck, C. H. (2011) What works best, a cemented or cementless primary total hip arthroplasty?: minimum 17-year followup of a randomized controlled trial. Clin. Orthop. Relat. Res. 469, 209-217
45. Jameson, S. S., Baker, P. N., Mason, J., Rymaszewska, M., Gregg, P. J., Deehan, D. J. and Reed, M. R. (2013) Independent predictors of failure up to 7.5 years after 35 386 single-brand cementless total hip replacements: a retrospective cohort study using National Joint Registry data, Bone Joint J. 95, 747-757
46. Onuora, S. (2012) Osteoarthritis: surgical options for hip OA: digging beneath the surface of implant survival. Nat. Rev. Rheumatol. 8, 631
47. Smith, A. J., Dieppe, P., Howard, P. W., Blom, A. W. and National Joint Registry for England and Wales. (2012) Failure rates of metal-on-metal hip resurfacings: analysis of data from the National Joint Registry for England and Wales. Lancet 380, 1759-1766
48. Fabbri, N., Rustemi, E., Masetti, C., Kreshak, J., Gambarotti, M., Vanel, D., Toni, A. and Mercuri, M. (2011) Severe osteolysis and soft tissue mass around total hip arthroplasty: description of four cases and review of the literature with respect to clinico-radiographic and pathologic differential diagnosis. Eur. J. Radiol. 77, 43-50
49. Gallo, J., Goodman, S. B., Konttinen, Y. T., Wimmer, M. A. and Holinka, M. (2013) Osteolysis around total knee arthroplasty: a review of pathogenetic mechanisms. Acta Biomaterialia 9, 8046-8058
50. Del Buono, A., Denaro, V. and Maffulli, N. (2012) Genetic susceptibility to aseptic loosening following total hip arthroplasty: a systematic review. Br. Med. Bull. 101, 39-55
51. Zolotarevova, E., Entlicher, G., Pavlova, E., Slouf, M., Pokorny, D., Vesely, F., Gallo, J. and Sosna, A. (2010) Distribution of polyethylene wear particles and bone fragments in periprosthetic tissue around total hip joint replacements. Acta Biomater. 6, 3595-3600
52. Wang, M. L., Sharkey, P. F. and Tuan, R. S. (2004) Particle bioreactivity and wear-mediated osteolysis. J. Arthrop. 19, 1028-1038
53. Richards, L., Brown, C., Stone, M. H., Fisher, J., Ingham, E. and Tipper, J. L. (2008) Identification of nanometre-sized ultra-high molecular weight polyethylene wear particles in samples retrieved in vivo. J. Bone Joint Surg. Br. 90, 1106-1113
54. Rao, A. J., Gibon, E., Ma, T., Yao, Z., Smith, R. L. and Goodman, S. B. (2012) Revision joint replacement, wear particles, and macrophage polarization. Acta Biomater. 8, 2815-2823
55. Mandelin, J., Li, T.-F., Hukkanen, M., Liljeström, M., Salo, J., Santavirta, S. and Konttinen, Y. T. (2005) Interface tissue fibroblasts from loose total hip replacement prosthesis produce receptor activator of nuclear factor-κB ligand, osteoprotegerin, and cathepsin K. J. Rheumatol. 32, 713-720
56. Ritchlin, C. T., Schwarz, E. M., O'Keefe, R. J. and Looney, R. J. (2004) RANK, RANKL and OPG in inflammatory arthritis and periprosthetic osteolysis, J. Musculoskelet. Neuronal Interact. 4, 276-284
57. Takei, I., Takagi, M., Santavirta, S., Ida, H., Ishii, M., Ogino, T., Ainola, M. and Konttinen, Y. T. (2000) Messenger ribonucleic acid expression of 16 matrix metalloproteinases in bone-implant interface tissues of loose artificial hip joints. J. Biomed. Mater. Res. 52, 613-620
58. Sasaki, K., Takagi, M., Mandelin, J., Takei, I., Santavirta, S., Ida, H., Ogino, T. and Konttinen, Y. T. (2001) Quantitative analysis of mRNA expression of TIMPs in the periprosthetic interface tissue of loose hips by real-time PCR system. J. Biomed. Mater. Res. 58, 605-612
59. Syggelos, S. A., Aletras, A. J., Smirlaki, I. and Skandalis, S. S. (2013) Extracellular matrix degradation and tissue remodeling in periprosthetic loosening and osteolysis: focus on matrix metalloproteinases, their endogenous tissue inhibitors, and the proteasome. Biomed. Res. Int. 2013, 230805
60. Ingham, E. and Fisher, J. (2000) Biological reactions to wear debris in total joint replacement. Proc. Inst. Mech. Eng. H 214, 21-37
61. Matthews, J. B., Green, T. R., Stone, M. H., Wroblewski, B. M., Fisher, J. and Ingham, E. (2001) Comparison of the response of three human monocytic cell lines to challenge with polyethylene particles of known size and dose. J. Mater. Sci. Mater. Med. 12, 249-258
62. Ingram, J. H., Stone, M., Fisher, J. and Ingham, E. (2004) The influence of molecular weight, crosslinking and counterface roughness on TNF-a production by macrophages in response to ultra high molecular weight polyethylene particles. Biomaterials 25, 3511-3522
63. Fang, H.-W., Ho, Y.-C., Yang, C.-B., Liu, H.-L., Ho, F.-Y., Lu, Y.-C., Ma, H.-M. and Huang, C.-H. (2006) Preparation of UHMWPE particles and establishment of inverted macrophage cell model to investigate wear particles induced bioactivites, J. Biochem. Biophys. Methods 68, 175-187
64. Cobelli, N., Scharf, B., Crisi, G. M., Hardin, J. and Santambrogio, L. (2011) Mediators of the inflammatory response to joint replacement devices. Nat. Rev. Rheumatol. 7, 600-608
65. Yao, Z., Keeney, M., Lin, T.-H., Pajarinen, J., Barcay, K., Waters, H., Egashira, K., Yang, F. and Goodman, S. (2013) Mutant MCP-1 protein attenuates migration of and inflammatory cytokine release by macrophages exposed to orthopaedic implant wear particles. J. Biomed. Mater. Res. A, doi:10.1002/jbm.a.34981
66. Yagil-Kelmer, E., Kazmier, P., Rahaman, M. N., Bal, B. S., Tessman, R. K. and Estes, D. M. (2004) Comparison of the response of primary human blood monocytes and the U937 human monocytic cell line to two different sizes of alumina ceramic particles. J. Orthop. Res. 22, 832-838
67. Yang, S.-Y., Ren, W., Park, Y., Sieving, A., Hsu, S., Nasser, S. and Wooley, P. H. (2002) Diverse cellular and apoptotic responses to variant shapes of UHMWPE particles in a murine model of inflammation. Biomaterials 23, 3535-3543
68. Shanbhag, A. S., Jacobs, J. J., Black, J., Galante, J. O. and Glant, T. T. (1994) Macrophage/particle interactions: effect of size, composition and surface area. J. Biomed. Mater. Res. 28, 81-90
69. Pal, N., Quah, B., Smith, P. N., Gladkis, L. L., Timmers, H. and Li, R. W. (2011) Nano-osteoimmunology as an important consideration in the design of future implants, Acta Biomater. 7, 2926-2934
70. Gordon, S. and Taylor, P. R. (2005) Monocyte and macrophage heterogeneity. Nat. Rev. Immunol. 5, 953-964
71. Mosser, D. M. and Edwards, J. P. (2008) Exploring the full spectrum of macrophage activation. Nat. Rev. Immunol. 8, 958-969
72. Broz, P. and Monack, D. M. (2013) Newly described pattern recognition receptors team up against intracellular pathogens. Nat. Rev. Immunol. 13, 551-565
73. Hoenders, C. S. M., Harmsen, M. C. and van Luyn, M. J. A. (2008) The local inflammatory environment and microorganisms in "aseptic" loosening of hip prostheses, J. Biomed. Mater. Res. B 86, 291-301
74. Bi, Y., Collier, T. O., Goldberg, V. M., Anderson, J. M. and Greenfield, E. M. (2002) Adherent endotoxin mediates biological responses of titanium particles without stimulating their phagocytosis. J. Orthop. Res. 20, 696-703
75. Greenfield, E. M., Bi, Y., Ragab, A. A., Goldberg, V. M., Nalepka, J. L. and Seabold, J. M. (2005) Does endotoxin contribute to aseptic loosening of orthopedic implants? J. Biomed. Mater. Res. B 72, 179-185
76. Cho, D. R., Shanbhag, A. S., Hong, C.-Y., Baran, G. R. and Goldring, S. R. (2002) The role of adsorbed endotoxin in particle-induced stimulation of cytokine release. J. Orthop. Res. 20, 704-713
77. Xing, Z., Pabst, M. J., Hasty, K. A. and Smith, R. A. (2006) Accumulation of LPS by polyethylene particles decreases bone attachment to implants. J. Orthop. Res. 24, 959-966
78. Smith, R. A., Maghsoodpour, A. and Hallab, N. J. (2010) In vivo response to cross-linked polyethylene and polycarbonate-urethane particles, J. Biomed. Mater. Res. A 93, 227-234
79. Hansen, J. D., Vojtech, L. N. and Laing, K. J. (2011) Sensing disease and danger: a survey of vertebrate PRRs and their origins. Dev. Comp. Immunol. 35, 886-897
80. Blander, J. M. and Sander, L. E. (2012) Beyond pattern recognition: five immune checkpoints for scaling the microbial threat. Nat. Rev. Immunol. 12, 215-225
81. Fukata, M., Vamadevan, A. S. and Abreu, M. T. (2009) Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in inflammatory disorders. Semin. Immunol. 21, 242-253
82. Doyle, S. L. and O'Neill, L. A. J. (2006) Toll-like receptors: from the discovery of NFκB to new insights into transcriptional regulations in innate immunity. Biochem. Pharmacol. 72, 1102-1113
83. Tyson-Capper, A. J., Lawrence, H., Holland, J. P., Deehan, D. J. and Kirby, J. A. (2013) Metal-on-metal hips: cobalt can induce an endotoxin-like response. Ann. Rheum. Dis. 72, 460-461
84. Zhao, D.-S., Ma, G.-F., Selenius, M., Salo, J., Pikkarainen, T. and Konttinen, Y. T. (2010) Ectopic expression of macrophage scavenger receptor MARCO in synovial membrane-like interface tissue in aseptic loosening of total hip replacement implants. J. Biomed. Mater. Res. A 92, 641-649
85. Nich, C., Rao, A. J., Valladares, R. D., Li, C., Christman, J. E., Antonios, J. K., Yao, Z., Zwingenberger, S., Petite, H., Hamadouche, M. and Goodman, S. B. (2013) Role of direct estrogen receptor signaling in wear particle-induced osteolysis. Biomaterials 34, 641-650
86. Burton, L., Paget, D., Binder, N. B., Bohnert, K., Nestor, B. J., Sculco, T. P., Santambrogio, L., Ross, F. P., Goldring, S. R. and Purdue, P. E. (2013) Orthopedic wear debris mediated inflammatory osteolysis is mediated in part by NALP3 inflammasome activation. J. Orthop. Res. 31, 73-80
87. Lochner, K., Fritsche, A., Jonitz, A., Hansmann, D., Mueller, P., Mueller-Hilke, B. and Bader, R. (2011) The potential role of human osteoblasts for periprosthetic osteolysis following exposure to wear particles. Int. J. Mol. Med. 28, 1055-1063
88. Kwon, S. Y., Lin, T., Takei, H., Ma, Q., Wood, D. J., O'Connor, D. and Sung, K. L. (2001) Alterations in the adhesion behavior of osteoblasts by titanium particle loading: inhibition of cell function and gene expression. Biorheology 38, 161-183
89. Lenz, R., Mittelmeier, W., Hansmann, D., Brem, R., Diehl, P., Fritsche, A. and Bader, R. (2009) Response of human osteoblasts exposed to wear particles generated at the interface of total hip stems and bone cement. J. Biomed. Mater. Res. A 89, 370-378
90. Sabokbar, A., Kudo, O. and Athanasou, N. A. (2003) Two distinct cellular mechanisms of osteoclast formation and bone resorption in periprosthetic osteolysis. J. Orthop. Res. 21, 73-80
91. Mandelin, J., Li, T. F., Liljeström, M., Kroon, M. E., Hanemaaijer, R., Santavirta, S. and Konttinen, Y. T. (2003) Imbalance of RANKL/RANK/OPG system in interface tissue in loosening of total hip replacement. J. Bone Joint Surg. Br. 85, 1196-1201
92. Granchi, D., Ciapetti, G., Amato, I., Pagani, S., Cenni, E., Savarino, L., Avnet, S., Peris, J. L., Pellacani, A., Baldini, N. and Giunti, A. (2004) The influence of alumina and ultra-high molecular weight polyethylene particles on osteoblast-osteoclast cooperation. Biomaterials 25, 4037-4045
93. Lee, H. G., Minematsu, H., Kim, K. O., Celil Aydemir, A. B., Shin, M. J., Nizami, S. A., Chung, K. J., Hsu, A. C. and Jacobs, C. R. (2011) Actin and ERK1/2-CEBPß signaling mediates phagocytosis-induced innate immune response of osteoprogenitor cells. Biomaterials 32, 9197-9206
94. Bostrom, M. and O'Keefe, R. (2008) What experimental approaches (eg, in vivo, in vitro, tissue retrieval) are effective in investigating the biologic effects of particles? J. Am. Acad. Orthop. Surg. 16, S63-S67
95. Shanbhag, A. S., Hasselman, C. T. and Rubash, H. E. (1997) The John Charnley Award. Inhibition of wear debris mediated osteolysis in a canine total hip arthroplasty model. Clin. Orthop. Relat. Res. 344, 33-43
96. Millett, P. J., Allen, M. J. and Bostrom, M. P. G. (2002) Effects of alendronate on particle-induced osteolysis in a rat model. J. Bone Joint. Surg. Am. 84, 236-249
97. Ren, W., Yang, S. and Wooley, P. (2004) A novel murine model of orthopaedic wear-debris associated osteolysis. Scand. J. Rehabil. Med. 33, 349-357
98. Yang, S., Yu, H., Gong, W., Wu, B., Mayton, L., Costello, R. and Wooley, P. H. (2007) Murine model of prosthesis failure for the long-term study of aseptic loosening. J. Orthop. Res. 25, 603-611
99. Wooley, P. H., Morren, R., Andary, J., Sud, S., Yang, S.-Y., Mayton, L., Markel, D., Sieving, A. and Nasser, S. (2002) Inflammatory responses to orthopaedic biomaterials in the murine air pouch. Biomaterials 23, 517-526
100. Goodman, S. B., Chin, R. C. and Magee, F. P. (1992) Prostaglandin E2 production by the membrane surrounding loose and fixated cemented tibial hemiarthroplasties in the rabbit knee. Clin. Orthop. Relat. Res. 284, 283-287
101. Spector, M., Shortkroff, S., Hsu, H. P., Lane, N., Sledge, C. B. and Thornhill, T. S. (1990) Tissue changes around loose prostheses. A canine model to investigate the effects of an antiinflammatory agent. Clin. Orthop. Relat. Res. 261, 140-152
102. Gelb, H., Schumacher, H. R., Cuckler, J., Ducheyne, P. and Baker, D. G. (1994) In vivo inflammatory response to polymethylmethacrylate particulate debris: effect of size, morphology, and surface area. J. Orthop. Res. 12, 83-92
103. Gibon, E., Ma, T., Ren, P.-G., Fritton, K., Biswal, S., Yao, Z., Smith, L. and Goodman, S. B. (2012) Selective inhibition of the MCP-1-CCR2 ligand-receptor axis decreases systemic trafficking of macrophages in the presence of UHMWPE particles. J. Orthop. Res. 30, 547-553
104. Takahashi, K., Onodera, S., Tohyama, H., Kwon, H. J., Honma, K. and Yasuda, K. (2011) In vivo imaging of particle-induced inflammation and osteolysis in the calvariae of NFκB/luciferase transgenic mice. J. Biomed. Biotechnol. 2011, 727063
105. Lai, W.-Q., Irwan, A. W., Goh, H. H., Melendez, A. J., McInnes, I. B. and Leung, B. P. (2009) Distinct roles of sphingosine kinase 1 and 2 in murine collagen-induced arthritis. J. Immunol. 183, 2097-2103
106. Nich, C., Langlois, J., Marchadier, A., Vidal, C., Cohen-Solal, M., Petite, H. and Hamadouche, M. (2011) Oestrogen deficiency modulates particle-induced osteolysis. Arthritis Res. Ther. 13, R100
107. St. Pierre, C. A., Chan, M., Iwakura, Y., Ayers, D. C., Kurt-Jones, E. A. and Finberg, R. W. (2010) Periprosthetic osteolysis: characterizing the innate immune response to titanium wear-particles. J. Orthop. Res. 28, 1418-1424
108. Taki, N., Tatro, J. M., Nalepka, J. L., Togawa, D., Goldberg, V. M., Rimnac, C. M. and Greenfield, E. M. (2005) Polyethylene and titanium particles induce osteolysis by similar, lymphocyte-independent, mechanisms. J. Orthop. Res. 23, 376-383
109. Ren, P.-G., Irani, A., Huang, Z., Ma, T., Biswal, S. and Goodman, S. B. (2011) Continuous infusion of UHMWPE particles induces increased bone macrophages and osteolysis. Clin. Orthop. Relat. Res. 469, 113-122
110. Ren, W., Wu, B., Peng, X., Hua, J., Hao, H.-N. and Wooley, P. H. (2006) Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK- /- mice. J. Orthop. Res. 24, 1575-1586
111. Nakashima, Y., Sun, D. H., Maloney, W. J., Goodman, S. B., Schurman, D. J. and Smith, R. L. (1998) Induction of matrix metalloproteinase expression in human macrophages by orthopaedic particulate debris in vitro. J. Bone Joint Surg. Br. 80, 694-700
112. Yao, J., Glant, T. T., Lark, M. W., Mikecz, K., Jacobs, J. J., Hutchinson, N. I., Hoerrner, L. A., Kuettner, K. E. and Galante, J. O. (1995) The potential role of fibroblasts in periprosthetic osteolysis: fibroblast response to titanium particles. J. Bone Miner. Res. 10, 1417-1427
113. Kauther, M. D., Neuerburg, C., Wefelnberg, F., Bachmann, H. S., Schlepper, R., Hilken, G., Broecker-Preuss, M., Grabellus, F., Schilling, A. F., Jäger, M. and Wedemeyer, C. (2013) RANKL-associated suppression of particle-induced osteolysis in an aged model of Calcitonin and a-CGRP deficiency. Biomaterials 34, 2911-2919
114. Ren, W., Zhang, R., Wu, B., Wooley, P. H., Hawkins, M. and Markel, D. C. (2011) Effects of SU5416 and a vascular endothelial growth factor neutralizing antibody on wear debris-induced inflammatory osteolysis in a mouse model. J. Inflamm. Res. 4, 29-38
115. Wooley, P. H., Morren, R., Andary, J., Sud, S., Yang, S.-Y., Mayton, L., Markel, D., Sieving, A. and Nasser, S. (2002) Inflammatory responses to orthopaedic biomaterials in the murine air pouch. Biomaterials 23, 517-526
116. Merkel, K. D., Erdmann, J. M., McHugh, K. P., Abu-Amer, Y., Ross, F. P. and Teitelbaum, S. L. (1999) Tumor necrosis factor-a mediates orthopedic implant osteolysis. Am. J. Pathol. 154, 203-210
117. Schwarz, E. M., Benz, E. B., Lu, A. P., Goater, J. J., Mollano, A. V., Rosier, R. N., Puzas, J. E. and O'Keefe, R. J. (2000) Quantitative small-animal surrogate to evaluate drug efficacy in preventing wear debris-induced osteolysis. J. Orthop. Res. 18, 849-855
118. Taki, N., Tatro, J. M., Lowe, R., Goldberg, V. M. and Greenfield, E. M. (2007) Comparison of the roles of IL-1, IL-6, and TNFa in cell culture and murine models of aseptic loosening. Bone 40, 1276-1283
119. Carmody, E. E., Schwarz, E. M., Puzas, J. E., Rosier, R. N. and O'Keefe, R. J. (2002) Viral interleukin-10 gene inhibition of inflammation, osteoclastogenesis, and bone resorption in response to titanium particles. Arthritis Rheum. 46, 1298-1308
120. Rao, A. J., Nich, C., Dhulipala, L. S., Gibon, E., Valladares, R., Zwingenberger, S., Smith, R. L. and Goodman, S. B. (2013) Local effect of IL-4 delivery on polyethylene particle induced osteolysis in the murine calvarium. J. Biomed. Mater. Res. A 101, 1926-1934
121. Rao, A. J., Zwingenberger, S., Valladares, R., Li, C., Lane Smith, R., Goodman, S. B. and Nich, C. (2013) Direct subcutaneous injection of polyethylene particles over the murine calvaria results in dramatic osteolysis. Int. Orthop. 37, 1393-1398
122. Zhang, X., Morham, S. G., Langenbach, R., Young, D. A., Xing, L., Boyce, B. F., Puzas, E. J., Rosier, R. N., O'Keefe, R. J. and Schwarz, E. M. (2001) Evidence for a direct role of cyclo-oxygenase 2 in implant wear debris-induced osteolysis. J. Bone Miner. Res. 16, 660-670
123. Valladares, R. D., Nich, C., Zwingenberger, S., Li, C., Swank, K. R., Gibon, E., Rao, A. J., Yao, Z. and Goodman, S. B. (2013) Toll-like receptors-2 and 4 are overexpressed in an experimental model of particle-induced osteolysis. J. Biomed. Mater. Res. A 2013, doi:10.1002/jbm.a.34972
124. Ren, K., Purdue, P. E., Burton, L., Quan, L., Fehringer, E. V., Thiele, G. M., Goldring, S. R. and Wang, D. (2011) Early detection and treatment of wear particle-induced inflammation and bone loss in a mouse calvarial osteolysis model using HPMA copolymer conjugates. Mol. Pharm. 8, 1043-1051
125. Warme, B. A., Epstein, N. J., Trindade, M. C. D., Miyanishi, K., Ma, T., Saket, R. R., Regula, D., Goodman, S. B. and Smith, R. L. (2004) Proinflammatory mediator expression in a novel murine model of titanium-particle-induced intramedullary inflammation. J. Biomed. Mater. Res. B 71, 360-366
126. Epstein, N. J., Warme, B. A., Spanogle, J., Ma, T., Bragg, B., Smith, R. L. and Goodman, S. B. (2005) Interleukin-1 modulates periprosthetic tissue formation in an intramedullary model of particle-induced inflammation. J. Orthop. Res. 23, 501-510
127. Shi, Y., Yang, X., Nestor, B., Bostrom, M., Camacho, N., Li, G., Purdue, E. and Sculco, T. (2007) Histologic and FTIR studies on long term effect of PMMA particle in a murine intramedullary osteolysis model. Trans. Orthop. Res. Soc. 53, 217
128. Epstein, N. J., Bragg, W. E., Ma, T., Spanogle, J., Smith, R. L. and Goodman, S. B. (2005) UHMWPE wear debris upregulates mononuclear cell proinflammatory gene expression in a novel murine model of intramedullary particle disease. Acta Orthop. 76, 412-420
129. Ortiz, S. G., Ma, T., Epstein, N. J., Smith, R. L. and Goodman, S. B. (2008) Validation and quantification of an in vitro model of continuous infusion of submicron-sized particles. J. Biomed. Mater. Res. B 84, 328-333
130. Ortiz, S. G., Ma, T., Regula, D., Smith, R. L. and Goodman, S. B. (2008) Continuous intramedullary polymer particle infusion using a murine femoral explant model. J. Biomed. Mater. Res. B 87, 440-446
131. Yang, S., Wu, B., Mayton, L., Evans, C. H., Robbins, P. D. and Wooley, P. H. (2002) IL-1Ra and vIL-10 gene transfer using retroviral vectors ameliorates particle-associated inflammation in the murine air pouch model. Inflamm. Res. 51, 342-350
132. Yang, S.-Y., Wu, B., Mayton, L., Mukherjee, P., Robbins, P. D., Evans, C. H. and Wooley, P. H. (2004) Protective effects of IL-1Ra or vIL-10 gene transfer on a murine model of wear debris-induced osteolysis. Gene Ther. 11, 483-491
133. Yang, S.-Y., Mayton, L., Wu, B., Goater, J. J., Schwarz, E. M. and Wooley, P. H. (2002) Adeno-associated virus-mediated osteoprotegerin gene transfer protects against particulate polyethylene-induced osteolysis in a murine model. Arthritis Rheum. 46, 2514-2523
134. Ren, W., Wu, B., Peng, X., Mayton, L., Yu, D., Ren, J., Chen, B. D. and Wooley, P. H. (2006) Erythromycin inhibits wear debris-induced inflammatory osteolysis in a murine model. J. Orthop. Res. 24, 280-290
135. Ren, W., Zhang, R., Markel, D. C., Wu, B., Peng, X., Hawkins, M. and Wooley, P. H. (2007) Blockade of vascular endothelial growth factor activity suppresses wear debris-induced inflammatory osteolysis. J. Rheumatol. 34, 27-35
136. Zhang, W., Peng, X., Cheng, T. and Zhang, X. (2011) Vascular endothelial growth factor gene silencing suppresses wear debris-induced inflammation. Int. Orthop. 35, 1883-1888
137. Wang, Y., Wu, N.-N., Hu, M., Mou, Y.-Q., Li, R.-D., Chen, L., He, B.-C. and Deng, Z.-L. (2012) Inhibitory effect of adenovirus-mediated siRNA-targeting BMPR-IB on UHMWPE-induced bone destruction in the murine air pouch model. Connect. Tissue Res. 53, 528-534
138. Chen, D., Zhang, X., Guo, Y., Shi, S., Mao, X., Pan, X. and Cheng, T. (2012) MMP-9 inhibition suppresses wear debris-induced inflammatory osteolysis through downregulation of RANK/RANKL in a murine osteolysis model. Int. J. Mol. Med. 30, 1417-1423
139. Dai, M., Zhong, Y., Zong, L., Yang, X., Cheng, M. and Yang, K. (2012) Inhibitory effects of vascular endothelial growth factor antibody on wear particle-induced osteolysis. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 26, 647-651
140. Chen, D., Guo, Y., Mao, X. and Zhang, X. (2012) Inhibition of p38 mitogen-activated protein kinase down-regulates the inflammatory osteolysis response to titanium particles in a murine osteolysis model. Inflammation 35, 1798-1806
141. Childs, L. M., Goater, J. J., O'Keefe, R. J. and Schwarz, E. M. (2001) Efficacy of etanercept for wear debris-induced osteolysis. J. Bone Miner. Res. 16, 338-347
142. Childs, L. M., Paschalis, E. P., Xing, L., Dougall, W. C., Anderson, D., Boskey, A. L., Puzas, J. E., Rosier, R. N., O'Keefe, R. J., Boyce, B. F. and Schwarz, E. M. (2002) In vivo RANK signaling blockade using the receptor activator of NF-κaB:Fc effectively prevents and ameliorates wear debris-induced osteolysis via osteoclast depletion without inhibiting osteogenesis. J. Bone Miner. Res. 17, 192-199
143. Von Knoch, F., Wedemeyer, C., Heckelei, A., Sprecher, C., Saxler, G., Hilken, G., Henschke, F., von Knoch, M., Bereiter, H., Löer, F. and von Knoch, M. (2005) A comparison of the antiresorptive effects of bisphosphonates and statins on polyethylene particle-induced osteolysis. Biomed. Tech. 50, 195-200
144. Von Knoch, F., Heckelei, A., Wedemeyer, C., Saxler, G., Hilken, G., Brankamp, J., Sterner, T., Landgraeber, S., Henschke, F., Löer, F. and von Knoch, M. (2005) Suppression of polyethylene particle-induced osteolysis by exogenous osteoprotegerin. J. Biomed. Mater. Res. A 75, 288-294
145. Zhang, C., Tang, T.-T., Ren, W.-P., Zhang, X.-L. and Dai, K.-R. (2007) Inhibiting wear particles-induced osteolysis with doxycycline. Acta Pharmacol. Sin. 28, 1603-1610
146. Landgraeber, S., Jaeckel, S., Löer, F., Wedemeyer, C., Hilken, G., Canbay, A., Totsch, M. and Knoch, M. (2009) Pan-caspase inhibition suppresses polyethylene particle-induced osteolysis. Apoptosis 14, 173-181
147. Kauther, M. D., Bachmann, H. S., Neuerburg, L., Broecker-Preuss, M., Hilken, G., Grabellus, F., Koehler, G., von Knoch, M. and Wedemeyer, C. (2011) Calcitonin substitution in calcitonin deficiency reduces particle-induced osteolysis. BMC Musculoskelet. Disord. 12, 186
148. Rao, A. J., Nich, C., Dhulipala, L. S., Gibon, E., Valladares, R., Zwingenberger, S., Smith, R. L. and Goodman, S. B. (2012) Local effect of IL-4 delivery on polyethylene particle induced osteolysis in the murine calvarium. J. Biomed. Mater. Res. A 101, 1926-1934
149. Yamanaka, Y., Clohisy, J. C. F., Ito, H., Matsuno, T. and Abu-Amer, Y. (2013) Blockade of JNK and NFAT pathways attenuates orthopedic particle-stimulated osteoclastogenesis of human osteoclast precursors and murine calvarial osteolysis. J. Orthop. Res. 31, 67-72