Numerous studies provide detailed insight into the triggering and amplification mechanisms of the inflammatory response associated with prosthetic wear particles, promoting final dominance of bone resorption over bone formation in multiple bone multicellular units around an implant. In fact, inflammation is a highly regulated process tightly linked to simultaneous stimulation of tissue protective and regenerative mechanisms in order to prevent collateral damage of periprosthetic tissues. A variety of cytokines, chemokines, hormones and specific cell populations, including macrophages, dendritic and stem cells, attempt to balance tissue architecture and minimize inflammation. Based on this fact, we postulate that the local tissue homeostatic mechanisms more effectively regulate the pro-inflammatory/pro-osteolytic cells/pathways in patients with none/mild periprosthetic osteolysis (PPOL) than in patients with severe PPOL. In this line of thinking, 'particle disease theory' can be understood, at least partially, in terms of the failure of local tissue homeostatic mechanisms. As a result, we envision focusing current research on homeostatic mechanisms in addition to traditional efforts to elucidate details of pro-inflammatory/pro-osteolytic pathways. We believe this approach could open new avenues for research and potential therapeutic strategies.

Department of Orthopaedics University Hospital Faculty of Medicine and Dentistry Palacky University Olomouc Czech Republic

Zobrazit více v PubMed

Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am 2007. 89:780–785. PubMed

Ulrich SD, Seyler TM, Bennett D, Delanois RE, Saleh KJ, Thongtrangan I, et al. Total hip arthroplasties: What are the reasons for revision? Int Orthop. 2008;32:597–604. PubMed PMC

Gallo J, Kaminek P, Zapletalova J, Cechova I, Spicka J, Ditmar R. Is osteolysis associated with a stable total hip replacement asymptomatic? Acta Chir Orthop Traumatol Cech. 2004;71:20–25. PubMed

Maloney W, Rosenberg A. What is the outcome of treatment for osteolysis? J Am Acad Orthop Surg. 2008;16(Suppl. 1):S26–S32. PubMed

Deirmengian GK, Zmistowski B, O'Neil JT, Hozack WJ. Management of acetabular bone loss in revision total hip arthroplasty. J Bone Joint Surg Am. 2011;93:1842–1852. PubMed

Garcia-Cimbrelo E, Garcia-Rey E, Cruz-Pardos A. The extent of the bone defect affects the outcome of femoral reconstruction in revision surgery with impacted bone grafting: a five-to 17-year follow-up study. J Bone Joint Surg Br. 2011;93:1457–1464. PubMed

Dumbleton JH, Manley MT, Edidin AA. A literature review of the association between wear rate and osteolysis in total hip arthroplasty. J Arthroplasty. 2002;17:649–661. PubMed

Kurtz SM, Gawel HA, Patel JD. History and systematic review of wear and osteolysis outcomes for first-generation highly crosslinked polyethylene. Clin Orthop Relat Res. 2011;469:2262–2277. PubMed PMC

Gallo J, Slouf M, Goodman SB. The relationship of polyethylene wear to particle size, distribution, and number: A possible factor explaining the risk of osteolysis after hip arthroplasty. J Biomed Mater Res B Appl Biomater. 2010;94:171–177. PubMed

Aspenberg P, van der Vis H. Fluid pressure may cause periprosthetic osteolysis. Particles are not the only thing. Acta Orthop Scand. 1998;69:1–4. PubMed

Willert HG, Semlitsch M. Reactions of the articular capsule to wear products of artificial joint prostheses. J Biomed Mater Res. 1977;11:157–164. PubMed

Maloney WJ, Jasty M, Harris WH, Galante JO, Callaghan JJ. Endosteal erosion in association with stable uncemented femoral components. J Bone Joint Surg Am. 1990;72:1025–1034. PubMed

Goodman SB, Chin RC, Chiou SS, Schurman DJ, Woolson ST, Masada MP. A clinical-pathologic-biochemical study of the membrane surrounding loosened and nonloosened total hip arthroplasties. Clin Orthop Relat Res. 1989 Jul;:182–187. PubMed

Tallroth K, Eskola A, Santavirta S, Konttinen YT, Lindholm TS. Aggressive granulomatous lesions after hip arthroplasty. J Bone Joint Surg Br. 1989;71:571–575. PubMed

Santavirta S, Konttinen YT, Bergroth V, Eskola A, Tallroth K, Lindholm TS. Aggressive granulomatous lesions associated with hip arthroplasty. Immunopathological studies. J Bone Joint Surg Am. 1990;72:252–258. PubMed

Harris WH. Osteolysis and particle disease in hip replacement. A review. Acta Orthop Scand. 1994;65:113–123. PubMed

Konttinen YT, Zhao D, Beklen A, Ma G, Takagi M, Kivela-Rajamaki M, et al. The microenvironment around total hip replacement prostheses. Clin Orthop Relat Res. 2005 Jan;:28–38. PubMed

Ren PG, Irani A, Huang Z, Ma T, Biswal S, Goodman SB. Continuous infusion of UHMWPE particles induces increased bone macrophages and osteolysis. Clin Orthop Relat Res. 2011;469:113–122. PubMed PMC

Gallo J, Raska M, Mrazek F, Petrek M. Bone remodeling, particle disease and individual susceptibility to periprosthetic osteolysis. Physiol Res. 2008;57:339–349. PubMed

Schmalzried TP, Jasty M, Harris WH. Periprosthetic bone loss in total hip arthroplasty. Polyethylene wear debris and the concept of the effective joint space. J Bone Joint Surg Am. 1992;74:849–863. PubMed

Gallo J, Havranek V, Cechova I, Zapletalova J. Influence of demographic, surgical and implant variables on wear rate and osteolysis in ABG I hip arthroplasty. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2006;150:135–141. PubMed

Engh CA, Hooten JP, Jr, Zettl-Schaffer KF, Ghaffarpour M, McGovern TF, Bobyn JD. Evaluation of bone ingrowth in proximally and extensively porous-coated anatomic medullary locking prostheses retrieved at autopsy. J Bone Joint Surg Am. 1995;77:903–910. PubMed

Wilkinson JM, Wilson AG, Stockley I, Scott IR, Macdonald DA, Hamer AJ, et al. Variation in the TNF gene promoter and risk of osteolysis after total hip arthroplasty. J Bone Miner Res. 2003;18:1995–2001. PubMed

Gallo J, Mrazek F, Petrek M. Variation in cytokine genes can contribute to severity of acetabular osteolysis and risk for revision in patients with ABG 1 total hip arthroplasty: a genetic association study. BMC Med Genet. 2009;10:109. PubMed PMC

Gordon A, Kiss-Toth E, Stockley I, Eastell R, Wilkinson JM. Polymorphisms in the interleukin-1 receptor antagonist and interleukin-6 genes affect risk of osteolysis in patients with total hip arthroplasty. Arthritis Rheum. 2008;58:3157–3165. PubMed

Mrazek F, Gallo J, Stahelova A, Petrek M. Functional variants of the P2RX7 gene, aseptic osteolysis, and revision of the total hip arthroplasty: a preliminary study. Hum Immunol. 2010;71:201–205. PubMed

Del Buono A, Denaro V, Maffulli N. Genetic susceptibility to aseptic loosening following total hip arthroplasty: a systematic review. Br Med Bull. 2012;101:39–55. PubMed

Fornasier V, Wright J, Seligman J. The histomorphologic and morphometric study of asymptomatic hip arthroplasty. A postmortem study. Clin Orthop Relat Res. 1991;271:272–282. PubMed

Kwong LM, Jasty M, Mulroy RD, Maloney WJ, Bragdon C, Harris WH. The histology of the radiolucent line. J Bone Joint Surg Br. 1992;74:67–73. PubMed

Skurla CP, James SP. Assessing the dog as a model for human total hip replacement: analysis of 38 postmortem-retrieved canine cemented acetabular components. J Biomed Mater Res B Appl Biomater. 2005;73:260–270. PubMed

Ma T, Ortiz SG, Huang Z, Ren P, Smith RL, Goodman SB. In vivo murine model of continuous intramedullary infusion of particles–a preliminary study. J Biomed Mater Res B Appl Biomater. 2009;88:250–253. PubMed PMC

El-Warrak AO, Olmstead M, Schneider R, Meinel L, Bettschart-Wolfisberger R, Akens MK, et al. An experimental animal model of aseptic loosening of hip prostheses in sheep to study early biochemical changes at the interface membrane. BMC Musculoskelet Disord. 2004;5:7. PubMed PMC

Shanbhag AS, Kaufman AM, Hayata K, Rubash HE. Assessing osteolysis with use of high-throughput protein chips. J Bone Joint Surg Am. 2007;89:1081–1089. PubMed

Anderson JM. Biological responses to materials. Annu Rev Mater Res. 2001;31:81–110.

Cooper HJ, Ranawat AS, Potter HG, Foo LF, Koob TW, Ranawat CS. Early reactive synovitis and osteolysis after total hip arthroplasty. Clin Orthop Relat Res. 2010;468:3278–3285. PubMed PMC

Aspenberg P, Wagner P, Nilsson KG, Ranstam J. Fixed or loose? Dichotomy in RSA data for cemented cups. Acta Orthop. 2008;79:467–473. PubMed

Medzhitov R. Inflammation 2010: new adventures of an old flame. Cell. 2010;140:771–776. PubMed

Matzinger P. Tolerance, danger, and the extended family. Annu Rev Immunol. 1994;12:991–1045. PubMed

Nakashima T, Hayashi M, Fukunaga T, Kurata K, Oh-Hora M, Feng JQ, et al. Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat Med. 2011;17:1231–1234. PubMed

Konttinen Y, Imai S, Suda A. Neuropeptides and the puzzle of bone remodeling. State of the art. Acta Orthop Scand. 1996;67:632–639. PubMed

King KY, Goodell MA. Inflammatory modulation of HSCs: viewing the HSC as a foundation for the immune response. Nat Rev Immunol. 2011;11:685–692. PubMed PMC

Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol. 2011;11:723–737. PubMed PMC

Buckley CD. Why does chronic inflammation persist: An unexpected role for fibroblasts. Immunol Lett. 2011;138:12–14. PubMed PMC

Nathan C, Ding A. Nonresolving inflammation. Cell. 2010;140:871–882. PubMed

Perez-Losada J, Balmain A. Stem-cell hierarchy in skin cancer. Nat Rev Cancer. 2003;3:434–443. PubMed

Zlotnik A, Burkhardt AM, Homey B. Homeostatic chemokine receptors and organ-specific metastasis. Nat Rev Immunol. 2011;11:597–606. PubMed

O'Connell RM, Rao DS, Baltimore D. microRNA regulation of inflammatory responses. Annu Rev Immunol. 2012;30:295–312. PubMed

Karouzakis E, Gay RE, Gay S, Neidhart M. Epigenetic control in rheumatoid arthritis synovial fibroblasts. Nat Rev Rheumatol. 2009;5:266–272. PubMed

Goodman SB, Ma T. Cellular chemotaxis induced by wear particles from joint replacements. Biomaterials. 2010;31:5045–5050. PubMed PMC

Anderson JM, Rodriguez A, Chang DT. Foreign body reaction to biomaterials. Semin Immunol. 2008;20:86–100. PubMed PMC

Anttila A, Lappalainen R, Heinonen H, Santavirta S, Konttinen YT. Superiority of diamondlike carbon coating on articulating surfaces of artificial hip joints. New Diamond Frontier Carbon Technol. 1999;9:283–288.

Callaghan JJ, Cuckler JM, Huddleston JI, Galante JO. How have alternative bearings (such as metal-on-metal, highly cross-linked polyethylene, and ceramic-on-ceramic) affected the prevention and treatment of osteolysis? J Am Acad Orthop Surg. 2008;16(Suppl. 1):S33–S38. PubMed

Catelas I, Jacobs JJ. Biologic activity of wear particles. Instr Course Lect. 2010;59:3–16. PubMed

Landgraeber S, Jaeckel S, Loer F, Wedemeyer C, Hilken G, Canbay A, et al. Pan-caspase inhibition suppresses polyethylene particle-induced osteolysis. Apoptosis. 2009;14:173–181. PubMed

Santavirta S, Takagi M, Gomez-Barrena E, Nevalainen J, Lassus J, Salo J, et al. Studies of host response to orthopedic implants and biomaterials. J Long Term Eff Med Implants. 1999;9:67–76. PubMed

Hubbi ME, Luo W, Baek JH, Semenza GL. MCM proteins are negative regulators of hypoxia-inducible factor 1. Mol Cell. 2011;42:700–712. PubMed PMC

Knowles HJ, Athanasou NA. Acute hypoxia and osteoclast activity: a balance between enhanced resorption and increased apoptosis. J Pathol. 2009;218:256–264. PubMed

Waris V, Sillat T, Waris E, Virkki L, Mandelin J, Takagi M, et al. Role and regulation of VEGF and its receptors 1 and 2 in the aseptic loosening of total hip implants. J Orthop Res. Epub ahead of print 23 April 2012. DOI: 10.1002/jor.22138. PubMed

Gross TS, King KA, Rabaia NA, Pathare P, Srinivasan S. Upregulation of osteopontin by osteocytes deprived of mechanical loading or oxygen. J Bone Miner Res. 2005;20:250–256. PubMed PMC

Seong SY, Matzinger P. Hydrophobicity: an ancient damage-associated molecular pattern that initiates innate immune responses. Nat Rev Immunol. 2004;4:469–478. PubMed

Janeway CA., Jr Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol. 1989;54:1–13. PubMed

Oppenheim JJ, Yang D. Alarmins: chemotactic activators of immune responses. Curr Opin Immunol. 2005;17:359–365. PubMed

Greenfield EM, Beidelschies MA, Tatro JM, Goldberg VM, Hise AG. Bacterial pathogen-associated molecular patterns stimulate biological activity of orthopaedic wear particles by activating cognate Toll-like receptors. J Biol Chem. 2010;285:32378–32384. PubMed PMC

Pearl JI, Ma T, Irani AR, Huang Z, Robinson WH, Smith RL, et al. Role of the Toll-like receptor pathway in the recognition of orthopedic implant wear-debris particles. Biomaterials. 2011;32:5535–5542. PubMed PMC

Takagi M, Tamaki Y, Hasegawa H, Takakubo Y, Konttinen L, Tiainen VM, et al. Toll-like receptors in the interface membrane around loosening total hip replacement implants. J Biomed Mater Res A. 2007;81:1017–1026. PubMed

Maitra R, Clement CC, Scharf B, Crisi GM, Chitta S, Paget D, et al. Endosomal damage and TLR2 mediated inflammasome activation by alkane particles in the generation of aseptic osteolysis. Mol Immunol. 2009;47:175–184. PubMed PMC

Medzhitov R, Shevach EM, Trinchieri G, Mellor AL, Munn DH, Gordon S, et al. Highlights of 10 years of immunology in Nature Reviews Immunology. Nat Rev Immunol. 2011;11:693–702. PubMed PMC

Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008;454:428–435. PubMed

Fujii J, Yasunaga Y, Yamasaki A, Ochi M. Wear debris stimulates bone-resorbing factor expression in the fibroblasts and osteoblasts. Hip Int. Epub ahead of print 11 April 2011. DOI: 511AE461-986F-4E4E-91C3-C511BBA83406. PubMed

Garrigues GE, Cho DR, Rubash HE, Goldring SR, Herndon JH, Shanbhag AS. Gene expression clustering using self-organizing maps: analysis of the macrophage response to particulate biomaterials. Biomaterials. 2005;26:2933–2945. PubMed

Grom AA, Mellins ED. Macrophage activation syndrome: advances towards understanding pathogenesis. Curr Opin Rheumatol. 2010;22:561–566. PubMed PMC

Zhang Y, Hou C, Yu S, Xiao J, Zhang Z, Zhai Q, et al. IRAK-M in macrophages around septically and aseptically loosened hip implants. J Biomed Mater Res A. 2012;100:261–268. PubMed

Liddiard K, Rosas M, Davies LC, Jones SA, Taylor PR. Macrophage heterogeneity and acute inflammation. Eur J Immunol. 2011;41:2503–2508. PubMed

Matzinger P, Kamala T. Tissue-based class control: the other side of tolerance. Nat Rev Immunol. 2011;11:221–230. PubMed

Ma J, Chen T, Mandelin J, Ceponis A, Miller NE, Hukkanen M, et al. Regulation of macrophage activation. Cell Mol Life Sci. 2003;60:2334–2346. PubMed PMC

Valledor AF, Comalada M, Santamaria-Babi LF, Lloberas J, Celada A. Macrophage proinflammatory activation and deactivation: a question of balance. Adv Immunol. 2010;108:1–20. PubMed

Huss RS, Huddleston JI, Goodman SB, Butcher EC, Zabel BA. Synovial tissue-infiltrating natural killer cells in osteoarthritis and periprosthetic inflammation. Arthritis Rheum. 2010;62:3799–3805. PubMed PMC

Koreny T, Tunyogi-Csapo M, Gal I, Vermes C, Jacobs JJ, Glant TT. The role of fibroblasts and fibroblast-derived factors in periprosthetic osteolysis. Arthritis Rheum. 2006;54:3221–3232. PubMed

Josefowicz SZ, Lu LF, Rudensky AY. Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol. 2012;30:531–564. PubMed PMC

Thyssen JP, Jakobsen SS, Engkilde K, Johansen JD, Soballe K, Menne T. The association between metal allergy, total hip arthroplasty, and revision. Acta Orthop. 2009;80:646–652. PubMed PMC

Monticelli LA, Sonnenberg GF, Abt MC, Alenghat T, Ziegler CG, Doering TA, et al. Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus. Nat Immunol. 2011;12:1045–1054. PubMed PMC

The Cytological Energy Detection of Purulent Inflammation in Synovial Fluid Is Not All Black and White

Analysis of Chemisorbed Tribo-Film for Ceramic-on-Ceramic Hip Joint Prostheses by Raman Spectroscopy

Diagnosis and management of implant debris-associated inflammation

Periprosthetic Osteolysis: Mechanisms, Prevention and Treatment

Particle disease really does exist

The Role of the Chemokine System in Tissue Response to Prosthetic By-products Leading to Periprosthetic Osteolysis and Aseptic Loosening

Innate immunity sensors participating in pathophysiology of joint diseases: a brief overview

Contributions of human tissue analysis to understanding the mechanisms of loosening and osteolysis in total hip replacement

Osteolysis around total knee arthroplasty: a review of pathogenetic mechanisms

Long-term survival of the uncemented Balgrist total hip replacement cup