Mechanically Induced Periprosthetic Osteolysis: A Systematic Review



Peri-prosthetic bone loss can result from chemical, biological, and mechanical factors. Mechanical stimulation via fluid pressure and flow at the bone–implant interface may be a significant cause. Evidence supporting mechanically induced osteolysis continues to grow, but there is no synthesis of published clinical and basic science data.


We sought to review the literature on two questions: (1) What published evidence supports the concept of mechanically induced osteolysis? (2) What is the proposed mechanism of mechanically induced osteolysis, and does it differ from that of particle-induced osteolysis?


A systematic review was performed of the PubMed and Web of Science databases. Additional relevant articles were recommended by the senior authors based on their expert opinion. Abstracts were reviewed and the manuscripts pertaining to the study questions were read in full. Studies showing support of mechanically induced osteolysis were quantified and findings summarized.


We identified 49 articles of experimental design supporting the hypothesis that mechanical stimulation of peri-prosthetic bone from fluid pressure and flow can induce osteolysis. While the molecular mechanisms may overlap with those implicated in particle-induced osteolysis, mechanically induced osteolysis appears to be mediated by distinct and parallel pathways.


The role of mechanical stimuli is increasingly recognized in the pathogenesis of peri-prosthetic osteolysis. Current research aims to elucidate the molecular mechanisms to better target therapeutic interventions.

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Change history

  • 17 December 2019

    Figure 2 and its caption were inadvertently omitted from the original article. The figure and caption are given below.

  • 17 December 2019

    Figure 2 and its caption were inadvertently omitted from the original article. The figure and caption are given below.


  1. 1.

    Adell R, Lekholm U, Rockler B, Brånemark PI. A 15-year study of osseointegrated implants in the treatment of the edentulous jaw. Int J Oral Surg. 1981;10(6):387–416.

    CAS  PubMed  Google Scholar 

  2. 2.

    Alidousti H, Bressloff NW. The implication of the osteolysis threshold and interfacial gaps on periprosthetic osteolysis in cementless total hip replacement. J Biomech. 2017;58:1–10.

    PubMed  Google Scholar 

  3. 3.

    Alidousti H, Taylor M, Bressloff NW. Do capsular pressure and implant motion interact to cause high pressure in the periprosthetic bone in total hip replacement?. J Biomech Eng. 2011;133(12):121001.

    PubMed  Google Scholar 

  4. 4.

    Alidousti H, Taylor M, Bressloff NW. Periprosthetic wear particle migration and distribution modelling and the implication for osteolysis in cementless total hip replacement. J Mech Behav Biomed Mater. 2014;32:225–244.

    CAS  PubMed  Google Scholar 

  5. 5.

    Amirhosseini M, Andersson G, Aspenberg P, Fahlgren A. Mechanical instability and titanium particles induce similar transcriptomic changes in a rat model for periprosthetic osteolysis and aseptic loosening. Bone Rep. 2017;7:17–25.

    PubMed  PubMed Central  Google Scholar 

  6. 6.

    Amirhosseini M, Madsen RV, Escott KJ, Bostrom MP, Ross FP, Fahlgren A. GSK-3β inhibition suppresses instability-induced osteolysis by a dual action on osteoblast and osteoclast differentiation. J Cell Physiol. 2018;233(3):2398–2408.

    CAS  PubMed  Google Scholar 

  7. 7.

    Amstutz HC, Campbell P, Kossovsky N, Clarke IC. Mechanism and clinical significance of wear debris-induced osteolysis. Clin Orthop Relat Res. 1992;(276):7–18.

    Google Scholar 

  8. 8.

    Anthony PP, Gie GA, Howie CR, Ling RS. Localised endosteal bone lysis in relation to the femoral components of cemented total hip arthroplasties. J Bone Joint Surg Br. 1990;72(6):971–979.

    CAS  PubMed  Google Scholar 

  9. 9.

    Aspenberg P, Goodman S, Toksvig-Larsen S, Ryd L, Albrektsson T. Intermittent micromotion inhibits bone ingrowth. Titanium implants in rabbits. Acta Orthop Scand. 1992;63(2):141–145.

    CAS  PubMed  Google Scholar 

  10. 10.

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

    CAS  PubMed  Google Scholar 

  11. 11.

    Astrand J, Skripitz R, Skoglund B, Aspenberg P. A rat model for testing pharmacologic treatments of pressure-related bone loss. Clin Orthop Relat Res. 2003;(409):296–305.

    Google Scholar 

  12. 12.

    Beaule PE, Campbell P, Mirra J, Hooper JC, Schmalzried TP. Osteolysis in a cementless, second generation metal-on-metal hip replacement. Clin Orthop Rel Res. 2001;(386):159–165.

    Google Scholar 

  13. 13.

    Boyce BF, Xing L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys. 2008;473(2):139–146.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Bozic KJ, Kurtz SM, Lau E, Ong K, Vail TP, Berry DJ. The epidemiology of revision total hip arthroplasty in the United States. J Bone Joint Surg Am. 2009;91(1):128–133.

    PubMed  Google Scholar 

  15. 15.

    De Jong PT, Tigchelaar W, Van Noorden CJF, Van der Vis HM. Polyethylene wear particles do not induce inflammation or gelatinase (MMP-2 and MMP-9) activity in fibrous tissue interfaces of loosening total hip arthroplasties. Acta Histochem. 2011;113(5):556–563.

    PubMed  Google Scholar 

  16. 16.

    De Man FHR, Tigchelaar W, Marti RK, Van Noorden CJF, Van der Vis HM. Effects of mechanical compression of a fibrous tissue interface on bone with or without high-density polyethylene particles in a rabbit model of prosthetic loosening. J Bone Joint Surg Am. 2005;87(7):1522–1533.

    PubMed  Google Scholar 

  17. 17.

    Ducheyne P, De Meester P, Aernoudt E. Influence of a functional dynamic loading on bone ingrowth into surface pores of orthopedic implants. J Biomed Mater Res. 1977;11(6):811–838.

    CAS  PubMed  Google Scholar 

  18. 18.

    Evans CE, Mylchreest S, Mee AP, Berry JL, Andrew JG. Cyclic hydrostatic pressure and particles increase synthesis of 1,25-dihydroxyvitamin D3 by human macrophages in vitro. Int J Biochem Cell Biol. 2006;38(9):1540–1546.

    CAS  PubMed  Google Scholar 

  19. 19.

    Fahlgren A, Bostrom MPG, Yang X, et al. Fluid pressure and flow as a cause of bone resorption. Acta Orthop. 2010;81(4):508–516.

    PubMed  PubMed Central  Google Scholar 

  20. 20.

    Fahlgren A, Bratengeier C, Semeins CM, Klein-Nulend J, Bakker AD. Supraphysiological loading induces osteocyte-mediated osteoclastogenesis in a novel in vitro model for bone implant loosening. J Orthop Res. 2018;36(5):1425–1434.

    CAS  PubMed  Google Scholar 

  21. 21.

    Freeman MA, Plante-Bordeneuve P. Early migration and late aseptic failure of proximal femoral prostheses. J Bone Joint Surg Br. 1994;76(3):432–438.

    CAS  PubMed  Google Scholar 

  22. 22.

    Gallo J, Goodman SB, Konttinen YT, Wimmer MA, Holinka M. Osteolysis around total knee arthroplasty: a review of pathogenetic mechanisms. Acta Biomater. 2013;9(9):8046–8058.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23.

    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  PubMed Central  Google Scholar 

  24. 24.

    Hilding M, Aspenberg P. Postoperative clodronate decreases prosthetic migration: 4-year follow-up of a randomized radiostereometric study of 50 total knee patients. Acta Orthop. 2006;77(6):912–916.

    PubMed  Google Scholar 

  25. 25.

    Hilding M, Aspenberg P. Local perioperative treatment with a bisphosphonate improves the fixation of total knee prostheses: a randomized, double-blind radiostereometric study of 50 patients. Acta Orthop. 2007;78(6):795–799.

    PubMed  Google Scholar 

  26. 26.

    Hilding M, Ryd L, Toksvig-Larsen S, Aspenberg P. Clodronate prevents prosthetic migration: a randomized radiostereometric study of 50 total knee patients. Acta Orthop Scand. 2000;71(6):553–557.

    CAS  PubMed  Google Scholar 

  27. 27.

    Huiskes R, Van Driel WD, Prendergast PJ, Soballe K. A biomechanical regulatory model for periprosthetic fibrous-tissue differentiation. J Mater Sci Mater Med. 1997;8(12):785–788.

    CAS  PubMed  Google Scholar 

  28. 28.

    Johansson L, Edlund U, Fahlgren A, Aspenberg P. Fluid-induced osteolysis: modelling and experiments. Comput Methods Biomech Biomed Engin. 2011;14(4):305–318.

    PubMed  Google Scholar 

  29. 29.

    Jones LC, Frondoza C, Hungerford DS. Effect of PMMA particles and movement on an implant interface in a canine model. J Bone Joint Surg Br. 2001;83(3):448–458.

    CAS  PubMed  Google Scholar 

  30. 30.

    Kärrholm J, Borssén B, Löwenhielm G, Snorrason F. Does early micromotion of femoral stem prostheses matter? 4-7-year stereoradiographic follow-up of 84 cemented prostheses. J Bone Joint Surg Br. 1994;76(6):912–917.

    PubMed  Google Scholar 

  31. 31.

    Kim GW, Lee NR, Pi RH, et al. IL-6 inhibitors for treatment of rheumatoid arthritis: past, present, and future. Arch Pharm Res. 2015;38(5):575–584.

    CAS  PubMed  Google Scholar 

  32. 32.

    Klein-Nulend J, van der Plas A, Semeins CM, et al. Sensitivity of osteocytes to biomechanical stress in vitro. FASEB J. 1995;9(5):441–445.

    CAS  PubMed  Google Scholar 

  33. 33.

    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(4):780–785.

    PubMed  Google Scholar 

  34. 34.

    Li TF, Santavirta S, Virtanen I, Kononen M, Takagi M, Konttinen YT. Increased expression of EMMPRIN in the tissue around loosened hip prostheses. Acta Orthop Scand. 1999;70(5):446–451.

    CAS  PubMed  Google Scholar 

  35. 35.

    MacQuarrie RA, Fang Chen Y, Coles C, Anderson GI. Wear-particle-induced osteoclast osteolysis: the role of particulates and mechanical strain. J Biomed Mater Res Part B Appl Biomater. 2004;69(1):104–112.

    PubMed  Google Scholar 

  36. 36.

    Maloney WJ, Jasty M, Rosenberg A, Harris WH. Bone lysis in well-fixed cemented femoral components. J Bone Joint Surg Br. 1990;72(6):966–970.

    CAS  PubMed  Google Scholar 

  37. 37.

    Maloney WJ, Smith RL. Periprosthetic osteolysis in total hip arthroplasty: the role of particulate wear debris. Instr Course Lect. 1996;45:171–182.

    CAS  PubMed  Google Scholar 

  38. 38.

    Mann KA, Miller MA. Fluid-structure interactions in micro-interlocked regions of the cement-bone interface. Comput Methods Biomech Biomed Engin. 2014;17(16):1809–1820.

    PubMed  Google Scholar 

  39. 39.

    Matthews JB, Mitchell W, Stone MH, Fisher J, Ingham E. A novel three-dimensional tissue equivalent model to study the combined effects of cyclic mechanical strain and wear particles on the osteolytic potential of primary human macrophages in vitro. Proc Inst Mech Eng H. 2001;215(H5):479–486.

    CAS  Google Scholar 

  40. 40.

    McArthur BA, Madsen R, Dvorzhinskiy A, Ross FP, Bostrom MP, Fahlgren A. Profiling molecular pathways in mechanically induced prosthetic loosening: a microarray study. In: Hospital for Special Surgery Chief Resident Research Presentations. March 14, 2013.

  41. 41.

    McEvoy A, Jeyam M, Ferrier G, Evans CE, Andrew JG. Synergistic effect of particles and cyclic pressure on cytokine production in human monocyte/macrophages: proposed role in periprosthetic osteolysis. Bone. 2002;30(1):171–177.

    CAS  PubMed  Google Scholar 

  42. 42.

    Merkel KD, Erdmann JM, McHugh KP, Abu-Amer Y, Ross FP, Teitelbaum SL. Tumor necrosis factor-alpha mediates orthopedic implant osteolysis. Am J Pathol. 1999;154(1):203–210.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Mjöberg B. Theories of wear and loosening in hip prostheses. Wear-induced loosening vs loosening-induced wear—a review. Acta Orthop Scand. 1994;65(3):361–371.

    PubMed  Google Scholar 

  44. 44.

    Nam D, Bostrom MPG, Fahlgren A. Emerging ideas: Instability-induced periprosthetic osteolysis is not dependent on the fibrous tissue interface. Clin Orthop Relat Res. 2013;471(6):1758–1762.

    PubMed  PubMed Central  Google Scholar 

  45. 45.

    Nam D, Fahlgren A, Dvorzhinskiy A, Madsen R, Ross FP, Bostrom MP. Instability-induced bone resorption is independent of the fibrous tissue layer in a rat model of peri-implant osteolysis. In: Hosptial for Special Surgery Chief Resident Research Presentations. March 8, 2012.

  46. 46.

    Nilsson A, Norgard M, Andersson G, Fahlgren A. Fluid pressure induces osteoclast differentiation comparably to titanium particles but through a molecular pathway only partly involving TNF-alpha. J Cell Biochem. 2012;113(4):1224–1234.

    CAS  PubMed  Google Scholar 

  47. 47.

    Perren SM. Evolution of the internal fixation of long bone fractures. The scientific basis of biological internal fixation: choosing a new balance between stability and biology. J Bone Joint Surg Br. 2002;84(8):1093–1110.

    PubMed  Google Scholar 

  48. 48.

    Robertsson O, Wingstrand H, Kesteris U, Jonsson K, Onnerfalt R. Intracapsular pressure and loosening of hip prostheses. Preoperative measurements in 18 hips. Acta Orthop Scand. 1997;68(3):231–234.

    CAS  PubMed  Google Scholar 

  49. 49.

    Ryd L, Albrektsson BE, Carlsson L, et al. Roentgen stereophotogrammetric analysis as a predictor of mechanical loosening of knee prostheses. J Bone Joint Surg Br. 1995;77(3):377–383.

    CAS  PubMed  Google Scholar 

  50. 50.

    Sakai Y, Balam TA, Kuroda S, et al. CTGF and apoptosis in mouse osteocytes induced by tooth movement. J Dent Res. 2009;88(4):345–350.

    CAS  PubMed  Google Scholar 

  51. 51.

    Sampathkumar K, Jeyam M, Evans CE, Andrew JG. Role of cyclical pressure and particles in the release of M-CSF, chemokines, and PGE2 and their role in loosening of implants. J Bone Joint Surg Br. 2003;85(2):288–291.

    CAS  PubMed  Google Scholar 

  52. 52.

    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(6):849–863.

    CAS  PubMed  Google Scholar 

  53. 53.

    Sims NA, Martin TJ. Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit. Bonekey Rep. 2014;3:481.

    PubMed  PubMed Central  Google Scholar 

  54. 54.

    Skoglund B, Aspenberg P. PMMA particles and pressure—a study of the osteolytic properties of two agents proposed to cause prosthetic loosening. J Orthop Res. 2003;21(2):196–201.

    CAS  PubMed  Google Scholar 

  55. 55.

    Skripitz R, Aspenberg P. Pressure-induced periprosthetic osteolysis: a rat model. J Orthop Res. 2000;18(3):481–484.

    CAS  PubMed  Google Scholar 

  56. 56.

    Søballe K, Hansen ES, B-Rasmussen H, Jørgensen PH, Bünger C. Tissue ingrowth into titanium and hydroxyapatite-coated implants during stable and unstable mechanical conditions. J Orthop Res. 1992;10(2):285–299.

    PubMed  Google Scholar 

  57. 57.

    Srinivasan P, Miller MA, Verdonschot N, Mann KA, Janssen D. Experimental and computational micromechanics at the tibial cement-trabeculae interface. J Biomech. 2016;49(9):1641–1648.

    PubMed  PubMed Central  Google Scholar 

  58. 58.

    Stadelamann VA, Terrier A, Pioletti D-P. Osteoclastogenesis can be mechanically-induced in the peri-implant bone. Biocybern Biomed Eng. 2009;30(1):10–13.

    Google Scholar 

  59. 59.

    Szuszczewicz ES, Schmalzried TP, Petersen TD. Progressive bilateral pelvic osteolysis in a patient with McKee-Farrar metal-metal total hip prostheses. J Arthroplasty. 1997;12(7):819–824.

    CAS  PubMed  Google Scholar 

  60. 60.

    Uhthoff HK, Ferland MA, Côté MG. A possible contribution of undifferentiated cells to post-traumatic osteogenesis. Rev Can Biol. 1975;34(1–2):11–22.

    CAS  PubMed  Google Scholar 

  61. 61.

    Van der Vis HM, Aspenberg P, Marti RK, Tigchelaar W, Van Noorden CJ. Fluid pressure causes bone resorption in a rabbit model of prosthetic loosening. Clin Orthop Relat Res. 1998;(350):201–208.

    Google Scholar 

  62. 62.

    Walter WL, Clabeaux J, Wright TM, Walsh W, Walter WK, Sculco TP. Mechanisms for pumping fluid through cementless acetabular components with holes. J Arthroplasty. 2005;20(8):1042–1048.

    PubMed  Google Scholar 

  63. 63.

    Walter WL, Walter WK, O’Sullivan M. The pumping of fluid in cementless cups with holes. J Arthroplasty. 2004;19(2):230–234.

    PubMed  Google Scholar 

  64. 64.

    van Wijngaarden R, van der Plaat L, Weme RAN, Doets HC, Westerga J, Haverkamp D. Etiopathogenesis of osteolytic cysts associated with total ankle arthroplasty, a histological study. Foot Ankle Surg. 2015;21(2):132–136.

  65. 65.

    Yin C, Jiranek WA, Vaughan P, Cardea JA. Differential messenger ribonucleic acid expression in aggressive versus linear periprosthetic osteolysis. Clin Orthop Rel Res. 1998;(352):95–104.

    Google Scholar 

  66. 66.

    You L, Temiyasathit S, Lee P, et al. Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading. Bone. 2008;42(1):172–179.

    CAS  PubMed  Google Scholar 

  67. 67.

    Zhang Y, Hou C, Yu S, et al. IRAK-M in macrophages around septically and aseptically loosened hip implants. J Biomed Mater Res A. 2012;100(1):261–268.

    PubMed  Google Scholar 

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Correspondence to Benjamin A. McArthur MD.

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Ryan Scully, MD, F. Patrick Ross, PhD, and Anna Falghren, PhD, declare that they have no conflicts of interest. Benjamin A McArthur, MD, reports grants from Orthopedic Research and Education Foundation, during the conduct of the study. Mathias P.G. Bostrom, MD, reports being a paid consultant for Smith & Nephew, outside the submitted work.

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McArthur, B.A., Scully, R., Patrick Ross, F. et al. Mechanically Induced Periprosthetic Osteolysis: A Systematic Review. HSS Jrnl 15, 286–296 (2019).

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  • total hip replacement
  • total knee replacement
  • osteolysis
  • revision total joint replacement
  • aseptic loosening