Abstract
Small-animal models are useful for the in vivo study of particle-induced osteolysis, the most frequent cause of aseptic loosening after total joint replacement. Microstructural changes associated with particle-induced osteolysis have been extensively explored using two-dimensional (2D) techniques. However, relatively little is known regarding the 3D dynamic microstructure of particle-induced osteolysis. Therefore, we tested micro-computed tomography (micro-CT) as a novel tool for 3D analysis of wear debris-mediated osteolysis in a small-animal model of particle-induced osteolysis. The murine calvarial model based on polyethylene particles was utilized in 14 C57BL/J6 mice randomly divided into two groups. Group 1 received sham surgery, and group 2 was treated with polyethylene particles. We performed 3D micro-CT analysis and histological assessment. Various bone morphometric parameters were assessed. Regression was used to examine the relation between the results achieved by the two methods. Micro-CT analysis provides a fully automated means to quantify bone destruction in a mouse model of particle-induced osteolysis. This method revealed that the osteolytic lesions in calvaria in the experimental group were affected irregularly compared to the rather even distribution of osteolysis in the control group. This is an observation which would have been missed if histomorphometric analysis only had been performed, leading to false assessment of the actual situation. These irregularities seen by micro-CT analysis provide new insight into individual bone changes which might otherwise be overlooked by histological analysis and can be used as baseline information on which future studies can be designed.








References
Silva MJ, Sandell LJ (2002) What’s new in orthopaedic research. J Bone Joint Surg Am 84:1490–1496
Willert HG, Bertram H, Buchhorn GH (1990) Osteolysis in alloarthroplasty of the hip. The role of ultra-high molecular weight polyethylene wear particles. Clin Orthop 258:95–107
Shanbhag AS, Hasselman CT, Rubash HE (1997) The John Charnley Award. Inhibition of wear debris mediated osteolysis in a canine total hip arthroplasty model. Clin Orthop 344:33–43
Merkel KD, Erdmann JM, McHugh KP, Abu-Amer Y, Ross FP, Teitelbaum SL (1999) Tumor necrosis factor α mediates orthopedic implant osteolysis. Am J Pathol 154:203–210
Schwarz EM, Benz EB, Lu AP, Goater JJ, Mollano AV, Rosier RN, Puzas JE, O’Keefe RJ (2000) Quantitative small animal surrogate to evaluate drug efficacy in preventing wear debris-induced osteolysis. J Orthop Res 18:849–855
Von Knoch M, Sprecher C, Barden B, Saxler G, Loer F, Wimmer M (2004) Grösse und Form kommerziell erhältlicher Polyethylenpartikel für in vitro und in vivo Versuche. Z Orthop 142:366–370
Child LM, Goater JJ, O’Keefe RJ, Schwarz EM (2001) Effect of anti-tumor necrosis factor-alpha gene on wear debris-induced osteolysis. J Bone Joint Surg Am 83:1789–1797
Taki N, Tatro JM, Lower R, Goldberg VM, Greenfield EM (2007) Comparison of the roles of IL-1, IL-6, and TNF-α in cell culture and murine models of aseptic loosening. Bone 40:1276–1283
Von Knoch M, Wedemeyer C, Pingsmann A, Von Knoch F, Hilken G, Sprecher C, Henschke F, Barden B, Löer F (2005) A single dose of zoledronic acid markedly decreases particle-induced bone resorption. Biomaterials 26:1803–1808
Wedemeyer C, Von Knoch F, Pingsmann A, Hilken G, Sprecher C, Saxler G, Henschke F, Löer F, Von Knoch M (2005) Stimulation of bone formation by zoledronic acid in particle-induced osteolysis. Biomaterials 26:3719–3725
Schwarz EM, Lu AP, Goater JJ, Benz EB, Kollias G, Rosier RN, Puzas JE, O’Keefe RJ (2000) Tumor necrosis factor-alpha/nuclear transcription factor-kappaB signaling in periprosthetic osteolysis. J Orthop Res 18:472–480
Wedemeyer C, Neuerburg C, Pfeiffer A, Heckelei A, Von Knoch F, Hilken G, Brankamp J, Henschke F, Von Knoch M, Loer F, Saxler G (2007) Polyethylene particle-induced bone resorption in substance P deficient mice. Calcif Tissue Int 80:268–274
Wedemeyer C, Neuerburg C, Pfeiffer A, Bylski D, Heckelei A, von Knoch F, Hilken G, Schinke T, Gosheger G, von Knoch M, Löer F, Saxler G (2007) Polyethylene particle induced bone resorption in alpha-calcitonin gene related peptide deficient mice. J Bone Miner Res 22:1011–1019
Feldkamp LA, Davis LC, Kress JW (1984) Practical cone-beam algorithm. J Opt Soc Am 1:612–619
Zhao S, Yu H, Wang G (2005) A unified framework for exact cone-beam reconstruction formulas. Med Phys 32:1712–1721
Perilli E, Baruffaldi F (2003) Proposal for shared collections of X-ray micro CT datasets of bone specimens. International Conference of Computional Bioengineering, Zaragoza, Spain
Parfitt AM (1988) Bone histomorphometry: proposed system for standardization of nomenclature, symbols, and units. Calcif Tissue Int 42:284–286
Sinha RK, Shanbhag AS, Maloney WJ, Hasselman CT, Rubash HE (1998) Osteolysis: cause and effect. Instr Course Lect 47:307–320
Willert HG, Semlitsch M (1977) Reactions of the articular capsule to wear products of artificial joint prostheses. J Biomed Mater Res 11:157–164
Kobayashi A, Freeman MAR, Bonfield W, Kadoya Y, Yamac T, Al-Saffar N, Scott G, Revell PA (1997) Number of polyethylene particles and osteolysis in total joint replacements. J Bone Joint Surg Br 79:844–848
Schuh A, Thomas P, Holzwarth U, Zeiler G (2004) Bilateral localized osteolysis after cemented total hip replacement. Orthopade 33:727–732
Park JS, Ryu KN, Hong HP, Park YK, Chun YS, Yoo MC (2004) Focal osteolysis in total hip replacement: CT findings. Skeletal Radiol 33:632–640
Uchiyama T, Tanizawa T, Muramatsu H, Endo N, Takahashi HE, Hara T (1997) A morphometric comparison of trabecular structure of human ileum between micro computed tomography and conventional histomorphometry. Calcif Tissue Int 61:493–498
Sran MM, Boyd SK, Cooper DM, Khan KM, Zernicke RF, Oxland TR (2007) Regional trabecular morphology assessed by micro-CT is correlated with failure of aged thoracic vertebrae under a posteroanterior load and may determine the site of fracture. Bone 40:751–757
Kinney JH, Lane NE, Haupt DL (1995) In vivo, three-dimensional microscopy of trabecular bone. J Bone Miner Res 10:264–270
Ruegsegger P, Koller B, Muller R (1996) A microtomographic system for the nondestructive evaluation of bone architecture. Calcif Tissue Int 58:24–29
Mitton D, Cendre E, Roux JP, Arlot ME, Peix G, Rumelhart C, Babot D, Meunier PJ (1998) Mechanical properties of ewe vertebral cancellous bone compared with histomorphometry and high-resolution computed tomography parameters. Bone 22:651–658
Yang SY, Yu H, Gong W, Wu B, Mayton L, Costello R, Wooley PH (2007) Murine model of prosthesis failure for the long-term study of aseptic loosening. J Orthop Res 25:603–611
Manley MT, Capello WN, D’Antonio JA, Edidin AA, Geesink RG (1998) Fixation of acetabular cups without cement in total hip arthroplasty: a comparison of three different implant surfaces at a minimum duration of follow-up of five years. J Bone Joint Surg Am 80:1175–1185
Capello WN, D’Antonio JA, Feinberg JR, Manley MT (1997) Hydroxyapatite-coated total hip femoral components in patients less than fifty years old: clinical and radiographic results after five to eight years of follow up. J Bone Joint Surg Am 79:1023–1029
Acknowledgements
The study was supported by Biomaterialien NRW/Ministerium für Forschung und Wissenschaft. The authors thank Kaye Schreyer for editorial assistance with the manuscript and Priv. Doz. Dr. med. Frank Henschke for preparing the histology.
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Wedemeyer, C., Xu, J., Neuerburg, C. et al. Particle-Induced Osteolysis in Three-Dimensional Micro-Computed Tomography. Calcif Tissue Int 81, 394–402 (2007). https://doi.org/10.1007/s00223-007-9077-2
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DOI: https://doi.org/10.1007/s00223-007-9077-2