[en] Although osteoporotic bone, with low bone mass and deteriorated bone architecture, provides a less favorable mechanical environment than healthy bone for implant fixation, there is no general agreement on the impact of osteoporosis on peri-implant bone (re)modeling, which is ultimately responsible for the long term stability of the bone-implant system. Here, we inserted an implant in a mouse model mimicking estrogen deficiency-induced bone loss and we monitored with longitudinal in vivo micro-computed tomography the spatio-temporal changes in bone (re)modeling and architecture, considering the separate contributions of trabecular, endocortical and periosteal surfaces. Specifically, 12 week-old C57BL/6J mice underwent OVX/SHM surgery; 9 weeks after we inserted special metal-ceramics implants into the 6th caudal vertebra and we measured bone response with in vivo micro-CT weekly for the following 6 weeks. Our results indicated that ovariectomized mice showed a reduced ability to increase the thickness of the cortical shell close to the implant because of impaired peri-implant bone formation, especially at the periosteal surface. Moreover, we observed that healthy mice had a significantly higher loss of trabecular bone far from the implant than estrogen depleted animals. Such behavior suggests that, in healthy mice, the substantial increase in peri-implant bone formation which rapidly thickened the cortex to secure the implant may raise bone resorption elsewhere and, specifically, in the trabecular network of the same bone but far from the implant. Considering the already deteriorated bone structure of estrogen depleted mice, further bone loss seemed to be hindered. The obtained knowledge on the dynamic response of diseased bone following implant insertion should provide useful guidelines to develop advanced treatments for osteoporotic fracture fixation based on local and selective manipulation of bone turnover in the peri-implant region.
Disciplines :
Engineering, computing & technology: Multidisciplinary, general & others
Author, co-author :
Li, Zihui
Kuhn, Gisela
Schirmer, Michael
Müller, Ralph
Ruffoni, Davide ; Université de Liège - ULiège > Département d'aérospatiale et mécanique > Mécanique des matériaux biologiques et bioinspirés
Language :
English
Title :
Impaired bone formation in ovariectomized mice reduces implant integration as indicated by longitudinal in vivo micro-computed tomography
Schulte FA, Ruffoni D, Lambers FM, Christen D, Webster DJ, Kuhn G, et al. Local mechanical stimuli regulate bone formation and resorption in mice at the tissue level. Plos One. 2013; 8(4):e62172. https://doi.org/10.1371/journal.pone.0062172 PMID: 23637993;
Garnero P, SornayRendu E, Chapuy MC, Delmas PD. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res. 1996; 11(3):337–49. https://doi.org/10.1002/jbmr.5650110307 PMID: 8852944
Fratzl P, Gupta HS, Paschalis EP, Roschger P. Structure and mechanical quality of the collagen-mineral nano-composite in bone. J Mater Chem. 2004; 14(14):2115–23. https://doi.org/10.1039/B402005g
Ruffoni D, Fratzl P, Roschger P, Phipps R, Klaushofer K, Weinkamer R. Effect of temporal changes in bone turnover on the bone mineralization density distribution: A computer simulation study. J Bone Miner Res. 2008; 23(12):1905–14. https://doi.org/10.1359/jbmr.080711 PMID: 18665790
Hernandez CJ, Keaveny TM. A biomechanical perspective on bone quality. Bone. 2006; 39(6):1173–81. https://doi.org/10.1016/j.bone.2006.06.001 PMID: 16876493
Farr JN, Khosla S. Skeletal changes through the lifespan-from growth to senescence. Nature Reviews Endocrinology. 2015; 11(9):513–21. https://doi.org/10.1038/nrendo.2015.89 PMID: 26032105
Goldhahn J, Suhm N, Goldhahn S, Blauth M, Hanson B. Influence of osteoporosis on fracture fixation—a systematic literature review. Osteoporosis Int. 2008; 19(6):761–72. https://doi.org/10.1007/s00198-007-0515-9 PMID: 18066697
Ruffoni D, Müller R, van Lenthe GH. Mechanisms of reduced implant stability in osteoporotic bone. Biomech Model Mechan. 2012; 11(3–4):313–23. https://doi.org/10.1007/s10237-011-0312-4 PMID: 21562831
Gabet Y, Kohavi D, Voide R, Mueller TL, Mueller R, Bab I. Endosseous implant anchorage is critically dependent on mechanostructural determinants of pen-implant bone trabeculae. J Bone Miner Res. 2010; 25(3):575–83. https://doi.org/10.1359/jbmr.090808 PMID: 19653813
Basler SE, Traxler J, Muller R, van Lenthe GH. Peri-implant bone microstructure determines dynamic implant cut-out. Med Eng Phys. 2013; 35(10):1442–9. https://doi.org/10.1016/j.medengphy.2013.03. 016 PMID: 23623173
Ruffoni D, Wirth AJ, Steiner JA, Parkinson IH, Müller R, van Lenthe GH. The different contributions of cortical and trabecular bone to implant anchorage in a human vertebra. Bone. 2012; 50(3):733–8. https://doi.org/10.1016/j.bone.2011.11.027 PMID: 22178777
Rocca M, Fini M, Giaveresi G, Aldini NN, Giardino R. Osteointegration of hydroxyapatite-coated and uncoated titanium screws in long-term ovariectomized sheep. Biomaterials. 2002; 23(4):1017–23. https://doi.org/10.1016/s0142-9612(01)00213-7 PMID: 11791904
Marquezan M, Osorio A, Sant’Anna E, Souza MM, Maia L. Does bone mineral density influence the primary stability of dental implants? A systematic review. Clinical Oral Implants Research. 2012; 23 (7):767–74. https://doi.org/10.1111/j.1600-0501.2011.02228.x PMID: 21635560
Marco F, Milena F, Gianluca G, Vittoria O. Peri-implant osteogenesis in health and osteoporosis. Micron. 2005; 36(7–8):630–44. https://doi.org/10.1016/j.micron.2005.07.008 PMID: 16182543
Jenny G, Jauernik J, Bierbaum S, Bigler M, Gratz KW, Rucker M, et al. A systematic review and meta-analysis on the influence of biological implant surface coatings on periimplant bone formation. J Biomed Mater Res A. 2016; 104(11):2898–910. https://doi.org/10.1002/jbm.a.35805 PMID: 27301790
Wang L, Ye T, Deng L, Shao J, Qi J, Zhou Q, et al. Repair of microdamage in osteonal cortical bone adjacent to bone screw. Plos One. 2014; 9(2):e89343. https://doi.org/10.1371/journal.pone.0089343 PMID: 24586702
Recker R, Lappe J, Davies KM, Heaney R. Bone remodeling increases substantially in the years after menopause and remains increased in older osteoporosis patients. J Bone Miner Res. 2004; 19 (10):1628–33. https://doi.org/10.1359/JBMR.040710 PMID: 15355557
Tarantino U, Cerocchi I, Scialdoni A, Saturnino L, Feola M, Celi M, et al. Bone healing and osteoporosis. Aging Clin Exp Res. 2011; 23:62–4. PMID: 21970927
Cheung WH, Miclau T, Chow SKH, Yang FF, Alt V. Fracture healing in osteoporotic bone. Injury. 2016; 47:S21–S6.
Li Z, Kuhn G, von Salis-Soglio M, Cooke SJ, Schirmer M, Müller R, et al. In vivo monitoring of bone architecture and remodeling after implant insertion: The different responses of cortical and trabecular bone. Bone. 2015; 81:468–77. http://dx.doi.org/10.1016/j.bone.2015.08.017. PMID: 26303288
Kettenberger U, Ston J, Thein E, Procter P, Pioletti DP. Does locally delivered Zoledronate influence pen-implant bone formation?—Spatio-temporal monitoring of bone remodeling in vivo. Biomaterials. 2014; 35(37):9995–10006. https://doi.org/10.1016/j.biomaterials.2014.09.005 PMID: 25241159
Kurth AHA, Eberhardt C, Muller S, Steinacker M, Schwarz M, Bauss F. The bisphosphonate ibandronate improves implant integration in osteopenic ovariectomized rats. Bone. 2005; 37(2):204–10. https://doi.org/10.1016/j.bone.2004.12.017 PMID: 15936997
Yamazaki M, Shirota T, Tokugawa Y, Motohashi M, Ohno K, Michi K, et al. Bone reactions to titanium screw implants in ovariectomized animals. Oral Surg Oral Med O. 1999; 87(4):411–8. https://doi.org/10.1016/S1079-2104(99)70239-8
Chatterjee M, Hatori K, Duyck J, Sasaki K, Naert I, Vandamme K. High-frequency loading positively impacts titanium implant osseointegration in impaired bone. Osteoporosis Int. 2015; 26(1):281–90. https://doi.org/10.1007/s00198-014-2824-0 PMID: 25164696
Fini M, Aldini NN, Gandolfi MG, Belmonte MM, Giavaresi G, Zucchini C, et al. Biomaterials for orthopedic surgery in osteoporotic bone: A comparative study in osteopenic rats. Int J Artif Organs. 1997; 20 (5):291–7. PMID: 9209931
Fini M, Giavaresi G, Rimondini L, Giardino R. Titanium alloy osseointegration in cancellous and cortical bone of ovariectomized animals: Histomorphometric and bone hardness measurements. Int J Oral Max Impl. 2002; 17(1):28–37.
Vidigal GM, Groisman M, Gregorio LH, Soares GD. Osseointegration of titanium alloy and HA-coated implants in healthy and ovariectomized animals: a histomorphometric study. Clinical Oral Implants Research. 2009; 20(11):1272–7. https://doi.org/10.1111/j.1600-0501.2009.01739.x PMID: 19832768
Irish J, Virdi AS, Sena K, McNulty MA, Sumner DR. Implant placement increases bone remodeling transiently in a rat model. J Orthop Res. 2013; 31(5):800–6. https://doi.org/10.1002/jor.22294 PMID: 23280449
Ozawa S, Ogawa T, Iida K, Sukotjo C, Hasegawa H, Nishimura RD, et al. Ovariectomy hinders the early stage of bone-implant integration: Histomorphometric, biomechanical, and molecular analyses. Bone. 2002; 30(1):137–43. PMID: 11792576
Schulte FA, Lambers FM, Kuhn G, Müller R. In vivo micro-computed tomography allows direct three-dimensional quantification of both bone formation and bone resorption parameters using time-lapsed imaging. Bone. 2011; 48(3):433–42. https://doi.org/10.1016/j.bone.2010.10.007 PMID: 20950723
Birkhold AI, Razi H, Duda GN, Weinkamer R, Checa S, Willie BM. Mineralizing surface is the main target of mechanical stimulation independent of age: 3D dynamic in vivo morphometry. Bone. 2014; 66:15–25. https://doi.org/10.1016/j.bone.2014.05.013 PMID: 24882735
Lambers FM, Kuhn G, Schulte FA, Koch K, Müller R. Longitudinal Assessment of In Vivo Bone Dynamics in a Mouse Tail Model of Postmenopausal Osteoporosis. Calcified Tissue Int. 2012; 90(2):108–19. https://doi.org/10.1007/s00223-011-9553-6 PMID: 22159822
Webster DJ, Morley PL, van Lenthe GH, Müller R. A novel in vivo mouse model for mechanically stimulated bone adaptation—a combined experimental and computational validation study. Comput Method Biomec. 2008; 11(5):435–41. https://doi.org/10.1080/10255840802078014 PMID: 18612871
Lambers FM, Kuhn G, Weigt C, Koch KM, Schulte FA, Müller R. Bone adaptation to cyclic loading in murine caudal vertebrae is maintained with age and directly correlated to the local micromechanical environment. J Biomech. 2015; 48(6):1179–87. https://doi.org/10.1016/j.jbiomech.2014.11.020 PMID: 25543278
Brouwers JEM, Van Rietbergen B, Huiskes R. No effects of in vivo micro-CT radiation on structural parameters and bone marrow cells in proximal tibia of Wistar rats detected after eight weekly scans. J Orthop Res. 2007; 25(10):1325–32. https://doi.org/10.1002/jor.20439 PMID: 17568420
Willie BM, Birkhold AI, Razi H, Thiele T, Aido M, Kruck B, et al. Diminished response to in vivo mechanical loading in trabecular and not cortical bone in adulthood of female C57Bl/6 mice coincides with a reduction in deformation to load. Bone. 2013; 55(2):335–46. http://dx.doi.org/10.1016/j.bone.2013.04.023. PMID: 23643681
Lambers FM, Schulte FA, Kuhn G, Webster DJ, Müller R. Mouse tail vertebrae adapt to cyclic mechanical loading by increasing bone formation rate and decreasing bone resorption rate as shown by time-lapsed in vivo imaging of dynamic bone morphometry. Bone. 2011; 49(6):1340–50. https://doi.org/10.1016/j.bone.2011.08.035 PMID: 21964411
Lambers FM, Koch K, Kuhn G, Ruffoni D, Weigt C, Schulte FA, et al. Trabecular bone adapts to long-term cyclic loading by increasing stiffness and normalization of dynamic morphometric rates. Bone. 2013; 55(2):325–34. https://doi.org/10.1016/j.bone.2013.04.016 PMID: 23624292
Schulte FA, Lambers FM, Mueller TL, Stauber M, Mueller R. Image interpolation allows accurate quantitative bone morphometry in registered micro-computed tomography scans. Comput Method Biomec. 2014; 17(5):539–48. https://doi.org/10.1080/10255842.2012.699526 PMID: 22746535
Thevenaz P, Ruttimann UE, Unser M. A pyramid approach to subpixel registration based on intensity. Ieee Transactions on Image Processing. 1998; 7(1):27–41. https://doi.org/10.1109/83.650848 PMID: 18267377
Kohler T, Stauber M, Donahue LR, Müller R. Automated compartmental analysis for high-throughput skeletal phenotyping in femora of genetic mouse models. Bone. 2007; 41(4):659–67. https://doi.org/10.1016/j.bone.2007.05.018 PMID: 17662679
Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Müller R. Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res. 2010; 25 (7):1468–86. https://doi.org/10.1002/jbmr.141 PMID: 20533309
Szulc P, Seeman E, Duboeuf F, Sornay-Rendu E, Delmas PD. Bone fragility: Failure of periosteal apposition to compensate for increased endocortical resorption in postmenopausal women. J Bone Miner Res. 2006; 21(12):1856–63. https://doi.org/10.1359/jbmr.060904 PMID: 17002580
Birkhold AI, Razi H, Duda GN, Weinkamer R, Checa S, Willie BM. The Periosteal Bone Surface is Less Mechano-Responsive than the Endocortical. Sci Rep-Uk. 2016; 6. ARTN 23480 https://doi.org/10.1038/srep23480 PMID: 27004741
Namkung-Matthai H, Appleyard R, Jansen J, Lin JH, Maastricht S, Swain M, et al. Osteoporosis influences the early period of fracture healing in a rat osteoporotic model. Bone. 2001; 28(1):80–6. https://doi.org/10.1016/S8756-3282(00)00414-2 PMID: 11165946
Weitzmann MN, Pacifici R. Estrogen deficiency and bone loss: an inflammatory tale. J Clin Invest. 2006; 116(5):1186–94. https://doi.org/10.1172/JCI28550 PMID: 16670759
Cenci S, Weitzmann MN, Roggia C, Namba N, Novack D, Woodring J, et al. Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-alpha. J Clin Invest. 2000; 106(10):1229–37. https://doi.org/10.1172/JCI11066 PMID: 11086024
Weigt C. Interaction of mechanical loading with osteoporosis treatment in ovariectomized mice: Zürich; 2013.
Altman AR, Tseng WJ, de Bakker CMJ, Chandra A, Lan SH, Huh BK, et al. Quantification of skeletal growth, modeling, and remodeling by in vivo micro computed tomography. Bone. 2015; 81:370–9. https://doi.org/10.1016/j.bone.2015.07.037 PMID: 26254742
Lu YT, Boudiffa M, Dall’Ara E, Bellantuono I, Viceconti M. Development of a protocol to quantify local bone adaptation over space and time: Quantification of reproducibility. J Biomech. 2016; 49(10):2095–9. https://doi.org/10.1016/j.jbiomech.2016.05.022 PMID: 27262181
Webster D, Wasserman E, Ehrbar M, Weber F, Bab I, Müller R. Mechanical loading of mouse caudal vertebrae increases trabecular and cortical bone mass-dependence on dose and genotype. Biomech Model Mechan. 2010; 9(6):737–47. https://doi.org/10.1007/s10237-010-0210-1 PMID: 20352279
Verdelis K, Lukashova L, Atti E, Mayer-Kuckuk P, Peterson MG, Tetradis S, et al. MicroCT morphometry analysis of mouse cancellous bone: intra- and inter-system reproducibility. Bone. 2011; 49(3):580–7. https://doi.org/10.1016/j.bone.2011.05.013 PMID: 21621659;
Lukas C, Ruffoni D, Lambers FM, Schulte FA, Kuhn G, Kollmannsberger P, et al. Mineralization kinetics in murine trabecular bone quantified by time-lapsed in vivo micro-computed tomography. Bone. 2013; 56(1):55–60. https://doi.org/10.1016/j.bone.2013.05.005 PMID: 23684803
Jariwala SH, Wee H, Roush EP, Whitcomb TL, Murter C, Kozlansky G, et al. Time course of periimplant bone regeneration around loaded and unloaded implants in a rat model. J Orthop Res. 2016:n/a–n/a. https://doi.org/10.1002/jor.23360 PMID: 27381807.
Parfitt AM. Osteonal and Hemi-Osteonal Remodeling—the Spatial and Temporal Framework for Signal Traffic in Adult Human Bone. J Cell Biochem. 1994; 55(3):273–86. https://doi.org/10.1002/jcb. 240550303 PMID: 7962158
Mueller M, Schilling T, Minne HW, Ziegler R. A Systemic Acceleratory Phenomenon (Sap) Accompanies the Regional Acceleratory Phenomenon (Rap) during Healing of a Bone Defect in the Rat. J Bone Miner Res. 1991; 6(4):401–10. https://doi.org/10.1002/jbmr.5650060412 PMID: 1858523
Funk JF, Krummrey G, Perka C, Raschke MJ, Bail HJ. Distraction Osteogenesis Enhances Remodeling of Remote Bones of the Skeleton: A Pilot Study. Clin Orthop Rel Res. 2009; 467(12):3199–205. https://doi.org/10.1007/s11999-009-0902-y PMID: 19475465
Lambers FM. Functional bone imaging in an in vivo mouse model of bone adaptation, aging and disease: Zürich: ETH; 2011.
Chambers TJ, Evans M, Gardner TN, Turner-Smith A, Chow JW. Induction of bone formation in rat tail vertebrae by mechanical loading. Bone Miner. 1993; 20(2):167–78. PMID: 8453332.
Chow JWM, Jagger CJ, Chambers TJ. Characterization of Osteogenic Response to Mechanical Stimulation in Cancellous Bone of Rat Caudal Vertebrae. Am J Physiol. 1993; 265(2):E340–E7.