Living with cracks:​ damage and repair in human bone

Taylor, David; Hazenberg, Jan G.; Lee, T. Clive

Affiliations

¹Trinity Centre for Bioengineering, Mechanical Engineering Department, Trinity College, Dublin 2, Ireland

²Department of Anatomy, Royal College of Surgeons in Ireland, St. Stephen’s Green, Dublin 2, Ireland

Abstract

Our bones are full of cracks, which form and grow as a result of daily loading activities. Bone is the major structural material in our bodies. Although weaker than many engineering materials, it has one trick that keeps it ahead — it can repair itself. Small cracks, which grow under cyclic stresses by the mechanism of fatigue, can be detected and removed before they become long enough to be dangerous. This article reviews the work that has been done to understand how cracks form and grow in bone, and how they can be detected and repaired in a timely manner. This is truly an interdisciplinary research field, requiring the close cooperation of materials scientists, biologists and engineers.

Links

DOI: 10.1038/nmat1866

PubMed: 17401419

WoS: 000245360000014

Cited Works (43)

Year	Entry
1998	Taylor D. Fatigue of bone and bones: an analysis based on stressed volume. J Orthop Res. March 1998;16(2):163-169.
2005	Nalla RK, Kruzic JJ, Kinney JH, Ritchie RO. Mechanistic aspects of fracture and R-curve behavior in human cortical bone. Biomaterials. January 2005;26(2):217-231.
2005	Qiu S, Rao DS, Fyhrie DP, Palnitkar S, Parfitt AM. The morphological association between microcracks and osteocyte lacunae in human cortical bone. Bone. July 2005;37(1):10-15.
2003	Malik CL, Stover SM, Martin RB, Gibeling JC. Equine cortical bone exhibits rising R-curve fracture mechanics. J Biomech. February 2003;36(2):191-198.
1993	Mori S, Burr DB. Increased intracortical remodeling following fatigue damage. Bone. March–April 1993;14(2):103-109.
2004	Nalla RK, Kruzic JJ, Kinney JH, Ritchie RO. Effect of aging on the toughness of human cortical bone: evaluation by R-curves. Bone. December 2004;35(6):1240-1246.
2006	Nyman JS, Roy A, Shen X, Acuna RL, Tyler JH, Wang X. The influence of water removal on the strength and toughness of cortical bone. J Biomech. 2006;39(5):931-938.
1997	Mori S, Harruff R, Ambrosius W, Burr DB. Trabecular bone volume and microdamage accumulation in the femoral heads of women with and without femoral neck fractures. Bone. December 1997;21(6):521-526.
2005	Nyman JS, Reyes M, Wang X. Effect of ultrastructural changes on the toughness of bone. Micron. October–December 2005;36(7-8):566-582.
2003	Noble BS, Peet N, Stevens HY, Brabbs A, Mosley JR, Reilly GC, Reeve J, Skerry TM, Lanyon LE. Mechanical loading: biphasic osteocyte survival and targeting of osteoclasts for bone destruction in rat cortical bone. Am J Physiol Cell Physiol. April 2003;284(4):C934-C943.
1979	Currey JD. Mechanical properties of bone tissues with greatly differing functions. J Biomech. 1979;12(4):313-319.
2005	O'Brien FJ, Taylor D, Lee TC. The effect of bone microstructure on the initiation and growth of microcracks. J Orthop Res. March 2005;23(2):475-480.
2003	Lee TC, Mohsin S, Taylor D, Parkesh R, Gunnlaugsson T, O'Brien FJ, Giehl M, Gowin W. Detecting microdamage in bone. J Anat. August 2003;203(2):161-172.
2003	O’Brien FJ, Taylor D, Lee TC. Microcrack accumulation at different intervals during fatigue testing of compact bone. J Biomech. July 2003;36(7):973-980.
2002	O’Brien FJ, Taylor D, Lee TC. An improved labelling technique for monitoring microcrack growth in compact bone. J Biomech. April 2002;35(4):523-526.
2003	Yeni YN, Fyhrie DP. A rate-dependent microcrack-bridging model that can explain the strain rate dependency of cortical bone apparent yield strength. J Biomech. September 2003;36(9):1343-1353.
2005	Nalla RK, Stölken JS, Kinney JH, Ritchie RO. Fracture in human cortical bone: local fracture criteria and toughening mechanisms. J Biomech. July 2005;38(7):1517-1525.
1994	Prendergast P, Taylor D. Prediction of bone adaptation using damage accumulation. J Biomech. August 1994;27(8):1067-1076.
1995	Schaffler MB, Choi K, Milgrom C. Aging and matrix microdamage accumulation in human compact bone. Bone. December 1995;17(6):521-525.
1992	Choi K, Goldstein SA. A comparison of the fatigue behavior of human trabecular and cortical bone tissue. J Biomech. 1992;25(12):1371-1381.
2003	Boyde A. The real response of bone to exercise. J Anat. August 2003;203(2):173-189.
2004	Sobelman OS, Gibeling JC, Stover SM, Hazelwood SJ, Yeh OC, Shelton DR, Martin RB. Do microcracks decrease or increase fatigue resistance in cortical bone? J Biomech. September 2004;37(9):1295-1303.
2003	Burger EH, Klein-Nulend J, Smit TH. Strain-derived canalicular fluid flow regulates osteoclast activity in a remodelling osteon: a proposal. J Biomech. October 2003;36(10):1453-1459.
2003	Taylor D, Lee TC. Microdamage and mechanical behaviour: predicting failure and remodelling in compact bone. J Anat. August 2003;203(2):203-211.
1982	Martin RB, Burr DB. A hypothetical mechanism for the stimulation of osteonal remodelling by fatigue damage. J Biomech. 1982;15(3):137-139.
2002	Burr DB. Targeted and nontargeted remodeling. Bone. January 2002;30(1):2-4.
2000	Verborgt O, Gibson GJ, Schaffler MB. Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo. J Bone Miner Res. January 2000;15(1):60-67.
1993	Burr DB, Martin RB. Calculating the probability that microcracks initiate resorption spaces. J Biomech. April–May 1993;26(4-5):613-616.
1984	Currey JD. Effects of differences in mineralization on the mechanical properties of bone. Philos Trans R Soc Lond B Biol Sci. February 13, 1984;304(1121):509-518.
1998	Fazzalari NL, Forwood MR, Smith K, Manthey BA, Herreen P. Assessment of cancellous bone quality in severe osteoarthrosis: bone mineral density, mechanics, and microdamage. Bone. 1998;22(4):381-388.
1998	Bentolila V, Boyce TM, Fyhrie DP, Drumb R, Skerry TM, Schaffler MB. Intracortical remodeling in adult rat long bones after fatigue loading. Bone. September 1998;23(3):275-281.
2001	Hazelwood SJ, Martin RB, Rashid MM, Rodrigo JJ. A mechanistic model for internal bone remodeling exhibits different dynamic responses in disuse and overload. J Biomech. March 2001;34(3):299-308.
2002	Turner CH, Robling AG, Duncan RL, Burr DB. Do bone cells behave like a neuronal network? Calcif Tiss Int. June 2002;70(6):435-442.
2003	Heaney RP. Is the paradigm shifting? Bone. October 2003;33(4):457-465.
1999	Zioupos P, Currey JD, Hamer AJ. The role of collagen in the declining mechanical properties of aging human cortical bone. J Biomed Mater Res. May 1999;A45(2):108-116.
2000	Vashishth D, Koontz J, Qiu SJ, Lundin-Cannon D, Yeni YN, Schaffler MB, Fyhrie DP. In vivo diffuse damage in human vertebral trabecular bone. Bone. February 2000;26(2):147-152.
2003	Vashishth D, Tanner KE, Bonfield W. Experimental validation of a microcracking-based toughening mechanism for cortical bone. J Biomech. January 2003;36(1):121-124.
1960	Frost HM. Presence of microscopic cracks in vivo in bone. Henry Ford Hosp Med Bull. 1960;8(1):25-35.
1995	Martin B. Mathematical model for repair of fatigue damage and stress fracture in osteonal bone. J Orthop Res. May 1995;13(3):309-316.
2001	Akkus O, Rimnac CM. Cortical bone tissue resists fatigue fracture by deceleration and arrest of microcrack growth. J Biomech. June 2001;34(6):757-764.
2000	Huiskes R, Ruimerman R, van Lenthe GH, Janssen JD. Effects of mechanical forces on maintenance and adaptation of form in trabecular bone. Nature. June 8, 2000;405(6787):704-706.
2006	Tsuji K, Bandyopadhyay A, Harfe BD, Cox K, Kakar S, Gerstenfeld L, Einhorn T, Tabin CJ, Rosen V. BMP2 activity, although dispensable for bone formation, is required for the initiation of fracture healing. Nat Genet. December 2006;38(12):1424-1429.
2000	Lee TC, Staines A, Taylor D. Bone adaptation to load: microdamage as a stimulus for bone remodelling. J Anat. December 2000;201(6):437-446.

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Year	Entry
2011	Wang R, Gupta HS. Deformation and fracture mechanisms of bone and nacre. Ann Rev Mater Res. August 2011;41:41-73.
2019	Ampaw E, Owoseni TA, Du F, Pinilla N, Obayemi J, Hu J, Nigay P-M, Nzihou A, Uzonwanne V, Zebaze-Kana MG, Dewoolkar M, Tan T, Soboyejo W. Compressive deformation and failure of trabecular structures in a turtle shell. Acta Biomater. October 1, 2019;97:535-543.
2010	Launey ME, Buehler MJ, Ritchie RO. On the mechanistic origins of toughness in bone. Ann Rev Mater Sci. 2010;40:25-53.
2008	Shen ZL, Dodge MR, Kahn H, Ballarini R, Eppell SJ. Stress-strain experiments on individual collagen fibrils. Biophys J. October 2008;95(8):3956-3963.
2008	Ritchie RO, Koester KJ, Ionova S, Yao W, Lane NE, Ager JW III. Measurement of the toughness of bone: a tutorial with special reference to small animal studies. Bone. November 2008;43(5):798-812.
2015	Wagermaier W, Klaushofer K, Fratzl P. Fragility of bone material controlled by internal interfaces. Calcif Tiss Int. September 2015;97(3):201-212.
2017	Rodriguez-Florez N, Carriero A, Shefelbine SJ. The use of XFEM to assess the influence of intra-cortical porosity on crack propagation. Comput Methods Biomech Biomed Eng. 2017;20(4):385-392.
2014	Peyrin F, Dong P, Pacureanu A, Langer M. Micro- and nano-CT for the study of bone ultrastructure. Curr Osteoporos Rep. December 2014;12(4):465-474.
2020	Milovanovic P, Busse B. Phenomenon of osteocyte lacunar mineralization: indicator of former osteocyte death and a novel marker of impaired bone quality? Endocr Connect. April 2020;9(4):R70-R80.
2020	Soni A, Kumar S, Kumar N. Effect of parametric uncertainties on fracture behavior of cortical bone using XIGA. Eng Fract Mech. June 15, 2020;233:107079.
2022	Buccino F, Bagherifard S, D'Amico L, Zagra L, Banfi G, Tromba G, Vergani LM. Assessing the intimate mechanobiological link between human bone micro-scale trabecular architecture and micro-damages. Eng Fract Mech. July 2022;270:108582.
2018	Marco M, Belda R, Miguélez MH, Giner E. A heterogeneous orientation criterion for crack modelling in cortical bone using a phantom-node approach. Finite Elem Anal Des. July 2018;146:107-117.
2020	Mirzaali MJ, Libonati F, Böhm C, Rinaudo L, Cesana BM, Ulivieri FM, Vergani L. Fatigue-caused damage in trabecular bone from clinical, morphological and mechanical perspectives. Int J Fatigue. April 2020;133:105451.
2009	Budyn É, Hoc T. Analysis of micro fracture in human Haversian cortical bone under transverse tension using extended physical imaging. Int J Num Meth Eng. 2009;82(8):940-965.
2011	Mischinski S, Ural A. Finite element modeling of microcrack growth in cortical bone. J Appl Mech. July 2011;78(4):041016.
2021	Frank M, Fischer J-T, Thurner PJ. Microdamage formation in individual bovine trabeculae during fatigue testing. J Biomech. January 22, 2021;115:110131.
2010	Diez‐Perez A, Güerri R, Nogues X, Cáceres E, Peña MJ, Mellibovsky L, Randall C, Bridges D, Weaver JC, Proctor A, Brimer D, Koester KJ, Ritchie RO, Hansma PK. Microindentation for in vivo measurement of bone tissue mechanical properties in humans. J Bone Miner Res. 2010;25(8):1877-1885.
2012	Currey JD. The structure and mechanics of bone. J Mater Sci. January 2012;47(1):41-54.
2012	Yin L, Venkatesan S, Webb D, Kalyanasundaram S, Qin Q-H. 2D and 3D mapping of microindentations in hydrated and dehydrated cortical bones using confocal laser scanning microscopy. J Mater Sci. May 2012;47(10):4432-4438.
2011	Hartmann MA, Dunlop JWC, Bréchet YJM, Fratzl P, Weinkamer R. Trabecular bone remodelling simulated by a stochastic exchange of discrete bone packets from the surface. J Mech Behav Biomed Mater. August 2011;4(6):879-887.
2021	Ma Z, Qiang Z, Zeng K, Xiao J, Zhou L, Zu L, Zhao H, Ren L. Prediction of cross section fracture path of cortical bone through nanoindentation array. J Mech Behav Biomed Mater. April 2021;116:104303.
2020	Hart NH, Newton RU, Tan2 J, Rantalainen T, Chivers P, Siafarikas A, Nimphius S. Biological basis of bone strength: anatomy, physiology and measurement. J Musculoskel Neuron Interact. September 2020;20(3):347-371.
2008	Gupta HS, Zioupos P. Fracture of bone tissue: the ‘hows’ and the ‘whys’. Med Eng Phys. December 2008;30(10):1209-1226.
2012	Russell NA, Pelletier MH, Bruce WJ, Walsh WR. The effect of gamma irradiation on the anisotropy of bovine cortical bone. Med Eng Phys. October 2012;34(8):1117-1122.
2007	Buehler MJ. Molecular nanomechanics of nascent bone: fibrillar toughening by mineralization. Nanotechnology. July 25, 2007;18(9):295102.
2013	Nair AK, Gautieri A, Chang S-W, Buehler MJ. Molecular mechanics of mineralized collagen fibrils in bone. Nat Commun. 2013;r:1724.
2008	Koester KJ, Ager JW III, Ritchie RO. The true toughness of human cortical bone measured with realistically short cracks. Nat Mater. August 2008;7(8):672-677.
2009	Ritchie R, Buehler M, Hansma P. Plasticity and toughness in bone. Phys Today. June 2009;62(6):41-47.
2011	Larrue A, Rattner A, Peter Z-A, Olivier C, Laroche N, Vico L, Peyrin F. Synchrotron radiation micro-CT at the micrometer scale for the analysis of the three-dimensional morphology of microcracks in human trabecular bone. PLoS One. 2011;6(7):e21297.
2016	Torres AM, Matheny JB, Keaveny TM, Taylor D, Rimnac CM, Hernandez CJ. Material heterogeneity in cancellous bone promotes deformation recovery after mechanical failure. Proc Natl Acad Sci USA. March 15, 2016;113(11):2892-2897.
2010	Shen ZL. Tensile Mechanical Properties of Isolated Collagen Fibrils Obtained by Microelectromechanical Systems Technology [PhD thesis]. Cleveland, OH: Case Western Reserve University; August 2010.
2015	Brock GR Jr. Changes in Bone Tissue Properties With Osteoporosis Treatment [PhD thesis]. Ithaca, NY: Cornell University; January 2015.
2017	Matheny JB. Interactions Between Bone Remodeling and Microdamage in Cancellous Bone [PhD thesis]. Ithaca, NY: Cornell University; August 2017.
2018	Chen JTH. Alterations in Bone Tissue Properties With Parathyroid Hormone Treatment [PhD thesis]. Ithaca, NY: Cornell University; May 2018.
2018	Torres AM. Fatigue Behavior of Cancellous Bone, Microdamage Accumulation, and Biologically Inspired Cellular Solids [PhD thesis]. Ithaca, NY: Cornell University; August 2018.
2014	Seref-Ferlengez Z. Diffused Microdamage in Bone Vivo: Structural and Mechanical Bases of Repair [PhD thesis]. New York, NY: The City University of New York; 2014.
2022	Goff E. Osteocyte Lacunar Biomarkers in Human Rare Bone Diseases [PhD thesis]. Swiss Federal Institute of Technology Zürich; 2022.
2022	Peruzzi CRP. Nanoscale Deformation Mechanisms and Yield Prediction of Lamellar Bone [PhD thesis]. Swiss Federal Institute of Technology Zürich; 2022.
2015	Rodriguez-Florez N. Mechanics of Cortical Bone: Exploring the Micro- and Nano-Scale [PhD thesis]. Imperial College London; January 2015.
2012	Pacureanu AJ. Imaging the Bone Cell Network With Nanoscale Synchrotron Computed Tomography [PhD thesis]. Institut national des sciences appliquées de Lyon (INSA Lyon); 2012.
2022	Rahovich P. Effects of Bone Structural Unit (BSU) Geometry and Material Properties on Crack Growth Through Idealized Trabecular Microstructures [Master's thesis]. Sudbury, ON: Laurentian University; 2022.
2019	Gustafsson A. The Role of Microstructure for Crack Propagation in Cortical Bone [PhD thesis]. Lund, Sweden: Lund University; December 2019.
2011	Garrison JG. The Relative Importance of Stress State, Microarchitecture, and Damage Burden in the Failure Behavior of Trabecular Bone [PhD thesis]. University of Notre Dame; April 2011.
2011	Ross RD. Functionalized Gold Nanoparticles as Damage-Specific X-Ray Computed Tomography Contrast Agents in Bone Tissue [PhD thesis]. University of Notre Dame; November 2011.
2013	Turnbull TL. The Spatial Distribution of Fatigue Microdamage Accumulation in Cortical Bone and Factors Influencing Fracture Risk [PhD thesis]. University of Notre Dame; July 2013.
2018	Dominguez VM. Defining Bone Quality: Cortical Microdamage and Its Contribution to Fracture Risk in the Human Rib [PhD thesis]. The Ohio State University; 2018.
2012	Sun X. Mechanically Induced Calcium Efflux from Bone Matrix Stimulates Osteoblasts [PhD thesis]. Purdue University; May 2012.
2011	Wulliamoz PM. Micromechanical Modelling of Normal, Drug Treated and Osteoporotic Bone Using Scanning Acoustic Microsopy and Finite Element Analysis [PhD thesis]. Trinity College Dublin; December 2011.
2021	Frank M. Mechanical Characterization of Individual Trabeculae [PhD thesis]. Vienna University of Technology; February 2021.
2011	Ebacher V. Experimental Study of Deformation and Microcracking in Human Cortical Bone [PhD thesis]. Vancouver, BC: University of British Columbia; May 2011.
2016	Firminger CR. Effects of Minimalist Footwear and Stride Length Reduction on Metatarsal Strains and the Probability of Stress Fracture in Running [Master's thesis]. Calgary, AB: University of Calgary; July 2016.
2017	Fung A. Experimental Validation of Finite Element Predicted Bone Strain in the Human Metatarsal [Master's thesis]. Calgary, AB: University of Calgary; April 2017.
2016	Arango Villegas C. Study of the Mechanical Behavior of Cortical Bone Microstructure by the Finite Element Method [PhD thesis]. Universität Politècnica de València; May 2016.