Bone microdamage and skeletal fragility in osteoporotic and stress fractures

Burr, David B.; Forwood, Mark R.; Fyhrie, David P.; Martin, R. Bruce; Schaffler, Mitchell B.; Turner, Charles H.

Abstract

The accumulation of bone microdamage has been proposed as one factor that contributes to increased skeletal fragility with age and that may increase the risk for fracture in older women. This paper reviews the current status and understanding of microdamage physiology and its importance to skeletal fragility. Several questions are addressed: Does microdamage exist in vivo in bone? If it does, does it impair bone quality? Does microdamage accumulate with age, and is the accumulation of damage with age sufficient to cause a fracture? The nature of the damage repair mechanism is reviewed, and it is proposed that osteoporotic fracture may be a consequence of a positive feedback between damage accumulation and the increased remodeling space associated with repair.

Links

DOI: 10.1359/jbmr.1997.12.1.6

PubMed: 9240720

ISI: A1997WB37700005

Affiliations

¹Departments of Anatomy and Orthopedic Surgery, Biomechanics and Biomaterials Research Center, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.

²Department of Anatomical Sciences, University of Queensland, Brisbane, Queensland, Australia

³Bone and Joint Center, Henry Ford Hospital, Detroit, Michigan, U.S.A.

⁴Department of Orthopedic Surgery, University of California, Davis, California, U.S.A.

⁵Department of Orthopedic Surgery, Biomechanics and Biomaterials Research Center, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.

History

Received: 1996-01-29

Revised: 1996-06-24

Accepted: 1996-07-23

Online: 1997-01-01

Cited Works (28)

Year	Entry
1990	Schaffler MB, Radin EL, Burr DB. Long-term fatigue behavior of compact bone at low strain magnitude and rate. Bone. 1990;11(5):321-326.
1993	Goldstein SA, Goulet R, McCubbrey D. Measurement and significance of three-dimensional architecture to the mechanical integrity of trabecular bone. Calcif Tiss Int. February 1993;53(suppl 1):S127-S133.
1988	Schaffler MB, Burr DB. Stiffness of compact bone: effects of porosity and density. J Biomech. 1988;21(1):13-16.
1993	Balena R, Toolan BC, Shea M, Markatos A, Myers ER, Lee SC, Opas EE, Seedor JG, Klein H, Frankenfield D, Quartuccio H, Fioravanti C, Clair J, Brown E, Hayes WC, Rodan GA. The effects of 2-year treatment with the aminobisphosphonate alendronate on bone metabolism, bone histomorphometry, and bone strength in ovariectomized nonhuman primates. J Clin Invest. December 1993;92(6):2577-2586.
1960	Frost HM. Presence of microscopic cracks in vivo in bone. Henry Ford Hosp Med Bull. 1960;8:25-35.
1977	Carter DR, Hayes WC. Compact bone fatigue damage, I: residual strength and stiffness. J Biomech. 1977;10(5-6):325-337.
1977	Carter DR, Hayes WC. Compact bone fatigue damage: a microscopic examination. Clin Orthop Relat Res. September 1977;127:265-274.
1993	Mori S, Burr DB. Increased intracortical remodeling following fatigue damage. Bone. March–April 1993;14(2):103-109.
1994	Compston JE. Connectivity of cancellous bone: assessment and mechanical implications. Bone. September–October 1994;15(5):463-466.
1991	Consensus development conference: prophylaxis and treatment of osteoporosis. Am J Med. January 1991;90(1):107-110.
1985	Burr DB, Martin RB, Schaffler MB, Radin EL. Bone remodeling in response to in vivo fatigue microdamage. J Biomech. 1985;18(3):189-200.
1977	Carter DR, Hayes WC. The compressive behavior of bone as a two-phase porous structure. J Bone Joint Surg. 1977;59A(7):954-962.
1996	Pattin CA, Caler WE, Carter DR. Cyclic mechanical property degradation during fatigue loading of cortical bone. J Biomech. January 1996;29(1):69-79.
1988	Rice JC, Cowin SC, Bowman JA. On the dependence of the elasticity and strength of cancellous bone on apparent density. J Biomech. 1988;21(2):155-168.
1989	Forwood MR, Parker AW. Microdamage in response to repetitive torsional loading in the rat tibia. Calcif Tiss Int. July 1989;45(1):47-53.
1988	Hui SL, Slemenda CW, Johnston CC Jr. Age and bone mass as predictors of fracture in a prospective study. J Clin Invest. June 1988;81(6):1804-1809.
1994	Schaffler MB, Pitchford WC, Choi K, Riddle JM. Examination of compact bone microdamage using back-scattered electron microscopy. Bone. September–October 1994;15(5):483-488.
1995	Schaffler MB, Choi K, Milgrom C. Aging and matrix microdamage accumulation in human compact bone. Bone. December 1995;17(6):521-525.
1996	Wenzel TE, Schaffler MB, Fyhrie DP. In vivo trabecular microcracks in human vertebral bone. Bone. August 1996;19(2):89-95.
1990	Jensen KS, Mosekilde L, Mosekilde L. A model of vertebral trabecular bone architecture and its mechanical properties. Bone. 1990;11(6):417-423.
1994	Fyhrie DP, Schaffler MB. Failure mechanisms in human vertebral cancellous bone. Bone. 1994;15(1):105-109.
1994	Greenspan SL, Myers ER, Maitland LA, Resnick NM, Hayes WC. Fall severity and bone mineral density as risk factors for hip fracture in ambulatory elderly. JAMA. January 12, 1994;271(2):128-133.
1995	Burr DB, Hooser M. Alterations to the en bloc basic fuchsin staining protocol for the demonstration of microdamage produced in vivo. Bone. October 1995;17(4):431-433.
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.
1993	Burr DB. Remodeling and the repair of fatigue damage. Calcif Tiss Int. February 1993;53(suppl 1):S75-S81.
1990	Burr DB, Stafford T. Validity of the bulk-staining technique to separate artifactual from in vivo bone microdamage. Clin Orthop Relat Res. November 1990;260:305-308.
1994	Zioupos P, Currey JD. The extent of microcracking and the morphology of microcracks in damaged bone. J Mater Sci. 1994;29(4):978-986.
1998	Burr DB, Turner CH, Naick P, Forwood MR, Ambrosius W, Hasan MS, Pidaparti R. Does microdamage accumulation affect the mechanical properties of bone? J Biomech. April 1998;31(4):337-345.

Cited By (60)

Year	Entry
2001	Arthur Moore TL. Microdamage Accumulation in Bovine Trabecular Bone [PhD thesis]. Cambridge, MA: Massachusetts Institute of Technology; June 2001.
2014	Bradke BS. The Role of Cortical and Cancellous Bone Quality on Vertebral Fragility [PhD thesis]. Troy, NY: Rensselaer Polytechnic Institute; April 2014.
2003	Bredbenner TL. Damage Modeling of Vertebral Trabecular Bone [PhD thesis]. Cleveland, OH: Case Western Reserve University; January 2003.
2010	Fang G, Ji B, Liu XS, Guo XE. Quantification of trabecular bone microdamage using the virtual internal bond model and the individual trabeculae segmentation technique. Comput Methods Biomech Biomed Eng. October 2010;13(5):605-15.
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.
2001	Keaveny TM, Morgan EF, Niebur GL, Yeh OC. Biomechanics of trabecular bone. Ann Rev Biomed Eng. 2001;3:307-333.
2013	Lambers FM, Bouman AR, Rimnac CM, Hernandez CJ. Microdamage caused by fatigue loading in human cancellous bone: relationship to reductions in bone biomechanical performance. PLoS One. December 2013;8(12):e83662.
1998	Martin RB, Burr DB, Sharkey NA. Skeletal Tissue Mechanics. New York, NY: Springer-Verlag; 1998.
2002	Morgan EF-i. The Dependence on Anatomic Site of Trabecular Bone Structure-Function Relationships [PhD thesis]. Berkeley, CA: Berkeley, University of California; 2002.
2006	Nagaraja S. Microstructural Stresses and Strains Associated With Trabecular Bone Microdamage [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; December 2006.
2012	Nikodem A. Correlations between structural and mechanical properties of human trabecular femur bone. Acta Bioeng Biomech. 2012;14(2).
2015	Nicolella DP, Bredbenner TL. Computational analysis of bone fracture. In: Yoganandan N, Nahum AM, Melvin JW, eds. Accidental Injury: Biomechanics and Prevention. 3rd ed. New York: Springer; 2015:183-201.
1999	Reilly GC, Currey JD. The development of microcracking and failure in bone depends on the loading mode to which it is adapted. J Exp Biol. 1999;202:543-552.
2005	Seref-Ferlengez Z, Kennedy OD, Schaffler MB. Bone microdamage, remodeling and bone fragility: how much damage is too much damage? BoneKEy Rep. March 18, 2005;4:644.
2018	Yan C. Effect of Fatigue Loading on Impact Response of Rat Ulna [Master's thesis]. Urbana, IL: University of Illinois at Urbana-Champaign; 2018.
1998	Yeni YN. Fracture Mechanics of Human Cortical Bone: The Relationship of Geometry, Microstructure and Composition With the Fracture of the Tibia, Femoral Shaft and the Femoral Neck [PhD thesis]. Morgantown, WV: West Virginia University; 1998.
2000	Yeni YN, Norman TL. Calculation of porosity and osteonal cement line effects on the effective fracture toughness of cortical bone in longitudinal crack growth. J Biomed Mater Res. September 5, 2000;51(3):504-509.
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.
2001	Zioupos P. Accumulation of in-vivo fatigue microdamage and its relation to biomechanical properties in ageing human cortical bone. J Microsc (Oxford). February 2001;201(pt 2):270-278.
2002	Banse X. When density fails to predict bone strength. Acta Orthop Scand. 2002;73(2)(suppl 303):2-57.
2003	Yeni YN, Hou FJ, Ciarelli T, Vashishth D, Fyhrie DP. Trabecular shear stresses predict in vivo linear microcrack density but not diffuse damage in human vertebral cancellous bone. Annals Biomed Eng. June 2003;31(6):726-732.
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.
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	Norman TL, Yeni YN, Brown CU, Wang Z. Influence of microdamage on fracture toughness of the human femur and tibia. Bone. September 1998;23(3):303-306.
1998	Fazzalari NL, Forwood MR, Manthey BA, Smith K, Kolesik P. Three-dimensional confocal images of microdamage in cancellous bone. Bone. October 1998;23(4):373-378.
1999	Uchiyama T, Tanizawa T, Muramatsu H, Endo N, Takahashi HE, Hara T. Three-dimensional microstructural analysis of human trabecular bone in relation to its mechanical properties. Bone. 1999;25(4):487-491.
2000	Hoffler CE, Moore KE, Kozloff K, Zysset PK, Brown MB, Goldstein SA. Heterogeneity of bone lamellar-level elastic moduli. Bone. June 2000;26(6):603-609.
2000	Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB. Does suppression of bone turnover impair mechanical properties by allowing microdamage accumulation? Bone. July 2000;27(1):13-20.
2001	Mashiba T, Turner CH, Hirano T, Forwood MR, Johnston CC, Burr DB. Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sites in beagles. Bone. May 2001;28(5):524-531.
2007	Hulme PA, Boyd SK, Ferguson SJ. Regional variation in vertebral bone morphology and its contribution to vertebral fracture strength. Bone. December 2007;41(6):946-957.
2006	Hoc T, Henry L, Verdier M, Aubry D, Sedel L, Meunier A. Effect of microstructure on the mechanical properties of Haversian cortical bone. Bone. April 2006;38(4):466-474.
2009	Garrison JG, Slaboch CL, Niebur GL. Density and architecture have greater effects on the toughness of trabecular bone than damage. Bone. 2009;44(5):924-929.
2014	Hernandez CJ, Lambers FM, Widjaja J, Chapa C, Rimnac CM. Quantitative relationships between microdamage and cancellous bone strength and stiffness. Bone. September 2014;66:205-213.
2000	Reilly GC, Currey JD. The effects of damage and microcracking on the impact strength of bone. J Biomech. March 2000;33(3):337-343.
2000	Reilly GC. Observations of microdamage around osteocyte lacunae in bone. J Biomech. September 2000;33(9):1131-1134.
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	Nagaraja S, Couse TL, Guldberg RE. Trabecular bone microdamage and microstructural stresses under uniaxial compression. J Biomech. 2005;38(4):707-716.
2009	Mc Donnell P, Harrison N, Liebschner MAK, Mc Hugh PE. Simulation of vertebral trabecular bone loss using voxel finite element analysis. J Biomech. 2009;42(16):2789-2796.
2011	Wolfram U, Wilke H-J, Zysset PK. Damage accumulation in vertebral trabecular bone depends on loading mode and direction. J Biomech. April 7, 2011;44(7):1164-1169.
2011	Green JO, Nagaraja S, Diab T, Vidakovic B, Guldberg RE. Age-related changes in human trabecular bone: relationship between microstructural stress and strain and damage morphology. J Biomech. 2011;44(12):2279-2285.
2011	Turnbull TL, Gargac JA, Niebur GL, Roeder RK. Detection of fatigue microdamage in whole rat femora using contrast-enhanced micro-computed tomography. J Biomech. September 2, 2011;44(13):2395-2400;
2011	Green JO, Wang J, Diab T, Vidakovic B, Guldberg RE. Age-related differences in the morphology of microdamage propagation in trabecular bone. J Biomech. October 13, 2011;44(15):2659-2666.
2002	Arthur Moore TL, Gibson LJ. Microdamage accumulation in bovine trabecular bone in uniaxial compression. J Biomech Eng. February 2002;124(1):63-71.
2003	Moore TLA, Gibson LJ. Fatigue microdamage in bovine trabecular bone. J Biomech Eng. December 2003;125(6):769-776.
2015	Oftadeh R, Perez-Viloria M, Villa-Camacho JC, Vaziri A, Nazarian A. Biomechanics and mechanobiology of trabecular bone: a review. J Biomech Eng. January 2015;137(1):010802.
1998	Kinney JH, Ladd AJC. The relationship between three-dimensional connectivity and the elastic properties of trabecular bone. J Bone Miner Res. May 1998;13(5):839-845.
2003	Komatsubara S, Mori S, Mashiba T, Ito M, Li J, Kaji Y, Akiyama T, Miyamoto K, Cao Y, Kawanishi J, Norimatsu H. Long‐term treatment of incadronate disodium accumulates microdamage but improves the trabecular bone microarchitecture in dog vertebra. J Bone Miner Res. March 2003;18(3):512-520.
2008	Arlot ME, Burt‐Pichat B, Roux J, Vashishth D, Bouxsein ML, Delmas PD. Microarchitecture influences microdamage accumulation in human vertebral trabecular bone. J Bone Miner Res. 2008;23(10):1613-1618.
1997	Wachtel EF, Keaveny TM. Dependence of trabecular damage on mechanical strain. J Orthop Res. September 1997;15(5):781-787.
1998	Boyce TM, Fyhrie DP, Glotkowski MC, Radin EL, Schaffler MB. Damage type and strain mode associations in human compact bone bending fatigue. J Orthop Res. May 1998;16(3):322-329.
1999	Keaveny TM, Wachtel EF, Kopperdahl DL. Mechanical behavior of human trabecular bone after overloading. J Orthop Res. May 1999;17(3):346-353.
2000	Hoffler CE, Moore KE, Kozloff K, Zysset PK, Goldstein SA. Age, gender, and bone lamellae elastic moduli. J Orthop Res. May 2000;18(3):432-437.
2008	Kosmopoulos V, Keller TS. Predicting trabecular bone microdamage initiation and accumulation using a non-linear perfect damage model. Med Eng Phys. July 2008;30(6):725-732.
2002	Turner CH. Biomechanics of bone: determinants of skeletal fragility and bone quality. Osteoporos Int. February 2002;13(2):97-104.
2003	Burr D. Microdamage and bone strength. Osteoporos Int. September 2003;14(suppl 5):S67-S72.
2008	Chen H, Shoumura S, Emura S, Bunai Y. Regional variations of vertebral trabecular bone microstructure with age and gender. Osteoporos Int. October 2008;19(10):1473-1483.
2012	Slyfield CR Jr. The Biomechanics of Bone Turnover [PhD thesis]. Ithaca, NY: Cornell University; January 2012.
2011	Garrison JG. The Relative Importance of Stress State, Microarchitecture, and Damage Burden in the Failure Behavior of Trabecular Bone [PhD thesis]. Notre Dame, Indiana: University of Notre Dame; April 2011.
2015	Gargac J. Evaluation of Bone Healing, Damage, and Adaptation Using Computational Modeling and Image Processing Techniques [PhD thesis]. Notre Dame, IN: University of Notre Dame; July 2015.
2017	Kreipke TC. Structural, Mechanical, and Biological Relationships of Trabecular Bone in Osteoporosis [PhD thesis]. Notre Dame, IN: University of Notre Dame; April 2017.