The Toughness of Cortical Bone and Its Relationship with Age

Toughness is a quantitative measure of bone quality in terms of its susceptibility to fracture. Thus, to elucidate the underlying mechanisms of age-related bone fractures, it is necessary to understand age-related changes in the toughness of bone. The objective of this review is to provide current understanding on the structure–function relationships of cortical bone and its correlation with the toughness of the tissue from the perspective of basic engineering principles. The review is written for the readers in the musculoskeletal research field, who may not have a strong engineering background. For better understanding of toughening mechanisms, this review intends to focus on correlations of the toughness of cortical bone with its constituents and microstructural characteristics. In addition, a special emphasis is placed on age-related changes in the toughness of bone.

[1]  A J Bailey,et al.  Biochemical changes in the collagenous matrix of osteoporotic avian bone. , 1995, The Biochemical journal.

[2]  F. Kaplan,et al.  Osteon morphometry in females with femoral neck fractures. , 1992, Clinical orthopaedics and related research.

[3]  S. Grant,et al.  An Sp1 Binding Site Polymorphism in the COLIA1 Gene Predicts Osteoporotic Fractures in Both Men and Women , 1998, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[4]  M. Freeman,et al.  The role of fatigue in the pathogenesis of senile femoral neck fractures. , 1974, The Journal of bone and joint surgery. British volume.

[5]  Y. Yeni,et al.  Influence of bone composition and apparent density on fracture toughness of the human femur and tibia. , 1998, Bone.

[6]  W. Bonfield,et al.  Orientation dependence of the fracture mechanics of cortical bone. , 1989, Journal of biomechanics.

[7]  G. Reilly,et al.  The effects of damage and microcracking on the impact strength of bone. , 2000, Journal of biomechanics.

[8]  E. Seeman.  Reduced bone formation and increased bone resorption: rational targets for the treatment of osteoporosis , 2003, Osteoporosis International.

[9]  C. M. Agrawal,et al.  Microstructural heterogeneity and the fracture toughness of bone. , 2000, Journal of biomedical materials research.

[10]  W. Bonfield,et al.  Advances in the fracture mechanics of cortical bone. , 1987, Journal of biomechanics.

[11]  C Milgrom,et al.  Aging and matrix microdamage accumulation in human compact bone. , 1995, Bone.

[12]  J A McGeough,et al.  Age-related changes in the tensile properties of cortical bone. The relative importance of changes in porosity, mineralization, and microstructure. , 1993, The Journal of bone and joint surgery. American volume.

[13]  V. A. Gibson,et al.  Collagen fiber organization is related to mechanical properties and remodeling in equine bone. A comparison of two methods. , 1996, Journal of biomechanics.

[14]  G. Reilly,et al.  The development of microcracking and failure in bone depends on the loading mode to which it is adapted. , 1999, The Journal of experimental biology.

[15]  C. M. Agrawal,et al.  Age-related changes in the collagen network and toughness of bone. , 2002, Bone.

[16]  C. M. Agrawal,et al.  Fracture toughness of bone using a compact sandwich specimen: effects of sampling sites and crack orientations. , 1996, Journal of biomedical materials research.

[17]  D. Burr,et al.  Bone Microdamage and Skeletal Fragility in Osteoporotic and Stress Fractures , 1997, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[18]  S. Goldstein,et al.  Age, gender, and bone lamellae elastic moduli , 2000, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[19]  Y. Yeni,et al.  Influence of microdamage on fracture toughness of the human femur and tibia. , 1998, Bone.

[20]  S A Goldstein,et al.  Type I collagen mutation alters the strength and fatigue behavior of Mov13 cortical tissue. , 1997, Journal of biomechanics.

[21]  Paul K. Hansma,et al.  Bone indentation recovery time correlates with bond reforming time , 2001, Nature.

[22]  C. Slemenda,et al.  Age and bone mass as predictors of fracture in a prospective study. , 1988, The Journal of clinical investigation.

[23]  D Vashishth,et al.  Experimental validation of a microcracking-based toughening mechanism for cortical bone. , 2003, Journal of biomechanics.

[24]  J. Broz,et al.  Effects of rehydration state on the flexural properties of whole mouse long bones. , 1993, Journal of biomechanical engineering.

[25]  Roberta Carroll,et al.  Cortical bone senescence and mineral bone density of the humerus , 1983, Calcified Tissue International.

[26]  H. Ranta,et al.  Growth changes of collagen cross-linking, calcium, and water content in bone , 2004, Archives of orthopaedic and traumatic surgery.

[27]  R. Pidaparti,et al.  Experimental investigation of Poisson's ratio as a damage parameter for bone fatigue. , 2002, Journal of biomedical materials research.

[28]  Bruce Martin,et al.  Aging and strength of bone as a structural material , 2005, Calcified Tissue International.

[29]  N. Sasaki,et al.  Viscoelastic properties of bone as a function of water content. , 1995, Journal of biomechanics.

[30]  R. Martin,et al.  The effects of collagen fiber orientation, porosity, density, and mineralization on bovine cortical bone bending properties. , 1993, Journal of biomechanics.

[31]  R. Young,et al.  Crack velocity and the fracture of bone. , 1978, Journal of biomechanics.

[32]  M. Pineri,et al.  Water–collagen interactions: Calorimetric and mechanical experiments , 1978, Biopolymers.

[33]  R. Heaney,et al.  The natural history of vertebral osteoporosis. Is low bone mass an epiphenomenon? , 1992, Bone.

[34]  D Vashishth,et al.  Contribution, development and morphology of microcracking in cortical bone during crack propagation. , 2000, Journal of biomechanics.

[35]  D. Vashishth,et al.  Influence of nonenzymatic glycation on biomechanical properties of cortical bone. , 2001, Bone.

[36]  C. M. Agrawal,et al.  Age Dependence of In Situ Termostability of Collagen in Human Bone , 2003, Calcified Tissue International.

[37]  A. Bailey,et al.  Molecular changes in bone collagen in osteoporosis and osteoarthritis in the elderly , 1999, Experimental Gerontology.

[38]  J. Katz.  Hard tissue as a composite material. I. Bounds on the elastic behavior. , 1971, Journal of biomechanics.

[39]  Y. Yeni,et al.  The influence of bone morphology on fracture toughness of the human femur and tibia. , 1997, Bone.

[40]  P. Goldhaber.  COLLAGEN AND BONE. , 1964, Journal of the American Dental Association.

[41]  D. Burr.  The contribution of the organic matrix to bone's material properties. , 2002, Bone.

[42]  S A Goldstein,et al.  Type‐I collagen mutation compromises the post‐yield behavior of Mov13 long bone , 1996, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[43]  D B Burr,et al.  Alterations to the en bloc basic fuchsin staining protocol for the demonstration of microdamage produced in vivo. , 1995, Bone.

[44]  Glimcher Mj.  The nature of the mineral component of bone and the mechanism of calcification. , 1987 .

[45]  D. Burr,et al.  A hypothetical mechanism for the stimulation of osteonal remodelling by fatigue damage. , 1982, Journal of biomechanics.

[46]  J. Currey,et al.  Mechanical properties of bone tissues with greatly differing functions. , 1979, Journal of biomechanics.

[47]  D. T. Green,et al.  Diabetic and age-related enhancement of collagen-linked fluorescence in cortical bones of rats. , 1994, Life sciences.

[48]  Y. Yeni,et al.  Calculation of porosity and osteonal cement line effects on the effective fracture toughness of cortical bone in longitudinal crack growth. , 2000, Journal of biomedical materials research.

[49]  H. Kuivaniemi,et al.  Mutations in collagen genes: causes of rare and some common diseases in humans , 1991, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[50]  M. Harmand,et al.  Molecular interface characterization in human bone matrix. I. Biochemical and IR spectroscopic studies. , 1993, Biomaterials.

[51]  J. Vahle,et al.  Abnormal bone architecture and biomechanical properties with near-lifetime treatment of rats with PTH. , 2002, Endocrinology.

[52]  R. Robinson.  Bone tissue: composition and function. , 1979, The Johns Hopkins medical journal.

[53]  D P Fyhrie,et al.  Damage type and strain mode associations in human compact bone bending fatigue , 1998, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[54]  D. Krajcinovic,et al.  Simple constitutive model for a cortical bone. , 1987, Journal of biomechanics.

[55]  K. Heiple,et al.  Contribution of collagen and mineral to the elastic-plastic properties of bone. , 1975, The Journal of bone and joint surgery. American volume.

[56]  M. Swain,et al.  Fracture toughness of bovine bone: influence of orientation and storage media. , 2001, Biomaterials.

[57]  M. Glimcher,et al.  Hydroxyl groups in bone mineral. , 1995, Bone.

[58]  W. Bonfield,et al.  Fracture mechanics of bone--the effects of density, specimen thickness and crack velocity on longitudinal fracture. , 1984, Journal of biomechanics.

[59]  P Zioupos,et al.  Exploring the Effects of Hypermineralisation in Bone Tissue by Using an Extreme Biological Example , 2000, Connective tissue research.

[60]  C. M. Agrawal,et al.  Use of a compact sandwich specimen to evaluate fracture toughness and interfacial bonding of bone. , 1994, Journal of applied biomaterials : an official journal of the Society for Biomaterials.

[61]  P. Byers,et al.  Brittle bones--fragile molecules: disorders of collagen gene structure and expression. , 1990, Trends in genetics : TIG.

[62]  D. Burr,et al.  Suppressed Bone Turnover by Bisphosphonates Increases Microdamage Accumulation and Reduces Some Biomechanical Properties in Dog Rib , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[63]  P. Muir,et al.  In vivo matrix microdamage in a naturally occurring canine fatigue fracture. , 1999, Bone.

[64]  N. Ruse,et al.  Fracture toughness of human dentin. , 2003, Journal of biomedical materials research. Part A.

[65]  Peter Zioupos,et al.  Accumulation of in‐vivo fatigue microdamage and its relation to biomechanical properties in ageing human cortical bone , 2001, Journal of microscopy.

[66]  C. M. Agrawal,et al.  The use of dynamic mechanical analysis to assess the viscoelastic properties of human cortical bone. , 2001, Journal of biomedical materials research.

[67]  P Zioupos,et al.  Ageing Human Bone: Factors Affecting its Biomechanical Properties and the Role of Collagen , 2001, Journal of biomaterials applications.

[68]  P Zioupos,et al.  An examination of the micromechanics of failure of bone and antler by acoustic emission tests and Laser Scanning Confocal Microscopy. , 1994, Medical engineering & physics.

[69]  D B Burr,et al.  Resistance to crack growth in human cortical bone is greater in shear than in tension. , 1996, Journal of biomechanics.

[70]  J. Currey,et al.  Effects of differences in mineralization on the mechanical properties of bone. , 1984, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[71]  G Van der Perre,et al.  Development of an above-knee prosthesis equipped with a microcomputer-controlled knee joint: first test results. , 1992, Journal of biomedical engineering.

[72]  W. Huff,et al.  Factors regulating bone maturity and strength in poultry. , 2000, Poultry science.

[73]  C. Milgrom,et al.  Stress fractures , 1991, The American journal of sports medicine.

[74]  S. Weiner,et al.  Rotated plywood structure of primary lamellar bone in the rat: orientations of the collagen fibril arrays. , 1997, Bone.

[75]  D. Moyle,et al.  Fracture properties of bovine tibial bone. , 1986, Journal of biomechanics.

[76]  T. Norman,et al.  Microdamage of human cortical bone: incidence and morphology in long bones. , 1997, Bone.

[77]  M. Pope,et al.  On the fracture toughness of equine metacarpi. , 1979, Journal of biomechanics.

[78]  R M Aspden,et al.  A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. , 2001, The Journal of clinical investigation.

[79]  C. M. Agrawal,et al.  The effects of diabetes mellitus on the material properties of human metatarsal bones. , 1998, The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons.

[80]  D D Moyle,et al.  Work to fracture of canine femoral bone. , 1978, Journal of biomechanics.

[81]  A H Burstein,et al.  Permanent deformation of compact bone monitored by acoustic emission. , 1981, Journal of biomechanics.

[82]  Handschin Rg,et al.  Crystallographic and chemical analysis of human bone apatite (Crista Iliaca). , 1994 .

[83]  A J Bailey,et al.  Collagen cross-links in mineralizing tissues: a review of their chemistry, function, and clinical relevance. , 1998, Bone.

[84]  James Laney Williams,et al.  Videodensitometry of osteons in females with femoral neck fractures , 1993, Calcified Tissue International.

[85]  W. C. Hayes,et al.  Tensile testing of bone over a wide range of strain rates: effects of strain rate, microstructure and density , 1976, Medical and biological engineering.

[86]  Y. Yeni,et al.  Fracture toughness is dependent on bone location--a study of the femoral neck, femoral shaft, and the tibial shaft. , 2000, Journal of biomedical materials research.

[87]  Y. Yeni,et al.  Fracture toughness of human femoral neck: effect of microstructure, composition, and age. , 2000, Bone.

[88]  A. Bailey,et al.  Biochemical changes in the collagen of human osteoporotic bone matrix. , 1993, Connective tissue research.

[89]  W. Bonfield,et al.  Fracture toughness of compact bone. , 1976, Journal of biomechanics.

[90]  T. Dufresne,et al.  Evaluation of Changes in Trabecular Bone Architecture and Mechanical Properties of Minipig Vertebrae by Three‐Dimensional Magnetic Resonance Microimaging and Finite Element Modeling , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[91]  D Vashishth,et al.  Fracture toughness of human bone under tension. , 1995, Journal of biomechanics.

[92]  L. Moro,et al.  Posttranslational Modifications of Bone Collagen Type I are Related to the Function of Rat Femoral Regions , 2000, Calcified Tissue International.

[93]  D D Moyle,et al.  Fracture of human femoral bone. , 1984, Journal of biomechanics.

[94]  Peter Zioupos,et al.  Mechanical properties of nacre and highly mineralized bone , 2001, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[95]  Snyder,et al.  Vertebral structure and strength in vivo and in vitro. Discussion , 1993 .

[96]  A. Hiltner,et al.  Interaction of water with native collagen , 1977, Biopolymers.

[97]  G. Reilly,et al.  Effects of ionizing radiation on the mechanical properties of human bone , 1997, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[98]  P. Christel,et al.  The effects of remodeling on the elastic properties of bone , 2006, Calcified Tissue International.

[99]  Bill Kahler,et al.  Fracture-toughening mechanisms responsible for differences in work to fracture of hydrated and dehydrated dentine. , 2003, Journal of biomechanics.

[100]  C. M. Agrawal,et al.  Effect of Collagen Denaturation on the Toughness of Bone , 2000, Clinical orthopaedics and related research.

[101]  C. Nyssen-Behets,et al.  Structural changes with aging in cortical bone of the human tibia. , 1997, Gerontology.

[102]  P Zioupos,et al.  The effects of ageing and changes in mineral content in degrading the toughness of human femora. , 1997, Journal of biomechanics.

[103]  H. Wahner,et al.  Defining osteoporosis , 1989, Calcified Tissue International.

[104]  V. Kalscheur,et al.  Aging and accumulation of microdamage in canine bone. , 2002, Bone.

[105]  M. Hyttinen,et al.  Do More Highly Organized Collagen Fibrils Increase Bone Mechanical Strength in Loss of Mineral Density After One‐Year Running Training? , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[106]  J. Currey,et al.  The effects of drying and re-wetting on some mechanical properties of cortical bone. , 1988, Journal of biomechanics.

[107]  W. Landis.  The strength of a calcified tissue depends in part on the molecular structure and organization of its constituent mineral crystals in their organic matrix. , 1995, Bone.

[108]  D. Eyre,et al.  Molecular Site Specificity of Pyridinoline and Pyrrole Cross-links in Type I Collagen of Human Bone* , 1996, The Journal of Biological Chemistry.

[109]  W C Hayes,et al.  Age-related differences in post-yield damage in human cortical bone. Experiment and model. , 1996, Journal of biomechanics.

[110]  T. Wright,et al.  Collagen and Bone Strength , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[111]  W. Walsh,et al.  The effect ofin vitro fluoride ion treatment on the ultrasonic properties of cortical bone , 1994, Annals of Biomedical Engineering.

[112]  C. M. Agrawal,et al.  The role of collagen in determining bone mechanical properties , 2001, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[113]  D Vashishth,et al.  Effect of groove on bone fracture toughness. , 1991, Journal of biomechanics.

[114]  K. Singer,et al.  Prediction of thoracic and lumbar vertebral body compressive strength: correlations with bone mineral density and vertebral region. , 1995, Bone.

[115]  S A Goldstein,et al.  Micromechanics of osteonal cortical bone fracture. , 1998, Journal of biomechanical engineering.

[116]  S. Stover,et al.  Osteon pullout in the equine third metacarpal bone: Effects of ex vivo fatigue , 2003, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[117]  H. Oxlund,et al.  Reduced concentration of collagen reducible cross links in human trabecular bone with respect to age and osteoporosis. , 1996, Bone.

[118]  D. Burr,et al.  Contribution of collagen and mineral to the elastic anisotropy of bone , 1994, Calcified Tissue International.

[119]  J. Currey,et al.  Changes in the impact energy absorption of bone with age. , 1979, Journal of biomechanics.

[120]  M. Collazo-Clavell,et al.  Paget's disease is associated with changes in the immunohistochemical distribution of noncollagenous matrix proteins in bone. , 1996, The Journal of clinical endocrinology and metabolism.

[121]  S. Stover,et al.  Equine cortical bone exhibits rising R-curve fracture mechanics. , 2003, Journal of biomechanics.

[122]  T. M. Boyce,et al.  Cortical aging differences and fracture implications for the human femoral neck. , 1993, Bone.

[123]  P Zioupos,et al.  The role of collagen in the declining mechanical properties of aging human cortical bone. , 1999, Journal of biomedical materials research.

[124]  A. Parfitt,et al.  Bone age, mineral density, and fatigue damage , 2005, Calcified Tissue International.

[125]  P. Freisinger,et al.  Collagen fibrils of osteoid in osteogenesis imperfecta: morphometrical analysis of the fibril diameter. , 1993, American journal of medical genetics.

[126]  C. M. Agrawal,et al.  Effects of Collagen Unwinding and Cleavage on the Mechanical Integrity of the Collagen Network in Bone , 2002, Calcified Tissue International.

[127]  M. Panjabi,et al.  Effects of freezing and freeze‐drying on the biomechanical properties of rat bone , 1984, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[128]  H. Lehmann,et al.  Comparative study on the thermostability of collagen I of skin and bone: Influence of posttranslational hydroxylation of prolyl and lysyl residues , 1992, Journal of protein chemistry.

[129]  S Majumdar,et al.  A review of magnetic resonance (MR) imaging of trabecular bone micro-architecture: contribution to the prediction of biomechanical properties and fracture prevalence. , 1998, Technology and health care : official journal of the European Society for Engineering and Medicine.

[130]  Gang Chen,et al.  Radiographic and histologic analyses of stress fracture in rabbit tibias , 1985 .

[131]  D. Cody,et al.  Decrease in canine proximal femoral ultimate strength and stiffness due to fatigue damage. , 1997, Journal of biomechanics.

[132]  P. Fratzl,et al.  Age- and genotype-dependence of bone material properties in the osteogenesis imperfecta murine model (oim). , 2001, Bone.

[133]  M. Cresswell,et al.  Impaired mechanical strength of bone in experimental copper deficiency. , 1993, Annals of nutrition & metabolism.

[134]  E. Wachtel,et al.  The structure of mineralized collagen fibrils. , 1989, Connective tissue research.

[135]  D Vashishth,et al.  Crack growth resistance in cortical bone: concept of microcrack toughening. , 1997, Journal of biomechanics.

[136]  H. Oxlund,et al.  Reduced concentrations of collagen cross-links are associated with reduced strength of bone. , 1995, Bone.

[137]  W C Hayes,et al.  Fracture mechanics parameters for compact bone--effects of density and specimen thickness. , 1977, Journal of biomechanics.

[138]  Structural changes of collagen fibrils in skeletal dysplasias , 1985, Virchows Archiv A.

[139]  Y. Açil,et al.  Glycosylation of human bone collagen I in relation to lysylhydroxylation and fibril diameter. , 1997, Journal of biochemistry.

[140]  C. M. Agrawal,et al.  Changes in the fracture toughness of bone may not be reflected in its mineral density, porosity, and tensile properties. , 1998, Bone.

[141]  John P. Bilezikian,et al.  Principles of Bone Biology , 1996 .

[142]  B. Martin,et al.  Mathematical model for repair of fatigue damage and stress fracture in osteonal bone , 1995, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[143]  T. Tait,et al.  A clinical and biochemical assessment of methotrexate in rheumatoid arthritis , 1994, Clinical Rheumatology.

[144]  B. Manthey,et al.  Three-dimensional confocal images of microdamage in cancellous bone. , 1998, Bone.

[145]  D M Robertson,et al.  Fracture toughness, critical crack length and plastic zone size in bone. , 1978, Journal of biomechanics.

[146]  A L Boskey,et al.  Mineral-matrix interactions in bone and cartilage. , 1992, Clinical orthopaedics and related research.

[147]  D A Smith,et al.  Relations between age, mineral density and mechanical properties of human femoral compacta. , 1976, Acta orthopaedica Scandinavica.

[148]  P. Kronick,et al.  Thermal stabilization of collagen fibers by calcification. , 1996, Connective tissue research.

[149]  W. Walsh,et al.  Compressive properties of cortical bone: mineral-organic interfacial bonding. , 1994, Biomaterials.

[150]  Robinson Ra.  Bone tissue: composition and function. , 1979 .

[151]  P Zioupos,et al.  Changes in the stiffness, strength, and toughness of human cortical bone with age. , 1998, Bone.

[152]  J. Currey.  Physical characteristics affecting the tensile failure properties of compact bone. , 1990, Journal of biomechanics.

[153]  R. Lakes,et al.  Cosserat micromechanics of human bone: strain redistribution by a hydration sensitive constituent. , 1986, Journal of biomechanics.

[154]  W. Hayes,et al.  Relations between tensile impact properties and microstructure of compact bone , 1977, Calcified Tissue Research.

[155]  J. Bollerslev,et al.  Thermal stability of cortical bone collagen in relation to age in normal individuals and in individuals with osteopetrosis. , 1994, Bone.

[156]  J A McGeough,et al.  Age-Related Changes in the Compressive Strength of Cancellous Bone. The Relative Importance of Changes in Density and Trabecular Architecture* , 1997, The Journal of bone and joint surgery. American volume.

[157]  G. Corondan,et al.  Untersuchungen über die Anordnungen des Bindegewebes im Knochen , 1967 .

[158]  W. Huff,et al.  Comparative differences in the composition and biomechanical properties of tibiae of seven- and seventy-two-week-old male and female broiler breeder chickens. , 1999, Poultry science.