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Fracture, aging, and disease in bone

Published online by Cambridge University Press:  01 August 2006

J.W. Ager III ,
G. Balooch  and
R.O. Ritchie
J.W. Ager III
Affiliation:
Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720
G. Balooch
Affiliation:
Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720; and Department of Preventive & Restorative Dental Sciences, University of California, San Francisco, California 94143
R.O. Ritchie*
Affiliation:
Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720; and Department of Materials Science and Engineering, University of California, Berkeley, California 94720
*
a) Address all correspondence to this author. e-mail: RORitchie@lbl.gov
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Abstract

From a public health perspective, developing a detailed mechanistic understanding of the well-known increase with age in fracture risk of human bone is essential. This also represents a challenge from materials science and fracture mechanics viewpoints. Bone has a complex, hierarchical structure with characteristic features ranging from nanometer to macroscopic dimensions; it is therefore significantly more complex than most engineering materials. Nevertheless, by examining the micro-/nanostructural changes accompanying the process of aging using appropriate multiscale experimental methods and relating them to fracture mechanics data, it is possible to obtain a quantitative picture of how bone resists fracture. As human cortical bone exhibits rising ex vivo crack-growth resistance with crack extension, its fracture toughness must be evaluated in terms of resistance-curve (R-curve) behavior. While the crack initiation toughness declines with age, the more striking finding is that the crack-growth toughness declines even more significantly and is essentially absent in bone from donors exceeding 85 years in age. To explain such an age-induced deterioration in the toughness of bone, we evaluate its fracture properties at multiple length scales, specifically at the molecular and nano dimensions using vibrational spectroscopies, at the microscale using electron microscopy and hard/soft x-ray computed tomography, and at the macroscale using R-curve measurements. We show that the reduction in crack-growth toughness is associated primarily with a degradation in the degree of extrinsic toughening, in particular involving crack bridging, and that this occurs at relatively coarse size scales in the range of tens to hundreds of micrometers. Finally, we briefly describe how specific clinical treatments, e.g., with steroid hormones to treat various inflammatory conditions, can prematurely damage bone, thereby reducing its fracture resistance, whereas regulating the level of the cytokine Transforming Growth Factor-β can offer significant improvements in the stiffness, strength, and toughness of bone and as such may be considered a therapeutic target to treat increased bone fragility induced by aging, drugs, and disease.

Keywords

BiologicalBoneFracture
Type
Reviews
Information
Journal of Materials Research , Volume 21 , Issue 8 , August 2006 , pp. 1878 - 1892
Copyright
Copyright © Materials Research Society 2006

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References

REFERENCES

1.Jennings, A.G., de Boer, P.: Should we operate on nonagenarians with hip fractures? Injury 30, 169 (1999).CrossRefGoogle ScholarPubMed
2.Heaney, R.: Is the paradigm shifting? Bone 33, 457 (2003).CrossRefGoogle ScholarPubMed
3.Miller, P.D., Hochberg, M.C., Wehren, L.E., Ross, P.D., Wasnich, R.D.: How useful are measures of BMD and bone turnover? Curr. Med. Res. Opin. 21, 545 (2005).CrossRefGoogle ScholarPubMed
4.Hui, S.L., Slemenda, C.W., Johnston, C.C.: Age and bone mass as predictors of fracture in a prospective study. J. Clin. Invest. 81, 1804 (1988).CrossRefGoogle ScholarPubMed
5.Aspray, T.J., Prentice, A., Cole, T.J., Sawo, Y., Reeve, J., Francis, R.M.: Low bone mineral content is common but osteoporotic fractures are rare in elderly rural Gambian women. J. Bone Miner. Res. 11, 1019 (1996).CrossRefGoogle ScholarPubMed
6.Burstein, A., Reilly, D., Martens, M.: Aging of bone tissue: Mechanical properties. J. Bone Joint Surg. 58A, 82 (1976).CrossRefGoogle Scholar
7.Zioupos, P., Currey, J.D.: Changes in the stiffness, strength, and toughness of human cortical bone with age—An underexplored frontier. Bone 22, 57 (1998).CrossRefGoogle Scholar
8.Yeni, Y.N., Norman, T.L.: Fracture toughness of human femoral neck: Effect of microstructure, composition, and age. Bone 26, 499 (2000).CrossRefGoogle ScholarPubMed
9.Akkus, O., Adar, F., Schaffler, M.B.: Age-related changes in physicochemical properties of mineral crystals are related to impaired mechanical function of cortical bone. Bone 34, 443 (2004).CrossRefGoogle ScholarPubMed
10.Nalla, R.K., Kruzic, J.J., Kinney, J.H., Ritchie, R.O.: Effect of aging on the toughness of human cortical bone: Evaluation by R-curves. Bone 35, 1240 (2004).CrossRefGoogle ScholarPubMed
11.Rho, J-Y., Kuhn-Spearing, L., Zioupos, P.: Mechanical properties and the hierarchical structure of bone. Med. Eng. Phys. 20, 92 (1998).CrossRefGoogle ScholarPubMed
12.Weiner, S., Wagner, H.D.: The material bone: Structure-mechanical function relations. Annu. Rev. Mater. Sci. 28, 271 (1998).CrossRefGoogle Scholar
13.Eyre, D.R., Paz, M.A., Gallop, P.M.: Cross-linking in collagen and elastin. Annu. Rev. Biochem. 53, 717 (1984).CrossRefGoogle ScholarPubMed
14.Knott, L., Bailey, A.J.: Collagen cross-links in mineralizing tissues: A review of their chemistry, function, and clinical relevance. Bone 22, 181 (1998).CrossRefGoogle ScholarPubMed
15.Veis, A.: Collagen fibrallar structure in mineralized and nonmineralized tissues. Curr. Opin. Solid State Mater. Sci. 2, 370 (1997).CrossRefGoogle Scholar
16.Currey, J.D.: Osteons in biomechanical literature. J. Biomech. 15, 717 (1982).CrossRefGoogle ScholarPubMed
17.Nalla, R.K., Kruzic, J.J., Kinney, J.H., Ritchie, R.O.: Mechanistic aspects of fracture and R-curve behavior in human cortical bone. Biomaterials 26, 217 (2005).CrossRefGoogle ScholarPubMed
18.Lee, T.C., Staines, A., Taylor, D.: Bone adaptation to load: Microdamage as a stimulus for bone remodeling. J. Anat. 201, 437 (2002).CrossRefGoogle Scholar
19.Bonfield, W.: Advances in the fracture mechanics of cortical bone. J. Biomech. 20, 1071 (1987).CrossRefGoogle ScholarPubMed
20.Norman, T.L., Vashishth, D., Burr, D.B.: Fracture toughness of human bone under tension. J. Biomech. 28, 309 (1995).CrossRefGoogle ScholarPubMed
21.Wang, X.D., Masilamani, N.S., Mabrey, J.D., Alder, M.E., Agrawal, C.M.: Changes in the fracture toughness of bone may not be reflected in its mineral density, porosity, and tensile properties—Effects of sampling sites and crack orientations. Bone 23, 67 (1998).CrossRefGoogle ScholarPubMed
22.Brown, C.U., Yeni, Y.N., Norman, T.L.: Fracture toughness is dependent on bone location- A study of the femoral neck, femoral shaft, and the tibial shaft. J. Biomed. Mater. Res. 49, 380 (2000).3.0.CO;2-W>CrossRefGoogle Scholar
23.Phelps, J.B., Hubbard, G.B., Wang, X., Agrawal, C.M.: Microstructural heterogeneity and the fracture toughness of bone. J. Biomed. Mater. Res. 51, 735 (2000).3.0.CO;2-G>CrossRefGoogle ScholarPubMed
24.Lucksanambool, P., Higgs, W.A.J., Higgs, R.J.E.D., Swain, M.W.: Fracture toughness of bovine bone: Influence of orientation and storage media. Biomaterials 22, 3127 (2001).CrossRefGoogle Scholar
25.Behiri, J.C., Bonfield, W.: Fracture mechanics of bone—The effects of density, specimen thickness, and crack velocity on longitudinal fracture. J. Biomech. 22, 863 (1989).CrossRefGoogle Scholar
26.Ritchie, R.O.: Mechanisms of fatigue-crack propagation in metals, ceramics and composites: Role of crack tip shielding. Mater. Sci. Eng. 103, 15 (1988).CrossRefGoogle Scholar
27.Evans, A.G.: Perspective on the development of high-toughness ceramics. J. Am. Ceram. Soc. 73, 187 (1990).CrossRefGoogle Scholar
28.Ritchie, R.O.: Mechanisms of fatigue-crack propagation in ductile and brittle solids. Int. J. Fract. 100, 55 (1999).CrossRefGoogle Scholar
29.Steinbrech, R., Knehans, R., Schaawächter, W.: Increase of crack resistance during slow crack growth in Al2O3 bend specimens. J. Mater. Sci. 18, 265 (1983).CrossRefGoogle Scholar
30.Swanson, P.L., Fairbanks, C.J., Lawn, B.R., Mai, Y-W., Hockey, B.J.: Crack-interface grain bridging as a fracture resistance mechanism in ceramics: I. Experimental study on alumina. J. Am. Ceram. Soc. 70, 279 (1987).CrossRefGoogle Scholar
31.Mai, Y-W., Lawn, B.R.: Crack–interface grain bridging as a fracture resistance mechanism in ceramics: II. Theoretical fracture mechanics model. J. Am. Ceram. Soc. 70, 289 (1987).CrossRefGoogle Scholar
32.Vashishth, D., Behiri, J.C., Bonfield, W.: Crack growth resistance in cortical bone: Concept of microcrack toughening. J. Biomech. 30, 763 (1997).CrossRefGoogle ScholarPubMed
33.Wu, P-C. and Vashishth, D.: Age-related changes in cortical bone toughness: Initiation vs. propagation, in Proceedings of the 2nd Joint EMBS/BMES Conference Vol. 1, edited by Clark, J.W. and McIntire, L.V. (IEEE, 2002), p. 425 .Google Scholar
34.Yang, Q.D., Cox, B.N., Nalla, R.K., Ritchie, R.O.: Fracture length scales in human cortical bone: The necessity of nonlinear fracture models. Biomaterials 27, 2095 (2006).CrossRefGoogle ScholarPubMed
35.Nalla, R.K., Kinney, J.H., Ritchie, R.O.: Mechanistic fracture criteria for the failure of human cortical bone. Nat. Mater. 2, 164 (2003).CrossRefGoogle ScholarPubMed
36.Bilby, B.A., Cardew, G.E., Howard, I.C. Stress intensity factors at the tips of kinked and forked cracks, in Fracture 1977, Vol. 3, edited by Taplin, D.M.R. (Pergamon Press, Oxford, UK, 1978), pp. 197–200.Google Scholar
37.Cotterell, B., Rice, J.R.: Slightly curved or kinked cracks. Int. J. Fract. 16, 155 (1980).CrossRefGoogle Scholar
38.Nalla, R. K., Kruzic, J.J., Kinney, J.H., Balooch, M., Ager, J.W., III, and R.O. Ritchie: Role of microstructure in the aging-related deterioration of the toughness of human cortical bone. Mater. Sci. Eng., C 26 (2006, in press).CrossRefGoogle Scholar
39.Shang, J-K., Ritchie, R.O.: Crack bridging by uncracked ligaments during fatigue-crack growth in SiC-reinforced aluminum-alloy composites. Metall. Trans. A 20A, 897 (1989).CrossRefGoogle Scholar
40.Yeni, Y.N., Fyhrie, D.P.: Fatigue damage-fracture mechanics interaction in cortical bone. Bone 30, 509 (2002).CrossRefGoogle ScholarPubMed
41.Evans, A.G., McMeeking, R.M.: On the toughening of ceramics by strong reinforcements. Acta Metall. 34, 2435 (1986).CrossRefGoogle Scholar
42.Peterlik, H., Roschger, P., Klaushofer, K., Fratzl, P.: From brittle to ductile fracture of bone. Nat. Mater. 5, 53 (2006).CrossRefGoogle ScholarPubMed
43.Fantner, G.E., Hassenkam, T., Kindt, J.H., Weaver, J.C., Birkedal, H., Pechenik, L., Cutroni, J.A., Cidade, G.A.G., Stucky, G.D., Morse, D.E., Hansma, P.K.: Sacrificial bonds and hidden length dissipate energy as mineralized fibrils separate during bone fracture. Nat. Mater. 4, 612 (2005).CrossRefGoogle ScholarPubMed
44.Sahar, N.D., Hong, S-I., Koln, D.K.: Micro- and nano-structural analysis of damage in bone. Micron 36, 617 (2005).CrossRefGoogle ScholarPubMed
45.Vashishth, D., Tanner, K.E., Bonfield, W.: Contribution, development and morphology of microcracking in cortical bone during crack propagation. J. Biomech. 33, 1169 (2000).CrossRefGoogle ScholarPubMed
46.Vashishth, D., Tanner, K.E., Bonfield, W.: Experimental validation of a microcracking-based toughening mechanism for cortical bone. J. Biomech. 36, 121 (2003).CrossRefGoogle ScholarPubMed
47.Evans, A.G., Faber, K.T.: Crack-growth resistance of microcracking brittle materials. J. Am. Ceram. Soc. 67, 255 (1984).CrossRefGoogle Scholar
48.Hutchinson, J.W.: Crack tip shielding by micro-cracking in brittle solids. Acta Metall. 35, 1605 (1987).CrossRefGoogle Scholar
49.Nalla, R.K., Kruzic, J.J., Ritchie, R.O.: On the origin of the toughness of mineralized tissue: Microcracking or crack bridging. Bone 34, 790 (2004).CrossRefGoogle ScholarPubMed
50.Brown, C.U., Yeni, Y.N., Norman, T.L.: Fracture toughness is dependent on bone location—A study of the femoral neck, femoral shaft, and the tibial shaft. J. Biomed. Mater. Res. 49, 380 (2000).3.0.CO;2-W>CrossRefGoogle Scholar
51.Zioupos, P., Currey, J.D., Hamer, A.J.: The role of collagen in the declining mechanical properties of aging human cortical bone. J. Biomed. Mater. Res. 2, 108 (1999).3.0.CO;2-A>CrossRefGoogle Scholar
52.Wang, X., Shen, X., Li, X., Agrawal, C.M.: Age-related changes in the collagen network and toughness of bone. Bone 31, 1 (2002).CrossRefGoogle ScholarPubMed
53.Currey, J.D., Brear, K., Zioupos, P.: The effects of ageing and changes in mineral content in degrading the toughness of human femora. J. Biomech. 29, 257 (1996).CrossRefGoogle ScholarPubMed
54.Gibson, V.A., Stover, S.M., Gibeling, J.C., Hazelwood, S.J., Martin, R.B.: Osteonal effects on elastic modulus and fatigue life in equine bone. J. Biomech. 39, 217 (2006).CrossRefGoogle ScholarPubMed
55.Paschalis, E.P., Shane, E., Lyritis, G., Skarantavos, G., Mendelsohn, R., Boskey, A.L.: Bone fragility and collagen cross-links. J. Bone Miner. Res. 19, 2000 (2004).CrossRefGoogle ScholarPubMed
56.Boskey, A., Mendelsohn, R.: Infrared analysis of bone in health and disease. J. Biomed. Opt. 10, 031102 (2005).CrossRefGoogle ScholarPubMed
57.Carden, A., Morris, M.D.: Application of vibrational spectroscopy to the study of mineralized tissues (review). J. Biomed. Opt. 5, 259 (2000).CrossRefGoogle Scholar
58.Freeman, J.J., Silva, M.J.: Separation of the Raman spectral signatures of bioapatite and collagen in compact mouse bone bleached with hydrogen peroxide. Appl. Spectrosc. 56, 770 (2002).CrossRefGoogle Scholar
59.Timlin, J.A., Carden, A., Morris, M.D., Bonadio, J.F., II, C.E. Hoffler, Kozloff, K.M., Goldstein, S.A.: Spatial distribution of phosphate species in mature and newly generated mammalian bone by hyperspectral Raman imaging. J. Biomed. Opt. 4, 8 (1999).CrossRefGoogle ScholarPubMed
60.Kontoyannis, C.G., Vagenas, N.V.: FT-Raman spectroscopy: A tool for monitoring the demineralization of bones. Appl. Spectrosc. 54, 1605 (2000).CrossRefGoogle Scholar
61.Lakshmi, R.J., Alexander, M., Kurien, J., Mahato, K.K., Kartha, V.B.: Osteoradionecrosis (ORN) of the mandible: A laser Raman spectroscopic study. Appl. Spectrosc. 57, 1100 (2003).CrossRefGoogle ScholarPubMed
62.Carden, A., Rajachar, R.M., Morris, M.D., Kohn, D.H.: Ultrastructural changes accompanying the mechanical deformation of bone tissue: A Raman imaging study. Calcif. Tissue Int. 72, 166 (2003).CrossRefGoogle ScholarPubMed
63.Ager, J.W. IIINalla, R.K., Breeden, K.L., Ritchie, R.O.: Deep-ultraviolet Raman spectroscopy study of the effect of aging on human cortical bone. J. Biomed. Opt. 10, 034012 (2005).CrossRefGoogle ScholarPubMed
64.Nalla, R.K., Balooch, M.Ager, J.W. IIIKruzic, J.J., Kinney, J.H., Ritchie, R.O.: Effects of polar solvents on the fracture resistance of dentin: Role of water hydration. Acta Biomater. 1, 31 (2005).CrossRefGoogle ScholarPubMed
65.Kiebzak, G.M.: Age-related bone changes. Exp. Gerontol. 26, 171 (1991).CrossRefGoogle ScholarPubMed
66.Cooper, C., Coupland, C., Mitchell, M.: Rheumatoid arthritis, corticosteroid therapy, and hip fracture. Ann. Rheum. Dis. 54, 49 (1995).CrossRefGoogle ScholarPubMed
67.Lane, N.E.: An update on glucocorticoid-induced osteoporosis. Rheum. Disease Clin. N. Am. 27, 235 (2001).CrossRefGoogle ScholarPubMed
68.Saag, K.G.: Glucocorticoid-induced osteoporosis. Endocrinol. Metab. Clin. N. Am. 32, 135 (2003).CrossRefGoogle ScholarPubMed
69.Van Staa, T.P., Leufkens, H.S., Cooper, C.: The epidemiology of cortico-steroid osteoporosis. A meta-analysis. Osteoporos. Int. 13, 777 (2002).CrossRefGoogle Scholar
70.Van Staa, T.P., Laan, R.F., Barton, I.P., Cohen, S., Reid, D.M., Cooper, C.: Bone density threshold and other predictors of vertebral fractures in patients receiving oral Glucocorticoid therapy. Arthritis Rheum. 48, 3224 (2003).CrossRefGoogle ScholarPubMed
71.Lane, N.E., Yao, W., Balooch, M., Nalla, R.K., Balooch, G., Habelitz, S., Kinney, J.H., Bonewald, L.: Glucocorticoid treated mice have localized changes in trabecular bone material properties and osteocyte lacunar size that are not observed in placebo treated or estrogen deficient mice. J. Bone Miner. Res. 21, 466 (2006).CrossRefGoogle ScholarPubMed
72.Balooch, G., Balooch, M., Nalla, R.K., Schilling, S., Filvaroff, E.H., Marshall, G.W., Marshall, S.J., Ritchie, R.O., Derynck, R., Alliston, T.: TGF-β regulates the mechanical properties and composition of bone matrix. Proc. Natl. Acad. Sci. USA 102, 18813 (2005).CrossRefGoogle ScholarPubMed
73.Kruzic, J.J., Nalla, R.K., Kinney, J.H., Ritchie, R.O.: Crack blunting, crack bridging and resistance-curve fracture mechanics of dentin: Effect of hydration. Biomaterials 24, 5209 (2003).CrossRefGoogle ScholarPubMed
74.Kinney, J.H., Nalla, R.K., Pople, J.A., Breunig, T.M., Ritchie, R.O.: Age-related transparent root dentin: Mineral concentration, crystallite size, and mechanical properties. Biomaterials 26, 3363 (2005).CrossRefGoogle ScholarPubMed
75.Akkus, O., Polyakova-Akkus, A., Adar, F., Schaffler, M.B.: Aging of microstructural compartments in human compact bone. J. Bone Miner. Res. 18, 1012 (2003).CrossRefGoogle ScholarPubMed
76.Schaffler, M.B., Choi, K., Milgrom, C.: Aging and matrix microdamage accumulation in human compact bone. Bone 17, 521 (1995).CrossRefGoogle ScholarPubMed
77.McCalden, R.W., McGeough, J.A., Barker, M.B., Court-Brown, C.M.: Age-related changes in the tensile properties of cortical bone. The relative importance of changes in porosity, mineralization, and microstructure. J. Bone Joint Surg. Am. 75, 1193 (1993).CrossRefGoogle ScholarPubMed