Bone Biomechanics and the Determinants of Skeletal Fragility

  • Lamya Karim
  • Mary L. BouxseinEmail author
Part of the Nutrition and Health book series (NH)


Fractures are among the most dramatic and devastating sequelae of aging of the human skeleton. In the USA alone, there are over 1.5 million fractures each year, including 280,000 hip fractures and 500,000 vertebral fractures. Of greater importance, however, is the fact that based on current demographic trends predicting a “graying” of the population worldwide, the number of fractures is projected to double or triple in the next 30–50 years. Whereas low BMD is among the strongest risk factors for fracture, a number of clinical studies have demonstrated the limitations of BMD measurements in assessing fracture risk and monitoring the response to therapy. These observations have brought renewed attention to the broader array of factors that influence fracture risk, including those that are directly related to skeletal fragility as well as those related to skeletal loading. This chapter reviews the etiology of age-related fractures from a biomechanics viewpoint, by introducing a standard engineering concept used to evaluate structural failures and considering the various components that influence whole bone strength, with discussion of how key dietary factors may influence the determinants of bone strength.


Biomechanics Skeletal fragility Bone strength Bone mineral density Microarchitecture Bone matrix properties Vitamin D IGF-1 Bone biomechanics Fractures Osteoporosis Structural properties Bone geometry Bone microarchitecture Nutrition 


  1. 1.
    U.S. Department of Health and Human Services. Bone health and osteoporosis: a report of the surgeon general. Rockville, MD: U.S. Department of Health and Human Services, Office of the Surgeon General; 2004.Google Scholar
  2. 2.
    NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001;285(6):785–95.Google Scholar
  3. 3.
    Bouxsein ML. Determinants of skeletal fragility. Best Pract Res Clin Rheumatol. 2005;19(6):897–911.PubMedGoogle Scholar
  4. 4.
    Bouxsein M. Biomechanics of age-related fractures. In: Marcus R, Feldman D, Nelson D, Rosen C, editors. Osteoporosis, vol. I. 3rd ed. San Diego, CA: Elsevier Academic Press; 2007. p. 601–16.Google Scholar
  5. 5.
    Keyak JH, Rossi SA, Jones KA, Skinner HB. Prediction of femoral fracture load using automated finite element modeling. J Biomech. 1998;31(2):125–33.PubMedGoogle Scholar
  6. 6.
    Nevitt MC, Cummings SR. Type of fall and risk of hip and wrist fractures: the study of osteoporotic fractures. J Am Geriatr Soc. 1993;41(11):1226–34.PubMedGoogle Scholar
  7. 7.
    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. 1994;271(2):128–33.PubMedGoogle Scholar
  8. 8.
    Dufour AB, Roberts B, Broe KE, Kiel DP, Bouxsein ML, Hannan MT. The factor-of-risk biomechanical approach predicts hip fracture in men and women: the Framingham Study. Osteoporos Int. 2012;23(2):513–20.PubMedCentralPubMedGoogle Scholar
  9. 9.
    Jones HH, Priest JD, Hayes WC, Tichenor CC, Nagel DA. Humeral hypertrophy in response to exercise. J Bone Joint Surg. 1977;59-A:204–8.Google Scholar
  10. 10.
    Bonadio J, Jepsen KJ, Mansoura MK, Jaenisch R, Kuhn JL, Goldstein SA. A murine skeletal adaptation that significantly increases cortical bone mechanical properties. Implications for human skeletal fragility. J Clin Invest. 1993;92(4):1697–705.PubMedCentralPubMedGoogle Scholar
  11. 11.
    Bouxsein ML, Seeman E. Quantifying the material and structural determinants of bone strength. Best Pract Res Clin Rheumatol. 2009;23(6):741–53.PubMedGoogle Scholar
  12. 12.
    Carter DR, Hayes WC. Bone compressive strength: the influence of density and strain rate. Science. 1976;194:1174–6.PubMedGoogle Scholar
  13. 13.
    Carter DR, Hayes WC. The compressive behavior of bone as a two-phase porous structure. J Bone Joint Surg. 1977;59-A(7):954–62.Google Scholar
  14. 14.
    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):155–68.PubMedGoogle Scholar
  15. 15.
    Keaveny TM, Morgan EF, Niebur GL, Yeh OC. Biomechanics of trabecular bone. Annu Rev Biomed Eng. 2001;3:307–33.PubMedGoogle Scholar
  16. 16.
    Currey J. Effects of porosity and mineral content on the Young’s modulus of bone. Eur Soc Biomech. 1986;5:104.Google Scholar
  17. 17.
    Currey J. Physical characteristics affecting the tensile failure properties of compact bone. J Biomech. 1990;23:837–44.PubMedGoogle Scholar
  18. 18.
    Schaffler M, Burr D. Stiffness of compact bone: effects of porosity and density. J Biomech. 1988;21:13–6.PubMedGoogle Scholar
  19. 19.
    McCalden R, McGeough J, Barker M, Court-Brown C. Age-related changes in the tensile properties of cortical bone. J Bone Joint Surg. 1993;75-A:1193–205.Google Scholar
  20. 20.
    Anderson DE, Bruno AG, Bouxsein ML. Biomechanics of age-related fractures. In: Marcus R, Feldman D, Nelson D, Dempster D, editors. Osteoporosis. 4th ed. San Diego, CA: Elsevier Academic Press; 2013. p. 497–516.Google Scholar
  21. 21.
    Karim L, Hussein A, Morgan EF, Bouxsein ML. Bone biomechanics. In: Marcus R, Feldman D, Nelson D, Dempster D, editors. Osteoporosis. 4th ed. San Diego, CA: Elsevier Academic Press; 2013. p. 431–52.Google Scholar
  22. 22.
    Bouxsein ML, Karasik D. Bone geometry and skeletal fragility. Curr Osteoporos Rep. 2006;4(2):49–56.PubMedGoogle Scholar
  23. 23.
    Bouxsein ML, Coan BS, Lee SC. Prediction of the strength of the elderly proximal femur by bone mineral density and quantitative ultrasound measurements of the heel and tibia. Bone. 1999;25(1):49–54.PubMedGoogle Scholar
  24. 24.
    Lochmuller EM, Groll O, Kuhn V, Eckstein F. Mechanical strength of the proximal femur as predicted from geometric and densitometric bone properties at the lower limb versus the distal radius. Bone. 2002;30(1):207–16.PubMedGoogle Scholar
  25. 25.
    Lochmuller EM, Burklein D, Kuhn V, Glaser C, Muller R, Gluer CC, Eckstein F. Mechanical strength of the thoracolumbar spine in the elderly: prediction from in situ dual-energy X-ray absorptiometry, quantitative computed tomography (QCT), upper and lower limb peripheral QCT, and quantitative ultrasound. Bone. 2002;31(1):77–84.PubMedGoogle Scholar
  26. 26.
    Lochmuller EM, Lill CA, Kuhn V, Schneider E, Eckstein F. Radius bone strength in bending, compression, and falling and its correlation with clinical densitometry at multiple sites. J Bone Miner Res. 2002;17(9):1629–38.PubMedGoogle Scholar
  27. 27.
    Muller ME, Webber CE, Bouxsein ML. Predicting the failure load of the distal radius. Osteoporos Int. 2003;14(4):345–52.PubMedGoogle Scholar
  28. 28.
    Skaggs DL, Loro ML, Pitukcheewanont P, Tolo V, Gilsanz V. Increased body weight and decreased radial cross-sectional dimensions in girls with forearm fractures. J Bone Miner Res. 2001;16(7):1337–42.PubMedGoogle Scholar
  29. 29.
    Ahlborg HG, Johnell O, Turner CH, Rannevik G, Karlsson MK. Bone loss and bone size after menopause. N Engl J Med. 2003;349(4):327–34.PubMedGoogle Scholar
  30. 30.
    Szulc P, Munoz F, Duboeuf F, Marchand F, Delmas PD. Low width of tubular bones is associated with increased risk of fragility fracture in elderly men—the MINOS study. Bone. 2006;38(4):595–602.PubMedGoogle Scholar
  31. 31.
    Gilsanz V, Boechat MI, Gilsanz R, Loro ML, Roe TF, Goodman WG. Gender differences in vertebral sizes in adults: biomechanical implications. Radiology. 1994;190(3):678–82.PubMedGoogle Scholar
  32. 32.
    Gilsanz V, Loro ML, Roe TF, Sayre J, Gilsanz R, Schulz EE. Vertebral size in elderly women with osteoporosis. Mechanical implications and relationship to fractures. J Clin Invest. 1995;95(5):2332–7.PubMedCentralPubMedGoogle Scholar
  33. 33.
    Duan Y, Seeman E, Turner CH. The biomechanical basis of vertebral body fragility in men and women. J Bone Miner Res. 2001;16(12):2276–83.PubMedGoogle Scholar
  34. 34.
    Black DM, Bouxsein ML, Marshall LM, Cummings SR, Lang TF, Cauley JA, Ensrud KE, Nielson CM, Orwoll ES. Proximal femoral structure and the prediction of hip fracture in men: a large prospective study using QCT. J Bone Miner Res. 2008;23(8):1326–33.PubMedCentralPubMedGoogle Scholar
  35. 35.
    Smith R, Walker R. Femoral expansion in aging women: implications for osteoporosis and fractures. Science. 1964;145:156–7.PubMedGoogle Scholar
  36. 36.
    Ruff C, Hayes W. Subperiosteal expansion and cortical remodeling of the human femur and tibia with aging. Science. 1982;217:945–7.PubMedGoogle Scholar
  37. 37.
    Seeman E. Pathogenesis of bone fragility in women and men. Lancet. 2002;359(9320):1841–50.PubMedGoogle Scholar
  38. 38.
    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.PubMedGoogle Scholar
  39. 39.
    Ruff C, Hayes W. Sex differences in age-related remodeling of the femur and tibia. J Orthop Res. 1988;6:886–96.PubMedGoogle Scholar
  40. 40.
    Beck TJ, Ruff CB, Bissessur K. Age-related changes in female femoral neck geometry: implications for bone strength. Calcif Tissue Int. 1993;53 Suppl 1:S41–6.PubMedGoogle Scholar
  41. 41.
    Seeman E. From density to structure: growing up and growing old on the surfaces of bone. J Bone Miner Res. 1997;12(4):509–21.PubMedGoogle Scholar
  42. 42.
    Riggs BL, Melton III LJ, Robb RA, Camp JJ, Atkinson EJ, Peterson JM, Rouleau PA, McCollough CH, Bouxsein ML, Khosla S. Population-based study of age and sex differences in bone volumetric density, size, geometry, and structure at different skeletal sites. J Bone Miner Res. 2004;19(12):1945–54.PubMedGoogle Scholar
  43. 43.
    Samelson EJ, Christiansen BA, Demissie S, Broe KE, Louie-Gao Q, Cupples LA, Roberts BJ, Manoharam R, D’Agostino J, Lang T, Kiel DP, Bouxsein ML. QCT measures of bone strength at the thoracic and lumbar spine: the Framingham Study. J Bone Miner Res. 2012;27(3):654–63.PubMedCentralPubMedGoogle Scholar
  44. 44.
    Gibson L. The mechanical behaviour of cancellous bone. J Biomech. 1985;18:317–28.PubMedGoogle Scholar
  45. 45.
    Parkinson IH, Badiei A, Stauber M, Codrington J, Muller R, Fazzalari NL. Vertebral body bone strength: the contribution of individual trabecular element morphology. Osteoporos Int. 2012;23(7):1957–65.PubMedGoogle Scholar
  46. 46.
    Liu XS, Zhang XH, Guo XE. Contributions of trabecular rods of various orientations in determining the elastic properties of human vertebral trabecular bone. Bone. 2009;45(2):158–63.PubMedCentralPubMedGoogle Scholar
  47. 47.
    Liu XS, Stein EM, Zhou B, Zhang CA, Nickolas TL, Cohen A, Thomas V, McMahon DJ, Cosman F, Nieves J, Shane E, Guo XE. Individual trabecula segmentation (ITS)-based morphological analyses and microfinite element analysis of HR-pQCT images discriminate postmenopausal fragility fractures independent of DXA measurements. J Bone Miner Res. 2012;27(2):263–72.PubMedCentralPubMedGoogle Scholar
  48. 48.
    Hildebrand T, Laib A, Muller R, Dequeker J, Ruegsegger P. Direct three-dimensional morphometric analysis of human cancellous bone: microstructural data from spine, femur, iliac crest, and calcaneus. J Bone Miner Res. 1999;14(7):1167–74.PubMedGoogle Scholar
  49. 49.
    Majumdar S, Kothari M, Augat P, Newitt DC, Link TM, Lin JC, Lang T, Lu Y, Genant HK. High-resolution magnetic resonance imaging: three-dimensional trabecular bone architecture and biomechanical properties. Bone. 1998;22(5):445–54.PubMedGoogle Scholar
  50. 50.
    Genant HK, Gordon C, Jiang Y, Link TM, Hans D, Majumdar S, Lang TF. Advanced imaging of the macrostructure and microstructure of bone. Horm Res. 2000;54 Suppl 1:24–30.PubMedGoogle Scholar
  51. 51.
    Boutroy S, Bouxsein ML, Munoz F, Delmas PD. In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography. J Clin Endocrinol Metab. 2005;90(12):6508–15.PubMedGoogle Scholar
  52. 52.
    Macdonald HM, Nishiyama KK, Kang J, Hanley DA, Boyd SK. Age-related patterns of trabecular and cortical bone loss differ between sexes and skeletal sites: a population-based HR-pQCT study. J Bone Miner Res. 2011;26(1):50–62.PubMedGoogle Scholar
  53. 53.
    Putman MS, Yu EW, Lee H, Neer RM, Schindler E, Taylor AP, Cheston E, Bouxsein ML, Finkelstein JS. Differences in skeletal microarchitecture and strength in African-American and white women. J Bone Miner Res. 2013;28(10):2177–85.PubMedCentralPubMedGoogle Scholar
  54. 54.
    Rozental TD, Deschamps LN, Taylor A, Earp B, Zurakowski D, Day CS, Bouxsein ML. Premenopausal women with a distal radial fracture have deteriorated trabecular bone density and morphology compared with controls without a fracture. J Bone Joint Surg Am. 2013;95(7):633–42.PubMedCentralPubMedGoogle Scholar
  55. 55.
    Goulet R, Goldstein S, Ciarelli M, Kuhn J, Brown M, Feldkamp L. The relationship between the structural and orthogonal compressive properties of trabecular bone. J Biomech. 1994;27:375–89.PubMedGoogle Scholar
  56. 56.
    Bouxsein M, Radloff S. Quantitative ultrasound of the calcaneus reflects the material properties of calcaneal trabecular bone. J Bone Miner Res. 1997;12:839–46.PubMedGoogle Scholar
  57. 57.
    Goldstein S, Goulet R, McCubbrey D. Measurement and significance of three-dimensional architecture to the mechanical integrity of trabecular bone. Calcif Tissue Int. 1993;53 Suppl 1:S127–33.PubMedGoogle Scholar
  58. 58.
    Snyder BD, Hayes WC. Multiaxial structure-property relations in trabecular bone. In: Mow VC, Ratcliffe A, Woo SL-Y, editors. Biomechanics of diarthrodial joints. New York: Springer; 1990. p. 31–59.Google Scholar
  59. 59.
    Ulrich D, van Rietbergen B, Laib A, Ruegsegger P. The ability of three-dimensional structural indices to reflect mechanical aspects of trabecular bone. Bone. 1999;25(1):55–60.PubMedGoogle Scholar
  60. 60.
    van der Linden JC, Weinans H. Effects of microarchitecture on bone strength. Curr Osteoporos Rep. 2007;5(2):56–61.PubMedGoogle Scholar
  61. 61.
    Silva MJ, Gibson LJ. Modeling the mechanical behavior of vertebral trabecular bone: effects of age-related changes in microstructure. Bone. 1997;21(2):191–9.PubMedGoogle Scholar
  62. 62.
    van der Linden JC, Homminga J, Verhaar JA, Weinans H. Mechanical consequences of bone loss in cancellous bone. J Bone Miner Res. 2001;16(3):457–65.PubMedGoogle Scholar
  63. 63.
    Yeh OC, Keaveny TM. Biomechanical effects of intraspecimen variations in trabecular architecture: a three-dimensional finite element study. Bone. 1999;25(2):223–8.PubMedGoogle Scholar
  64. 64.
    Parfitt A. Age-related structural changes in trabecular and cortical bone: cellular mechanisms and biomechanical consequences. Calcif Tissue Int. 1984;36(1 Suppl):123–8.Google Scholar
  65. 65.
    Ciarelli TE, Fyhrie DP, Schaffler MB, Goldstein SA. Variations in three-dimensional cancellous bone architecture of the proximal femur in female hip fractures and in controls. J Bone Miner Res. 2000;15(1):32–40.PubMedGoogle Scholar
  66. 66.
    Legrand E, Chappard D, Pascaretti C, Duquenne M, Krebs S, Rohmer V, Basle MF, Audran M. Trabecular bone microarchitecture, bone mineral density, and vertebral fractures in male osteoporosis. J Bone Miner Res. 2000;15(1):13–9.PubMedGoogle Scholar
  67. 67.
    Link TM, Lotter A, Beyer F, Christiansen S, Newitt D, Lu Y, Schmid C, Majumdar S. Changes in calcaneal trabecular bone structure after heart transplantation: an MR imaging study. Radiology. 2000;217(3):855–62.PubMedGoogle Scholar
  68. 68.
    Aaron JE, Shore PA, Shore RC, Beneton M, Kanis JA. Trabecular architecture in women and men of similar bone mass with and without vertebral fracture: II. Three-dimensional histology. Bone. 2000;27(2):277–82.PubMedGoogle Scholar
  69. 69.
    Sornay-Rendu E, Boutroy S, Munoz F, Delmas PD. Alterations of cortical and trabecular architecture are associated with fractures in postmenopausal women, partially independent of decreased BMD measured by DXA: the OFELY study. J Bone Miner Res. 2007;22(3):425–33.PubMedGoogle Scholar
  70. 70.
    Szulc P, Boutroy S, Vilayphiou N, Chaitou A, Delmas PD, Chapurlat R. Cross-sectional analysis of the association between fragility fractures and bone microarchitecture in older men: The STRAMBO study. J Bone Miner Res. 2011;26(6):1358–67.PubMedGoogle Scholar
  71. 71.
    Nishiyama KK, Macdonald HM, Hanley DA, Boyd SK. Women with previous fragility fractures can be classified based on bone microarchitecture and finite element analysis measured with HR-pQCT. Osteoporos Int. 2013;24(5):1733–40.PubMedGoogle Scholar
  72. 72.
    Patsch JM, Burghardt AJ, Yap SP, Baum T, Schwartz AV, Joseph GB, Link TM. Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures. J Bone Miner Res. 2013;28(2):313–24.PubMedCentralPubMedGoogle Scholar
  73. 73.
    Burghardt AJ, Issever AS, Schwartz AV, Davis KA, Masharani U, Majumdar S, Link TM. High-resolution peripheral quantitative computed tomographic imaging of cortical and trabecular bone microarchitecture in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2010;95(11):5045–55.PubMedCentralPubMedGoogle Scholar
  74. 74.
    Walker MD, McMahon DJ, Udesky J, Liu G, Bilezikian JP. Application of high-resolution skeletal imaging to measurements of volumetric BMD and skeletal microarchitecture in Chinese-American and white women: explanation of a paradox. J Bone Miner Res. 2009;24(12):1953–9.PubMedCentralPubMedGoogle Scholar
  75. 75.
    Wang XF, Wang Q, Ghasem-Zadeh A, Evans A, McLeod C, Iuliano-Burns S, Seeman E. Differences in macro- and microarchitecture of the appendicular skeleton in young Chinese and white women. J Bone Miner Res. 2009;24(12):1946–52.PubMedGoogle Scholar
  76. 76.
    Bouxsein ML. Bone quality: where do we go from here? Osteoporos Int. 2003;14 Suppl 5:118–27.Google Scholar
  77. 77.
    Currey J. The mechanical consequences of variation in the mineral content of bone. J Biomech. 1969;2:1–11.PubMedGoogle Scholar
  78. 78.
    Currey JD. What determines the bending strength of compact bone? J Exp Biol. 1999;202(Pt 18):2495–503.PubMedGoogle Scholar
  79. 79.
    Turner CH. Biomechanics of bone: determinants of skeletal fragility and bone quality. Osteoporos Int. 2002;13(2):97–104.PubMedGoogle Scholar
  80. 80.
    Roschger P, Paschalis EP, Fratzl P, Klaushofer K. Bone mineralization density distribution in health and disease. Bone. 2008;42(3):456–66.PubMedGoogle Scholar
  81. 81.
    Roschger P, Gupta HS, Berzlanovich A, Ittner G, Dempster DW, Fratzl P, Cosman F, Parisien M, Lindsay R, Nieves JW, Klaushofer K. Constant mineralization density distribution in cancellous human bone. Bone. 2003;32(3):316–23.PubMedGoogle Scholar
  82. 82.
    Keaveny TM, Hayes WC. A 20-year perspective on the mechanical properties of trabecular bone. J Biomech Eng. 1993;115:534–42.PubMedGoogle Scholar
  83. 83.
    Meunier PJ, Arlot M, Chavassieux P, Yates AJ. The effects of alendronate on bone turnover and bone quality. Int J Clin Pract Suppl. 1999;101:14–7.PubMedGoogle Scholar
  84. 84.
    Meunier PJ, Boivin G. Bone mineral density reflects bone mass but also the degree of mineralization of bone: therapeutic implications. Bone. 1997;21(5):373–7.PubMedGoogle Scholar
  85. 85.
    Boivin GY, Chavassieux PM, Santora AC, Yates J, Meunier PJ. Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone. 2000;27(5):687–94.PubMedGoogle Scholar
  86. 86.
    Roschger P, Rinnerthaler S, Yates J, Rodan GA, Fratzl P, Klaushofer K. Alendronate increases degree and uniformity of mineralization in cancellous bone and decreases the porosity in cortical bone of osteoporotic women. Bone. 2001;29(2):185–91.PubMedGoogle Scholar
  87. 87.
    Boivin G, Lips P, Ott SM, Harper KD, Sarkar S, Pinette KV, Meunier PJ. Contribution of raloxifene and calcium and vitamin D3 supplementation to the increase of the degree of mineralization of bone in postmenopausal women. J Clin Endocrinol Metab. 2003;88(9):4199–205.PubMedGoogle Scholar
  88. 88.
    Boivin G, Meunier PJ. Methodological considerations in measurement of bone mineral content. Osteoporos Int. 2003;14:22–8.Google Scholar
  89. 89.
    Misof BM, Roschger P, Cosman F, Kurland ES, Tesch W, Messmer P, Dempster DW, Nieves J, Shane E, Fratzl P, Klaushofer K, Bilezikian J, Lindsay R. Effects of intermittent parathyroid hormone administration on bone mineralization density in iliac crest biopsies from patients with osteoporosis: a paired study before and after treatment. J Clin Endocrinol Metab. 2003;88(3):1150–6.PubMedGoogle Scholar
  90. 90.
    Roschger P, Lombardi A, Misof BM, Maier G, Fratzl-Zelman N, Fratzl P, Klaushofer K. Mineralization density distribution of postmenopausal osteoporotic bone is restored to normal after long-term alendronate treatment: qBEI and sSAXS data from the fracture intervention trial long-term extension (FLEX). J Bone Miner Res. 2010;25(1):48–55.PubMedGoogle Scholar
  91. 91.
    Vashishth D. The role of the collagen matrix in skeletal fragility. Curr Osteoporos Rep. 2007;5(2):62–6.PubMedGoogle Scholar
  92. 92.
    Currey J. Role of collagen and other organics in the mechanical properties of bone. Osteoporos Int. 2003;14:S29–36.Google Scholar
  93. 93.
    Viguet-Carrin S, Garnero P, Delmas PD. The role of collagen in bone strength. Osteoporos Int. 2006;17(3):319–36.PubMedGoogle Scholar
  94. 94.
    Knott L, Whitehead CC, Fleming RH, Bailey AJ. Biochemical changes in the collagenous matrix of osteoporotic avian bone. Biochem J. 1995;310(Pt 3):1045–51.PubMedCentralPubMedGoogle Scholar
  95. 95.
    Saito M, Fujii K, Mori Y, Marumo K. Role of collagen enzymatic and glycation induced cross-links as a determinant of bone quality in spontaneously diabetic WBN/Kob rats. Osteoporos Int. 2006;17(10):1514–23.PubMedGoogle Scholar
  96. 96.
    Karim L, Vashishth D. Heterogeneous glycation of cancellous bone and its association with bone quality and fragility. PLoS One. 2012;7(4):e35047.PubMedCentralPubMedGoogle Scholar
  97. 97.
    Fantner GE, Hassenkam T, Kindt JH, Weaver JC, Birkedal H, Pechenik L, Cutroni JA, Cidade GA, Stucky GD, Morse DE, Hansma PK. Sacrificial bonds and hidden length dissipate energy as mineralized fibrils separate during bone fracture. Nat Mater. 2005;4(8):612–6.PubMedGoogle Scholar
  98. 98.
    Sroga GE, Vashishth D. Effects of bone matrix proteins on fracture and fragility in osteoporosis. Curr Osteoporos Rep. 2012;10(2):141–50.PubMedCentralPubMedGoogle Scholar
  99. 99.
    Ducy P, Desbois C, Boyce B, Pinero G, Story B, Dunstan C, Smith E, Bonadio J, Goldstein S, Gundberg C, Bradley A, Karsenty G. Increased bone formation in osteocalcin-deficient mice. Nature. 1996;382(6590):448–52.PubMedGoogle Scholar
  100. 100.
    Fantner GE, Oroudjev E, Schitter G, Golde LS, Thurner P, Finch MM, Turner P, Gutsmann T, Morse DE, Hansma H, Hansma PK. Sacrificial bonds and hidden length: unraveling molecular mesostructures in tough materials. Biophys J. 2006;90(4):1411–8.PubMedCentralPubMedGoogle Scholar
  101. 101.
    Powell Jr WF, Barry KJ, Tulum I, Kobayashi T, Harris SE, Bringhurst FR, Pajevic PD. Targeted ablation of the PTH/PTHrP receptor in osteocytes impairs bone structure and homeostatic calcemic responses. J Endocrinol. 2011;209(1):21–32.PubMedCentralPubMedGoogle Scholar
  102. 102.
    Burr D. Microdamage and bone strength. Osteoporos Int. 2003;14 Suppl 5:67–72.Google Scholar
  103. 103.
    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. 2000;15(1):60–7.PubMedGoogle Scholar
  104. 104.
    Schaffler M. Role of bone turnover in microdamage. Osteoporos Int. 2003;14:73–80.Google Scholar
  105. 105.
    Mashiba T, Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB. Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib [see comments]. J Bone Miner Res. 2000;15(4):613–20.PubMedGoogle Scholar
  106. 106.
    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. 2001;28(5):524–31.PubMedGoogle Scholar
  107. 107.
    Allen MR, Iwata K, Phipps R, Burr DB. Alterations in canine vertebral bone turnover, microdamage accumulation, and biomechanical properties following 1-year treatment with clinical treatment doses of risedronate or alendronate. Bone. 2006;39(4):872–9.PubMedGoogle Scholar
  108. 108.
    Allen MR, Burr DB. Three years of alendronate treatment results in similar levels of vertebral microdamage as after one year of treatment. J Bone Miner Res. 2007;22(11):1759–65.PubMedGoogle Scholar
  109. 109.
    Allen MR, Reinwald S, Burr DB. Alendronate reduces bone toughness of ribs without significantly increasing microdamage accumulation in dogs following 3 years of daily treatment. Calcif Tissue Int. 2008;82(5):354–60.PubMedCentralPubMedGoogle Scholar
  110. 110.
    Allen MR, Burr DB. Bisphosphonate effects on bone turnover, microdamage, and mechanical properties: what we think we know and what we know that we don’t know. Bone. 2011;49(1):56–65.PubMedGoogle Scholar
  111. 111.
    Oyen J, Apalset EM, Gjesdal CG, Brudvik C, Lie SA, Hove LM. Vitamin D inadequacy is associated with low-energy distal radius fractures: a case-control study. Bone. 2011;48(5):1140–5.PubMedGoogle Scholar
  112. 112.
    Maier S, Sidelnikov E, Dawson-Hughes B, Egli A, Theiler R, Platz A, Staehelin HB, Simmen HP, Meier C, Dick W, Grob D, von Eckardstein A, Bischoff-Ferrari HA. Before and after hip fracture, vitamin D deficiency may not be treated sufficiently. Osteoporos Int. 2013;24(11):2765–73.PubMedGoogle Scholar
  113. 113.
    Busse B, Bale HA, Zimmermann EA, Panganiban B, Barth HD, Carriero A, Vettorazzi E, Zustin J, Hahn M, Ager III JW, Puschel K, Amling M, Ritchie RO. Vitamin D deficiency induces early signs of aging in human bone, increasing the risk of fracture. Sci Transl Med. 2013;5(193):193ra88.PubMedGoogle Scholar
  114. 114.
    Yakar S, Courtland HW, Clemmons D. IGF-1 and bone: new discoveries from mouse models. J Bone Miner Res. 2010;25(12):2543–52.PubMedCentralPubMedGoogle Scholar
  115. 115.
    Devlin MJ, Cloutier AM, Thomas NA, Panus DA, Lotinun S, Pinz I, Baron R, Rosen CJ, Bouxsein ML. Caloric restriction leads to high marrow adiposity and low bone mass in growing mice. J Bone Miner Res. 2010;25(9):2078–88.PubMedCentralPubMedGoogle Scholar
  116. 116.
    Bredella MA, Misra M, Miller KK, Madisch I, Sarwar A, Cheung A, Klibanski A, Gupta R. Distal radius in adolescent girls with anorexia nervosa: trabecular structure analysis with high-resolution flat-panel volume CT. Radiology. 2008;249(3):938–46.PubMedCentralPubMedGoogle Scholar
  117. 117.
    Faje AT, Karim L, Taylor A, Lee H, Miller KK, Mendes N, Meenaghan E, Goldstein MA, Bouxsein ML, Misra M, Klibanski A. Adolescent girls with anorexia nervosa have impaired cortical and trabecular microarchitecture and lower estimated bone strength at the distal radius. J Clin Endocrinol Metab. 2013;98(5):1923–9.PubMedCentralPubMedGoogle Scholar
  118. 118.
    Faje AT, Fazeli PK, Miller KK, Katzman DK, Ebrahimi S, Lee H, Mendes N, Snelgrove D, Meenaghan E, Misra M, Klibanski A. Fracture risk and areal bone mineral density in adolescent females with anorexia nervosa. Int J Eat Disord. 2014;47(5):458–66.PubMedGoogle Scholar
  119. 119.
    Prieto-Alhambra D, Premaor MO, Fina Aviles F, Hermosilla E, Martinez-Laguna D, Carbonell-Abella C, Nogues X, Compston JE, Diez-Perez A. The association between fracture and obesity is site-dependent: a population-based study in postmenopausal women. J Bone Miner Res. 2012;27(2):294–300.PubMedGoogle Scholar
  120. 120.
    Compston JE, Flahive J, Hosmer DW, Watts NB, Siris ES, Silverman S, Saag KG, Roux C, Rossini M, Pfeilschifter J, Nieves JW, Netelenbos JC, March L, LaCroix AZ, Hooven FH, Greenspan SL, Gehlbach SH, Diez-Perez A, Cooper C, Chapurlat RD, Boonen S, Anderson Jr FA, Adami S, Adachi JD. Relationship of weight, height, and body mass index with fracture risk at different sites in postmenopausal women: the Global Longitudinal study of Osteoporosis in Women (GLOW). J Bone Miner Res. 2014;29(2):487–93.PubMedGoogle Scholar
  121. 121.
    Leslie WD, Rubin MR, Schwartz AV, Kanis JA. Type 2 diabetes and bone. J Bone Miner Res. 2012;27(11):2231–7.PubMedGoogle Scholar
  122. 122.
    Sornay-Rendu E, Boutroy S, Vilayphiou N, Claustrat B, Chapurlat RD. In obese postmenopausal women, bone microarchitecture and strength are not commensurate to greater body weight: the Os des Femmes de Lyon (OFELY) study. J Bone Miner Res. 2013;28(7):1679–87.PubMedGoogle Scholar
  123. 123.
    Rocher E, El Hage R, Chappard C, Portier H, Rochefort GY, Benhamou CL. Bone mineral density, hip bone geometry, and calcaneus trabecular bone texture in obese and normal-weight children. J Clin Densitom. 2013;16(2):244–9.PubMedGoogle Scholar
  124. 124.
    Cohen A, Dempster DW, Recker RR, Lappe JM, Zhou H, Zwahlen A, Muller R, Zhao B, Guo X, Lang T, Saeed I, Liu XS, Guo XE, Cremers S, Rosen CJ, Stein EM, Nickolas TL, McMahon DJ, Young P, Shane E. Abdominal fat is associated with lower bone formation and inferior bone quality in healthy premenopausal women: a transiliac bone biopsy study. J Clin Endocrinol Metab. 2013;98(6):2562–72.PubMedCentralPubMedGoogle Scholar
  125. 125.
    Andersen S, Frederiksen KD, Hansen S, Brixen K, Gram J, Stoving RK. Bone structure and estimated bone strength in obese patients evaluated by high-resolution peripheral quantitative computed tomography. Calcif Tissue Int. 2014;95(1):19–28.PubMedGoogle Scholar
  126. 126.
    Engelke K. Assessment of bone quality and strength with new technologies. Curr Opin Endocrinol Diabetes Obes. 2012;19(6):474–82.PubMedGoogle Scholar
  127. 127.
    Cheung AM, Adachi JD, Hanley DA, Kendler DL, Davison KS, Josse R, Brown JP, Ste-Marie LG, Kremer R, Erlandson MC, Dian L, Burghardt AJ, Boyd SK. High-resolution peripheral quantitative computed tomography for the assessment of bone strength and structure: a review by the Canadian Bone Strength Working Group. Curr Osteoporos Rep. 2013;11(2):136–46.PubMedCentralPubMedGoogle Scholar
  128. 128.
    Silva BC, Leslie WD, Resch H, Lamy O, Lesnyak O, Binkley N, McCloskey EV, Kanis JA, Bilezikian JP. Trabecular bone score: a noninvasive analytical method based upon the DXA image. J Bone Miner Res. 2014;29(3):518–30.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Center for Advanced Orthopedic Studies, RN115, Beth Israel Deaconess Medical CenterBostonUSA
  2. 2.Department of Orthopaedic SurgeryHarvard Medical SchoolBostonUSA

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