Skip to main content

Advertisement

Springer Nature Link
Log in

Bone quality: where do we go from here?

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

As was true 10 years ago, tremendous interest surrounds the concept of "bone quality," as shown by the intense and growing research activity in the field. The urgency to advance knowledge in this area is motivated by the need to understand not only the causes of increased skeletal fragility with aging and disease, but also the mechanisms by which drugs reduce fracture risk. As reflected in the preceding articles, in the past decade collaborations between biologists, physicists, engineers and clinicians have led to new insights regarding the biological, material and structural features that contribute to skeletal fragility. Despite these new insights, important issues remain unresolved. Our challenges lie in identifying, describing and understanding the totality of features and characteristics that determine a bone's ability to resist fracture, and using this information to identify new therapeutic targets and develop better biomarkers and noninvasive imaging modalities. This summary is intended to integrate reports in the literature with presentations and discussions that occurred during the meeting, to highlight areas of consensus and those of continued controversy, and thus to identify critical areas for future research.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Currey JD (2003) Role of collagen and other organics in the mechanical properties of bone. Osteoporos Int 14:tbd

    Google Scholar 

  2. Jepsen K (2003) The aging cortex: to crack or not to crack. Osteoporos Int 14:tbd

    Google Scholar 

  3. Currey JD (2001) Bone strength: what are we trying to measure? Calcif Tissue Int 68:205–210

    CAS  PubMed  Google Scholar 

  4. Meunier PJ, Boivin G (1997) Bone mineral density reflects bone mass but also the degree of mineralization of bone: therapeutic implications. Bone 21:373–377

    Article  CAS  PubMed  Google Scholar 

  5. Currey JD (1999) What determines the bending strength of compact bone? J Exp Biol 202:2495–2503

    PubMed  Google Scholar 

  6. Currey JD (1969) The mechanical consequences of variation in the mineral content of bone. J Biomech 2:1–11

    Google Scholar 

  7. Boivin GY, Chavassieux PM, Santora AC, Yates J, Meunier PJ (2000) Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone 27:687–694

    Google Scholar 

  8. Roschger P, Rinnerthaler S, Yates J, et al (2001) Alendronate increases degree and uniformity of mineralization in cancellous bone and decreases the porosity in cortical bone of osteoporotic women. Bone 29:185–191

    Article  CAS  PubMed  Google Scholar 

  9. Cranney A, Wells G, Willan A, et al (2002) Meta-analysis of therapies for postmenopausal osteoporosis. II. Meta-analysis of alendronate for the treatment of postmenopausal women. Endocr Rev 23:508–516

    Article  CAS  PubMed  Google Scholar 

  10. Misof BM, Roschger P, Cosman F, et al (2003) 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 88:1150–1156

    Article  CAS  PubMed  Google Scholar 

  11. Neer RM, Arnaud CD, Zanchetta JR, et al (2001) Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441

    CAS  PubMed  Google Scholar 

  12. van der Linden JC, Homminga J, Verhaar JA, Weinans H (2001) Mechanical consequences of bone loss in cancellous bone. J Bone Miner Res 16:457–465

    PubMed  Google Scholar 

  13. Yeh OC, Keaveny TM (2001) Relative roles of microdamage and microfracture in the mechanical behavior of trabecular bone. J Orthop Res 19:1001–1007

    Article  CAS  PubMed  Google Scholar 

  14. Boskey AL (2003) Bone mineral crystal size. Osteoporos Int 14:tbd

    Google Scholar 

  15. Zioupos P, Currey JD, Hamer AJ (1999) The role of collagen in the declining mechanical properties of aging human cortical bone. J Biomed Mater Res 45:108–116

    Article  CAS  PubMed  Google Scholar 

  16. Burr D (2002) The contribution of the organic matrix to the bone's material properties. Bone 31:8–11

    Article  CAS  PubMed  Google Scholar 

  17. Gao H, Ji B, Jager IL, Arzt E, Fratzl P (2003) Materials become insensitive to flaws at nanoscale: lessons from nature. Proc Natl Acad Sci USA 100:5597–5600

    Article  CAS  PubMed  Google Scholar 

  18. Mann V, Hobson EE, Li B, et al (2001) A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest 107:899–907

    CAS  PubMed  Google Scholar 

  19. Efstathiadou Z, Tsatsoulis A, Ioannidis JP (2001) Association of collagen Ialpha 1 Sp1 polymorphism with the risk of prevalent fractures: a meta-analysis. J Bone Miner Res 16:1586–1592

    CAS  PubMed  Google Scholar 

  20. Garnero P, Cloos P, Sornay-Rendu E, Qvist P, Delmas PD (2002) Type I collagen racemization and isomerization and the risk of fracture in postmenopausal women: the OFELY prospective study. J Bone Miner Res 17:826–833

    CAS  PubMed  Google Scholar 

  21. Gundberg C (2003) Matrix proteins. Osteoporos Int 14:tbd

    Google Scholar 

  22. Zioupos P (1999) On microcracks, microcracking, in-vivo, in vitro, in-situ and other issues. J Biomech 32:209–211, 13–59

    Article  CAS  PubMed  Google Scholar 

  23. Parfitt AM (2002) Targeted and nontargeted bone remodeling: relationship to basic multicellular unit origination and progression. Bone 30:5–7

    Article  CAS  PubMed  Google Scholar 

  24. Burr DB (2002) Targeted and nontargeted remodeling. Bone 30:2–4

    Article  CAS  PubMed  Google Scholar 

  25. Schaffler MB (2003) Role of bone turnover in microdamage. Osteoporos Int 14:tbd

    Google Scholar 

  26. Mashiba T, Hirano T, Turner CH, et al (2000) Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res 15:613–620

    CAS  PubMed  Google Scholar 

  27. Mashiba T, Turner CH, Hirano T, et al (2001) Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sites in beagles. Bone 28:524–531

    Article  CAS  PubMed  Google Scholar 

  28. Komatsubara S, Mori S, Mashiba T, et al (2003) Long-term treatment of incadronate disodium accumulates microdamage but improves the trabecular bone microarchitecture in dog vertebra. J Bone Miner Res 18:512–520

    CAS  PubMed  Google Scholar 

  29. Tonino RP, Meunier PJ, Emkey R, et al (2000) Skeletal benefits of alendronate: 7-year treatment of postmenopausal osteoporotic women. Phase III Osteoporosis Treatment Study Group. J Clin Endocrinol Metab 85:3109–3115

    Google Scholar 

  30. Sorensen OH, Crawford GM, Mulder H, et al (2003) Long-term efficacy of risedronate: a 5-year placebo-controlled clinical experience. Bone 32:120–126

    Article  CAS  PubMed  Google Scholar 

  31. Vashishth D, Behiri JC, Bonfield W (1997) Crack growth resistance in cortical bone: concept of microcrack toughening. J Biomech 30:763–769

    Article  CAS  PubMed  Google Scholar 

  32. Zioupos P (1998) Recent developments in the study of failure of solid biomaterials and bone: 'fracture' and 'prefracture' toughness. Mat Sci Eng 6

  33. Vashishth D, Tanner KE, Bonfield W (2003) Experimental validation of a microcracking-based toughening mechanism for cortical bone. J Biomech 36:121–124

    Article  CAS  PubMed  Google Scholar 

  34. Burr DB (2003) Microdamage and bone strength. Osteoporos Int 14:tbd

    Google Scholar 

  35. Ciarelli TE, Fyhrie DP, Parfitt AM (2003) Effects of vertebral bone fragility and bone formation rate on the mineralization levels of cancellous bone from white females. Bone 32:311–315

    Article  CAS  PubMed  Google Scholar 

  36. Lanyon L, Skerry T (2001) Postmenopausal osteoporosis as a failure of bone's adaptation to functional loading: a hypothesis. J Bone Miner Res 16:1937–1947

    PubMed  Google Scholar 

  37. Ciarelli TE, Fyhrie DP, Schaffler MB, Goldstein SA (2000) Variations in three-dimensional cancellous bone architecture of the proximal femur in female hip fractures and in controls. J Bone Miner Res 15:32–40

    CAS  PubMed  Google Scholar 

  38. Yeh OC, Keaveny TM (1999) Biomechanical effects of intraspecimen variations in trabecular architecture: a three-dimensional finite element study. Bone 25:223–228

    Article  CAS  PubMed  Google Scholar 

  39. Marshall D, Johnell O, Wedel H (1996) Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 312:1254–1259

    CAS  PubMed  Google Scholar 

  40. Cummings SR, Bates D, Black DM (2002) Clinical use of bone densitometry: scientific review. JAMA 288:1889–1897

    Article  PubMed  Google Scholar 

  41. Garnero P (2000) Markers of bone turnover for the prediction of fracture risk. Osteoporos Int 11 [Suppl 6]:S55–65

    Google Scholar 

  42. Garnero P, Delmas P (2001) Biochemical markers of bone turnover in osteoporosis. In: Marcus R, Kelsey J, Feldman D (eds) Osteoporosis. Academic Press, San Diego, pp 459–478

  43. Eastell R, Barton I, Hannon RA, et al (2003) Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate. J Bone Miner Res 18:1051–1056

    CAS  PubMed  Google Scholar 

  44. Delmas PD, Eastell R, Garnero P, Seibel MJ, Stepan J (2000) The use of biochemical markers of bone turnover in osteoporosis. Committee of scientific advisors of the International Osteoporosis Foundation. Osteoporos Int 11:S2–17

    Article  PubMed  Google Scholar 

  45. Johnell O, Oden A, De Laet C, et al (2002) Biochemical indices of bone turnover and the assessment of fracture probability. Osteoporos Int 13:523–526

    Article  Google Scholar 

  46. Riggs BL, Melton LJ 3rd (2002) Bone turnover matters: the raloxifene treatment paradox of dramatic decreases in vertebral fractures without commensurate increases in bone density. J Bone Miner Res 17:11–14

    PubMed  Google Scholar 

  47. Beck TJ (2003) Measuring the structural strength of bones with dual-energy X-ray absorptiometry: principles, technical limitations, and future possibilities. Osteoporos Int 14:tbd

    Google Scholar 

  48. Muller R (2003) Bone microarchitecture assessment—current and future trends. Osteoporos Int 14:tbd

    Google Scholar 

  49. Dempster D (2003) Bone microarchitecture and strength. Osteoporos Int 14:tbd

    Google Scholar 

  50. Beck TJ, Oreskovic TL, Stone KL, et al (2001) Structural adaptation to changing skeletal load in the progression toward hip fragility: the study of osteoporotic fractures. J Bone Miner Res 16:1108–1119

    CAS  PubMed  Google Scholar 

  51. Beck TJ, Stone KL, Oreskovic TL, et al (2001) Effects of current and discontinued estrogen replacement therapy on hip structural geometry: the study of osteoporotic fractures. J Bone Miner Res 16:2103–2110

    CAS  PubMed  Google Scholar 

  52. Beck TJ, Looker AC, Ruff CB, Sievanen H, Wahner HW (2000) Structural trends in the aging femoral neck and proximal shaft: analysis of the Third National Health and Nutrition Examination Survey dual-energy X-ray absorptiometry data. J Bone Miner Res 15:2297–2304

    CAS  PubMed  Google Scholar 

  53. Crabtree N, Lunt M, Holt G, et al (2000) Hip geometry, bone mineral distribution, and bone strength in European men and women: the EPOS study. Bone 27:151–159

    Article  CAS  PubMed  Google Scholar 

  54. Nelson DA, Barondess DA, Hendrix SL, Beck TJ (2000) Cross-sectional geometry, bone strength, and bone mass in the proximal femur in black and white postmenopausal women. J Bone Miner Res 15:1992–1997

    CAS  PubMed  Google Scholar 

  55. Crabtree NJ, Kroger H, Martin A, et al (2002) Improving risk assessment: hip geometry, bone mineral distribution and bone strength in hip fracture cases and controls. The EPOS study. European Prospective Osteoporosis Study. Osteoporos Int 13:48–54

    Article  Google Scholar 

  56. Looker AC, Beck TJ, Orwoll ES (2001) Does body size account for gender differences in femur bone density and geometry? J Bone Miner Res 16:1291–1299

    Google Scholar 

  57. Link TM, Majumdar S, Grampp S, et al (1999) Imaging of trabecular bone structure in osteoporosis. Eur Radiol 9:1781–1788

    CAS  PubMed  Google Scholar 

  58. Wehrli FW, Saha PK, Gomberg BR, et al (2002) Role of magnetic resonance for assessing structure and function of trabecular bone. Top Magn Reson Imaging 13:335–355

    Article  PubMed  Google Scholar 

  59. Wehrli FW, Hilaire L, Fernandez-Seara M, et al (2002) Quantitative magnetic resonance imaging in the calcaneus and femur of women with varying degrees of osteopenia and vertebral deformity status. J Bone Miner Res 17:2265–2273

    PubMed  Google Scholar 

  60. Link TM, Majumdar S, Augat P, et al (1998) Proximal femur: assessment for osteoporosis with T2* decay characteristics at MR imaging. Radiology 209:531–536

    CAS  PubMed  Google Scholar 

  61. Brismar TB (2000) MR relaxometry of lumbar spine, hip, and calcaneus in healthy premenopausal women: relationship with dual energy X-ray absorptiometry and quantitative ultrasound. Eur Radiol 10:1215–1221

    Article  CAS  PubMed  Google Scholar 

  62. Link TM, Vieth V, Stehling C, et al (2003) High-resolution MRI vs multislice spiral CT: which technique depicts the trabecular bone structure best? Eur Radiol 13:663–671

    PubMed  Google Scholar 

  63. Majumdar S, Genant HK, Grampp S, et al (1997) Correlation of trabecular bone structure with age, bone mineral density, and osteoporotic status: in vivo studies in the distal radius using high resolution magnetic resonance imaging. J Bone Miner Res 12:111–118

    CAS  PubMed  Google Scholar 

  64. Wehrli FW, Hwang SN, Ma J, et al (1998) Cancellous bone volume and structure in the forearm: noninvasive assessment with MR microimaging and image processing. Radiology 206:347–357

    CAS  PubMed  Google Scholar 

  65. Link TM, Majumdar S, Augat P, et al (1998) In vivo high resolution MRI of the calcaneus: differences in trabecular structure in osteoporosis patients. J Bone Miner Res 13:1175–1182

    CAS  PubMed  Google Scholar 

  66. Wehrli FW, Gomberg BR, Saha PK, et al (2001) Digital topological analysis of in vivo magnetic resonance microimages of trabecular bone reveals structural implications of osteoporosis. J Bone Miner Res 16:1520–1531

    CAS  PubMed  Google Scholar 

  67. Link TM, Vieth V, Matheis J, et al (2002) Bone structure of the distal radius and the calcaneus vs BMD of the spine and proximal femur in the prediction of osteoporotic spine fractures. Eur Radiol 12:401–408

    PubMed  Google Scholar 

  68. Majumdar S, Link TM, Augat P, et al (1999) Trabecular bone architecture in the distal radius using magnetic resonance imaging in subjects with fractures of the proximal femur. Magnetic Resonance Science Center and Osteoporosis and Arthritis Research Group. Osteoporos Int 10:231–239

    CAS  PubMed  Google Scholar 

  69. Lang TF, Li J, Harris ST, Genant HK (1999) Assessment of vertebral bone mineral density using volumetric quantitative CT. J Comput Assist Tomogr 23:130–137

    Article  CAS  PubMed  Google Scholar 

  70. Lang TF, Guglielmi G, van Kuijk C, et al (2002) Measurement of bone mineral density at the spine and proximal femur by volumetric quantitative computed tomography and dual-energy X-ray absorptiometry in elderly women with and without vertebral fractures. Bone 30:247–250

    Article  CAS  PubMed  Google Scholar 

  71. Lane NE, Sanchez S, Modin GW, et al (1998) Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis. Results of a randomized controlled clinical trial. J Clin Invest 102:1627–1633

    CAS  PubMed  Google Scholar 

  72. Lane NE, Sanchez S, Modin GW, et al (2000) Bone mass continues to increase at the hip after parathyroid hormone treatment is discontinued in glucocorticoid-induced osteoporosis: results of a randomized controlled clinical trial. J Bone Miner Res 15:944–951

    CAS  PubMed  Google Scholar 

  73. Rehman Q, Lang T, Modin G, Lane NE (2002) Quantitative computed tomography of the lumbar spine, not dual X-ray absorptiometry, is an independent predictor of prevalent vertebral fractures in postmenopausal women with osteopenia receiving long-term glucocorticoid and hormone-replacement therapy. Arthritis Rheum 46:1292–1297

    Article  CAS  PubMed  Google Scholar 

  74. Rehman Q, Lang TF, Arnaud CD, Modin GW, Lane NE (2003) Daily treatment with parathyroid hormone is associated with an increase in vertebral cross-sectional area in postmenopausal women with glucocorticoid-induced osteoporosis. Osteoporos Int 14:77–81

    CAS  PubMed  Google Scholar 

  75. Ahlborg HG, Johnell O, Nilsson BE, et al (2001) Bone loss in relation to menopause: a prospective study during 16 years. Bone 28:327–331

    Article  CAS  PubMed  Google Scholar 

  76. Chevalier F, Laval-Jeantet AM, Laval-Jeantet M, Bergot C (1992) CT image analysis of the vertebral trabecular network in vivo. Calcif Tissue Int 51:8–13

    CAS  PubMed  Google Scholar 

  77. Ito M, Ohki M, Hayashi K, et al (1995) Trabecular texture analysis of CT images in the relationship with spinal fracture. Radiology 194:55–59

    CAS  PubMed  Google Scholar 

  78. Pistoia W, van Rietbergen B, Laib A, Ruegsegger P (2001) High-resolution three-dimensional-pQCT images can be an adequate basis for in-vivo microFE analysis of bone. J Biomech Eng 123:176–183

    Article  CAS  PubMed  Google Scholar 

  79. van Rietbergen B, Majumdar S, Newitt D, MacDonald BR (2002) High-resolution MRI and micro-FE for the evaluation of changes in bone mechanical properties during longitudinal clinical trials: application to calcaneal bone in postmenopausal women after 1 year of idoxifene treatment. Clin Biomech (Bristol, Avon) 17:81–88

    Google Scholar 

  80. Newitt DC, van Rietbergen B, Majumdar S (2002) Processing and analysis of in vivo high-resolution MR images of trabecular bone for longitudinal studies: reproducibility of structural measures and micro-finite element analysis derived mechanical properties. Osteoporos Int 13:278–287

    Article  Google Scholar 

  81. Newitt DC, Majumdar S, van Rietbergen B, et al (2002) In vivo assessment of architecture and micro-finite element analysis derived indices of mechanical properties of trabecular bone in the radius. Osteoporos Int 13:6–17

    Article  Google Scholar 

  82. Brandenburger G (1993) Clinical determination of bone quality: Is ultrasound an answer? Calif Tissue Int 53:S151–S156

    Google Scholar 

  83. Gluer CC (1997) Quantitative ultrasound techniques for the assessment of osteoporosis: expert agreement on current status. The International Quantitative Ultrasound Consensus Group. J Bone Miner Res 12:1280–1288

    PubMed  Google Scholar 

  84. Hans D, Dargent-Molina P, Schott AM, et al (1996) Ultrasonographic heel measurements to predict hip fracture in elderly women: the EPIDOS prospective study. Lancet 348:511–514

    CAS  PubMed  Google Scholar 

  85. Bauer DC, Gluer CC, Cauley JA, et al (1997) Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women. A prospective study of the Osteoporotic Fractures Research Group. Arch Intern Med 157:629–634

    CAS  PubMed  Google Scholar 

  86. Wear KA (2003) Characterization of trabecular bone using the backscattered spectral centroid shift. IEEE Trans Ultrason Ferroelectr Freq Control 50:402–407

    Article  PubMed  Google Scholar 

  87. Chaffai S, Peyrin F, Nuzzo S, et al (2002) Ultrasonic characterization of human cancellous bone using transmission and backscatter measurements: relationships to density and microstructure. Bone 30:229–237

    Article  CAS  PubMed  Google Scholar 

  88. Jenson F, Padilla F, Laugier P (2003) Prediction of frequency-dependent ultrasonic backscatter in cancellous bone using statistical weak scattering model. Ultrasound Med Biol 29:455–464

    Article  PubMed  Google Scholar 

  89. Ouedraogo E, Lasaygues P, Lefebvre JP, et al (2002) Contrast and velocity ultrasonic tomography of long bones. Ultrason Imaging 24:139–160

    CAS  PubMed  Google Scholar 

  90. Padilla F, Peyrin F, Laugier P (2003) Prediction of backscatter coefficient in trabecular bones using a numerical model of three-dimensional microstructure. J Acoust Soc Am 113:1122–1129

    Article  PubMed  Google Scholar 

  91. Wear KA (2001) Fundamental precision limitations for measurements of frequency dependence of backscatter: applications in tissue-mimicking phantoms and trabecular bone. J Acoust Soc Am 110:3275–3282.

    Article  CAS  PubMed  Google Scholar 

  92. Wear KA, Armstrong DW 3rd (2001) Relationships among calcaneal backscatter, attenuation, sound speed, hip bone mineral density, and age in normal adult women. J Acoust Soc Am 110:573–578

    Article  CAS  PubMed  Google Scholar 

  93. Wu Y, Ackerman JL, Chesler DA, et al (2003) Density of organic matrix of native mineralized bone measured by water- and fat-suppressed proton projection MRI. Magn Reson Med 50:59–68

    Article  PubMed  Google Scholar 

  94. Wu Y, Ackerman JL, Strawich ES, et al (2003) Phosphate ions in bone: identification of a calcium-organic phosphate complex by 31P solid-state NMR spectroscopy at early stages of mineralization. Calcif Tissue Int 72:610–626

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

I wish to thank all of the symposium participants for freely sharing their insights on bone quality and critical areas for future research. I also thank Drs. Robert Marcus, Stephen Morris and Ego Seeman for their critical reviews of this manuscript.

Authors
  1. Mary L. Bouxsein
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bouxsein, M.L. Bone quality: where do we go from here?. Osteoporos Int 14 (Suppl 5), 118–127 (2003). https://doi.org/10.1007/s00198-003-1489-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-003-1489-x

Keywords

Search

Navigation