Microindentation for in vivo measurement of bone tissue mechanical properties in humans

Abstract

Bone tissue mechanical properties are deemed a key component of bone strength, but their assessment requires invasive procedures. Here we validate a new instrument, a reference point indentation (RPI) instrument, for measuring these tissue properties in vivo. The RPI instrument performs bone microindentation testing (BMT) by inserting a probe assembly through the skin covering the tibia and, after displacing periosteum, applying 20 indentation cycles at 2 Hz each with a maximum force of 11 N. We assessed 27 women with osteoporosis-related fractures and 8 controls of comparable ages. Measured total indentation distance (46.0 ± 14 versus 31.7 ± 3.3 µm, p = .008) and indentation distance increase (18.1 ± 5.6 versus 12.3 ± 2.9 µm, p = .008) were significantly greater in fracture patients than in controls. Areas under the receiver operating characteristic (ROC) curve for the two measurements were 93.1% (95% confidence interval [CI] 83.1–100) and 90.3% (95% CI 73.2–100), respectively. Interobserver coefficient of variation ranged from 8.7% to 15.5%, and the procedure was well tolerated. In a separate study of cadaveric human bone samples (n = 5), crack growth toughness and indentation distance increase correlated (r = –0.9036, p = .018), and scanning electron microscope images of cracks induced by indentation and by experimental fractures were similar. We conclude that BMT, by inducing microscopic fractures, directly measures bone mechanical properties at the tissue level. The technique is feasible for use in clinics with good reproducibility. It discriminates precisely between patients with and without fragility fracture and may provide clinicians and researchers with a direct in vivo measurement of bone tissue resistance to fracture. © 2010 American Society for Bone and Mineral Research

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References 47

1. 1.

   Ettinger MP. Aging bone and osteoporosis: strategies for preventing fractures in the elderly. Arch Intern Med. 2003;163:2237-2246.

   Not in our library10.1001/archinte.163.18.2237

2. 2.

   Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. JAMA. 2001;285:785-795.

   Not in our library10.1001/jama.285.6.785

3. 3.

   Rivadeneira F, Zillikens MC, Laet CED, et al. Femoral neck BMD is a strong predictor of hip fracture susceptibility in elderly men and women because it detects cortical bone instability: the Rotterdam Study. J Bone Miner Res. 2007;22:1781-1790.

   Not in our library10.1359/jbmr.070712

4. 4.

   Yang L, Peel N, Clowes JA, McCloskey EV, Eastell R. Use of DXA-based structural engineering models of the proximal femur to discriminate hip fracture. J Bone Miner Res. 2009;24:33-42.

   Not in our library10.1359/jbmr.080906

5. 5.

   Cummings SR, Karpf DB, Harris F, et al. Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs. Am J Med. 2002;112:281-289.

   Not in our library10.1016/s0002-9343(01)01124-x

6. 6.

   Boutroy S, Rietbergen BV, Sornay-Rendu E, Munoz F, Bouxsein ML, Delmas PD. Finite Element Analysis Based on In Vivo HR-pQCT Images of the Distal Radius Is Associated With Wrist Fracture in Postmenopausal Women. J Bone Miner Res. 2008;23:392-399.

   Not in our library10.1359/jbmr.071108

7. 7.

   Garnero PS-RE, Claustrat B, Delmas PD. Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: The OFELY study. J Bone Miner Res. 2000;15:1526-1536.

   Not in our library10.1359/jbmr.2000.15.8.1526

8. 8.

   Chavassieux P, Seeman E, Delmas PD. Insights into Material and Structural Basis of Bone Fragility from Diseases Associated with Fractures: How Determinants of the Biomechanical Properties of Bone Are Compromised by Disease. Endocrine Reviews. 2007;28:151-164.

   Not in our library10.1210/er.2006-0029

9. 9.

   Vashishth D. Age-dependent biomechanical modifications in bone. Crit Rev Eukar Gene. 2005;15:343-357.

   Not in our library10.1615/critreveukargeneexpr.v15.i4.40

10. 10.

    Currey JD. Changes in impact energy absorption with age. J Biomech. 1979;12:459-469.

    Not in our library10.1016/0021-9290(79)90031-9

11. 11.

    Currey J. Incompatible mechanical properties in compact bone. J Theor Biol. 2004;231:569-580.

    Not in our library10.1016/j.jtbi.2004.07.013

12. 12.

    Turner CH. Biomechanics of bone: Determinants of skeletal fragility and bone quality. Osteoporosis Int. 2002;13:97-104.

    Not in our library10.1007/s001980200000

13. 13.

    Bouxsein ML. Bone quality: where do we go from here? Osteoporosis Int. 2003;14:S118-S127.

    Not in our library10.1007/s00198-003-1489-x

14. 14.

    Jepsen KJ. The aging cortex: to crack or not to crack. Osteoporos Int. 2003;14(Suppl 5):S57-S62.

    Not in our library10.1007/s00198-003-1475-3

15. 15.

    Seeman E, Delmas PD. Mechanisms of disease - Bone quality - The material and structural basis of bone strength and fragility. New Engl J Med. 2006;354:2250-2261.

    Not in our library10.1056/nejmra053077

16. 16.

    Saito M, Marumo K. 2009.

    Not in our library

17. 17.

    Hansma PK, Yu H, Schultz D, et al. The tissue diagnostic instrument. Rev Sci Instrum. 2009;80:054303.

    Not in our library10.1063/1.3127602

18. 18.

    Hansma PK, Turner PJ, Fantner GE. Bone diagnostic instrument. Rev Sci Instrum. 2006;77:075105.

    Not in our library

19. 19.

    Hansma PK, Turner P, Drake B, et al. The bone diagnostic instrument II: Indentation distance increase. Rev Sci Instrum. 2008;79:064303.

    Not in our library10.1063/1.2937199

20. 20.

    Randall C, Mathews P, Yurtsev E, Sahar N, Kohn D, Hansma P. The bone diagnostic instrument III: testing mouse femora. Rev Sci Instrum. 2009;80:065108.

    Not in our library10.1063/1.3147383

21. 21.

    Habelitz S, Marshall GW, Balooch M, Marshall SJ. Nanoindentation and storage of teeth. J Biomech. 2002;35:995-998.

    Not in our library10.1016/s0021-9290(02)00039-8

22. 22.

    Koester KJ, Ager JW, Ritchie RO. The true toughness of human cortical bone measured with realistically short cracks. Nat Mater. 2008;7:672-677.

    Not in our library10.1038/nmat2221

23. 23.

    Nalla RK, Kruzic JJ, Kinney JH, Ritchie RO. Mechanistic aspects of fracture and R-curve behavior of human cortical bone. Biomaterials. 2005;26:217-231.

    Not in our library10.1016/j.biomaterials.2004.02.017

24. 24.

    Vashishth D, Behiri JC, Bonfield W. Crack growth resistance in cortical bone: Concept of microcrack toughening. J Biomech. 1997;30:763-769.

    Not in our library10.1016/s0021-9290(97)00029-8

25. 25.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

26. 26.

    Fawcett T. An introduction to ROC analysis. Pattern Recognition Letters. 2006;27:861-874.

    Not in our library

27. 27.

    Thurner PJ, Erickson B, Jungmann R, et al. High-speed photography of compressed human trabecular bone correlates whitening to microscopic damage. Engineering Fracture Mechanics. 2007;74:1928-1941.

    Not in our library

28. 28.

    Thurner PJ, Erickson B, Turner P, et al. The Effect of NaF In Vitro on the Mechanical and Material Properties of Trabecular and Cortical Bone. Adv Mater. 2009;21:451-457.

    Not in our library

29. 29.

    Fratzl P, Gupta HS, Paschalis EP, Roschger P. Structure and mechanical quality of the collagen-mineral nano-composite in bone. J Mater Chem. 2004;14:2115-2123.

    Not in our library

30. 30.

    Taylor D, Hazenberg JG, Lee TC. Living with cracks: damage and repair in human bone. Nat Mater. 2007;6:263-268.

    Not in our library10.1038/nmat1866

31. 31.

    Burr D. Microdamage and bone strength. Osteoporos Int. 2003;14(Suppl 5):S67-S72.

    Not in our library10.1007/s00198-003-1476-2

32. 32.

    Boskey A. Bone mineral crystal size. Osteoporosis Int. 2003;14:S16-S20.

    Not in our library10.1007/s00198-003-1468-2

33. 33.

    Burr DB. The contribution of the organic matrix to bone's material properties. Bone. 2002;31:8-11.

    Not in our library10.1016/s8756-3282(02)00815-3

34. 34.

    Garnero P, Borel O, Gineyts E, et al. Extracellular post-translational modifications of collagen are major determinants of biomechanical properties of fetal bovine cortical bone. Bone. 2006;38:300-309.

    Not in our library10.1016/j.bone.2005.09.014

35. 35.

    Peterlik H, Roschger P, Klaushofer K, Fratzl P. From brittle to ductile fracture of bone. Nat Mater. 2006;5:52-55.

    Not in our library10.1038/nmat1545

36. 36.

    Carando S, Portigliatti Barbos M, Ascenzi A, Boyde A. Orientation of collagen in human tibial and fibular shaft and possible correlation with mechanical properties. Bone. 1989;10:139-142.

    Not in our library10.1016/8756-3282(89)90012-4

37. 37.

    Ascenzi MG, Gill J, Lomovtsev A. Orientation of collagen at the osteocyte lacunae in human secondary osteons. J Biomech. 2008;41:3426-3435.

    Not in our library10.1016/j.jbiomech.2008.09.010

38. 38.

    Fantner GE, Hassenkam T, Kindt JH, et al. Sacrificial bonds and hidden length dissipate energy as mineralized fibrils separate during bone fracture. Nat Mater. 2005;4:612-616.

    Not in our library10.1038/nmat1428

39. 39.

    Gupta HS, Fratzl P, Kerschnitzki M, Benecke G, Wagermaier W, Kirchner HOK. Evidence for an elementary process in bone plasticity with an activation enthalpy of 1 eV. J R Soc Interface. 2007;4:277-282.

    Not in our library10.1098/rsif.2006.0172

40. 40.

    Fantner GE, Oroudjev E, Schitter G, et al. Sacrificial bonds and hidden length: Unraveling molecular mesostructures in tough materials. Biophys J. 2006;90:1411-1418.

    Not in our library10.1529/biophysj.105.069344

41. 41.

    Fantner GE, Rabinovych O, Schitter G, et al. Hierarchical interconnections in the nano-composite material bone: Fibrillar cross-links resist fracture on several length scales. Compos Sci Technol. 2006;66:1205-1211.

    Not in our library

42. 42.

    Thurner PJ, Erickson B, Schriock Z, et al. High-speed photography of the development of microdamage in trabecular bone during compression. J Mater Res. 2006;21:1093-1100.

    Not in our library

43. 43.

    Ritchie RO, Buehler MJ, Hansma P. Plasticity and toughness in bone. Phys Today. 2009;62:41-47.

    Not in our library

44. 44.

    Gupta HS, Wagermaier W, Zickler GA, et al. Nanoscale deformation mechanisms in bone. Nano Lett. 2005;5:2108-2111.

    Not in our library10.1021/nl051584b

45. 45.

    Thurner PJ, Muller R, Kindt J, Amini Amir A, Manduca Armando, et al. Novel Techniques for High-Resolution Functional Imaging of Trabecular Bone. Proceedings of SPIE - Medical Imaging 2005: Physiology, Function, and Structure from Medical Images. 2005;5746:515-526.

    Not in our library

46. 46.

    Thurner P. 2009.

    Not in our library

47. 47.

    Hvid I, An YH, Draughn RA, Linde F. Penetration Testing of Bone Using the Osteopenetrometer. Mechanical Testing of Bone and the Bone-Implant Interface. 2000;241-246.

    Not in our library

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• Women with previous stress fractures show reduced bone material strength: Microindentation measurements in a retrospective case-control study of 60 subjects · 2016
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