Article thumbnail

Microindentation for In Vivo Measurement of Bone Tissue Mechanical Properties in Humans

By Adolfo Diez-Perez, Roberto Güerri, Xavier Nogues, Enric Cáceres, Maria Jesus Peña, Leonardo Mellibovsky, Connor Randall, Daniel Bridges, James C Weaver, Alexander Proctor, Davis Brimer, Kurt J Koester, Robert O Ritchie and Paul K Hansma


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

Topics: Original Article
Publisher: Wiley Subscription Services, Inc., A Wiley Company
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. (2005). Age-dependent biomechanical modifications in bone. Crit Rev Eukar Gene.
  2. (2003). Aging bone and osteoporosis: strategies for preventing fractures in the elderly. Arch Intern Med.
  3. (2006). An introduction to ROC analysis. Pattern Recognition Letters.
  4. (2009). Atomic force microscopy and indentation force measurement of bone. Available at: Accessed
  5. Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: The OFELY study.
  6. (2002). Biomechanics of bone: Determinants of skeletal fragility and bone quality. Osteoporosis Int.
  7. (2006). Bone diagnostic instrument. Rev Sci Instrum.
  8. Bone mineral crystal size. Osteoporosis Int.
  9. (2003). Bone quality: where do we go from here? Osteoporosis Int.
  10. (2009). Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus Osteoporosis Int. Available at: http:// Accessed
  11. Crack growth resistance in cortical bone: Concept of microcrack toughening.
  12. (2008). DelmasPD.FiniteElementAnalysisBasedonInVivoHR-pQCTImages of the Distal Radius Is Associated With Wrist Fracture in Postmenopausal Women. J Bone Miner Res.
  13. Evidence for an elementary process in bone plasticity with an activationenthalpyof 1eV.
  14. (2006). Extracellular post-translational modifications of collagen are major determinants of biomechanical properties of fetal bovine cortical bone.
  15. (2007). 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.
  16. From brittle to ductile fracture of bone.
  17. Hierarchical interconnections in the nano-composite material bone: Fibrillar cross-links resist fracture on severallength scales.
  18. High-speed photography of compressed human trabecular bone correlates whitening to microscopic damage. Engineering Fracture Mechanics.
  19. High-speed photography of the development of microdamage in trabecular bone during compression.
  20. Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs.
  21. Incompatible mechanical properties in compact bone.
  22. 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.
  23. KoesterKJ,AgerJW,RitchieRO.Thetruetoughnessofhumancortical bone measured with realistically short cracks.
  24. Living with cracks: damage and repair in human bone.
  25. Mechanisms of disease - Bone quality - The material and structural basis of bone strength and fragility.
  26. Mechanistic aspects of fracture and R-curve behavior of human cortical bone.
  27. Nanoindentation and storage of teeth.
  28. (2005). Nanoscale deformation mechanisms in bone. Nano Lett.
  29. (2005). Novel Techniques for HighResolution Functional Imaging of Trabecular Bone.
  30. (2008). Orientation of collagen at the osteocyte lacunae in human secondary osteons.
  31. (1989). Orientation of collagen in human tibial and fibular shaft and possible correlation with mechanical properties.
  32. Penetration Testing of Bone Using the Osteopenetrometer. In: An
  33. (2009). Plasticity and toughness in bone. Phys Today.
  34. (2009). Project for Statistical Computing. Available at: http://www.
  35. Sacrificial bonds and hidden length: Unraveling molecular mesostructures in tough materials.
  36. Structure and mechanical quality of the collagen-mineral nano-composite in bone.
  37. The aging cortex: to crack or not to crack.
  38. (2008). The bone diagnostic instrument II: Indentation distance increase. Rev Sci Instrum.
  39. (2009). The bone diagnostic instrument III: testing mouse femora. Rev Sci Instrum.
  40. (2002). The contribution of the organic matrix to bone’s material properties.
  41. The tissue diagnostic instrument. Rev Sci Instrum.
  42. Use of DXA-based structural engineering models of the proximal femur to discriminate hip fracture. J Bone Miner Res.