Advertisement

Journal of Bone and Mineral Metabolism

, Volume 37, Issue 6, pp 1048–1057 | Cite as

Functional disuse initiates medullary endosteal micro-architectural impairment in cortical bone characterized by nanoindentation

  • Kartikey Grover
  • Minyi Hu
  • Liangjun Lin
  • Jesse Muir
  • Yi-Xian QinEmail author
Original Article
  • 86 Downloads

Abstract

In this study, we evaluated the effect of functional disuse-induced bone remodeling on its mechanical properties, individually at periosteum and medullary endosteum regions of the cortical bone. Left middle tibiae were obtained from 5-month-old female Sprague–Dawley rats for the baseline control as well as hindlimb suspended (disuse) groups. Micro-nano-mechanical elastic moduli (at lateral region) was evaluated along axial (Z), circumferential (C) and radial (R) orientations using nanoindentation. Results indicated an anisotropic microstructure with axial orientation having the highest and radial orientation with the lowest moduli at periosteum and medullary endosteum for both baseline control as well as disuse groups. Between the groups: at periosteum, an insignificant difference was evaluated for each of the orientations (p > 0.05) and at endosteum, a significant decrease of elastic moduli in the radial (p < 0.0001), circumferential (p < 0.001) and statistically insignificant difference in axial (p > 0.05) orientation. For the moduli ratios between groups: at periosteum, only significant difference in the Z/R (p < 0.05) anisotropy ratio, whereas at endosteum, a statistically significant difference in Z/C (p < 0.001), and Z/R (p < 0.001), as well as C/R (p < 0.05) anisotropy ratios, was evaluated. The results suggested initial bone remodeling impaired bone micro-architecture predominantly at the medullary endosteum with possible alterations in the geometric orientations of collagen and mineral phases inside the bone. The findings could be significant for studying the mechanotransduction pathways involved in maintaining the bone micro-architecture and possibly have high clinical significance for drug use against impairment from functional disuse.

Keywords

Nanoindentation Orientation Periosteum Endosteum Micro-architecture 

Notes

Acknowledgements

This work is kindly supported by the National Institute of Health (R01 AR52379 and R01AR61821), the US Army Medical Research and Materiel Command, The National Space Biomedical Research Institute through NASA contract NCC 9-58. I would also like to acknowledge Tony Zhang for his technical assistance.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflicts of interest to disclose in relation to this manuscript.

Ethical approval

The experimental setting, data analyses, manuscript writing are all following ethical guidelines.

Informed consent

There is no human nor live animal experiment involved in this study.

References

  1. 1.
    Burger EH, Klein-Nulend J (1999) Mechanotransduction in bone–role of the lacuno-canalicular network. FASEB J 13(Suppl):S101–S112CrossRefGoogle Scholar
  2. 2.
    Qin YX, Lam H, Ferreri S, Rubin C (2010) Dynamic skeletal muscle stimulation and its potential in bone adaptation. J Musculoskelet Neuronal Interact 10:12–24PubMedPubMedCentralGoogle Scholar
  3. 3.
    Qin YX, Rubin CT, McLeod KJ (1998) Nonlinear dependence of loading intensity and cycle number in the maintenance of bone mass and morphology. J Orthop Res 16:482–489.  https://doi.org/10.1002/jor.1100160414 CrossRefPubMedGoogle Scholar
  4. 4.
    Weinbaum S, Cowin SC, Zeng Y (1994) A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses. J Biomech 27:339–360CrossRefGoogle Scholar
  5. 5.
    Reich KM, Gay CV, Frangos JA (1990) Fluid shear stress as a mediator of osteoblast cyclic adenosine monophosphate production. J Cell Physiol 143:100–104.  https://doi.org/10.1002/jcp.1041430113 CrossRefPubMedGoogle Scholar
  6. 6.
    Knothe Tate ML, Niederer P, Knothe U (1998) In vivo tracer transport through the lacunocanalicular system of rat bone in an environment devoid of mechanical loading. Bone 22:107–117.  https://doi.org/10.1016/S8756-3282(97)00234-2 CrossRefPubMedGoogle Scholar
  7. 7.
    Rubin J, Biskobing D, Fan X, Rubin C, McLeod K, Taylor WR (1997) Pressure regulates osteoclast formation and MCSF expression in marrow culture. J Cell Physiol 170:81–87.  https://doi.org/10.1002/(SICI)1097-4652(199701)170:1%3c81:AID-JCP9%3e3.0.CO;2-H CrossRefPubMedGoogle Scholar
  8. 8.
    Huang C, Ogawa R (2010) Mechanotransduction in bone repair and regeneration. FASEB J 24:3625–3632.  https://doi.org/10.1096/fj.10-157370fj.10-157370 CrossRefPubMedGoogle Scholar
  9. 9.
    Turner CH, Forwood MR, Otter MW (1994) Mechanotransduction in bone: do bone cells act as sensors of fluid flow? FASEB J 8:875–878CrossRefGoogle Scholar
  10. 10.
    Donaldson CL, Hulley SB, Vogel JM, Hattner RS, Bayers JH, McMillan DE (1970) Effect of prolonged bed rest on bone mineral. Metabolism 19:1071–1084CrossRefGoogle Scholar
  11. 11.
    Huang C, Holfeld J, Schaden W, Orgill D, Ogawa R (2013) Mechanotherapy: revisiting physical therapy and recruiting mechanobiology for a new era in medicine. Trends Mol Med 19:555–564.  https://doi.org/10.1016/j.molmed.2013.05.005S1471-4914(13)00092-0 CrossRefPubMedGoogle Scholar
  12. 12.
    Manske SL, Lorincz CR, Zernicke RF (2009) Bone health: part 2, physical activity. Sports Health 1:341–346.  https://doi.org/10.1177/194173810933882310.1177_1941738109338823 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Rubin CT, Lanyon LE (1987) Kappa delta award paper. osteoregulatory nature of mechanical stimuli: function as a determinant for adaptive remodeling in bone. J Orthop Res 5:300–310.  https://doi.org/10.1002/jor.1100050217 CrossRefPubMedGoogle Scholar
  14. 14.
    van der Meulen MC, Morgan TG, Yang X, Baldini TH, Myers ER, Wright TM, Bostrom MP (2006) Cancellous bone adaptation to in vivo loading in a rabbit model. Bone 38:871–877.  https://doi.org/10.1016/j.bone.2005.11.026 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Wallace JM, Ron MS, Kohn DH (2009) Short-term exercise in mice increases tibial post-yield mechanical properties while 2 weeks of latency following exercise increases tissue-level strength. Calcif Tissue Int 84:297–304.  https://doi.org/10.1007/s00223-009-9228-8 CrossRefPubMedGoogle Scholar
  16. 16.
    Wolf JH (1995) Julis Wolff and his “law of bone remodeling” (in ger). Orthopade (Julius Wolff und sein “Gesetz der Transformation der Knochen”) 24:378–386Google Scholar
  17. 17.
    Gross TS, Rubin CT (1995) Uniformity of resorptive bone loss induced by disuse. J Orthop Res 13:708–714.  https://doi.org/10.1002/jor.1100130510 CrossRefPubMedGoogle Scholar
  18. 18.
    Kaneps AJ, Stover SM, Lane NE (1997) Changes in canine cortical and cancellous bone mechanical properties following immobilization and remobilization with exercise. Bone 21:419–423.  https://doi.org/10.1016/S8756-3282(97)00167-1 CrossRefPubMedGoogle Scholar
  19. 19.
    Li CY, Price C, Delisser K, Nasser P, Laudier D, Clement M, Jepsen KJ, Schaffler MB (2005) Long-term disuse osteoporosis seems less sensitive to bisphosphonate treatment than other osteoporosis. J Bone Miner Res 20:117–124.  https://doi.org/10.1359/JBMR.041010 CrossRefPubMedGoogle Scholar
  20. 20.
    Lau RY, Guo X (2011) A review on current osteoporosis research: with special focus on disuse bone loss. J Osteoporos 2011:293808.  https://doi.org/10.4061/2011/293808 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Weiner S, Traub W, Wagner HD (1999) Lamellar bone: structure-function relations. J Struct Biol 126:241–255.  https://doi.org/10.1006/jsbi.1999.4107 CrossRefPubMedGoogle Scholar
  22. 22.
    Manjubala I, Liu Y, Epari DR, Roschger P, Schell H, Fratzl P, Duda GN (2009) Spatial and temporal variations of mechanical properties and mineral content of the external callus during bone healing. Bone 45:185–192.  https://doi.org/10.1016/j.bone.2009.04.249S8756-3282(09)01565-8 CrossRefPubMedGoogle Scholar
  23. 23.
    Martin RB, Boardman DL (1993) The effects of collagen fiber orientation, porosity, density, and mineralization on bovine cortical bone bending properties. J Biomech 26:1047–1054CrossRefGoogle Scholar
  24. 24.
    Martin RB, Ishida J (1989) The relative effects of collagen fiber orientation, porosity, density, and mineralization on bone strength. J Biomech 22:419–426CrossRefGoogle Scholar
  25. 25.
    Skedros JG, Dayton MR, Sybrowsky CL, Bloebaum RD, Bachus KN (2006) The influence of collagen fiber orientation and other histocompositional characteristics on the mechanical properties of equine cortical bone. J Exp Biol 209:3025–3042.  https://doi.org/10.1242/jeb.02304 CrossRefPubMedGoogle Scholar
  26. 26.
    Roberts BJ, Thrall E, Muller JA, Bouxsein ML (2010) Comparison of hip fracture risk prediction by femoral aBMD to experimentally measured factor of risk. Bone 46:742–746.  https://doi.org/10.1016/j.bone.2009.10.020S8756-3282(09)01988-7 CrossRefPubMedGoogle Scholar
  27. 27.
    Bouxsein ML, Seeman E (2009) Quantifying the material and structural determinants of bone strength. Best Pract Res Clin Rheumatol 23:741–753.  https://doi.org/10.1016/j.berh.2009.09.008S1521-6942(09)00101-6 CrossRefPubMedGoogle Scholar
  28. 28.
    Gao J, Gong H, Huang X, Fang J, Zhu D, Fan Y (2013) Relationship between microstructure, material distribution, and mechanical properties of sheep tibia during fracture healing process. Int J Med Sci 10:1560–1569.  https://doi.org/10.7150/ijms.6611ijmsv10p1560 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Yeni YN, Wu B, Huang L, Oravec D (2013) Mechanical loading causes detectable changes in morphometric measures of trabecular structure in human cancellous bone. J Biomech Eng 135:54505.  https://doi.org/10.1115/1.40241361681767 CrossRefPubMedGoogle Scholar
  30. 30.
    Currey JD (2003) The many adaptations of bone. J Biomech 36:1487–1495.  https://doi.org/10.1016/S0021-9290(03)00124-6 CrossRefPubMedGoogle Scholar
  31. 31.
    Rho JY, Kuhn-Spearing L, Zioupos P (1998) Mechanical properties and the hierarchical structure of bone. Med Eng Phys 20:92–102.  https://doi.org/10.1016/S1350-4533(98)000071 CrossRefPubMedGoogle Scholar
  32. 32.
    Courtland HW, Nasser P, Goldstone AB, Spevak L, Boskey AL, Jepsen KJ (2008) Fourier transform infrared imaging microspectroscopy and tissue-level mechanical testing reveal intraspecies variation in mouse bone mineral and matrix composition. Calcif Tissue Int 83:342–353.  https://doi.org/10.1007/s00223-008-9176-8 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Donnelly E, Boskey AL, Baker SP, van der Meulen MC (2010) Effects of tissue age on bone tissue material composition and nanomechanical properties in the rat cortex. J Biomed Mater Res A 92:1048–1056.  https://doi.org/10.1002/jbm.a.32442 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Lewis G, Nyman JS (2008) The use of nanoindentation for characterizing the properties of mineralized hard tissues: state-of-the art review. J Biomed Mater Res B Appl Biomater 87:286–301.  https://doi.org/10.1002/jbm.b.31092 CrossRefPubMedGoogle Scholar
  35. 35.
    Clarke B (2008) Normal bone anatomy and physiology. Clin J Am Soc Nephrol 3(Suppl 3):S131–S139.  https://doi.org/10.2215/CJN.041512063/Supplement_3/S131 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Ved N, Haller JO (2002) Periosteal reaction with normal-appearing underlying bone: a child abuse mimicker. Emerg Radiol 9:278–282.  https://doi.org/10.1007/s10140-002-0252-5 CrossRefPubMedGoogle Scholar
  37. 37.
    Dwek JR (2010) The periosteum: what is it, where is it, and what mimics it in its absence? Skeletal Radiol 39:319–323.  https://doi.org/10.1007/s00256-009-0849-9 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Seeman E (2003) Reduced bone formation and increased bone resorption: rational targets for the treatment of osteoporosis. Osteoporos Int 14(Suppl 3):S2–S8.  https://doi.org/10.1007/s00198-002-1340-9 CrossRefPubMedGoogle Scholar
  39. 39.
    Szulc P, Seeman E, Duboeuf F, Sornay-Rendu E, Delmas PD (2006) Bone fragility: failure of periosteal apposition to compensate for increased endocortical resorption in postmenopausal women. J Bone Miner Res 21:1856–1863.  https://doi.org/10.1359/jbmr.060904 CrossRefPubMedGoogle Scholar
  40. 40.
    LaMothe JM, Hamilton NH, Zernicke RF (2005) Strain rate influences periosteal adaptation in mature bone. Med Eng Phys 27:277–284.  https://doi.org/10.1016/j.medengphy.2004.04.012 CrossRefPubMedGoogle Scholar
  41. 41.
    Kodama Y, Umemura Y, Nagasawa S, Beamer WG, Donahue LR, Rosen CR, Baylink DJ, Farley JR (2000) Exercise and mechanical loading increase periosteal bone formation and whole bone strength in C57BL/6 J mice but not in C3H/Hej mice. Calcif Tissue Int 66:298–306.  https://doi.org/10.1007/s002230010060 CrossRefPubMedGoogle Scholar
  42. 42.
    Hoffmeister BK, Smith SR, Handley SM, Rho JY (2000) Anisotropy of Young’s modulus of human tibial cortical bone. Med Biol Eng Comput 38:333–338CrossRefGoogle Scholar
  43. 43.
    Angker L, Swain MV, Kilpatrick N (2005) Characterising the micro-mechanical behaviour of the carious dentine of primary teeth using nano-indentation. J Biomech 38:1535–1542.  https://doi.org/10.1016/j.jbiomech.2004.07.012 CrossRefPubMedGoogle Scholar
  44. 44.
    Ebenstein DM, Pruitt LA (2004) Nanoindentation of soft hydrated materials for application to vascular tissues. J Biomed Mater Res A 69:222–232.  https://doi.org/10.1002/jbm.a.20096 CrossRefPubMedGoogle Scholar
  45. 45.
    Fan Z, Swadener JG, Rho JY, Roy ME, Pharr GM (2002) Anisotropic properties of human tibial cortical bone as measured by nanoindentation. J Orthop Res 20:806–810.  https://doi.org/10.1016/S0736-0266(01)00186-3 CrossRefPubMedGoogle Scholar
  46. 46.
    Hoffler CE, Guo XE, Zysset PK, Goldstein SA (2005) An application of nanoindentation technique to measure bone tissue Lamellae properties. J Biomech Eng 127:1046–1053CrossRefGoogle Scholar
  47. 47.
    Imbert L, Auregan JC, Pernelle K, Hoc T (2014) Mechanical and mineral properties of osteogenesis imperfecta human bones at the tissue level. Bone 65:18–24.  https://doi.org/10.1016/j.bone.2014.04.030S8756-3282(14)00165-3 CrossRefPubMedGoogle Scholar
  48. 48.
    Pathak S, Vachhani SJ, Jepsen KJ, Goldman HM, Kalidindi SR (2012) Assessment of lamellar level properties in mouse bone utilizing a novel spherical nanoindentation data analysis method. J Mech Behav Biomed Mater 13:102–117.  https://doi.org/10.1016/j.jmbbm.2012.03.018S1751-6161(12)00107-5 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Khandaker M, Ekwaro-Osire S (2013) Weibull analysis of fracture test data on bovine cortical bone: influence of orientation. Int J Biomater 2013:639841.  https://doi.org/10.1155/2013/639841 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Carnelli D, Vena P, Dao M, Ortiz C, Contro R (2013) Orientation and size-dependent mechanical modulation within individual secondary osteons in cortical bone tissue. J R Soc Interface 10:20120953.  https://doi.org/10.1098/rsif.2012.0953rsif.2012.0953 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Faingold A, Cohen SR, Wagner HD (2012) Nanoindentation of osteonal bone lamellae. J Mech Behav Biomed Mater 9:198–206.  https://doi.org/10.1016/j.jmbbm.2012.01.014S1751-6161(12)00034-3 CrossRefPubMedGoogle Scholar
  52. 52.
    Franzoso G, Zysset PK (2009) Elastic anisotropy of human cortical bone secondary osteons measured by nanoindentation. J Biomech Eng 131:021001.  https://doi.org/10.1115/1.3005162 CrossRefPubMedGoogle Scholar
  53. 53.
    Reisinger AG, Pahr DH, Zysset PK (2011) Principal stiffness orientation and degree of anisotropy of human osteons based on nanoindentation in three distinct planes. J Mech Behav Biomed Mater 4:2113–2127.  https://doi.org/10.1016/j.jmbbm.2011.07.010S1751-6161(11)00197-4 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Hu M, Cheng J, Qin YX (2012) Dynamic hydraulic flow stimulation on mitigation of trabecular bone loss in a rat functional disuse model. Bone 51:819–825.  https://doi.org/10.1016/j.bone.2012.06.030S8756-3282(12)00963-5 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Milstead JR, Simske SJ, Bateman TA (2004) Spaceflight and hindlimb suspension disuse models in mice (in eng). Biomed Sci Instrum 40:105–110PubMedGoogle Scholar
  56. 56.
    Hoc T, Henry L, Verdier M, Aubry D, Sedel L, Meunier A (2006) Effect of microstructure on the mechanical properties of Haversian cortical bone. Bone 36:466–474CrossRefGoogle Scholar
  57. 57.
    Faingold A, Cohen SR, Shahar R, Weiner S, Rapoport L, Wagner HD (2014) The effect of hydration on mechanical anisotropy, topography and fibril organization of the osteonal lamellae. J Biomech 47:367–372.  https://doi.org/10.1016/j.jbiomech.2013.11.022S0021-9290(13)00574-5 CrossRefPubMedGoogle Scholar
  58. 58.
    Knott L, Bailey AJ (1998) Collagen cross-links in mineralizing tissues: a review of their chemistry, function, and clinical relevance. Bone 22:181–187.  https://doi.org/10.1016/S8756-3282(97)00279-2 CrossRefPubMedGoogle Scholar
  59. 59.
    Viguet-Carrin S, Garnero P, Delmas PD (2006) The role of collagen in bone strength. Osteoporos Int 17:319–336.  https://doi.org/10.1007/s00198-005-2035-9 CrossRefPubMedGoogle Scholar
  60. 60.
    Marzban A, Canavan P, Warner G, Vaziri A, Nayeb-Hashemi H (2012) Parametric investigation of load-induced structure remodeling in the proximal femur. Proc Inst Mech Eng H 226:450–460.  https://doi.org/10.1177/0954411912444067 CrossRefPubMedGoogle Scholar
  61. 61.
    Meakin LB, Price JS, Lanyon LE (2014) The contribution of experimental in vivo models to understanding the mechanisms of adaptation to mechanical loading in bone. Front Endocrinol (Lausanne) 5:154.  https://doi.org/10.3389/fendo.2014.00154 CrossRefGoogle Scholar
  62. 62.
    Frost HM (1994) Wolff’s Law and bone’s structural adaptations to mechanical usage: an overview for clinicians. Angle Orthod 64:175–188.  https://doi.org/10.1043/0003-3219(1994)064%3c0175:WLABSA%3e2.0.CO;2 CrossRefPubMedGoogle Scholar
  63. 63.
    Main RP (2007) Ontogenetic relationships between in vivo strain environment, bone histomorphometry and growth in the goat radius. J Anat 210:272–293.  https://doi.org/10.1111/j.1469-7580.2007.00696.x CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Cristofolini L, Angeli E, Juszczyk JM, Juszczyk MM (2013) Shape and function of the diaphysis of the human tibia. J Biomech 46:1882–1892.  https://doi.org/10.1016/j.jbiomech.2013.04.026S0021-9290(13)00220-0 CrossRefPubMedGoogle Scholar
  65. 65.
    Funk JR, Crandall JR (2006) Calculation of tibial loading using strain gauges. Biomed Sci Instrum 42:160–165PubMedGoogle Scholar
  66. 66.
    Boskey AL (2006) Assessment of bone mineral and matrix using backscatter electron imaging and FTIR imaging. Curr Osteoporos Rep 4:71–75CrossRefGoogle Scholar
  67. 67.
    Tranquilli Leali P, Doria C, Zachos A, Ruggiu A, Milia F, Barca F (2009) Bone fragility: current reviews and clinical features. Clin Cases Miner Bone Metab 6:109–113PubMedGoogle Scholar
  68. 68.
    Saito M, Marumo K (2010) Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporos Int 21:195–214.  https://doi.org/10.1007/s00198-009-1066-z CrossRefPubMedGoogle Scholar
  69. 69.
    Saito M, Marumo K (2010) Musculoskeletal rehabilitation and bone. Mechanical stress and bone quality: do mechanical stimuli alter collagen cross-link formation in bone? “Yes” (in jpn). Clin Calcium 20:520–528 (pii: CliCa10045205281004520528) PubMedGoogle Scholar
  70. 70.
    Sroga GE, Vashishth D (2012) Effects of bone matrix proteins on fracture and fragility in osteoporosis. Curr Osteoporos Rep 10:141–150.  https://doi.org/10.1007/s11914-012-0103-6 CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Vashishth D, Gibson GJ, Khoury JI, Schaffler MB, Kimura J, Fyhrie DP (2001) Influence of nonenzymatic glycation on biomechanical properties of cortical bone. Bone 28:195–201.  https://doi.org/10.1016/S8756-3282(00)00434-8 CrossRefPubMedGoogle Scholar
  72. 72.
    Boskey AL, Coleman R (2010) Aging and bone. J Dent Res 89:1333–1348.  https://doi.org/10.1177/00220345103777910022034510377791 CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Tang SY, Vashishth D (2011) The relative contributions of non-enzymatic glycation and cortical porosity on the fracture toughness of aging bone. J Biomech 44:330–336.  https://doi.org/10.1016/j.jbiomech.2010.10.016S0021-9290(10)00568-3 CrossRefPubMedGoogle Scholar
  74. 74.
    Brama PA, Bank RA, Tekoppele JM, Van Weeren PR (2001) Training affects the collagen framework of subchondral bone in foals. Vet J 162:24–32.  https://doi.org/10.1053/tvjl.2001.0570S1090023301905702 CrossRefPubMedGoogle Scholar
  75. 75.
    Paschalis EP, Shane E, Lyritis G, Skarantavos G, Mendelsohn R, Boskey AL (2004) Bone fragility and collagen cross-links. J Bone Miner Res 19:2000–2004.  https://doi.org/10.1359/JBMR.040820 CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Salem GJ, Zernicke RF, Martinez DA, Vailas AC (1993) Adaptations of immature trabecular bone to moderate exercise: geometrical, biochemical, and biomechanical correlates. Bone 14:647–654CrossRefGoogle Scholar
  77. 77.
    van de Lest CH, Brama PA, van Weeren PR (2003) The influence of exercise on bone morphogenic enzyme activity of immature equine subchondral bone. Biorheology 40:377–382PubMedGoogle Scholar
  78. 78.
    Bromage TG, Goldman HM, McFarlin SC, Warshaw J, Boyde A, Riggs CM (2003) Circularly polarized light standards for investigations of collagen fiber orientation in bone. Anat Rec B New Anat 274:157–168.  https://doi.org/10.1002/ar.b.10031 CrossRefPubMedGoogle Scholar
  79. 79.
    Nyman JS, Roy A, Shen X, Acuna RL, Tyler JH, Wang X (2006) The influence of water removal on the strength and toughness of cortical bone. J Biomech 39:931–938.  https://doi.org/10.1016/j.jbiomech.2005.01.012 CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Grover K, Lin L, Hu M, Muir J, Qin YX (2016) Spatial distribution and remodeling of elastic modulus of bone in micro-regime as prediction of early stage osteoporosis. J Biomech 49:161–166.  https://doi.org/10.1016/j.jbiomech.2015.11.052S0021-9290(15)00694-6 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  • Kartikey Grover
    • 1
  • Minyi Hu
    • 1
  • Liangjun Lin
    • 1
  • Jesse Muir
    • 1
  • Yi-Xian Qin
    • 1
    Email author
  1. 1.Department of Biomedical EngineeringSUNY Stony Brook UniversityNew YorkUSA

Personalised recommendations