Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Mechanical signals as anabolic agents in bone

Nature Reviews Rheumatology volume 6, pages 50–59 (2010)Cite this article

Subjects

Abstract

Aging and a sedentary lifestyle conspire to reduce bone quantity and quality, decrease muscle mass and strength, and undermine postural stability, culminating in an elevated risk of skeletal fracture. Concurrently, a marked reduction in the available bone-marrow-derived population of mesenchymal stem cells (MSCs) jeopardizes the regenerative potential that is critical to recovery from musculoskeletal injury and disease. A potential way to combat the deterioration involves harnessing the sensitivity of bone to mechanical signals, which is crucial in defining, maintaining and recovering bone mass. To effectively utilize mechanical signals in the clinic as a non-drug-based intervention for osteoporosis, it is essential to identify the components of the mechanical challenge that are critical to the anabolic process. Large, intense challenges to the skeleton are generally presumed to be the most osteogenic, but brief exposure to mechanical signals of high frequency and extremely low intensity, several orders of magnitude below those that arise during strenuous activity, have been shown to provide a significant anabolic stimulus to bone. Along with positively influencing osteoblast and osteocyte activity, these low-magnitude mechanical signals bias MSC differentiation towards osteoblastogenesis and away from adipogenesis. Mechanical targeting of the bone marrow stem-cell pool might, therefore, represent a novel, drug-free means of slowing the age-related decline of the musculoskeletal system.

Key Points

  • Mechanical signals are anabolic to bone while their removal is permissive to osteoporosis

  • Mechanical signals need not be large to stimulate bone formation

  • Clinical studies suggest that low-magnitude mechanical signals can increase bone mineral density

  • Differentiation of mesenchymal stem cells towards osteoblastogenesis simultaneously suppresses adipogenesis

  • Mechanical signals can stem osteoporosis and augment and/or accelerate the healing of bone

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Bone is subjected to a range of mechanical strains.
Figure 2: Interrelationship between loading cycles and bone adaptation.
Figure 3: Low-magnitude mechanical signals are anabolic to bone.
Figure 4: Mechanical loading influences MSC differentiation.

Similar content being viewed by others

References

  1. Kruse, K. & Julicher, F. Oscillations in cell biology. Curr. Opin. Cell Biol. 17, 20–26 (2005).

    Article  CAS  PubMed  Google Scholar 

  2. Zhou, X. L. et al. The transient receptor potential channel on the yeast vacuole is mechanosensitive. Proc. Natl Acad. Sci. USA 100, 7105–7110 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Neel, P. L. & Harris, R. W. Motion-induced inhibition of elongation and induction of dormancy in liquidambar. Science 173, 58–59 (1971).

    Article  CAS  PubMed  Google Scholar 

  4. Ingber, D. E. Mechanical control of tissue growth: function follows form. Proc. Natl Acad. Sci. USA 102, 11571–11572 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Orr, A. W., Helmke, B. P., Blackman, B. R. & Schwartz, M. A. Mechanisms of mechanotransduction. Dev. Cell 10, 11–20 (2006).

    Article  CAS  PubMed  Google Scholar 

  6. Frost, H. M. Bone “mass” and the “mechanostat”: a proposal. Anat. Rec. 219, 1–9 (1987).

    Article  CAS  PubMed  Google Scholar 

  7. Lang, T. et al. Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight. J. Bone Miner. Res. 19, 1006–1012 (2004).

    Article  PubMed  Google Scholar 

  8. Jones, H. H., Priest, J. D., Hayes, W. C., Tichenor, C. C. & Nagel, D. A. Humeral hypertrophy in response to exercise. J. Bone Joint Surg. Am. 59, 204–208 (1977).

    Article  CAS  PubMed  Google Scholar 

  9. Heinonen, A. et al. Bone mineral density in female athletes representing sports with different loading characteristics of the skeleton. Bone 17, 197–203 (1995).

    Article  CAS  PubMed  Google Scholar 

  10. Leichter, I. et al. Gain in mass density of bone following strenuous physical activity. J. Orthop. Res. 7, 86–90 (1989).

    Article  CAS  PubMed  Google Scholar 

  11. McKay, H. A. et al. “Bounce at the Bell”: a novel program of short bouts of exercise improves proximal femur bone mass in early pubertal children. Br. J. Sports Med. 39, 521–526 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Heinonen, A., Sievanen, H., Kannus, P., Oja, P. & Vuori, I. Effects of unilateral strength training and detraining on bone mineral mass and estimated mechanical characteristics of the upper limb bones in young women. J. Bone Miner. Res. 11, 490–501 (1996).

    Article  CAS  PubMed  Google Scholar 

  13. Judex, S., Garman, R., Squire, M., Donahue, L. R. & Rubin, C. Genetically based influences on the site-specific regulation of trabecular and cortical bone morphology. J. Bone Miner. Res. 19, 600–606 (2004).

    Article  PubMed  Google Scholar 

  14. Peacock, M. et al. Sex-specific and non-sex-specific quantitative trait loci contribute to normal variation in bone mineral density in men. J. Clin. Endocrinol. Metab. 90, 3060–3066 (2005).

    Article  CAS  PubMed  Google Scholar 

  15. Qiu, S., Rao, D. S., Palnitkar, S. & Parfitt, A. M. Differences in osteocyte and lacunar density between Black and White American women. Bone 38, 130–135 (2006).

    Article  PubMed  Google Scholar 

  16. Heaney, R. P. et al. Peak bone mass. Osteoporos. Int. 11, 985–1009 (2000).

    Article  CAS  PubMed  Google Scholar 

  17. Weaver, C. M. The role of nutrition on optimizing peak bone mass. Asia Pac. J. Clin. Nutr. 17 (Suppl. 1), 135–137 (2008).

    PubMed  Google Scholar 

  18. Rosen, C. J. & Bouxsein, M. L. Mechanisms of disease: is osteoporosis the obesity of bone? Nat. Clin. Pract. Rheumatol. 2, 35–43 (2006).

    Article  CAS  PubMed  Google Scholar 

  19. Zayzafoon, M., Gathings, W. E. & McDonald, J. M. Modeled microgravity inhibits osteogenic differentiation of human mesenchymal stem cells and increases adipogenesis. Endocrinology 145, 2421–2432 (2004).

    Article  CAS  PubMed  Google Scholar 

  20. Lee, N. K. et al. Endocrine regulation of energy metabolism by the skeleton. Cell 130, 456–469 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lanyon, L. E. & Rubin, C. T. Static vs dynamic loads as an influence on bone remodelling. J. Biomech. 17, 897–905 (1984).

    Article  CAS  PubMed  Google Scholar 

  22. Judex, S., Lei, X., Han, D. & Rubin, C. Low-magnitude mechanical signals that stimulate bone formation in the ovariectomized rat are dependent on the applied frequency but not on the strain magnitude. J. Biomech. 40, 1333–1339 (2007).

    Article  PubMed  Google Scholar 

  23. Knothe Tate, M. L. & Knothe, U. An ex vivo model to study transport processes and fluid flow in loaded bone. J. Biomech. 33, 247–254 (2000).

    Article  CAS  PubMed  Google Scholar 

  24. Pollack, S. R., Salzstein, R. & Pienkowski, D. The electric double layer in bone and its influence on stress-generated potentials. Calcif. Tissue Int. 36 (Suppl. 1), S77–S81 (1984).

    Article  PubMed  Google Scholar 

  25. Fritton, S. P., McLeod, K. J. & Rubin, C. T. Quantifying the strain history of bone: spatial uniformity and self–similarity of low-magnitude strains. J. Biomech. 33, 317–325 (2000).

    Article  CAS  PubMed  Google Scholar 

  26. Huang, R. P., Rubin, C. T. & McLeod, K. J. Changes in postural muscle dynamics as a function of age. J. Gerontol. A Biol. Sci. Med. Sci. 54, B352–B357 (1999).

    Article  CAS  PubMed  Google Scholar 

  27. Rubin, C. T. & Lanyon, L. E. Regulation of bone mass by mechanical strain magnitude. Calcif. Tissue Int. 37, 411–417 (1985).

    Article  CAS  PubMed  Google Scholar 

  28. Rubin, C. T. & Lanyon, L. E. Regulation of bone formation by applied dynamic loads. J. Bone Joint Surg. Am. 66, 397–402 (1984).

    Article  CAS  PubMed  Google Scholar 

  29. Lanyon, L. E., Goodship, A. E., Pye, C. J. & MacFie, J. H. Mechanically adaptive bone remodelling. J. Biomech. 15, 141–154 (1982).

    Article  CAS  PubMed  Google Scholar 

  30. O'Connor, J. A., Lanyon, L. E. & MacFie, H. The influence of strain rate on adaptive bone remodelling. J. Biomech. 15, 767–781 (1982).

    Article  CAS  PubMed  Google Scholar 

  31. Bacabac, R. G. et al. Nitric oxide production by bone cells is fluid shear stress rate dependent. Biochem. Biophys. Res. Commun. 315, 823–829 (2004).

    Article  CAS  PubMed  Google Scholar 

  32. Srinivasan, S., Weimer, D. A., Agans, S. C., Bain, S. D. & Gross, T. S. Low-magnitude mechanical loading becomes osteogenic when rest is inserted between each load cycle. J. Bone Miner. Res. 17, 1613–1620 (2002).

    Article  PubMed  Google Scholar 

  33. O'Connell-Rodwell, C. E. Keeping an “ear” to the ground: seismic communication in elephants. Physiology (Bethesda) 22, 287–294 (2007).

    Google Scholar 

  34. Qin, Y. X., Rubin, C. T. & McLeod, K. J. Nonlinear dependence of loading intensity and cycle number in the maintenance of bone mass and morphology. J. Orthop. Res. 16, 482–489 (1998).

    Article  CAS  PubMed  Google Scholar 

  35. Rubin, C., Turner, A. S., Bain, S., Mallinckrodt, C. & McLeod, K. Anabolism: Low mechanical signals strengthen long bones. Nature 412, 603–604 (2001).

    Article  CAS  PubMed  Google Scholar 

  36. Rosenberg, I. H. Sarcopenia: origins and clinical relevance. J. Nutr. 127 (Suppl. 5), S990–S991 (1997).

    Article  Google Scholar 

  37. Lee, W. S., Cheung, W. H., Qin, L., Tang, N. & Leung, K. S. Age-associated decrease of type IIA/B human skeletal muscle fibers. Clin. Orthop. Relat. Res. 450, 231–237 (2006).

    Article  PubMed  Google Scholar 

  38. Rubin, C. T., Bain, S. D. & McLeod, K. J. Suppression of the osteogenic response in the aging skeleton. Calcif. Tissue Int. 50, 306–313 (1992).

    Article  CAS  PubMed  Google Scholar 

  39. Vico, L. et al. Effects of long-term microgravity exposure on cancellous and cortical weight-bearing bones of cosmonauts. Lancet 355, 1607–1611 (2000).

    Article  CAS  PubMed  Google Scholar 

  40. Burr, D. B. et al. Bone microdamage and skeletal fragility in osteoporotic and stress fractures. J. Bone Miner. Res. 12, 6–15 (1997).

    Article  CAS  PubMed  Google Scholar 

  41. Augat, P., Simon, U., Liedert, A. & Claes, L. Mechanics and mechano-biology of fracture healing in normal and osteoporotic bone. Osteoporos. Int. 16 (Suppl. 2), S36–S43 (2005).

    Article  PubMed  Google Scholar 

  42. Rubin, C. et al. Transmissibility of 15-hertz to 35-hertz vibrations to the human hip and lumbar spine: determining the physiologic feasibility of delivering low-level anabolic mechanical stimuli to skeletal regions at greatest risk of fracture because of osteoporosis. Spine 28, 2621–2627 (2003).

    Article  PubMed  Google Scholar 

  43. Xie, L., Rubin, C. & Judex, S. Enhancement of the adolescent murine musculoskeletal system using low-level mechanical vibrations. J. Appl. Physiol. 104, 1056–1062 (2008).

    Article  PubMed  Google Scholar 

  44. Rubin, C. et al. Quantity and quality of trabecular bone in the femur are enhanced by a strongly anabolic, noninvasive mechanical intervention. J. Bone Miner. Res. 17, 349–357 (2002).

    Article  PubMed  Google Scholar 

  45. Rubin, C. T. & Lanyon, L. E. Dynamic strain similarity in vertebrates; an alternative to allometric limb bone scaling. J. Theor. Biol. 107, 321–327 (1984).

    Article  CAS  PubMed  Google Scholar 

  46. Rubin, C., Xu, G. & Judex, S. The anabolic activity of bone tissue, suppressed by disuse, is normalized by brief exposure to extremely low-magnitude mechanical stimuli. FASEB J. 15, 2225–2229 (2001).

    Article  CAS  PubMed  Google Scholar 

  47. Garman, R., Rubin, C. & Judex, S. Small oscillatory accelerations, independent of matrix deformations, increase osteoblast activity and enhance bone morphology. PLoS ONE 2, e653 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Bacabac, R. G. et al. Bone cell responses to high-frequency vibration stress: does the nucleus oscillate within the cytoplasm? FASEB J. 20, 858–864 (2006).

    Article  CAS  PubMed  Google Scholar 

  49. Ozcivici, E., Garman, R. & Judex, S. High-frequency oscillatory motions enhance the simulated mechanical properties of non-weight bearing trabecular bone. J. Biomech. 40, 3404–3411 (2007).

    Article  PubMed  Google Scholar 

  50. Rubin, C. T. et al. Adipogenesis is inhibited by brief, daily exposure to high-frequency, extremely low-magnitude mechanical signals. Proc. Natl Acad. Sci. USA 104, 17879–17884 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  51. Luu, Y. K. et al. In vivo quantification of subcutaneous and visceral adiposity by micro-computed tomography in a small animal model. Med. Eng. Phys. 31, 34–41 (2009).

    Article  CAS  PubMed  Google Scholar 

  52. Luu, Y. K. et al. Mechanical stimulation of mesenchymal stem cell proliferation and differentiation promotes osteogenesis while preventing dietary-induced obesity. J. Bone Miner. Res. 24, 50–61 (2009).

    Article  CAS  PubMed  Google Scholar 

  53. Akune, T. et al. PPARgamma insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors. J. Clin. Invest. 113, 846–855 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Liu, J., Wang, H., Zuo, Y. & Farmer, S. R. Functional interaction between peroxisome proliferator-activated receptor gamma and beta-catenin. Mol. Cell Biol. 26, 5827–5837 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Krishnan, V., Bryant, H. U. & MacDougald, O. A. Regulation of bone mass by Wnt signaling. J. Clin. Invest. 116, 1202–1209 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Rosen, C. J. & Klibanski, A. Bone, fat, and body composition: evolving concepts in the pathogenesis of osteoporosis. Am. J. Med. 122, 409–414 (2009).

    Article  CAS  PubMed  Google Scholar 

  57. Taes, Y. E. et al. Fat mass is negatively associated with cortical bone size in young healthy male siblings. J. Clin. Endocrinol. Metab. 94, 2325–2331 (2009).

    Article  CAS  PubMed  Google Scholar 

  58. Rubin, J., Murphy, T., Nanes, M. S. & Fan, X. Mechanical strain inhibits expression of osteoclast differentiation factor by murine stromal cells. Am. J. Physiol. Cell Physiol. 278, C1126–C1132 (2000).

    Article  CAS  PubMed  Google Scholar 

  59. Kim, C. H. et al. Trabecular bone response to mechanical and parathyroid hormone stimulation: the role of mechanical microenvironment. J. Bone Miner. Res. 18, 2116–2125 (2003).

    Article  CAS  PubMed  Google Scholar 

  60. Cowin, S. C. & Weinbaum, S. Strain amplification in the bone mechanosensory system. Am. J. Med. Sci. 316, 184–188 (1998).

    CAS  PubMed  Google Scholar 

  61. Wang, L., Fritton, S. P., Cowin, S. C. & Weinbaum, S. Fluid pressure relaxation depends upon osteonal microstructure: modeling an oscillatory bending experiment. J. Biomech. 32, 663–672 (1999).

    Article  CAS  PubMed  Google Scholar 

  62. Han, Y., Cowin, S. C., Schaffler, M. B. & Weinbaum, S. Mechanotransduction and strain amplification in osteocyte cell processes. Proc. Natl Acad. Sci. USA 101, 16689–16694 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Burger, E. H., Klein-Nulend, J. & Veldhuijzen, J. P. Modulation of osteogenesis in fetal bone rudiments by mechanical stress in vitro. J. Biomech. 24 (Suppl. 1), 101–109 (1991).

    Article  PubMed  Google Scholar 

  64. Noble, B. S. et al. Mechanical loading: biphasic osteocyte survival and targeting of osteoclasts for bone destruction in rat cortical bone. Am. J. Physiol. Cell Physiol. 284, C934–C943 (2003).

    Article  CAS  PubMed  Google Scholar 

  65. Verborgt, O., Gibson, G. J. & Schaffler, M. B. Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo. J. Bone Miner. Res. 15, 60–67 (2000).

    Article  CAS  PubMed  Google Scholar 

  66. Frost, H. M. Perspectives: bone's mechanical usage windows. Bone Miner. 19, 257–271 (1992).

    Article  CAS  PubMed  Google Scholar 

  67. Judex, S., Lei, X., Han, D. & Rubin, C. Low-magnitude mechanical signals that stimulate bone formation in the ovariectomized rat are dependent on the applied frequency but not on the strain magnitude. J. Biomech. 40, 1333–1339 (2007).

    Article  PubMed  Google Scholar 

  68. Qin, Y. X., Kaplan, T., Saldanha, A. & Rubin, C. Fluid pressure gradients, arising from oscillations in intramedullary pressure, is correlated with the formation of bone and inhibition of intracortical porosity. J. Biomech. 36, 1427–1437 (2003).

    Article  PubMed  Google Scholar 

  69. Porada, C. D., Zanjani, E. D. & Almeida-Porad, G. Adult mesenchymal stem cells: a pluripotent population with multiple applications. Curr. Stem Cell Res. Ther. 1, 365–369 (2006).

    Article  CAS  PubMed  Google Scholar 

  70. Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006).

    Article  CAS  PubMed  Google Scholar 

  71. Discher, D. E., Mooney, D. J. & Zandstra, P. W. Growth factors, matrices, and forces combine and control stem cells. Science 324, 1673–1677 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Rubin, J., Rubin, C. & Jacobs, C. R. Molecular pathways mediating mechanical signaling in bone. Gene 367, 1–16 (2006).

    Article  CAS  PubMed  Google Scholar 

  73. Garman, R., Gaudette, G., Donahue, L. R., Rubin, C. & Judex, S. Low-level accelerations applied in the absence of weight bearing can enhance trabecular bone formation. J. Orthop. Res. 25, 732–740 (2007).

    Article  PubMed  Google Scholar 

  74. Sukharev, S. & Corey, D. P. Mechanosensitive channels: multiplicity of families and gating paradigms. Sci. STKE 2004, re4 (2004).

    PubMed  Google Scholar 

  75. Morris, C. E. Mechanosensitive ion channels. J. Membr. Biol. 113, 93–107 (1990).

    Article  CAS  PubMed  Google Scholar 

  76. Duncan, R. L., Hruska, K. A. & Misler, S. Parathyroid hormone activation of stretch-activated cation channels in osteosarcoma cells (UMR-106.01). FEBS Lett. 307, 219–223 (1992).

    Article  CAS  PubMed  Google Scholar 

  77. Ferrier, J., Ward, A., Kanehisa, J. & Heersche, J. N. Electrophysiological responses of osteoclasts to hormones. J. Cell Physiol. 128, 23–26 (1986).

    Article  CAS  PubMed  Google Scholar 

  78. Davidson, R. M., Tatakis, D. W. & Auerbach, A. L. Multiple forms of mechanosensitive ion channels in osteoblast-like cells. Pflugers Arch. 416, 646–651 (1990).

    Article  CAS  PubMed  Google Scholar 

  79. Rawlinson, S. C., Pitsillides, A. A. & Lanyon, L. E. Involvement of different ion channels in osteoblasts' and osteocytes' early responses to mechanical strain. Bone 19, 609–614 (1996).

    Article  CAS  PubMed  Google Scholar 

  80. McGarry, J. G., Klein-Nulend, J. & Prendergast, P. J. The effect of cytoskeletal disruption on pulsatile fluid flow-induced nitric oxide and prostaglandin E2 release in osteocytes and osteoblasts. Biochem. Biophys. Res. Commun. 330, 341–348 (2005).

    Article  CAS  PubMed  Google Scholar 

  81. Katsumi, A., Orr, A. W., Tzima, E. & Schwartz, M. A. Integrins in mechanotransduction. J. Biol. Chem. 279, 12001–12004 (2004).

    Article  CAS  PubMed  Google Scholar 

  82. Simons, K. & Toomre, D. Lipid rafts and signal transduction. Nat. Rev. Mol. Cell Biol. 1, 31–39 (2000).

    Article  CAS  PubMed  Google Scholar 

  83. Rizzo, V., Sung, A., Oh, P. & Schnitzer, J. E. Rapid mechanotransduction in situ at the luminal cell surface of vascular endothelium and its caveolae. J. Biol. Chem. 273, 26323–26329 (1998).

    Article  CAS  PubMed  Google Scholar 

  84. Bonewald, L. F. & Johnson, M. L. Osteocytes, mechanosensing and Wnt signaling. Bone 42, 606–615 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Li, X. et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J. Biol. Chem. 280, 19883–19887 (2005).

    Article  CAS  PubMed  Google Scholar 

  86. Robling, A. G. et al. Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J. Biol. Chem. 283, 5866–5875 (2008).

    Article  CAS  PubMed  Google Scholar 

  87. Santos, A., Bakker, A. D., Zandieh-Doulabi, B., Semeins, C. M. & Klein-Nulend, J. Pulsating fluid flow modulates gene expression of proteins involved in Wnt signaling pathways in osteocytes. J. Orthop. Res. 27, 1280–1287 (2009).

    Article  CAS  PubMed  Google Scholar 

  88. Armstrong, V. J. et al. Wnt/beta-catenin signaling is a component of osteoblastic bone cell early responses to load-bearing and requires estrogen receptor alpha. J. Biol. Chem. 282, 20715–20727 (2007).

    Article  CAS  PubMed  Google Scholar 

  89. Case, N. et al. Beta-catenin levels influence rapid mechanical responses in osteoblasts. J. Biol. Chem. 283, 29196–29205 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. David, V. et al. Mechanical loading down regulates PPAR gamma in bone marrow stromal cells and favours osteoblastogenesis at the expense of adipogenesis. Endocrinology 148, 2553–2562 (2007).

    Article  CAS  PubMed  Google Scholar 

  91. Sen, B. et al. Mechanical strain inhibits adipogenesis in mesenchymal stem cells by stimulating a durable beta-catenin signal. Endocrinology 149, 6065–6075 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Carmona, R. Bone Health and Osteoporosis: A Report of the Surgeon General. 1–404 10-10-2004. US. Dept of Health and Human Services, Public Health Service.

  93. Rubin, C. et al. Prevention of postmenopausal bone loss by a low-magnitude, high-frequency mechanical stimuli: a clinical trial assessing compliance, efficacy, and safety. J. Bone Miner. Res. 19, 343–351 (2004).

    Article  PubMed  Google Scholar 

  94. Ward, K. et al. Low magnitude mechanical loading is osteogenic in children with disabling conditions. J. Bone Miner. Res. 19, 360–369 (2004).

    Article  PubMed  Google Scholar 

  95. Gilsanz, V. et al. Low-level, high-frequency mechanical signals enhance musculoskeletal development of young women with low BMD. J. Bone Miner. Res. 21, 1464–1474 (2006).

    Article  PubMed  Google Scholar 

  96. Cardinale, M. & Bosco, C. The use of vibration as an exercise intervention. Exerc. Sport Sci. Rev. 31, 3–7 (2003).

    Article  PubMed  Google Scholar 

  97. Verschueren, S. M. et al. Effect of 6-month whole body vibration training on hip density, muscle strength, and postural control in postmenopausal women: a randomized controlled pilot study. J. Bone Miner. Res. 19, 352–359 (2004).

    Article  PubMed  Google Scholar 

  98. Armbrecht, G. et al. Resistive vibration exercise attenuates bone and muscle atrophy in 56 days of bed rest: biochemical markers of bone metabolism. Osteoporos. Int. doi:10.1007/s00198-009-0985-z.

  99. Kiiski, J., Heinonen, A., Jarvinen, T. L., Kannus, P. & Sievanen, H. Transmission of vertical whole body vibration to the human body. J. Bone Miner. Res. 23, 1318–1325 (2008).

    Article  PubMed  Google Scholar 

  100. Goodship, A. E., Lawes, T. J. & Rubin, C. T. Low-magnitude high-frequency mechanical signals accelerate and augment endochondral bone repair: preliminary evidence of efficacy. J. Orthop. Res. 27, 922–930 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  101. Rubin, C. T. & McLeod, K. J. Promotion of bony ingrowth by frequency-specific, low-amplitude mechanical strain. Clin. Orthop. 298, 165–174 (1994).

    Google Scholar 

  102. Carter, D. R., Caler, W. E., Spengler, D. M. & Frankel, V. H. Fatigue behavior of adult cortical bone: the influence of mean strain and strain range. Acta Orthop. Scand. 52, 481–490 (1981).

    Article  CAS  PubMed  Google Scholar 

  103. Rubin, C. T., Gross, T. S., McLeod, K. J. & Bain, S. D. Morphologic stages in lamellar bone formation stimulated by a potent mechanical stimulus. J. Bone Miner. Res. 10, 488–495 (1995).

    Article  CAS  PubMed  Google Scholar 

  104. Rubin, C. T. & Lanyon, L. E. Limb mechanics as a function of speed and gait: a study of functional strains in the radius and tibia of horse and dog. J. Exp. Biol. 101, 187–211 (1982).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by National Institutes of Health Grant AR 43498.

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, 11794-2580, NY, USA

    Engin Ozcivici, Yen Kim Luu, Ben Adler, Yi-Xian Qin, Stefan Judex & Clinton T. Rubin

  2. Department of Medicine, University of North Carolina, Chapel Hill, 27599, NC, USA

    Janet Rubin

Authors
  1. Engin Ozcivici
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yen Kim Luu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ben Adler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yi-Xian Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Janet Rubin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Stefan Judex
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Clinton T. Rubin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Clinton T. Rubin.

Ethics declarations

Competing interests

Clinton T. Rubin declares that he is a founder of Marodyne Medical, and that he is a shareholder in, and a holds a patent from, this company.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ozcivici, E., Luu, Y., Adler, B. et al. Mechanical signals as anabolic agents in bone. Nat Rev Rheumatol 6, 50–59 (2010). https://doi.org/10.1038/nrrheum.2009.239

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrrheum.2009.239

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing