Skip to main content
Log in

Mechanisms by which exercise improves bone strength

  • Invited paper
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Certain exercises can induce osteogenesis and improve bone strength, yet the biological processes involved in bone mechanotransduction are only beginning to be understood. Several pathways are emerging from current research, including calcium signaling associated with membrane ion channels, adenosine triphosphate signaling, second messengers such as prostaglandins and nitric oxide, and signaling involving mitogen-activated protein kinase. One characteristic of the mechanosensing apparatus that has only recently been studied is the important role of desensitization. Experimental protocols that insert “rest” periods to reduce the effects of desensitization can double anabolic responses to mechanical loading. Exercises that reduce desensitization may provide an effective means to build bone strength.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Frost HM (2003) Bone’s mechanostat: a 2003 update. Anat Rec 275A:1081–1101

    Article  Google Scholar 

  2. Robling AG, Hinant FM, Burr DB, Turner CH (2002) Improved bone structure and strength after long-term mechanical loading is greatest if loading is separated into short bouts. J Bone Miner Res 17: 1545–1554

    Article  PubMed  Google Scholar 

  3. Forwood MR, Burr DB (1993) Physical activity and bone mass: exercises in futility? Bone Miner 21: 89–112

    Article  PubMed  CAS  Google Scholar 

  4. Wallace BA, Cumming RG (2000) Systematic review of randomized trials of the effect of exercise on bone mass in pre-and postmenopausal women. Calcif Tissue Int 67: 10–18

    Article  PubMed  CAS  Google Scholar 

  5. Hert J, Liskova M, Landa J (1971) Reaction of bone to mechanical stimuli. 1. Continuous and intermittent loading of the tibia in rabbit. Folia Morphol (Praha) 19: 290–300

    CAS  Google Scholar 

  6. Lanyon LE, Rubin CT (1984) Static vs. dynamic loads as an influence on bone remodelling. J Biomech 17: 897–905

    Article  PubMed  CAS  Google Scholar 

  7. Robling AG, Duijvelaar KM, Geevers JV, Ohashi N, Turner CH (2001) Modulation of appositional and longitudinal bone growth in the rat ulna by applied static and dynamic force. Bone 29: 105- 113

    Article  PubMed  CAS  Google Scholar 

  8. Turner CH, Owan I, Takano Y (1995) Mechanotransduction in bone: role of strain rate. Am J Physiol 269: E438-E442

    PubMed  CAS  Google Scholar 

  9. Turner CH (1998) Three rules for bone adaptation to mechanical stimuli. Bone 23: 399–407

    Article  PubMed  CAS  Google Scholar 

  10. Rubin CT, Lanyon LE (1984) Regulation of bone formation by applied dynamic loads. J Bone Joint Surg [Am] 66: 397–402

    CAS  Google Scholar 

  11. Umemura Y, Ishiko T, Yamauchi T, Kurono M, Mashiko S (1997) Five jumps per day increase bone mass and breaking force in rats. J Bone Miner Res 12: 1480–1485

    Article  PubMed  CAS  Google Scholar 

  12. Hsieh YF, Turner CH (2001) Effects of loading frequency on mechanically induced bone formation. J Bone Miner Res 16: 918- 924

    Article  PubMed  CAS  Google Scholar 

  13. Rubin C, Turner AS, Bain S, Mallinckrodt C, McLeod K (2001) Anabolism: low mechanical signals strengthen long bones. Nature (Lond) 412: 603–604

    Article  CAS  Google Scholar 

  14. Li J, Duncan RL, Burr DB, Turner CH (2002) L-type calcium channels mediate mechanically induced bone formation in vivo. J Bone Miner Res 17: 1795–1800

    Article  PubMed  CAS  Google Scholar 

  15. Reich KM, McAllister TN, Gudi S, Frangos JA (1997) Activation of G proteins mediates flow-induced prostaglandin E2 production in osteoblasts. Endocrinology 138: 1014–1018

    Article  PubMed  CAS  Google Scholar 

  16. Robling AG, Burr DB, Turner CH (2001) Recovery periods restore mechanosensitivity to dynamically loaded bone. J Exp Biol 204: 3389–3399

    PubMed  CAS  Google Scholar 

  17. Poliachik SL, Agans SC, King KA, Gross TS, Srinivasan S (2003) Rest alleviates tissue saturation due to repetitive mechanical loading. J Bone Miner Res 18 (suppl 2): S73

    Google Scholar 

  18. Srinivasan S, Weimer DA, Agans SC, Bain SD, Gross TS (2002) Low-magnitude mechanical loading becomes osteogenic when rest is inserted between each load cycle. J Bone Miner Res 17: 1613- 1620

    Article  PubMed  Google Scholar 

  19. Torrance AG, Mosley JR, Suswillo RF, Lanyon LE (1994) Noninvasive loading of the rat ulna in vivo induces a strain-related modeling response uncomplicated by trauma or periosteal pressure. Calcif Tissue Int 54: 241–247

    Article  PubMed  CAS  Google Scholar 

  20. Robling AG, Hinant FM, Burr DB, Turner CH (2002) Improved bone structure and strength after long-term mechanical loading is greatest if loading is separated into short bouts. J Bone Miner Res 17: 1545–1554

    Article  PubMed  Google Scholar 

  21. Robling AG, Hinant FM, Burr DB, Turner CH (2002) Shorter, more frequent mechanical loading sessions enhance bone mass. Med Sci Sports Exerc 34: 196–202

    Article  PubMed  Google Scholar 

  22. Chen NX, Ryder KD, Pavalko FM, Turner CH, Burr DB, Qiu J, Duncan RL (2000) Ca2* regulates fluid shear-induced cytoskeletal reorganization and gene expression in osteoblasts. Am J Physiol Cell Physiol 278: C989-C997

    PubMed  CAS  Google Scholar 

  23. Pavalko FM, Chen NX, Turner CH, Burr DB, Atkinson S, Hsieh YF, Qiu J, Duncan RL (1998) Fluid shear-induced mechanical signaling in MC3T3-E1 osteoblasts requires cytoskeleton-integrin interactions. Am J Physiol 275: C1591-C1601

    PubMed  CAS  Google Scholar 

  24. Hung CT, Allen FD, Pollack SR, Brighton CT(1996) Intracellular Ca2+ stores and extracellular Ca2+ are required in the real-time Ca2+ response of bone cells experiencing fluid flow. J Biomech 29: 1411–1417

    Article  PubMed  CAS  Google Scholar 

  25. Rawlinson SC, Pitsillides AA, Lanyon LE (1996) Involvement of different ion channels in osteoblasts’ and osteocytes’ early responses to mechanical strain. Bone 19: 609–614

    Article  PubMed  CAS  Google Scholar 

  26. Li J, Duncan RL, Burr DB, Gattone VH, Turner CH (2003) Parathyroid hormone enhances mechanically induced bone formation, possibly involving L-type voltage-sensitive calcium channels. Endocrinology 144: 1226–1233

    Article  PubMed  CAS  Google Scholar 

  27. Ryder KD, Duncan RL (2001) Parathyroid hormone enhances fluid shear-induced [Ca2+]i signaling in osteoblastic cells through activation of mechanosensitive and voltage-sensitive Ca2+ channels. J Bone Miner Res 16: 240–248

    Article  PubMed  CAS  Google Scholar 

  28. You J, Reilly GC, Zhen X, Yellowley CE, Chen Q, Donahue HJ, Jacobs CR (2001) Osteopontin gene regulation by oscillary fluid flow via intracellular calcium mobilization and activation of mitogen-activated protein kinase in MC3T3-E1 osteoblasts. J Biol Chem 276: 13365–13371

    Article  PubMed  CAS  Google Scholar 

  29. Hatton JP, Pooran M, Li CF, Luzzio C, Hughes-Fulford M (2003) A short pulse of mechanical force induces gene expression and growth in MC3T3-E1 osteoblasts via an ERK 1/2 pathway. J Bone Miner Res 18: 58–66

    Article  PubMed  CAS  Google Scholar 

  30. Jessop HL, Rawlinson SC, Pitsillides AA, Lanyon LE (2002) Mechanical strain and fluid movement both activate extracellular regulated kinase (ERK) in osteoblast-like cells but via different signaling pathways. Bone 31: 186–194

    Article  PubMed  CAS  Google Scholar 

  31. Boutahar H, Guignandon A, Vico L, Lafage-Proust MH (2004) Mechanical strain on osteoblasts activates autophosphorylation of FAK and PYK2 tyrosine sites involved in ERK activation. J Biol Chem 279(29): 30588–30599

    Article  PubMed  CAS  Google Scholar 

  32. Pavalko FM, Burridge K (1991) Disruption of the actin cytoskel- eton after microinjection of proteolytic fragments of alpha-actinin. J Cell Biol 114: 481–491

    Article  PubMed  CAS  Google Scholar 

  33. You J, Jacobs CR, Steinberg TH, Donahue HJ (2002) P2Y purinoceptors are responsible for oscillatory fluid flow-induced intracellular calcium mobilization in osteoblastic cells. J Biol Chem 277: 48724–48729

    Article  PubMed  CAS  Google Scholar 

  34. 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

    Article  PubMed  CAS  Google Scholar 

  35. Klein-Nulend J, Burger EH, Semeins CM, Raisz LG, Pilbeam CC (1997) Pulsating fluid flow stimulates prostaglandin release and inducible prostaglandin G/H synthase mRNA expression in primary mouse bone cells. J Bone Miner Res 12: 45–51

    Article  PubMed  CAS  Google Scholar 

  36. Johnson DL, McAllister TN, Frangos JA (1996) Fluid flow stimulates rapid and continuous release of nitric oxide in osteoblasts. Am J Physiol 271: E205-E208

    PubMed  CAS  Google Scholar 

  37. Pitsillides AA, Rawlinson SC, Suswillo RF, Bourrin S, Zaman G, Lanyon LE (1995) Mechanical strain-induced NO production by bone cells: a possible role in adaptive bone (re)modeling? FASEB J 9: 1614–1622

    PubMed  CAS  Google Scholar 

  38. Rubin J, Biskobing D, Fan X, Rubin C, McLeod K, Taylor WR (1997) Pressure regulated osteoclast formation and MCSF expression in marrow cultures. J Cell Physiol 170: 81–87

    Article  PubMed  CAS  Google Scholar 

  39. Rubin J, Murphy T, Nanes MS, Fan X (2000) Mechanical strain inhibits expression of osteoclast differentiation factor by murine stromal cells. Am J Physiol 278: C1126-C1132

    CAS  Google Scholar 

  40. Jørgensen NR, Geist ST, Civitelli R, Steinberg TH (1997) ATP- and gap junction-dependent intercellular calcium signaling in osteoblastic cells. J Cell Biol 139: 497–506

    Article  PubMed  Google Scholar 

  41. Ke HZ, Qi H, Weidema AF, Zhang Q, Panupinthu N, Crawford DT, Grasser WA, Paralkar VM, Li M, Audoly LP, Gabei CA, Jee WS, Dixon SJ, Sims SM, Thompson DD (2003) Deletion of the P2X7 nucleotide receptor reveals its regulatory roles in bone formation and resorption. Mol Endocrinol 17: 1356–1367

    Article  PubMed  CAS  Google Scholar 

  42. Keila S, Kelner A, Weinreb M (2001) Systemic prostaglandin E2 increases cancellous bone formation and mass in aging rats and stimulates their bone marrow osteogenic capacity in vivo and in vitro. J Endocrinol 168: 131–139

    Article  PubMed  CAS  Google Scholar 

  43. Li XJ, Jee WS, Li YL, Patterson-Buckendahl P (1990) Transient effects of subcutaneously administered prostaglandin E2 on cancellous and cortical bone in young adult dogs. Bone 11: 353–364

    Article  PubMed  CAS  Google Scholar 

  44. Suda M, Tanaka K, Yasoda A, Natsui K, Sakuma Y, Tanaka I, Ushikubi F, Narumiya S, Nakao K (1998) Prostaglandin E2 (PGE2) autoamplifies its production through EP1 subtype of PGE receptor in mouse osteoblastic MC3T3-E1 cells. Calcif Tissue Int 62: 327–331

    Article  PubMed  CAS  Google Scholar 

  45. Machwate M, Harada S, Leu CT, Seedor G, Labelle M, Gallant M, Hutchins S, Lachance N, Sawyer N, Slipetz D, Metters KM, Rodan SB, Young R, Rodan GA (2001) Prostaglandin receptor EP4 mediates the bone anabolic effects of PGE2. Mol Pharmacol 60: 36–11

    PubMed  CAS  Google Scholar 

  46. Cheng B, Kato Y, Zhao S, Lau J, Sprague E, Bonewald LF, Jiang JX (2001) PGE2 is essential for gap junction-mediated intercellular communication between osteocyte-like MLO-Y4 cells in response to mechanical strain. Endocrinology 142: 3463–3473

    Google Scholar 

  47. Civitelli R, Ziambaras K, Warlow PM, Lecanda F, Nelson T, Harley J, Atal N, Beyer EC, Steinberg TH (1998) Regulation of connexin43 expression and function by prostaglandin E2 (PGE2) and parathyroid hormone (PTH) in osteoblastic cells. J Cell Biochem 68: 8–21

    Article  PubMed  CAS  Google Scholar 

  48. Cherian PP, Cheng B, Gu S, Sprague E, Bonewald LF, Jiang JX (2003) Effects of mechanical strain on the function of Gap junctions in osteocytes are mediated through the prostaglandin EP2 receptor. J Biol Chem 278: 43146–3156

    Article  PubMed  CAS  Google Scholar 

  49. Pavalko FM, Gerard RL, Ponik SM, Gallagher PJ, Jin Y, Norvell SM (2003) Fluid shear stress inhibits TNF-alpha-induced apoptosis in osteoblasts: a role for fluid shear stress-induced activation of PI3-kinase and inhibition of caspase 3. J Cell Physiol 194: 194–205

    Article  PubMed  CAS  Google Scholar 

  50. Forwood MR (1996) Inducible cyclo-oxygenase (COX-2) mediates the induction of bone formation by mechanical loading in vivo. J Bone Miner Res 11: 1688–1693

    Article  PubMed  CAS  Google Scholar 

  51. Li J, Burr DB, Turner CH (2002) Suppression of prostaglandin synthesis with NS-398 has different effects on endocortical and periosteal bone formation induced by mechanical loading. Calcif Tissue Int 70: 320–329

    Article  PubMed  CAS  Google Scholar 

  52. Chow JW, Fox SW, Lean JM, Chambers TJ (1999) Role of nitric oxide and prostaglandins in mechanically induced bone formation. J Bone Miner Res 13: 1039–1044

    Article  Google Scholar 

  53. Turner CH, Takano Y, Owan I, Murrell GA (1996) Nitric oxide inhibitor L-NAME suppresses mechanically induced bone formation in rats. Am J Physiol 270: E634-E639

    PubMed  CAS  Google Scholar 

  54. Rodan GA, Bourret LA, Harvey A, Mensi T (1975) Cyclic AMP and cyclic GMP: mediators of the mechanical effects on bone remodeling. Science 189: 467–469

    Article  PubMed  CAS  Google Scholar 

  55. Maclntyre I, Zaidi M, Alam AS, Datta HK, Moonga BS, Lidbury PS, Hecker M, Vane JR (1991) Osteoclastic inhibition: an action of nitric oxide not mediated by cyclic GMP. Proc Natl Acad Sci USA 88: 2936–2940

    Article  Google Scholar 

  56. Lowik CW, Nibbering PH, van de Ruit M, Papapoulos SE (1994) Inducible production of nitric oxide in osteoblast-like cells and in fetal mouse bone expiants is associated with suppression of osteoclastic bone resorption. J Clin Invest 93: 1465–1472

    Article  PubMed  CAS  Google Scholar 

  57. Kasten TP, Collin-Osdoby P, Patel N, Osdoby P, Krukowski M, Misko TP, Settle SL, Currie MG, Nickols GA (1994) Potentiation of osteoclast bone-resorption activity by inhibition of nitric oxide synthase. Proc Natl Acad Sci U S A 91: 3569–3573

    Article  PubMed  CAS  Google Scholar 

  58. Fan X, Roy E, Zhu L, Murphy TC, Ackert-Bicknell C, Hart CM, Rosen C, Nanes MS, Rubin J (2004) Nitric oxide regulates RANKL and OPG expression in bone marrow stromal cells. Endocrinology 145: 751–759

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Charles H. Turner.

About this article

Cite this article

Turner, C.H., Robling, A.G. Mechanisms by which exercise improves bone strength. J Bone Miner Metab 23 (Suppl 1), 16–22 (2005). https://doi.org/10.1007/BF03026318

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03026318

Key words

Navigation