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The Effect of Aging on Skeletal Mechanoresponsiveness: Animal Studies

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Skeletal Aging and Osteoporosis

Abstract

Growth and remodeling of skeletal tissue in response to its mechanical environment is a well established phenomenon. Relatively little is known regarding the interaction of aging and skeletal responses to mechanical loading, although several early studies have contributed to the “conventional wisdom” that old bones are relatively unresponsive. Development of non-pharmacological therapies for treatment of skeletal pathologies requires better understanding of such interactions, especially if aimed at maintaining or restoring bone mass in the elderly. The use of intrinsic (e.g., running) and extrinsic (e.g., tibial compression) loading models provide means to study age effects in animal studies. We identified 15 studies that address age effects explicitly, although only nine of these include a truly old group (e.g., 18–24 months old for mice). Though the outcomes of the studies have not been uniform, two general themes have emerged. First, bones from old animals are mechano-responsive provided they are presented with an appropriate stimulus. Second, it is unclear if bones from old animals are less responsive than from younger animals, as there is evidence for and against this view. Therefore, we advocate a re-examination of the conventional wisdom, and offer a few guidelines for designing studies to address the questions regarding aging and bone mechano-responsiveness.

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References

  1. Martin, R.B., Burr, D.B., Sharkey, N.A.: Skeletal Tissue Mechanics. Springer, New York (1998)

    Google Scholar 

  2. Carter, D.R.: Mechanical loading histories and cortical bone remodeling. Calcif. Tiss. Int. 36, S19–S24 (1984)

    Article  Google Scholar 

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

    Article  Google Scholar 

  4. 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  Google Scholar 

  5. Turner, C.H.: Three rules for bone adaptation to mechanical stimuli. Bone 23, 399–407 (1998)

    Article  Google Scholar 

  6. Robling, A.G., Castillo, A.B., Turner, C.H.: Biomechanical and molecular regulation of bone remodeling. Annu. Rev. Biomed. Eng. 8, 455–498 (2006)

    Article  Google Scholar 

  7. Busse, B., Djonic, D., Milovanovic, P., Hahn, M., Puschel, K., Ritchie, R.O., et al.: Decrease in the osteocyte lacunar density accompanied by hypermineralized lacunar occlusion reveals failure and delay of remodeling in aged human bone. Aging Cell 9, 1065–1075 (2010)

    Article  Google Scholar 

  8. Mullender, M.G., van der Meer, D.D., Huiskes, R., Lips, P.: Osteocyte density changes in aging and osteoporosis. Bone 18, 109–113 (1996)

    Article  Google Scholar 

  9. Vashishth, D., Verborgt, O., Divine, G., Schaffler, M.B., Fyhrie, D.P.: Decline in osteocyte lacunar density in human cortical bone is associated with accumulation of microcracks with age. Bone 26, 375–380 (2000)

    Article  Google Scholar 

  10. Perrini, S., Laviola, L., Carreira, M.C., Cignarelli, A., Natalicchio, A., Giorgino, F.: The GH/IGF1 axis and signaling pathways in the muscle and bone: mechanisms underlying age-related skeletal muscle wasting and osteoporosis. J. Endocrinol. 205, 201–210 (2010)

    Article  Google Scholar 

  11. Walsh, M.C., Hunter, G.R., Livingstone, M.B.: Sarcopenia in premenopausal and postmenopausal women with osteopenia, osteoporosis and normal bone mineral density. Osteoporos. Int. 17, 61–67 (2006)

    Article  Google Scholar 

  12. Osteoporosis Prevention, Diagnosis, and Therapy.: NIH Consensus Statement, 1–45 (2000)

    Google Scholar 

  13. Reginster, J.Y., Burlet, N.: Osteoporosis: a still increasing prevalence. Bone 38, S4–S9 (2006)

    Article  Google Scholar 

  14. Rosen, C.J.: Clinical practice. Postmenopausal osteoporosis. N. Engl. J. Med. 353, 595–603 (2005)

    Article  Google Scholar 

  15. Shane, E., Burr, D., Ebeling, P.R., Abrahamsen, B., Adler, R.A., Brown, T.D., et al.: Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research. J. Bone Miner. Res. 25, 2267–2294 (2010)

    Article  Google Scholar 

  16. Khosla, S., Westendorf, J.J., Oursler, M.J.: Building bone to reverse osteoporosis and repair fractures. J. Clin. Invest. 118, 421–428 (2008)

    Article  Google Scholar 

  17. Flurkey, K., Currer, J.M., Harrison, D.E.: Mouse models in aging research. In: Fox, J.G., Barthold, S.W., Davisson, M.T., Newcomer, C.E., Quimby, F.W., Smith, A.L. (eds.) The Mouse in Biomedical Research, 2nd edn, pp. 637–672. Academic Press, Burlington (2007)

    Chapter  Google Scholar 

  18. Robling, A.G., Burr, D.B., Turner, C.H.: Skeletal loading in animals. J. Musculoskelet. Neuronal Interact. 1, 249–262 (2001)

    Google Scholar 

  19. Fritton, S.P., Rubin, C.T.: In vivo measurement of bone deformations using strain gauges. In: Cowin, S.C. (ed.) Bone Mechanics Handbook, 2nd edn, pp. 8-1–8-41. CRC Press, Boca Raton (2001)

    Google Scholar 

  20. Sztefek, P., Vanleene, M., Olsson, R., Collinson, R., Pitsillides, A.A., Shefelbine, S.: Using digital image correlation to determine bone surface strains during loading and after adaptation of the mouse tibia. J. Biomech. 43, 599–605 (2010)

    Article  Google Scholar 

  21. Gross, T.S., Edwards, J.L., McLeod, K.J., Rubin, C.T.: Strain gradients correlate with sites of periosteal bone formation. J. Bone Miner. Res. 12, 982–988 (1997)

    Article  Google Scholar 

  22. Gross, T.S., Srinivasan, S., Liu, C.C., Clemens, T.L., Bain, S.D.: Noninvasive loading of the murine tibia: an in vivo model for the study of mechanotransduction. J. Bone Miner. Res. 17, 493–501 (2002)

    Article  Google Scholar 

  23. Kotha, S.P., Hsieh, Y.-F., Strigel, R.M., Muller, R., Silva, M.J.: Experimental and finite element analysis of the rat ulnar loading model—correlations between strain and bone formation following fatigue loading. J. Biomech. 37, 541–548 (2004)

    Article  Google Scholar 

  24. Silva, M.J., Brodt, M.D., Hucker, W.J.: Finite element analysis of the mouse tibia: estimating endocortical strain during three-point bending in SAMP6 osteoporotic mice. Anat. Rec. A. Discov. Mol. Cell. Evol. Biol. 283A, 380–390 (2005)

    Article  Google Scholar 

  25. Mosley, J.R., March, B.M., Lynch, J., Lanyon, L.E.: Strain magnitude related changes in whole bone architecture in growing rats. Bone 20, 191–198 (1997)

    Article  Google Scholar 

  26. Rabkin, B.A., Szivek, J.A., Schonfeld, J.E., Halloran, B.P.: Long-term measurement of bone strain in vivo: the rat tibia. J. Biomed. Mater. Res. 58, 277–281 (2001)

    Article  Google Scholar 

  27. Indrekvam, K., Husby, O.S., Gjerdet, N.R., Engester, L.B., Langeland, N.: Age-dependent mechanical properties of rat femur. Measured in vivo and in vitro. Acta Orthop. Scand. 62, 248–252 (1991)

    Article  Google Scholar 

  28. Keller, T.S., Spengler, D.M.: Regulation of bone stress and strain in the immature and mature rat femur. J. Biomech. 22, 1115–1127 (1989)

    Article  Google Scholar 

  29. Raab, D.M., Smith, E.L., Crenshaw, T.D., Thomas, D.P.: Bone mechanical properties after exercise training in young and old rats. J. Appl. Physiol. 68, 130–134 (1990)

    Google Scholar 

  30. Leppanen, O.V., Sievanen, H., Jokihaara, J., Pajamaki, I., Kannus, P., Jarvinen, T.L.: Pathogenesis of age-related osteoporosis: impaired mechano-responsiveness of bone is not the culprit. PLoS ONE 3, e2540 (2008)

    Article  Google Scholar 

  31. Bennell, K.L., Khan, K.M., Warmington, S., Forwood, M.R., Coleman, B.D., Bennett, M.B., et al.: Age does not influence the bone response to treadmill exercise in female rats. Med. Sci. Sports Exerc. 34, 1958–1965 (2002)

    Article  Google Scholar 

  32. Umemura, Y., Ishiko, T., Tsujimoto, H., Miura, H., Mokushi, N., Suzuki, H.: Effects of jump training on bone hypertrophy in young and old rats. Int. J. Sports Med. 16, 364–367 (1995)

    Article  Google Scholar 

  33. Jarvinen, T.L., Pajamaki, I., Sievanen, H., Vuohelainen, T., Tuukkanen, J., Jarvinen, M., et al.: Femoral neck response to exercise and subsequent deconditioning in young and adult rats. J. Bone Miner. Res. 18, 1292–1299 (2003)

    Article  Google Scholar 

  34. Hoshi, A., Watanabe, H., Chiba, M., Inaba, Y.: Effects of exercise at different ages on bone density and mechanical properties of femoral bone of aged mice. Tohoku J. Exp. Med. 185, 15–24 (1998)

    Article  Google Scholar 

  35. Buhl, K.M., Jacobs, C.R., Turner, R.T., Evans, G.L., Farrell, P.A., Donahue, H.J.: Aged bone displays an increased responsiveness to low-intensity resistance exercise. J. Appl. Physiol. 90, 1359–1364 (2001)

    Google Scholar 

  36. Honda, A., Sogo, N., Nagasawa, S., Kato, T., Umemura, Y.: Bones benefits gained by jump training are preserved after detraining in young and adult rats. J. Appl. Physiol. 105, 849–853 (2008)

    Article  Google Scholar 

  37. Rubin, C.T., Lanyon, L.E.: Regulation of bone formation by applied dynamic loads. J. Bone Jt. Surg. [Am] 66, 397–402 (1984)

    Google Scholar 

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

    Article  Google Scholar 

  39. Chambers, T.J., Evans, M., Gardner, T.N.: Turner- Smith A, Chow JWM. Induction of bone formation in rat tail vertebrae by mechanical loading. Bone Miner. 20, 167–178 (1993)

    Article  Google Scholar 

  40. Kroeber M, Unglaub F, Guehring T, Nerlich A, Hadi T, Lotz J, et al.: Effects of controlled dynamic disc distraction on degenerated intervertebral discs: an in vivo study on the rabbit lumbar spine model. Spine (Phila Pa 1976) 2005; 30:181–187

    Google Scholar 

  41. Rubin, C.T., Bain, S.D., McCleod, K.J.: Suppression of osteogenic response in the aging skeleton. Calcif. Tiss. Int. 50, 306–313 (1992)

    Article  Google Scholar 

  42. Turner, C.H., Akhter, M.P., Raab, D.M., Kimmel, D.B., Recker, R.R.: A noninvasive, in vivo model for studying strain adaptive bone modeling. Bone 12, 73–79 (1991)

    Article  Google Scholar 

  43. Akhter, M.P., Cullen, D.M., Pedersen, E.A., Kimmel, D.B., Recker, R.R.: Bone response to in vivo mechanical loading in two breeds of mice. Calcif. Tiss. Int. 63, 442–449 (1998)

    Article  Google Scholar 

  44. Turner, C.H., Forwood, M.R., Rho, J.Y., Yoshikawa, T.: Mechanical loading thresholds for lamellar and woven bone formation. J. Bone Min. Res. 9, 87–97 (1994)

    Article  Google Scholar 

  45. Turner, C.H., Takano, Y., Owan, I.: Aging changes mechanical loading thresholds for bone formation in rats. J. Bone Miner. Res. 10, 1544–1549 (1995)

    Article  Google Scholar 

  46. Kesavan, C., Mohan, S., Oberholtzer, S., Wergedal, J.E., Baylink, D.J.: Mechanical loading-induced gene expression and BMD changes are different in two inbred mouse strains. J. Appl. Physiol. 99, 1951–1957 (2005)

    Article  Google Scholar 

  47. Jilka, R.L., Weinstein, R.S., Takahashi, K., Parfitt, A.M., Manolagas, S.C.: Linkage of decreased bone mass with impaired osteoblastogenesis in a murine model of accelerated senescence. J. Clin. Invest. 97, 1732–1740 (1996)

    Article  Google Scholar 

  48. Silva, M.J., Brodt, M.B., Ettner, S.L.: Long bones from the senescence accelerated mouse SAMP6 have increased size but reduced whole-bone strength and resistance to fracture. J. Bone Miner. Res. 17, 1597–1603 (2002)

    Article  Google Scholar 

  49. Silva, M.J., Brodt, M.D., Ko, M., Abu-Amer, Y.: Impaired marrow osteogenesis is associated with reduced endocortical bone formation but does not impair periosteal bone formation in long bones of SAMP6 mice. J. Bone Miner. Res. 20, 419–427 (2005)

    Article  Google Scholar 

  50. Matsushita, M., Tsuboyama, T., Kasai, R., Okumura, H., Yamamuro, T., Higuchi, K., et al.: Age-related changes in bone mass in the senescence-accelerated mouse (SAM). SAM-R/3 and SAM-P/6 as new murine models for senile osteoporosis. Am. J. Pathol. 125, 276–283 (1986)

    Google Scholar 

  51. Silva, M.J., Brodt, M.D.: Mechanical stimulation of bone formation is normal in the SAMP6 mouse. Calcif. Tissue Int. 82, 489–497 (2008)

    Article  Google Scholar 

  52. Silva MJ, Brodt MD.: Bone biomechanics and mechanobiology in the SAMP6 mouse. In: Takeda T, (ed.) The Senescence-Accelerated Mouse (SAM): Achievements and Future Directions, Elsevier; London (2011) (estimated)

    Google Scholar 

  53. Srinivasan, S., Agans, S.C., King, K.A., Moy, N.Y., Poliachik, S.L., Gross, T.S.: Enabling bone formation in the aged skeleton via rest-inserted mechanical loading. Bone 33, 946–955 (2003)

    Article  Google Scholar 

  54. Fritton, J.C., Myers, E.R., Wright, T.M., van der Meulen, M.C.: Loading induces site-specific increases in mineral content assessed by microcomputed tomography of the mouse tibia. Bone 36, 1030–1038 (2005)

    Article  Google Scholar 

  55. De Souza, R.L., Matsuura, M., Eckstein, F., Rawlinson, S.C., Lanyon, L.E., Pitsillides, A.A.: Non-invasive axial loading of mouse tibiae increases cortical bone formation and modifies trabecular organization: a new model to study cortical and cancellous compartments in a single loaded element. Bone 37, 810–818 (2005)

    Article  Google Scholar 

  56. Christiansen, B.A., Bayly, P.V., Silva, M.J.: Constrained tibial vibration in mice: a method for studying the effects of vibrational loading of bone. J. Biomech. Eng. 130, 044502 (2008)

    Article  Google Scholar 

  57. Brodt, M.D., Silva, M.J.: Aged mice have enhanced endocortical response and normal periosteal response compared to young-adult mice following 1 week of axial tibial compression. J. Bone Miner. Res. 25, 2006–2015 (2010)

    Article  Google Scholar 

  58. Silva MJ, Brodt MD, Lynch MA, Stephens AL, Wood DJ, Civitelli R. (2012) Tibial Loading Increases Osteogenic Gene Expression and Cortical Bone Volume in Mature and Middle-Aged Mice. PLoS ONE 7(4), e34980. doi:10.1371/journal.pone.0034980

    Article  Google Scholar 

  59. Lynch, M.E., Main, R.P., Xu, Q., Walsh, D.J., Schaffler, M.B., Wright, T.M., et al.: Cancellous bone adaptation to tibial compression is not sex dependent in growing mice. J. Appl. Physiol. 109, 685–691 (2010)

    Article  Google Scholar 

  60. Lynch, M.E., Main, R.P., Xu, Q., Schmicker, T.L., Schaffler, M.B., Wright, T.M., et al.: Tibial compression is anabolic in the adult mouse skeleton despite reduced responsiveness with aging. Bone 49, 439–446 (2011)

    Article  Google Scholar 

  61. Ozcivici, E., Luu, Y.K., Adler, B., Qin, Y.X., Rubin, J., Judex, S., et al.: Mechanical signals as anabolic agents in bone. Nat. Rev. Rheumatol. 6, 50–59 (2010)

    Article  Google Scholar 

  62. 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  Google Scholar 

  63. Judex, S., Donahue, L.R., Rubin, C.: Genetic predisposition to low bone mass is paralleled by an enhanced sensitivity to signals anabolic to the skeleton. Faseb J 16, 1260–1262 (2002)

    Google Scholar 

  64. 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  Google Scholar 

  65. Lynch, M.A., Brodt, M.D., Silva, M.J.: Skeletal effects of whole-body vibration in adult and aged mice. J. Orthop. Res. 28, 241–247 (2010)

    Google Scholar 

  66. Uhthoff HK, Sekaly G, Jaworski ZF. Effect of long-term nontraumatic immobilization on metaphyseal spongiosa in young adult and old beagle dogs. Clin Orthop Relat Res 1985:278–283

    Google Scholar 

  67. Jaworski ZF, Liskova-Kiar M, Uhthoff HK. Effect of long-term immobilisation on the pattern of bone loss in older dogs. J Bone Joint Surg Br 1980; 62-B:104-10

    Google Scholar 

  68. Perrien, D.S., Akel, N.S., Dupont-Versteegden, E.E., Skinner, R.A., Siegel, E.R., Suva, L.J., et al.: Aging alters the skeletal response to disuse in the rat. Am. J. Physiol. Regul. Integr. Comp. Physiol. 292, R988–R996 (2007)

    Article  Google Scholar 

  69. Brodt, M.D., Ellis, C.B., Silva, M.J.: Growing C57Bl/6 mice increase whole bone mechanical properties by increasing geometric and material properties. J. Bone Miner. Res. 14, 2159–2166 (1999)

    Article  Google Scholar 

  70. Harrison, D.E.: Baseline life span data: twelve strains of commonly used laboratory mice. In: 2009

    Google Scholar 

  71. Holloszy, J.O.: Exercise increases average longevity of female rats despite increased food intake and no growth retardation. J Gerontol 48, B97–B100 (1993)

    Article  Google Scholar 

  72. Jee, W.S., Yao, W.: Overview: animal models of osteopenia and osteoporosis. J. Musculoskelet. Neuronal Interact. 1, 193–207 (2001)

    Google Scholar 

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Acknowledgments

We thank Blaine Christiansen and Nilsson Holguin for their thoughtful reviews of this chapter. We gratefully acknowledge support from the U.S. National Institutes of Health NIH/NIAMS R01AR047867 and R21AR054371.

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Kotiya, A.A., Silva, M.J. (2012). The Effect of Aging on Skeletal Mechanoresponsiveness: Animal Studies. In: Silva, M. (eds) Skeletal Aging and Osteoporosis. Studies in Mechanobiology, Tissue Engineering and Biomaterials, vol 5. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8415_2012_115

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