Top

Current Osteoporosis Reports

Published in:

Open Access 01-12-2019 | Osteoporosis | Osteocytes (J Klein-Nulend, Section editor)

Aging and Mechanoadaptive Responsiveness of Bone

Authors: Behzad Javaheri, Andrew A. Pitsillides

Published in: Current Osteoporosis Reports | Issue 6/2019

Abstract

Purpose of Review

Osteoporosis is an age-related disorder characterized by bone loss and increased fracture susceptibility. Whether this is due to reduced loading in less active elderly individuals or inherent modifications in bone cells is uncertain. We suppose that osteoporosis is nonetheless prima facie evidence for impaired mechanoadaptation; either capacity to accrue new bone declines, or the stimulus for such accrual is absent/can no longer be triggered in the aged. Herein, we provide only sufficient background to enable a focus on recent advances which seek to address such dilemmas.

Recent Findings

Recent advances from innovative high-impact loading regimes emphasize the priming of mechanoadaptation in the aged, such that low-to-moderate intensity loading becomes beneficial. These new findings lead us to speculate that aged bone mechanoadaptation is not driven solely by strain magnitude but is instead sensitive to high strain gradients.

Summary

Impaired mechanoadaptation is a feature of the aged skeleton. Recent advances indicate that novel interventional loading regimes can restore mechanoadaptive capacity, enabling new approaches for retaining bone health in the aged. Innovative exercise paradigms appear to be capable of “hacking” into the osteogenic signal produced by exercise such that low-to-moderate intensity activities may also become more beneficial. Deciphering the underpinning mechanism(s) will also enable new pharmacological intervention for retaining bone health in the aged.

Black DM, Rosen CJ. Postmenopausal osteoporosis. N Engl J Med. 2016;374(3):254–62. https://doi.org/10.1056/NEJMcp1513724.CrossRef

Seeman E. Pathogenesis of bone fragility in women and men. Lancet. 2002;359(9320):1841–50. https://doi.org/10.1016/S0140-6736(02)08706-8.CrossRefPubMed

Fuleihan GE-H, Chakhtoura M, Cauley JA, Chamoun N. Worldwide fracture prediction. J Clin Densitom. 2017;20(3):397–424. https://doi.org/10.1016/j.jocd.2017.06.008.CrossRef

Cauley JA. Burden of hip fracture on disability. Lancet Public Health. 2017;2(5):e209–e10. https://doi.org/10.1016/S2468-2667(17)30067-1.CrossRefPubMed

Javaheri B, Herbert E, Hopkinson M, Al-Jazzar A, Pitsillides AA. Sost haploinsufficiency provokes peracute lethal cardiac tamponade without rescuing the osteopenia in a mouse model of excess glucocorticoids. Am J Pathol. 2019;189(4):753–61. https://doi.org/10.1016/j.ajpath.2018.12.007.CrossRefPubMedPubMedCentral

Riggs BL, Khosla S, Melton LJ III. Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev. 2002;23(3):279–302. https://doi.org/10.1210/edrv.23.3.0465.CrossRefPubMed

Hamrick MW, Ding KH, Pennington C, Chao YJ, Wu YD, Howard B, et al. Age-related loss of muscle mass and bone strength in mice is associated with a decline in physical activity and serum leptin. Bone. 2006;39(4):845–53. https://doi.org/10.1016/j.bone.2006.04.011.CrossRefPubMed

Nordin BE, Need AG, Chatterton BE, Horowitz M, Morris HA. The relative contributions of age and years since menopause to postmenopausal bone loss. J Clin Endocrinol Metab. 1990;70(1):83–8. https://doi.org/10.1210/jcem-70-1-83.CrossRefPubMed

Slemenda C, Hui SL, Longcope C, Johnston CC. Sex steroids and bone mass. A study of changes about the time of menopause. J Clin Invest. 1987;80(5):1261–9. https://doi.org/10.1172/JCI113201.CrossRefPubMedPubMedCentral

10.

Villareal DT, Morley JE. Trophic factors in aging. Should older people receive hormonal replacement therapy? Drugs Aging. 1994;4(6):492–509. https://doi.org/10.2165/00002512-199404060-00005.CrossRefPubMed

11.

Frost HM. On the estrogen-bone relationship and postmenopausal bone loss: a new model. J Bone Miner Res. 1999;14(9):1473–7. https://doi.org/10.1359/jbmr.1999.14.9.1473.CrossRefPubMed

12.

Lee K, Jessop H, Suswillo R, Zaman G, Lanyon L. Endocrinology: bone adaptation requires oestrogen receptor-alpha. Nature. 2003;424(6947):389. https://doi.org/10.1038/424389a.CrossRefPubMed

13.

Sahin E, Depinho RA. Linking functional decline of telomeres, mitochondria and stem cells during ageing. Nature. 2010;464(7288):520–8. https://doi.org/10.1038/nature08982.CrossRefPubMedPubMedCentral

14.

Fedarko NS, Vetter UK, Robey PG. Age-related changes in bone matrix structure in vitro. Calcif Tissue Int. 1995;56(Suppl 1):S41–3.CrossRef

15.

Stanford CM, Welsch F, Kastner N, Thomas G, Zaharias R, Holtman K, et al. Primary human bone cultures from older patients do not respond at continuum levels of in vivo strain magnitudes. J Biomech. 2000;33(1):63–71. https://doi.org/10.1016/S0021-9290(99)00173-6.CrossRefPubMed

16.

Klein-Nulend J, Sterck JG, Semeins CM, Lips P, Joldersma M, Baart JA, et al. Donor age and mechanosensitivity of human bone cells. Osteoporos Int. 2002;13(2):137–46. https://doi.org/10.1007/s001980200005.CrossRefPubMed

17.

Sterck JG, Klein-Nulend J, Lips P, Burger EH. Response of normal and osteoporotic human bone cells to mechanical stress in vitro. Am J Phys. 1998;274(6 Pt 1):E1113–20. https://doi.org/10.1152/ajpendo.CrossRef

18.

Termine JD. Cellular activity, matrix proteins, and aging bone. Exp Gerontol. 1990;25(3-4):217–21. https://doi.org/10.1016/0531-5565(90)90055-7.CrossRefPubMed

19.

D'ippolito G, Schiller PC, Ricordi C, Roos BA, Howard GA. Age-related osteogenic potential of mesenchymal stromal stem cells from human vertebral bone marrow. J Bone Miner Res. 1999;14(7):1115–22. https://doi.org/10.1359/jbmr.1999.14.7.1115.CrossRefPubMed

20.

Muschler GF, Nitto H, Boehm CA, Easley KA. Age-and gender-related changes in the cellularity of human bone marrow and the prevalence of osteoblastic progenitors. J Orthop Res : official publication of the Orthopaedic Research Society. 2001;19(1):117–25. https://doi.org/10.1016/S0736-0266(00)00010-3.CrossRef

21.

Nishida S, Endo N, Yamagiwa H, Tanizawa T, Takahashi HE. Number of osteoprogenitor cells in human bone marrow markedly decreases after skeletal maturation. J Bone Miner Metab. 1999;17(3):171–7. https://doi.org/10.1007/s007740050081.CrossRefPubMed

22.

Yang Y-M, Li P, Cui D-C, Dang R-J, Zhang L, Wen N, et al. Effect of aged bone marrow microenvironment on mesenchymal stem cell migration. Age. 2015;37(2):16–9. https://doi.org/10.1007/s11357-014-9743-z.CrossRefPubMedPubMedCentral

23.

Kahn A, Gibbons R, Perkins S, Gazit D. Age-related bone loss. A hypothesis and initial assessment in mice. Clin Orthop Relat Res. 1995;313:69–75.

24.

Koshihara Y, Suematsu A, Feng D, Okawara R, Ishibashi H, Yamamoto S. Osteoclastogenic potential of bone marrow cells increases with age in elderly women with fracture. Mech Ageing Dev. 2002;123(10):1321–31. https://doi.org/10.1016/S0047-6374(02)00071-4.CrossRefPubMed

25.

Cao JJ, Wronski TJ, Iwaniec U, Phleger L, Kurimoto P, Boudignon B, et al. Aging increases stromal/osteoblastic cell-induced osteoclastogenesis and alters the osteoclast precursor pool in the mouse. J Bone Miner Res. 2005;20(9):1659–68. https://doi.org/10.1359/JBMR.050503.CrossRefPubMed

26.

Perkins S, Gibbons R, Kling S, Kahn A. Age-related bone loss in mice is associated with an increased osteoclast progenitor pool. Bone. 1994;15(1):65–72. https://doi.org/10.1016/8756-3282(94)90893-1.CrossRefPubMed

27.

Qiu S, Rao D, Palnitkar S, Parfitt A. Relationships between osteocyte density and bone formation rate in human cancellous bone. Bone. 2002;31(6):709–11. https://doi.org/10.1016/S8756-3282(02)00907-9.CrossRefPubMed

28.

Kita K, Kawai K, Hirohata K. Changes in bone marrow blood flow with aging. J Orthop Res : official publication of the Orthopaedic Research Society. 1987;5(4):569–75. https://doi.org/10.1002/jor.1100050412.CrossRef

29.

Tonna EA. Electron microscopic study of bone surface changes during aging. The loss of cellular control and biofeedback. J Gerontol. 1978;33(2):163–77. https://doi.org/10.1093/geronj/33.2.163.CrossRefPubMed

30.

Ashique AM, Hart LS, Thomas CDL, Clement JG, Pivonka P, Carter Y, et al. Lacunar-canalicular network in femoral cortical bone is reduced in aged women and is predominantly due to a loss of canalicular porosity. Bone Rep. 2017;7:9–16. https://doi.org/10.1016/j.bonr.2017.06.002.CrossRefPubMedPubMedCentral

31.

Cei S, Mair B, Kandler B, Gabriele M, Watzek G, Gruber R. Age-related changes of cell outgrowth from rat calvarial and mandibular bone in vitro. J Cranio-Maxillo-Facial Surg : official publication of the European Association for Cranio-Maxillo-Facial Surgery. 2006;34(7):387–94. https://doi.org/10.1016/j.jcms.2006.07.856.CrossRef

32.

Nunez J, Goring A, Gomez-Nicola D, Javaheri B, Pitsillides A, Thurner P, et al. Regional diversity in the murine cortical vascular network is revealed by synchrotron X-ray tomography and is amplified with age. eCM. 2018;35:281–99. https://doi.org/10.22203/eCM.v035a20.CrossRefPubMed

33.

Riggs BL, Melton LJ 3rd. Involutional osteoporosis. N Engl J Med. 1986;314(26):1676–86. https://doi.org/10.1056/NEJM198606263142605.CrossRefPubMed

34.

Lanyon LE, Armstrong V, Saxon L, Sunters A, Sugiyama T, Zaman G, et al. Estrogen receptors critically regulate bones’ adaptive responses to loading. Clin Rev Bone Mineral Metab. 2007;5(4):234–48. https://doi.org/10.1007/s12018-008-9011-9.CrossRef

35.

Seeman E. Bone modeling and remodeling. Crit Rev Eukaryot Gene Expr. 2009;19(3):219–33. https://doi.org/10.1615/CritRevEukarGeneExpr.v19.i3.40.CrossRefPubMed

36.

Ducher G, Prouteau S, Courteix D, Benhamou CL. Cortical and trabecular bone at the forearm show different adaptation patterns in response to tennis playing. J Clin Densitom. 2004;7(4):399–405. https://doi.org/10.1385/JCD:7:4:399.CrossRefPubMed

37.

Helge EW, Kanstrup IL. Bone density in female elite gymnasts: impact of muscle strength and sex hormones. Med Sci Sports Exerc. 2002;34(1):174–80. https://doi.org/10.1097/00005768-200201000-00026.CrossRefPubMed

38.

Spector ER, Smith SM, Sibonga JD. Skeletal effects of long-duration head-down bed rest. Aviat Space Environ Med. 2009;80(5 Suppl):A23–8. https://doi.org/10.3357/ASEM.BR02.2009.CrossRefPubMed

39.

Lanyon LE, Rubin CT. Static vs dynamic loads as an influence on bone remodelling. J Biomech. 1984;17(12):897–905. https://doi.org/10.1016/0021-9290(84)90003-4.CrossRefPubMed

40.

Mosley JR, Lanyon LE. Growth rate rather than gender determines the size of the adaptive response of the growing skeleton to mechanical strain. Bone. 2002;30(1):314–9. https://doi.org/10.1016/S8756-3282(01)00626-3.CrossRefPubMed

41.

Mosley JR, March BM, Lynch J, Lanyon LE. Strain magnitude related changes in whole bone architecture in growing rats. Bone. 1997;20(3):191–8. https://doi.org/10.1016/S8756-3282(96)00385-7.CrossRefPubMed

42.

Cullen DM, Smith RT, Akhter MP. Bone-loading response varies with strain magnitude and cycle number. J Appl Physiol. 2001;91(5):1971–6.CrossRef

43.

Lee KC, Maxwell A, Lanyon LE. Validation of a technique for studying functional adaptation of the mouse ulna in response to mechanical loading. Bone. 2002;31(3):407–12. https://doi.org/10.1016/S8756-3282(02)00842-6.CrossRefPubMed

44.

Javaheri B, Stern AR, Lara N, Dallas M, Zhao H, Liu Y, et al. Deletion of a single β-catenin allele in osteocytes abolishes the bone anabolic response to loading. J Bone Miner Res. 2014;29(3):705–15. https://doi.org/10.1002/jbmr.2064.CrossRefPubMedPubMedCentral

45.

Shimano MM, Volpon JB. Biomechanics and structural adaptations of the rat femur after hindlimb suspension and treadmill running. Braz J Med Biol Res. 2009;42(4):330–8. https://doi.org/10.1590/s0100-879x2009000400004.CrossRefPubMed

46.

Hanson AM, Ferguson VL, Simske SJ, Cannon CM, Stodieck S. Comparison of tail-suspension and sciatic nerve crush on the musculoskeletal system in young-adult mice. Biomed Sci Instrum. 2005;41:92–6.PubMed

47.

De Souza R, Javaheri B, Collinson R, Chenu C, Shefelbine S, Lee P, et al. Prolonging disuse in aged mice amplifies cortical but not trabecular bones’ response to mechanical loading. J Musculoskelet Neuronal Interact. 2017;17(3):218.PubMedCentral

48.

Liu C, Zhao Y, Cheung WY, Gandhi R, Wang L, You L. Effects of cyclic hydraulic pressure on osteocytes. Bone. 2010;46(5):1449–56. https://doi.org/10.1016/j.bone.2010.02.006.CrossRefPubMedPubMedCentral

49.

Ponik SM, Triplett JW, Pavalko FM. Osteoblasts and osteocytes respond differently to oscillatory and unidirectional fluid flow profiles. J Cell Biochem. 2007;100(3):794–807. https://doi.org/10.1002/jcb.21089.CrossRefPubMed

50.

Javaheri B, Sunters A, Zaman G, Suswillo RF, Saxon LK, Lanyon LE, et al. Lrp5 is not required for the proliferative response of osteoblasts to strain but regulates proliferation and apoptosis in a cell autonomous manner. PLoS One. 2012;7(5):e35726. https://doi.org/10.1371/journal.pone.0035726.CrossRefPubMedPubMedCentral

51.

Krolner B, Toft B. Vertebral bone loss: an unheeded side effect of therapeutic bed rest. Clin Sci (Lond). 1983;64(5):537–40. https://doi.org/10.1042/cs0640537.CrossRef

52.

Wronski TJ, Morey ER. Inhibition of cortical and trabecular bone formation in the long bones of immobilized monkeys. Clin Orthop Relat Res. 1983;181:269–76. https://doi.org/10.1097/00003086-198312000-00042.CrossRef

53.

Vico L, Chappard D, Alexandre C, Palle S, Minaire P, Riffat G, et al. Effects of weightlessness on osseous tissue of the rat after a space flight of 5 days (Cosmos 1514). Bone. 1987;8(2):95–103. https://doi.org/10.1016/8756-3282(87)90077-9.CrossRefPubMed

54.

Leblanc AD, Schneider VS, Evans HJ, Engelbretson DA, Krebs JM. Bone mineral loss and recovery after 17 weeks of bed rest. J Bone Miner Res. 1990;5(8):843–50. https://doi.org/10.1002/jbmr.5650050807.CrossRefPubMed

55.

Zerwekh JE, Ruml LA, Gottschalk F, Pak CY. The effects of twelve weeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects. J Bone Miner Res. 1998;13(10):1594–601. https://doi.org/10.1359/jbmr.1998.13.10.1594.CrossRefPubMed

56.

Krolner B, Toft B, Pors Nielsen S, Tondevold E. Physical exercise as prophylaxis against involutional vertebral bone loss: a controlled trial. Clin Sci (Lond). 1983;64(5):541–6. https://doi.org/10.1042/cs0640541.CrossRef

57.

Bassey EJ, Ramsdale SJ. Increase in femoral bone density in young women following high-impact exercise. Osteoporos Int. 1994;4(2):72–5. https://doi.org/10.1007/BF01623226.CrossRefPubMed

58.

Courteix D, Lespessailles E, Peres SL, Obert P, Germain P, Benhamou CL. Effect of physical training on bone mineral density in prepubertal girls: a comparative study between impact-loading and non-impact-loading sports. Osteoporos Int. 1998;8(2):152–8. https://doi.org/10.1007/BF02672512.CrossRefPubMed

59.

Iwamoto J, Yeh JK, Aloia JF. Differential effect of treadmill exercise on three cancellous bone sites in the young growing rat. Bone. 1999;24(3):163–9. https://doi.org/10.1016/S8756-3282(98)00189-6.CrossRefPubMed

60.

Haapasalo H, Sievanen H, Kannus P, Heinonen A, Oja P, Vuori I. Dimensions and estimated mechanical characteristics of the humerus after long-term tennis loading. J Bone Miner Res. 1996;11(6):864–72. https://doi.org/10.1002/jbmr.5650110619.CrossRefPubMed

61.

Bass SL, Saxon L, Daly R, Turner CH, Robling AG, Seeman E, et al. The effect of mechanical loading on the size and shape of bone in pre-, peri-, and postpubertal girls: a study in tennis players. J Bone Miner Res. 2002;17(12):2274–80. https://doi.org/10.1359/jbmr.2002.17.12.2274.CrossRefPubMed

62.

Saxon LK, Lanyon LE. Assessment of the in vivo adaptive response to mechanical loading. Methods Mol Biol. 2008;455:307–22. https://doi.org/10.1007/978-1-59745-104-8_21.CrossRefPubMed

63.

Lanyon LE. Control of bone architecture by functional load bearing. J Bone Miner Res. 1992;7(Suppl 2):S369–75. https://doi.org/10.1002/jbmr.5650071403.CrossRefPubMed

64.

Damien E, Price JS, Lanyon LE. Mechanical strain stimulates osteoblast proliferation through the estrogen receptor in males as well as females. J Bone Miner Res. 2000;15(11):2169–77. https://doi.org/10.1359/jbmr.2000.15.11.2169.CrossRefPubMed

65.

Sugiyama T, Price JS, Lanyon LE. Functional adaptation to mechanical loading in both cortical and cancellous bone is controlled locally and is confined to the loaded bones. Bone. 2009. https://doi.org/10.1016/j.bone.2009.08.054.CrossRef

66.

Collet P, Uebelhart D, Vico L, Moro L, Hartmann D, Roth M, et al. Effects of 1- and 6-month spaceflight on bone mass and biochemistry in two humans. Bone. 1997;20(6):547–51. https://doi.org/10.1016/s8756-3282(97)00052-5.CrossRefPubMed

67.

Rodan GA. Bone mass homeostasis and bisphosphonate action. Bone. 1997;20(1):1–4. https://doi.org/10.1016/s8756-3282(96)00318-3.CrossRefPubMed

68.

Bikle DD, Sakata T, Halloran BP. The impact of skeletal unloading on bone formation. Gravit Space Biol Bull. 2003;16(2):45–54.PubMed

69.

Bailey CA, Brooke-Wavell K. Optimum frequency of exercise for bone health: randomised controlled trial of a high-impact unilateral intervention. Bone. 2010;46(4):1043–9. https://doi.org/10.1016/j.bone.2009.12.001.CrossRefPubMed

70.

Vainionpää A, Korpelainen R, Sievänen H, Vihriälä E, Leppäluoto J, Jämsä T. Effect of impact exercise and its intensity on bone geometry at weight-bearing tibia and femur. Bone. 2007;40(3):604–11. https://doi.org/10.1016/j.bone.2006.10.005.CrossRefPubMed

71.

Karinkanta S, Heinonen A, Sievänen H, Uusi-Rasi K, Pasanen M, Ojala K, et al. A multi-component exercise regimen to prevent functional decline and bone fragility in home-dwelling elderly women: randomized, controlled trial. Osteoporos Int. 2007;18(4):453–62. https://doi.org/10.1007/s00198-006-0256-1.CrossRefPubMed

72.

Uusi-Rasi K, Kannus P, Cheng S, Sievänen H, Pasanen M, Heinonen A, et al. Effect of alendronate and exercise on bone and physical performance of postmenopausal women: a randomized controlled trial. Bone. 2003;33(1):132–43. https://doi.org/10.1016/s8756-3282(03)00082-6.CrossRefPubMed

73.

Holguin N, Brodt MD, Sanchez ME, Silva MJ. Aging diminishes lamellar and woven bone formation induced by tibial compression in adult C57BL/6. Bone. 2014;65:83–91. https://doi.org/10.1016/j.bone.2014.05.006.CrossRefPubMedPubMedCentral

74.

Rubin CT, Bain SD, McLeod KJ. Suppression of the osteogenic response in the aging skeleton. Calcif Tissue Int. 1992;50(4):306–13. https://doi.org/10.1007/bf00301627.CrossRefPubMed

75.

Turner CH, Takano Y, Owan I. Aging changes mechanical loading thresholds for bone formation in rats. J Bone Miner Res. 1995;10(10):1544–9. https://doi.org/10.1002/jbmr.5650101016.CrossRefPubMed

76.

Heveran CM, Rauff A, King KB, Carpenter RD, Ferguson VL. A new open-source tool for measuring 3D osteocyte lacunar geometries from confocal laser scanning microscopy reveals age-related changes to lacunar size and shape in cortical mouse bone. Bone. 2018;110:115–27. https://doi.org/10.1016/j.bone.2018.01.018.CrossRefPubMedPubMedCentral

77.

Tiede-Lewis LM, Xie Y, Hulbert MA, Campos R, Dallas MR, Dusevich V, et al. Degeneration of the osteocyte network in the C57BL/6 mouse model of aging. Aging (Albany NY). 2017;9(10):2190. https://doi.org/10.18632/aging.101308.CrossRef

78.

Akkus O, Adar F, Schaffler MB. Age-related changes in physicochemical properties of mineral crystals are related to impaired mechanical function of cortical bone. Bone. 2004;34(3):443–53. https://doi.org/10.1016/j.bone.2003.11.003.CrossRefPubMed

79.

Seeman E. The growth and age-related origins of bone fragility in men. Calcif Tissue Int. 2004;75(2):100–9. https://doi.org/10.1007/s00223-004-0289-4.CrossRefPubMed

80.

Leppanen OV, Sievanen H, Jokihaara J, Pajamaki I, Kannus P, Jarvinen TL. Pathogenesis of age-related osteoporosis: impaired mechano-responsiveness of bone is not the culprit. PLoS One. 2008;3(7):e2540. https://doi.org/10.1371/journal.pone.0002540.CrossRefPubMedPubMedCentral

81.

Lanyon LE. Strain-related control of bone (re)modeling: objectives, mechanisms and failures. J Musculoskelet Neuronal Interact. 2008;8(4):298–300.PubMed

82.

Lanyon LE, Skerry T. Postmenopausal osteoporosis as a failure of bone’s adaptation to functional loading: a hypothesis. J Bone Miner Res. 2001;16(11):1937–47. https://doi.org/10.1359/jbmr.2001.16.11.1937.CrossRefPubMed

83.

Lanyon LE. Functional strain as a determinant for bone remodeling. Calcif Tissue Int. 1984;36(Suppl 1):S56–61. https://doi.org/10.1007/bf02406134.CrossRefPubMed

84.

Lanyon LE. The success and failure of the adaptive response to functional load-bearing in averting bone fracture. Bone. 1992;13(Suppl 2):S17–21. https://doi.org/10.1016/8756-3282(92)90191-x.CrossRefPubMed

85.

Galea GL, Meakin LB, Harris MA, Delisser PJ, Lanyon LE, Harris SE, et al. Old age and the associated impairment of bones’ adaptation to loading are associated with transcriptomic changes in cellular metabolism, cell-matrix interactions and the cell cycle. Gene. 2017;599:36–52. https://doi.org/10.1016/j.gene.2016.11.006.CrossRefPubMedPubMedCentral

86.

•• Javaheri B, Carriero A, Wood M, De Souza R, Lee PD, Shefelbine S, et al. Transient peak-strain matching partially recovers the age-impaired mechanoadaptive cortical bone response. Sci Rep. 2018;8(1):6636. https://doi.org/10.1038/s41598-018-25084-6This study indicates that imposition of a brief high-magnitude, load-priming regime partially restores cortical mechanoadaptive responses in bones of aged mice in a manner that is spatially correlated with changes in osteocyte Sclerostin expression. CrossRefPubMedPubMedCentral

87.

•• Holguin N, Brodt MD, Silva MJ, et al. J Bone Miner Res. 2016;31(12):2215–26. https://doi.org/10.1002/jbmr.2900This study reports that the reduced bone anabolic response to loading in aged mice includes a failure to sustain Wnt activity, attributing this to a lower sensitivity to repeat loading in the aged mice. CrossRefPubMedPubMedCentral

88.

Meakin LB, Todd H, Delisser PJ, Galea GL, Moustafa A, Lanyon LE, et al. Parathyroid hormone’s enhancement of bones’ osteogenic response to loading is affected by ageing in a dose-and time-dependent manner. Bone. 2017;98:59–67. https://doi.org/10.1016/j.bone.2017.02.009.CrossRefPubMedPubMedCentral

89.

Naruse K, Uchida K, Suto M, Miyagawa K, Kawata A, Urabe K, et al. Alendronate does not prevent long bone fragility in an inactive rat model. J Bone Miner Metab. 2016;34(6):615–26. https://doi.org/10.1007/s00774-015-0714-y.CrossRefPubMed

90.

Brodt MD, Ellis CB, Silva MJ. Growing C57Bl/6 mice increase whole bone mechanical properties by increasing geometric and material properties. J Bone Miner Res. 1999;14(12):2159–66. https://doi.org/10.1359/jbmr.1999.14.12.2159.CrossRefPubMed

91.

Somerville JM, Aspden RM, Armour KE, Armour KJ, Reid DM. Growth of C57BL/6 mice and the material and mechanical properties of cortical bone from the tibia. Calcif Tissue Int. 2004;74(5):469–75. https://doi.org/10.1007/s00223-003-0101-x.CrossRefPubMed

92.

Razi H, Birkhold AI, Weinkamer R, Duda GN, Willie BM, Checa S. Aging leads to a dysregulation in mechanically driven bone formation and resorption. J Bone Miner Res. 2015;30(10):1864–73. https://doi.org/10.1002/jbmr.2528.CrossRefPubMed

93.

•• Razi H, Birkhold AI, Zaslansky P, Weinkamer R, Duda GN, Willie BM, et al. Skeletal maturity leads to a reduction in the strain magnitudes induced within the bone: a murine tibia study. Acta Biomater. 2015;13:301–10. https://doi.org/10.1016/j.actbio.2014.11.021This study reports reduction in the strains induced within the bone with increasing age and that changes in bone morphology largely influences these age-related differences in strain in mice. CrossRefPubMed

94.

Aido M, Kerschnitzki M, Hoerth R, Checa S, Spevak L, Boskey AL, et al. Effect of in vivo loading on bone composition varies with animal age. Exp Gerontol. 2015;63:48–58. https://doi.org/10.1016/j.exger.2015.01.048.CrossRefPubMedPubMedCentral

95.

Birkhold AI, Razi H, Duda GN, Weinkamer R, Checa S, Willie BM. The influence of age on adaptive bone formation and bone resorption. Biomaterials. 2014;35(34):9290–301. https://doi.org/10.1016/j.biomaterials.2014.07.051.CrossRefPubMed

96.

Birkhold AI, Razi H, Duda GN, Weinkamer R, Checa S, Willie BM. The periosteal bone surface is less mechano-responsive than the endocortical. Sci Rep. 2016;6:23480. https://doi.org/10.1038/srep23480.CrossRefPubMedPubMedCentral

97.

Piet J, Hu D, Meslier Q, Baron R, Shefelbine SJ. Increased cellular presence after sciatic neurectomy improves the bone mechano-adaptive response in aged mice. Calcif Tissue Int. 2019;105:1–15. https://doi.org/10.1007/s00223-019-00572-7.CrossRef

98.

Cunningham HC, West DWD, Baehr LM, Tarke FD, Baar K, Bodine SC, et al. Age-dependent bone loss and recovery during hindlimb unloading and subsequent reloading in rats. BMC Musculoskelet Disord. 2018;19(1):223. https://doi.org/10.1186/s12891-018-2156-x.CrossRefPubMedPubMedCentral

99.

Weaver C, Gordon C, Janz K, Kalkwarf H, Lappe JM, Lewis R, et al. The National Osteoporosis Foundation’s position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporos Int. 2016;27(4):1281–386. https://doi.org/10.1007/s00198-015-3440-3.CrossRefPubMedPubMedCentral

100.

Nikander R, Sievänen H, Heinonen A, Daly RM, Uusi-Rasi K, Kannus P. Targeted exercise against osteoporosis: a systematic review and meta-analysis for optimising bone strength throughout life. BMC Med. 2010;8(1):47. https://doi.org/10.1186/1741-7015-8-47.CrossRefPubMedPubMedCentral

101.

•• Allison SJ, Poole KE, Treece GM, Gee AH, Tonkin C, Rennie WJ, et al. The influence of high-impact exercise on cortical and trabecular bone mineral content and 3D distribution across the proximal femur in older men: a randomized controlled unilateral intervention. J Bone Miner Res. 2015;30(9):1709–16. https://doi.org/10.1002/jbmr.2499This controlled interventional study in middle-aged and aged humans found positive, site-specific effects on proximal femoral bone mass in response to high-impact training. CrossRefPubMed

102.

Kukuljan S, Nowson CA, Sanders KM, Nicholson GC, Seibel MJ, Salmon J, et al. Independent and combined effects of calcium-vitamin D3 and exercise on bone structure and strength in older men: an 18-month factorial design randomized controlled trial. J Clin Endocrinol Metab. 2011;96(4):955–63. https://doi.org/10.1210/jc.2010-2284.CrossRefPubMed

103.

Ashe M, Gorman E, Khan K, Brasher P, Cooper D, McKay H, et al. Does frequency of resistance training affect tibial cortical bone density in older women? A randomized controlled trial. Osteoporos Int. 2013;24(2):623–32. https://doi.org/10.1007/s00198-012-2000-3.CrossRefPubMed

104.

Gombos GC, Bajsz V, Pék E, Schmidt B, Sió E, Molics B, et al. Direct effects of physical training on markers of bone metabolism and serum sclerostin concentrations in older adults with low bone mass. BMC Musculoskelet Disord. 2016;17(1):254–8. https://doi.org/10.1186/s12891-016-1109-5.CrossRefPubMedPubMedCentral

105.

Bolam KA, Skinner TL, Jenkins DG, Galvão DA, Taaffe DR. The osteogenic effect of impact-loading and resistance exercise on bone mineral density in middle-aged and older men: a pilot study. Gerontology. 2016;62(1):22–32. https://doi.org/10.1159/000435837.CrossRef

106.

Seidelin K, Nyberg M, Piil P, Jørgensen NR, Hellsten Y, Bangsbo J. Adaptations with intermittent exercise training in post-and premenopausal women. Med Sci Sports Exerc. 2017;49(1):96–105. https://doi.org/10.1249/MSS.0000000000001071.CrossRefPubMed

107.

•• Suominen T, Korhonen M, Alén M, Heinonen A, Mero A, Törmäkangas T, et al. Effects of a 20-week high-intensity strength and sprint training program on tibial bone structure and strength in middle-aged and older male sprint athletes: a randomized controlled trial. Osteoporos Int. 2017;28(9):2663–73. https://doi.org/10.1007/s00198-017-4107-zIn a randomized, controlled, 20-week-long high-intensity interventional strength and sprint training trial in middle-aged and old male sprint athletes, this study reported significant albeit modest improvements in mid-tibial (not distal) structure and strength, which were most pronounced in the more compliant athletes. CrossRefPubMed

108.

Best A, Holt B, Troy K, Hamill J. Trabecular bone in the calcaneus of runners. PLoS One. 2017;12(11):e0188200. https://doi.org/10.1371/journal.pone.0188200.CrossRefPubMedPubMedCentral

109.

Luo J, Ratcliffe A, Chahal J, Brennan R, Lee R. Pattern of physical activity can influence its efficacy on muscle and bone health in middle-aged men and women. Sport Sci Health. 2018;14:1–7. https://doi.org/10.1007/s11332-018-0448-z.CrossRef

110.

•• Sundh D, Nilsson M, Zoulakis M, Pasco C, Yilmaz M, Kazakia GJ, et al. High-impact mechanical loading increases bone material strength in postmenopausal women—a 3-month intervention study. J Bone Miner Res. 2018;33(7):1242–51. https://doi.org/10.1002/jbmr.3431This interventional study reports that that unilateral high-impact mechanical loading improves bone material properties without altering bone microstructure and geometry. CrossRefPubMedPubMedCentral

111.

Niinimäki S, Narra N, Härkönen L, Abe S, Nikander R, Hyttinen J, et al. The relationship between loading history and proximal femoral diaphysis cross-sectional geometry. Am J Hum Biol. 2017;29(4):e22965. https://doi.org/10.1002/ajhb.22965.CrossRef

112.

Giarmatzis G, Jonkers I, Baggen R, Verschueren S. Less hip joint loading only during running rather than walking in elderly compared to young adults. Gait Posture. 2017;53:155–61. https://doi.org/10.1016/j.gaitpost.2017.01.020.CrossRefPubMed

Title: Aging and Mechanoadaptive Responsiveness of Bone
Authors: Behzad Javaheri
Andrew A. Pitsillides
Publication date: 01-12-2019
Publisher: Springer US
Keywords: Osteoporosis
Osteoporosis
Published in: Current Osteoporosis Reports / Issue 6/2019
Print ISSN: 1544-1873
Electronic ISSN: 1544-2241
DOI: https://doi.org/10.1007/s11914-019-00553-7

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Aging and Mechanoadaptive Responsiveness of Bone

Abstract

Purpose of Review

Recent Findings

Summary

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

Please log in to get access to this content

Other articles of this Issue 6/2019

Insulin Signaling in Bone Marrow Adipocytes

Effects of Diabetes on Bone Material Properties

Inflammation in Fibrodysplasia Ossificans Progressiva and Other Forms of Heterotopic Ossification

Bone Health in Men with Prostate Cancer: Review Article

Marrow Fat-Secreted Factors as Biomarkers for Osteoporosis

Mechanisms of Immune Evasion and Bone Tissue Colonization That Make Staphylococcus aureus the Primary Pathogen in Osteomyelitis