Pain in Women pp 255-275 | Cite as

Menopause and the Musculoskeletal System

  • Leslie R. Morse
  • Ricardo A. Battaglino
  • Jeffrey J. Widrick


Estrogen is a known regulator of both bone and muscle. Estrogen withdrawal, either iatrogenic or due to menopause, has a profound impact on the musculoskeletal system. Reductions in muscle power, strength, and endurance as well as accelerated bone turnover and increased fracture risk lead to increased morbidity and mortality.


Postmenopausal Woman Fracture Risk Postmenopausal Osteoporosis Major Osteoporotic Fracture Extensor Digitorum Longus Muscle 


  1. 1.
    Wei GS, Jackson JL, Hatzigeorgiou C, Tofferi JK. Osteoporosis management in the new millennium. Prim Care. 2003;30:711-vii.CrossRefGoogle Scholar
  2. 2.
    Haleem S, Lutchman L, Mayahi R, Grice JE, Parker MJ. Mortality following hip fracture: trends and geographical variations over the last 40 years. Injury. 2008;39:1157–63.PubMedCrossRefGoogle Scholar
  3. 3.
    U.S. Preventive Services Task Force. Screening for osteoporosis: U.S. preventive services task force recommendation statement. Ann Intern Med. 2011;154:356–64.Google Scholar
  4. 4.
    Moerman EJ, Teng K, Lipschitz DA, Lecka-Czernik B. Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: the role of PPAR-gamma2 transcription factor and TGF-beta/BMP signaling pathways. Aging Cell. 2004;3:379–89.PubMedCrossRefGoogle Scholar
  5. 5.
    Takada I, Suzawa M, Matsumoto K, Kato S. Suppression of PPAR transactivation switches cell fate of bone marrow stem cells from adipocytes into osteoblasts. Ann N Y Acad Sci. 2007;1116:182–95.PubMedCrossRefGoogle Scholar
  6. 6.
    Verma S, Rajaratnam JH, Denton J, Hoyland JA, Byers RJ. Adipocytic proportion of bone marrow is inversely related to bone formation in osteoporosis. J Clin Pathol. 2002;55:693–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Bredella MA, Fazeli PK, Miller KK, Misra M, Torriani M, Thomas BJ, Ghomi RH, Rosen CJ, Klibanski A. Increased bone marrow fat in anorexia nervosa. J Clin Endocrinol Metab. 2009;94(6):2129–36.PubMedCrossRefGoogle Scholar
  8. 8.
    Schellinger D, Lin CS, Hatipoglu HG, Fertikh D. Potential value of vertebral proton MR spectroscopy in determining bone weakness. AJNR Am J Neuroradiol. 2001;22:1620–7.PubMedGoogle Scholar
  9. 9.
    Schellinger D, Lin CS, Lim J, Hatipoglu HG, Pezzullo JC, Singer AJ. Bone marrow fat and bone mineral density on proton MR spectroscopy and dual-energy X-ray absorptiometry: their ratio as a new indicator of bone weakening. AJR Am J Roentgenol. 2004;183:1761–5.PubMedGoogle Scholar
  10. 10.
    Duque G. Bone and fat connection in aging bone. Curr Opin Rheumatol. 2008;20:429–34.PubMedCrossRefGoogle Scholar
  11. 11.
    Basso N, Bellows CG, Heersche JN. Effect of simulated weightlessness on osteoprogenitor cell number and proliferation in young and adult rats. Bone. 2005;36:173–83.PubMedCrossRefGoogle Scholar
  12. 12.
    Zayzafoon M, Gathings WE, McDonald JM. Modeled microgravity inhibits osteogenic differentiation of human mesenchymal stem cells and increases adipogenesis. Endocrinology. 2004;145:2421–32.PubMedCrossRefGoogle Scholar
  13. 13.
    Coupland CA, Cliffe SJ, Bassey EJ, Grainge MJ, Hosking DJ, Chilvers CE. Habitual physical activity and bone mineral density in postmenopausal women in England. Int J Epidemiol. 1999;28:241–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Almeida M, Han L, Martin-Millan M, Plotkin LI, Stewart SA, Roberson PK, Kousteni S, O’Brien CA, Bellido T, Parfitt AM, Weinstein RS, Jilka RL, Manolagas SC. Skeletal involution by age-associated oxidative stress and its acceleration by loss of sex steroids. J Biol Chem. 2007;282:27285–97.PubMedCrossRefGoogle Scholar
  15. 15.
    Zheng SX, Vrindts Y, Lopez M, De Groote D, Zangerle PF, Collette J, Franchimont N, Geenen V, Albert A, Reginster JY. Increase in cytokine production (IL-1 beta, IL-6, TNF-alpha but not IFN-gamma, GM-CSF or LIF) by stimulated whole blood cells in postmenopausal osteoporosis. Maturitas. 1997;26:63–71.PubMedCrossRefGoogle Scholar
  16. 16.
    Basu S, Michaelsson K, Olofsson H, Johansson S, Melhus H. Association between oxidative stress and bone mineral density. Biochem Biophys Res Commun. 2001;288:275–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Xue B, Zhao Y, Johnson AK, Hay M. Central estrogen inhibition of angiotensin II-induced hypertension in male mice and the role of reactive oxygen species. Am J Physiol Heart Circ Physiol. 2008;295:H1025–32.PubMedCrossRefGoogle Scholar
  18. 18.
    Juan SH, Chen JJ, Chen CH, Lin H, Cheng CF, Liu JC, Hsieh MH, Chen YL, Chao HH, Chen TH, Chan P, Cheng TH. 17beta-estradiol inhibits cyclic strain-induced endothelin-1 gene expression within vascular endothelial cells. Am J Physiol Heart Circ Physiol. 2004;287:H1254–61.PubMedCrossRefGoogle Scholar
  19. 19.
    Yen CH, Hsieh CC, Chou SY, Lau YT. 17beta-estradiol inhibits oxidized low density lipoprotein-induced generation of reactive oxygen species in endothelial cells. Life Sci. 2001;70:403–13.PubMedCrossRefGoogle Scholar
  20. 20.
    Lean JM, Jagger CJ, Kirstein B, Fuller K, Chambers TJ. Hydrogen peroxide is essential for estrogen-deficiency bone loss and osteoclast formation. Endocrinology. 2005;146:728–35.PubMedCrossRefGoogle Scholar
  21. 21.
    Lean JM, Davies JT, Fuller K, Jagger CJ, Kirstein B, Partington GA, Urry ZL, Chambers TJ. A crucial role for thiol antioxidants in estrogen-deficiency bone loss. J Clin Invest. 2003;112:915–23.PubMedGoogle Scholar
  22. 22.
    Asagiri M, Takayanagi H. The molecular understanding of osteoclast differentiation. Bone. 2007;40:251–64.PubMedCrossRefGoogle Scholar
  23. 23.
    Boyce BF, Yamashita T, Yao Z, Zhang Q, Li F, Xing L. Roles for NF-kappaB and c-Fos in osteoclasts. J Bone Miner Metab. 2005;23(Suppl):11–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Chow J, Tobias JH, Colston KW, Chambers TJ. Estrogen maintains trabecular bone volume in rats not only by suppression of bone resorption but also by stimulation of bone formation. J Clin Invest. 1992;89:74–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Kaptoge S, Welch A, McTaggart A, Mulligan A, Dalzell N, Day NE, Bingham S, Khaw KT, Reeve J. Effects of dietary nutrients and food groups on bone loss from the proximal femur in men and women in the 7th and 8th decades of age. Osteoporos Int. 2003;14:418–28.PubMedCrossRefGoogle Scholar
  26. 26.
    Morton DJ, Barrett-Connor EL, Schneider DL. Vitamin C supplement use and bone mineral density in postmenopausal women. J Bone Miner Res. 2001;16:135–40.PubMedCrossRefGoogle Scholar
  27. 27.
    Banfi G, Malavazos A, Iorio E, Dolci A, Doneda L, Verna R, Corsi MM. Plasma oxidative stress biomarkers, nitric oxide and heat shock protein 70 in trained elite soccer players. Eur J Appl Physiol. 2006;96:483–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Maggio D, Barabani M, Pierandrei M, Polidori MC, Catani M, Mecocci P, Senin U, Pacifici R, Cherubini A. Marked decrease in plasma antioxidants in aged osteoporotic women: results of a cross-sectional study. J Clin Endocrinol Metab. 2003;88:1523–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Banfi G, Iorio EL, Corsi MM. Minireview: oxidative stress, free radicals and bone remodeling. Clin Chem Lab Med. 2008;46:1550–5.PubMedGoogle Scholar
  30. 30.
    Goodman SR. Adiponectin is a metabolic link between obesity and bone mineral density. Exp Biol Med (Maywood). 2008;233:vi.Google Scholar
  31. 31.
    Agbaht K, Gurlek A, Karakaya J, Bayraktar M. Circulating adiponectin represents a biomarker of the association between adiposity and bone mineral density. Endocrine. 2009;35(3):371–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Jurimae J, Rembel K, Jurimae T, Rehand M. Adiponectin is associated with bone mineral density in perimenopausal women. Horm Metab Res. 2005;37:297–302.PubMedCrossRefGoogle Scholar
  33. 33.
    Cummings SR, Nevitt MC, Browner WS, Stone K, Fox KM, Ensrud KE, Cauley J, Black D, Vogt TM. Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med. 1995;332:767–73.PubMedCrossRefGoogle Scholar
  34. 34.
    De Laet C, Kanis JA, Oden A, Johanson H, Johnell O, Delmas P, Eisman JA, Kroger H, Fujiwara S, Garnero P, McCloskey EV, Mellstrom D, Melton III LJ, Meunier PJ, Pols HA, Reeve J, Silman A, Tenenhouse A. Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos Int. 2005;16:1330–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Hannan MT, Felson DT, Anderson JJ. Bone mineral density in elderly men and women: results from the Framingham osteoporosis study. J Bone Miner Res. 1992;7:547–53.PubMedCrossRefGoogle Scholar
  36. 36.
    Raska Jr I, Broulik P. The impact of diabetes mellitus on skeletal health: an established phenomenon with inestablished causes? Prague Med Rep. 2005;106:137–48.PubMedGoogle Scholar
  37. 37.
    Reid IR. Relationships among body mass, its components, and bone. Bone. 2002;31:547–55.PubMedCrossRefGoogle Scholar
  38. 38.
    Petit MA, Beck TJ, Hughes JM, Lin HM, Bentley C, Lloyd T. Proximal femur mechanical adaptation to weight gain in late adolescence: a six-year longitudinal study. J Bone Miner Res. 2008;23:180–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Takeda S, Karsenty G. Central control of bone formation. J Bone Miner Metab. 2001;19:195–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, Armstrong D, Ducy P, Karsenty G. Leptin regulates bone formation via the sympathetic nervous system. Cell. 2002;111:305–17.PubMedCrossRefGoogle Scholar
  41. 41.
    Enjuanes A, Supervia A, Nogues X, Diez-Perez A. Leptin receptor (OB-R) gene expression in human primary osteoblasts: confirmation. J Bone Miner Res. 2002;17:1135.PubMedCrossRefGoogle Scholar
  42. 42.
    Thomas T. Leptin: a potential mediator for protective effects of fat mass on bone tissue. Joint Bone Spine. 2003;70:18–21.PubMedCrossRefGoogle Scholar
  43. 43.
    Berner HS, Lyngstadaas SP, Spahr A, Monjo M, Thommesen L, Drevon CA, Syversen U, Reseland JE. Adiponectin and its receptors are expressed in bone-forming cells. Bone. 2004;35:842–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Basurto L, Galvan R, Cordova N, Saucedo R, Vargas C, Campos S, Halley E, Avelar F, Zarate A. Adiponectin is associated with low bone mineral density in elderly men. Eur J Endocrinol. 2009;160:289–93.PubMedCrossRefGoogle Scholar
  45. 45.
    Ealey KN, Kaludjerovic J, Archer MC, Ward WE. Adiponectin is a negative regulator of bone mineral and bone strength in growing mice. Exp Biol Med (Maywood). 2008;233:1546–53.CrossRefGoogle Scholar
  46. 46.
    Gonnelli S, Caffarelli C, Del SK, Cadirni A, Guerriero C, Lucani B, Franci B, Nuti R. The relationship of ghrelin and adiponectin with bone mineral density and bone turnover markers in elderly men. Calcif Tissue Int. 2008;83:55–60.PubMedCrossRefGoogle Scholar
  47. 47.
    Jurimae J, Kums T, Jurimae T. Adipocytokine and ghrelin levels in relation to bone mineral density in physically active older women: longitudinal associations. Eur J Endocrinol. 2009;160:381–5.PubMedCrossRefGoogle Scholar
  48. 48.
    Lenchik L, Register TC, Hsu FC, Lohman K, Nicklas BJ, Freedman BI, Langefeld CD, Carr JJ, Bowden DW. Adiponectin as a novel determinant of bone mineral density and visceral fat. Bone. 2003;33:646–51.PubMedCrossRefGoogle Scholar
  49. 49.
    Oh KW, Lee WY, Rhee EJ, Baek KH, Yoon KH, Kang MI, Yun EJ, Park CY, Ihm SH, Choi MG, Yoo HJ, Park SW. The relationship between serum resistin, leptin, adiponectin, ghrelin levels and bone mineral density in middle-aged men. Clin Endocrinol (Oxford). 2005;63:131–8.CrossRefGoogle Scholar
  50. 50.
    Peng XD, Xie H, Zhao Q, Wu XP, Sun ZQ, Liao EY. Relationships between serum adiponectin, leptin, resistin, visfatin levels and bone mineral density, and bone biochemical markers in Chinese men. Clin Chim Acta. 2008;387:31–5.PubMedCrossRefGoogle Scholar
  51. 51.
    Richards JB, Valdes AM, Burling K, Perks UC, Spector TD. Serum adiponectin and bone mineral density in women. J Clin Endocrinol Metab. 2007;92:1517–23.PubMedCrossRefGoogle Scholar
  52. 52.
    Shinoda Y, Ogata N, Kawaguchi H. Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways. Nippon Rinsho. 2007;65 Suppl 9:90–4.PubMedGoogle Scholar
  53. 53.
    Zoico E, Zamboni M, Di Francesco V, Mazzali G, Fantin F, De Pergola G, Zivelonghi A, Adami S, Bosello O. Relation between adiponectin and bone mineral density in elderly post-menopausal women: role of body composition, leptin, insulin resistance, and dehydroepiandrosterone sulfate. J Endocrinol Invest. 2008;31:297–302.PubMedGoogle Scholar
  54. 54.
    Gordon MD, Nusse R. Wnt signaling: multiple pathways, multiple receptors, and multiple transcription factors. J Biol Chem. 2006;281:22429–33.PubMedCrossRefGoogle Scholar
  55. 55.
    Huang H, He X. Wnt/beta-catenin signaling: new (and old) players and new insights. Curr Opin Cell Biol. 2008;20:119–25.PubMedCrossRefGoogle Scholar
  56. 56.
    Tatsumi S, Ishii K, Amizuka N, Li M, Kobayashi T, Kohno K, Ito M, Takeshita S, Ikeda K. Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab. 2007;5:464–75.PubMedCrossRefGoogle Scholar
  57. 57.
    Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, Harris SE, Wu D. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem. 2005;280:19883–7.PubMedCrossRefGoogle Scholar
  58. 58.
    Mao B, Wu W, Davidson G, Marhold J, Li M, Mechler BM, Delius H, Hoppe D, Stannek P, Walter C, Glinka A, Niehrs C. Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling. Nature. 2002;417:664–7.PubMedCrossRefGoogle Scholar
  59. 59.
    Balemans W, Ebeling M, Patel N, Van HE, Olson P, Dioszegi M, Lacza C, Wuyts W, Van Den EJ, Willems P, Paes-Alves AF, Hill S, Bueno M, Ramos FJ, Tacconi P, Dikkers FG, Stratakis C, Lindpaintner K, Vickery B, Foernzler D, Van HW. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet. 2001;10:537–43.PubMedCrossRefGoogle Scholar
  60. 60.
    Li X, Ominsky MS, Niu QT, Sun N, Daugherty B, D’Agostin D, Kurahara C, Gao Y, Cao J, Gong J, Asuncion F, Barrero M, Warmington K, Dwyer D, Stolina M, Morony S, Sarosi I, Kostenuik PJ, Lacey DL, Simonet WS, Ke HZ, Paszty C. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res. 2008;23:860–9.PubMedCrossRefGoogle Scholar
  61. 61.
    Staehling-Hampton K, Proll S, Paeper BW, Zhao L, Charmley P, Brown A, Gardner JC, Galas D, Schatzman RC, Beighton P, Papapoulos S, Hamersma H, Brunkow ME. A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12-q21 is associated with van Buchem disease in the Dutch population. Am J Med Genet. 2002;110:144–52.PubMedCrossRefGoogle Scholar
  62. 62.
    Ohnaka K, Tanabe M, Kawate H, Nawata H, Takayanagi R. Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts. Biochem Biophys Res Commun. 2005;329:177–81.PubMedCrossRefGoogle Scholar
  63. 63.
    Wang FS, Ko JY, Lin CL, Wu HL, Ke HJ, Tai PJ. Knocking down dickkopf-1 alleviates estrogen deficiency induction of bone loss. A histomorphological study in ovariectomized rats. Bone. 2007;40:485–92.PubMedCrossRefGoogle Scholar
  64. 64.
    Wang FS, Ko JY, Yeh DW, Ke HC, Wu HL. Modulation of Dickkopf-1 attenuates glucocorticoid induction of osteoblast apoptosis, adipocytic differentiation, and bone mass loss. Endocrinology. 2008;149:1793–801.PubMedCrossRefGoogle Scholar
  65. 65.
    Tian E, Zhan F, Walker R, Rasmussen E, Ma Y, Barlogie B, Shaughnessy Jr JD. The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med. 2003;349:2483–94.PubMedCrossRefGoogle Scholar
  66. 66.
    Weng LH, Wang CJ, Ko JY, Sun YC, Su YS, Wang FS. Inflammation induction of Dickkopf-1 mediates chondrocyte apoptosis in osteoarthritic joint. Osteoarthritis Cartilage. 2009;17:933–43.PubMedCrossRefGoogle Scholar
  67. 67.
    MacDonald BT, Joiner DM, Oyserman SM, Sharma P, Goldstein SA, He X, Hauschka PV. Bone mass is inversely proportional to Dkk1 levels in mice. Bone. 2007;41:331–9.PubMedCrossRefGoogle Scholar
  68. 68.
    Robling AG, Niziolek PJ, Baldridge LA, Condon KW, Allen MR, Alam I, Mantila SM, Gluhak-Heinrich J, Bellido TM, Harris SE, Turner CH. Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J Biol Chem. 2008;283:5866–75.PubMedCrossRefGoogle Scholar
  69. 69.
    Robling AG, Bellido T, Turner CH. Mechanical stimulation in vivo reduces osteocyte expression of sclerostin. J Musculoskelet Neuronal Interact. 2006;6:354.PubMedGoogle Scholar
  70. 70.
    Lin C, Jiang X, Dai Z, Guo X, Weng T, Wang J, Li Y, Feng G, Gao X, He L. Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt/beta-catenin signaling. J Bone Miner Res. 2009;24:1651–61.PubMedCrossRefGoogle Scholar
  71. 71.
    Mirza FS, Padhi ID, Raisz LG, Lorenzo JA. Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J Clin Endocrinol Metab. 2010;95:1991–7.PubMedCrossRefGoogle Scholar
  72. 72.
    Anastasilakis AD, Polyzos SA, Avramidis A, Toulis KA, Papatheodorou A, Terpos E. The effect of teriparatide on serum Dickkopf-1 levels in postmenopausal women with established osteoporosis. Clin Endocrinol (Oxford). 2010;72(6):752–7.CrossRefGoogle Scholar
  73. 73.
    Burr DB. Muscle strength, bone mass, and age-related bone loss. J Bone Miner Res. 1997;12:1547–51.PubMedCrossRefGoogle Scholar
  74. 74.
    Moisio KC, Hurwitz DE, Sumner DR. Dynamic loads are determinants of peak bone mass. J Orthop Res. 2004;22:339–45.PubMedCrossRefGoogle Scholar
  75. 75.
    Luu YK, Capilla E, Rosen CJ, Gilsanz V, Pessin JE, Judex S, Rubin CT. Mechanical stimulation of mesenchymal stem cell proliferation and differentiation promotes osteogenesis while preventing dietary-induced obesity. J Bone Miner Res. 2009;24:50–61.PubMedCrossRefGoogle Scholar
  76. 76.
    Hsieh YF, Robling AG, Ambrosius WT, Burr DB, Turner CH. Mechanical loading of diaphyseal bone in vivo: the strain threshold for an osteogenic response varies with location. J Bone Miner Res. 2001;16:2291–7.PubMedCrossRefGoogle Scholar
  77. 77.
    Hsieh YF, Turner CH. Effects of loading frequency on mechanically induced bone formation. J Bone Miner Res. 2001;16:918–24.PubMedCrossRefGoogle Scholar
  78. 78.
    Robling AG, Burr DB, Turner CH. Recovery periods restore mechanosensitivity to dynamically loaded bone. J Exp Biol. 2001;204:3389–99.PubMedGoogle Scholar
  79. 79.
    Robling AG, Hinant FM, Burr DB, Turner CH. Improved bone structure and strength after long-term mechanical loading is greatest if loading is separated into short bouts. J Bone Miner Res. 2002;17:1545–54.PubMedCrossRefGoogle Scholar
  80. 80.
    Turner CH, Robling AG. Designing exercise regimens to increase bone strength. Exerc Sport Sci Rev. 2003;31:45–50.PubMedCrossRefGoogle Scholar
  81. 81.
    Kerr D, Ackland T, Maslen B, Morton A, Prince R. Resistance training over 2 years increases bone mass in calcium-replete postmenopausal women. J Bone Miner Res. 2001;16:175–81.PubMedCrossRefGoogle Scholar
  82. 82.
    Kemmler W, Engelke K, Weineck J, Hensen J, Kalender WA. The Erlangen Fitness Osteoporosis Prevention Study: a controlled exercise trial in early postmenopausal women with low bone density-first-year results. Arch Phys Med Rehabil. 2003;84:673–82.PubMedGoogle Scholar
  83. 83.
    Kemmler W, von Stengel S, Weineck J, Lauber D, Kalender W, Engelke K. Exercise effects on menopausal risk factors of early postmenopausal women: 3-year Erlangen fitness osteoporosis prevention study results. Med Sci Sports Exerc. 2005;37:194–203.PubMedCrossRefGoogle Scholar
  84. 84.
    Engelke K, Kemmler W, Lauber D, Beeskow C, Pintag R, Kalender WA. Exercise maintains bone density at spine and hip EFOPS: a 3-year longitudinal study in early postmenopausal women. Osteoporos Int. 2006;17:133–42.PubMedCrossRefGoogle Scholar
  85. 85.
    Goessl C, Hei YJ. IV bisphosphonate therapy: making the case for calcium and vitamin D supplementation. Med Hypotheses. 2005;64:879–80.PubMedCrossRefGoogle Scholar
  86. 86.
    Mastaglia SR, Pellegrini GG, Mandalunis PM, Gonzales Chaves MM, Friedman SM, Zeni SN. Vitamin D insufficiency reduces the protective effect of bisphosphonate on ovariectomy-induced bone loss in rats. Bone. 2006;39:837–44.PubMedCrossRefGoogle Scholar
  87. 87.
    Giusti A, Hamdy NA, Dekkers OM, Ramautar SR, Dijkstra S, Papapoulos SE. Atypical fractures and bisphosphonate therapy: a cohort study of patients with femoral fracture with radiographic adjudication of fracture site and features. Bone. 2011;48:966–71.PubMedCrossRefGoogle Scholar
  88. 88.
    Puah KL, Tan MH. Bisphosphonate-associated atypical fracture of the femur: spontaneous healing with drug holiday and re-appearance after resumed drug therapy with bilateral simultaneous displaced fractures – a case report. Acta Orthop. 2011;82:380–2.PubMedCrossRefGoogle Scholar
  89. 89.
    Sellmeyer DE. Atypical fractures as a potential complication of long-term bisphosphonate therapy. JAMA. 2010;304:1480–4.PubMedCrossRefGoogle Scholar
  90. 90.
    Bhuriya R, Singh M, Molnar J, Arora R, Khosla S. Bisphosphonate use in women and the risk of atrial fibrillation: a systematic review and meta-analysis. Int J Cardiol. 2010;142:213–17.PubMedCrossRefGoogle Scholar
  91. 91.
    Bunch TJ, Anderson JL, May HT, Muhlestein JB, Horne BD, Crandall BG, Weiss JP, Lappe DL, Osborn JS, Day JD. Relation of bisphosphonate therapies and risk of developing atrial fibrillation. Am J Cardiol. 2009;103:824–8.PubMedCrossRefGoogle Scholar
  92. 92.
    Pazianas M, Compston J, Huang CL. Atrial fibrillation and bisphosphonate therapy. J Bone Miner Res. 2010;25:2–10.PubMedCrossRefGoogle Scholar
  93. 93.
    Rhee CW, Lee J, Oh S, Choi NK, Park BJ. Use of bisphosphonate and risk of atrial fibrillation in older women with osteoporosis. Osteoporos Int. 2012;23(1):247–54.PubMedCrossRefGoogle Scholar
  94. 94.
    Freeman TR. Teriparatide: a novel agent that builds new bone. J Am Pharm Assoc. 2003;43:535–7.CrossRefGoogle Scholar
  95. 95.
    Gamsjaeger S, Buchinger B, Zoehrer R, Phipps R, Klaushofer K, Paschalis EP. Effects of one year daily teriparatide treatment on trabecular bone material properties in postmenopausal osteoporotic women previously treated with alendronate or risedronate. Bone. 2011;49(6):1160–5.PubMedCrossRefGoogle Scholar
  96. 96.
    Marcus R, Wang O, Satterwhite J, Mitlak B. The skeletal response to teriparatide is largely independent of age, initial bone mineral density, and prevalent vertebral fractures in postmenopausal women with osteoporosis. J Bone Miner Res. 2003;18:18–23.PubMedCrossRefGoogle Scholar
  97. 97.
    Zanchetta JR, Bogado CE, Ferretti JL, Wang O, Wilson MG, Sato M, Gaich GA, Dalsky GP, Myers SL. Effects of teriparatide [recombinant human parathyroid hormone (1–34)] on cortical bone in postmenopausal women with osteoporosis. J Bone Miner Res. 2003;18:539–43.PubMedCrossRefGoogle Scholar
  98. 98.
    Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96:53–8.PubMedCrossRefGoogle Scholar
  99. 99.
    Lemoine S, Granier P, Tiffoche C, Rannou-Bekono F, Thieulant ML, Delamarche P. Estrogen receptor alpha mRNA in human skeletal muscles. Med Sci Sports Exerc. 2003;35:439–43.PubMedCrossRefGoogle Scholar
  100. 100.
    Wiik A, Glenmark B, Ekman M, Esbjornsson-Liljedahl M, Johansson O, Bodin K, Enmark E, Jansson E. Oestrogen receptor beta is expressed in adult human skeletal muscle both at the mRNA and protein level. Acta Physiol Scand. 2003;179:381–7.PubMedCrossRefGoogle Scholar
  101. 101.
    Wiik A, Ekman M, Morgan G, Johansson O, Jansson E, Esbjornsson M. Oestrogen receptor beta is present in both muscle fibres and endothelial cells within human skeletal muscle tissue. Histochem Cell Biol. 2005;124:161–5.PubMedCrossRefGoogle Scholar
  102. 102.
    Wiik A, Ekman M, Johansson O, Jansson E, Esbjornsson M. Expression of both oestrogen receptor alpha and beta in human skeletal muscle tissue. Histochem Cell Biol. 2009;131:181–9.PubMedCrossRefGoogle Scholar
  103. 103.
    Baltgalvis KA, Greising SM, Warren GL, Lowe DA. Estrogen regulates estrogen receptors and antioxidant gene expression in mouse skeletal muscle. PLoS One. 2010;5:e10164.PubMedCrossRefGoogle Scholar
  104. 104.
    Petrofsky JS, Lind AR. Aging, isometric strength and endurance, and cardiovascular responses to static effort. J Appl Physiol. 1975;38:91–5.PubMedGoogle Scholar
  105. 105.
    Phillips SK, Rook KM, Siddle NC, Bruce SA, Woledge RC. Muscle weakness in women occurs at an earlier age than in men, but strength is preserved by hormone replacement therapy. Clin Sci (London). 1993;84:95–8.Google Scholar
  106. 106.
    Skelton DA, Phillips SK, Bruce SA, Naylor CH, Woledge RC. Hormone replacement therapy increases isometric muscle strength of adductor pollicis in post-menopausal women. Clin Sci (London). 1999;96:357–64.CrossRefGoogle Scholar
  107. 107.
    Onambele NG, Skelton DA, Bruce SA, Woledge RC. Follow-up study of the benefits of hormone replacement therapy on isometric muscle strength of adductor pollicis in postmenopausal women. Clin Sci (London). 2001;100:421–2.CrossRefGoogle Scholar
  108. 108.
    Sarwar R, Niclos BB, Rutherford OM. Changes in muscle strength, relaxation rate and fatiguability during the human menstrual cycle. J Physiol. 1996;493(Pt 1):267–72.PubMedGoogle Scholar
  109. 109.
    Janse de Jonga XA, Boot CR, Thom JM, Ruell PA, Thompson MW. The influence of menstrual cycle phase on skeletal muscle contractile characteristics in humans. J Physiol. 2001;530:161–6.CrossRefGoogle Scholar
  110. 110.
    Greeves JP, Cable NT, Luckas MJ, Reilly T, Biljan MM. Effects of acute changes in oestrogen on muscle function of the first dorsal interosseus muscle in humans. J Physiol. 1997;500(Pt 1):265–70.PubMedGoogle Scholar
  111. 111.
    Greeves JP, Cable NT, Reilly T, Kingsland C. Changes in muscle strength in women following the menopause: a longitudinal assessment of the efficacy of hormone replacement therapy. Clin Sci (London). 1999;97:79–84.CrossRefGoogle Scholar
  112. 112.
    Armstrong AL, Oborne J, Coupland CA, Macpherson MB, Bassey EJ, Wallace WA. Effects of hormone replacement therapy on muscle performance and balance in post-menopausal women. Clin Sci (London). 1996;91:685–90.Google Scholar
  113. 113.
    Taaffe DR, Luz VM, Delay R, Marcus R. Maximal muscle strength of elderly women is not influenced by oestrogen status. Age Ageing. 1995;24:329–33.PubMedCrossRefGoogle Scholar
  114. 114.
    Ronkainen PH, Kovanen V, Alen M, Pollanen E, Palonen EM, Ankarberg-Lindgren C, Hamalainen E, Turpeinen U, Kujala UM, Puolakka J, Kaprio J, Sipila S. Postmenopausal hormone replacement therapy modifies skeletal muscle composition and function: a study with monozygotic twin pairs. J Appl Physiol. 2009;107:25–33.PubMedCrossRefGoogle Scholar
  115. 115.
    Greising SM, Baltgalvis KA, Lowe DA, Warren GL. Hormone therapy and skeletal muscle strength: a meta-analysis. J Gerontol A Biol Sci Med Sci. 2009;64:1071–81.PubMedCrossRefGoogle Scholar
  116. 116.
    Bruce SA, Newton D, Woledge RC. Effect of age on voluntary force and cross-sectional area of human adductor pollicis muscle. Q J Exp Physiol. 1989;74:359–62.PubMedGoogle Scholar
  117. 117.
    Fisher JS, Hasser EM, Brown M. Effects of ovariectomy and hindlimb unloading on skeletal muscle. J Appl Physiol. 1998;85:1316–21.PubMedGoogle Scholar
  118. 118.
    McCormick KM, Burns KL, Piccone CM, Gosselin LE, Brazeau GA. Effects of ovariectomy and estrogen on skeletal muscle function in growing rats. J Muscle Res Cell Motil. 2004;25:21–7.PubMedCrossRefGoogle Scholar
  119. 119.
    Moran AL, Warren GL, Lowe DA. Soleus and EDL muscle contractility across the lifespan of female C57BL/6 mice. Exp Gerontol. 2005;40:966–75.PubMedCrossRefGoogle Scholar
  120. 120.
    Greising SM, Carey RS, Blackford JE, Dalton LE, Kosir AM, Lowe DA. Estradiol treatment, physical activity, and muscle function in ovarian-senescent mice. Exp Gerontol. 2011;46:685–93.PubMedGoogle Scholar
  121. 121.
    Moran AL, Warren GL, Lowe DA. Removal of ovarian hormones from mature mice detrimentally affects muscle contractile function and myosin structural distribution. J Appl Physiol. 2006;100:548–59.PubMedCrossRefGoogle Scholar
  122. 122.
    Moran AL, Nelson SA, Landisch RM, Warren GL, Lowe DA. Estradiol replacement reverses ovariectomy-induced muscle contractile and myosin dysfunction in mature female mice. J Appl Physiol. 2007;102:1387–93.PubMedCrossRefGoogle Scholar
  123. 123.
    Brown M, Ning J, Ferreira JA, Bogener JL, Lubahn DB. Estrogen receptor-alpha and -beta and aromatase knockout effects on lower limb muscle mass and contractile function in female mice. Am J Physiol Endocrinol Metab. 2009;296:E854–61.PubMedCrossRefGoogle Scholar
  124. 124.
    Fitts RH. The cross-bridge cycle and skeletal muscle fatigue. J Appl Physiol. 2008;104:551–8.PubMedCrossRefGoogle Scholar
  125. 125.
    Hicks AL, Kent-Braun J, Ditor DS. Sex differences in human skeletal muscle fatigue. Exerc Sport Sci Rev. 2001;29:109–12.PubMedCrossRefGoogle Scholar
  126. 126.
    Glenmark B, Nilsson M, Gao H, Gustafsson JA, Dahlman-Wright K, Westerblad H. Difference in skeletal muscle function in males vs. females: role of estrogen receptor-beta. Am J Physiol Endocrinol Metab. 2004;287:E1125–31.PubMedCrossRefGoogle Scholar
  127. 127.
    Kendrick ZV, Steffen CA, Rumsey WL, Goldberg DI. Effect of estradiol on tissue glycogen metabolism in exercised oophorectomized rats. J Appl Physiol. 1987;63:492–6.PubMedGoogle Scholar
  128. 128.
    Widrick JJ, Stelzer JE, Shoepe TC, Garner DP. Functional properties of human muscle fibers after short-term resistance exercise training. Am J Physiol Regul Integr Comp Physiol. 2002;283:R408–16.PubMedGoogle Scholar
  129. 129.
    Kadi F, Karlsson C, Larsson B, Eriksson J, Larval M, Billig H, Jonsdottir IH. The effects of physical activity and estrogen treatment on rat fast and slow skeletal muscles following ovariectomy. J Muscle Res Cell Motil. 2002;23:335–9.PubMedCrossRefGoogle Scholar
  130. 130.
    Widrick JJ, Maddalozzo GF, Lewis D, Valentine BA, Garner DP, Stelzer JE, Shoepe TC, Snow CM. Morphological and functional characteristics of skeletal muscle fibers from hormone-replaced and nonreplaced postmenopausal women. J Gerontol A Biol Sci Med Sci. 2003;58:3–10.PubMedCrossRefGoogle Scholar
  131. 131.
    Wattanapermpool J, Reiser PJ. Differential effects of ovariectomy on calcium activation of cardiac and soleus myofilaments. Am J Physiol. 1999;277:H467–73.PubMedGoogle Scholar
  132. 132.
    Andrade FH, Reid MB, Allen DG, Westerblad H. Effect of nitric oxide on single skeletal muscle fibres from the mouse. J Physiol. 1998;509(Pt 2):577–86.PubMedCrossRefGoogle Scholar
  133. 133.
    Andrade FH, Reid MB, Allen DG, Westerblad H. Effect of hydrogen peroxide and dithiothreitol on contractile function of single skeletal muscle fibres from the mouse. J Physiol. 1998;509(Pt 2):565–75.PubMedCrossRefGoogle Scholar
  134. 134.
    Prochniewicz E, Spakowicz D, Thomas DD. Changes in actin structural transitions associated with oxidative inhibition of muscle contraction. Biochemistry. 2008;47:11811–17.PubMedCrossRefGoogle Scholar
  135. 135.
    Jackson MJ, McArdle A. Age-related changes in skeletal muscle reactive oxygen species generation and adaptive responses to reactive oxygen species. J Physiol. 2011;589:2139–45.PubMedCrossRefGoogle Scholar
  136. 136.
    Farrell SR, Ross JL, Howlett SE. Sex differences in mechanisms of cardiac excitation-contraction coupling in rat ventricular myocytes. Am J Physiol Heart Circ Physiol. 2010;299:H36–45.PubMedCrossRefGoogle Scholar
  137. 137.
    Delbono O. Expression and regulation of excitation-contraction coupling proteins in aging skeletal muscle. Curr Aging Sci. 2011;4(3):248–59.PubMedGoogle Scholar
  138. 138.
    Pollanen E, Fey V, Tormakangas T, Ronkainen PH, Taaffe DR, Takala T, Koskinen S, Cheng S, Puolakka J, Kujala UM, Suominen H, Sipila S, Kovanen V. Power training and postmenopausal hormone therapy affect transcriptional control of specific co-regulated gene clusters in skeletal muscle. Age (Dordrecht). 2010;32:347–63.CrossRefGoogle Scholar
  139. 139.
    Ronkainen PH, Pollanen E, Alen M, Pitkanen R, Puolakka J, Kujala UM, Kaprio J, Sipila S, Kovanen V. Global gene expression profiles in skeletal muscle of monozygotic female twins discordant for hormone replacement therapy. Aging Cell. 2010;9:1098–110.PubMedCrossRefGoogle Scholar
  140. 140.
    Russ DW, Lanza IR, Rothman D, Kent-Braun JA. Sex differences in glycolysis during brief, intense isometric contractions. Muscle Nerve. 2005;32:647–55.PubMedCrossRefGoogle Scholar
  141. 141.
    Widrick JJ, Costill DL, Fink WJ, Hickey MS, McConell GK, Tanaka H. Carbohydrate feedings and exercise performance: effect of initial muscle glycogen concentration. J Appl Physiol. 1993;74:2998–3005.PubMedGoogle Scholar
  142. 142.
    Stephenson DG, Nguyen LT, Stephenson GM. Glycogen content and excitation-contraction coupling in mechanically skinned muscle fibres of the cane toad. J Physiol. 1999;519(Pt 1): 177–87.PubMedCrossRefGoogle Scholar
  143. 143.
    Nicklas BJ, Hackney AC, Sharp RL. The menstrual cycle and exercise: performance, muscle glycogen, and substrate responses. Int J Sports Med. 1989;10:264–9.PubMedCrossRefGoogle Scholar
  144. 144.
    Dieli-Conwright CM, Spektor TM, Rice JC, Sattler FR, Schroeder ET. Influence of hormone replacement therapy on eccentric exercise induced myogenic gene expression in postmenopausal women. J Appl Physiol. 2009;107:1381–8.PubMedCrossRefGoogle Scholar
  145. 145.
    Teixeira PJ, Going SB, Houtkooper LB, Metcalfe LL, Blew RM, Flint-Wagner HG, Cussler EC, Sardinha LB, Lohman TG. Resistance training in postmenopausal women with and without hormone therapy. Med Sci Sports Exerc. 2003;35:555–62.PubMedCrossRefGoogle Scholar
  146. 146.
    Brown M, Birge SJ, Kohrt WM. Hormone replacement therapy does not augment gains in muscle strength or fat-free mass in response to weight-bearing exercise. J Gerontol A Biol Sci Med Sci. 1997;52:B166–70.PubMedCrossRefGoogle Scholar
  147. 147.
    Taaffe DR, Sipila S, Cheng S, Puolakka J, Toivanen J, Suominen H. The effect of hormone replacement therapy and/or exercise on skeletal muscle attenuation in postmenopausal women: a yearlong intervention. Clin Physiol Funct Imaging. 2005;25:297–304.PubMedCrossRefGoogle Scholar
  148. 148.
    Sipila S, Taaffe DR, Cheng S, Puolakka J, Toivanen J, Suominen H. Effects of hormone replacement therapy and high-impact physical exercise on skeletal muscle in post-menopausal women: a randomized placebo-controlled study. Clin Sci (London). 2001;101:147–57.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Leslie R. Morse
    • 1
  • Ricardo A. Battaglino
    • 2
  • Jeffrey J. Widrick
    • 3
  1. 1.Harvard Medical SchoolSpaulding Rehabilitation HospitalBostonUSA
  2. 2.Department of Oral Medicine, Infection and ImmunityHarvard School of Dental MedicineCambridgeUSA
  3. 3.Department of Physical Medicine and RehabilitationSpaulding Rehabilitation HospitalBostonUSA

Personalised recommendations