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Osteosarcopenia

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New Horizons in Osteoporosis Management

Abstract

The clinical manifestation of osteopenia/osteoporosis is the fragility fracture, which is associated with significant morbidity and mortality. It also causes a high risk of disability. Fragility fractures may occur spontaneously but most frequently they are the consequence of falls. Sarcopenia, the age-related loss of muscle mass and physical performance, is becoming an increasing medical and financial concern in aging societies. Sarcopenia is evident in around 20% of over 70-year-olds; the figure rises to 50% for those over the age of 80. Those affected by this syndrome exhibit impaired mobility, a higher disability rate, and also a higher risk for falls and fractures. There is an intensive and complex interaction, between bones and muscles, with a magnified negative impact on the individual health. Individuals suffering from both, sarcopenia and osteopenia, are identified as osteosarcopenic or sarcoosteopenic. Fracture risk is increased 3.5-fold in male osteosarcopenia patients and herewith significantly higher than in sarcopenia and osteopenia alone. The importance of osteosarcopenia is not just linked to such potential additive risk of negative functional outcome, but also the suggestion that osteosarcopenia results from progression of osteopenia and/or sarcopenia. Consequently, therapeutic interventions (nutrition, exercise, vitamin D) should be started early in the development of this “hazardous duet” in a trial to prevent or at least stop such negative synergistic effects of osteosarcopenia on physical performance and bone turnover. This chapter starts by discussing osteosarcopenia and the impact of aging on the human body and the potential mechanisms of age-related sarcopenia. It then highlights the biochemical communication between muscle and bone and how muscle and bone act as an endocrine organ. The chapter then discusses osteosarcopenia is standard practice, presenting a case finding practical algorithm as well as categories of sarcopenia and sarcopenia-like conditions. This is followed by tools of diagnosis and treatment protocols of osteosarcopenia. The chapter concludes by presenting patient-centered care approach for osteosarcopenia patients.

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References

  1. Hirschfeld H, Kinsella R, Duque G. Osteosarcopenia: where bone, muscle, and fat collide. Osteoporos Int. 2017;28(10):2781–90.

    CAS  PubMed  Google Scholar 

  2. Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48(1):16–31.

    PubMed  Google Scholar 

  3. Kanis JA, Adachi JD, Cooper C, Clark P, Cummings SR, Diaz-Curiel M, Harvey N, Hiligsmann M, Papaioannou A, Pierroz D, Silverman SL, Szulc P, the Epidemiology and Quality of Life Working Group of IOF. Standardising the descriptive epidemiology of osteoporosis: recommendations from the Epidemiology and Quality of Life Working Group of IOF. Osteoporos Int. 2013;24(11):2763–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Levinger I, Phu S, Duque G. Sarcopenia and osteoporotic fractures. Clin Rev Bone Miner Metab. 2016;14(1):38–44.

    CAS  Google Scholar 

  5. Binkley N, Buehring B. Beyond FRAX: it’s time to consider Bsarco-osteopenia^. J Clin Densitom. 2009;12:413–6.

    PubMed  Google Scholar 

  6. St-Onge M-P, Gallagher D. Body composition changes with aging: the cause or the result of alterations in metabolic rate and macronutrient oxidation? Nutrition. 2010;26:152–5.

    CAS  PubMed  Google Scholar 

  7. Hunter GR, Gower BA, Kane BL. Age related shift in visceral fat. Int J Body Compos Res. 2010;8:103–8.

    PubMed  PubMed Central  Google Scholar 

  8. Ilich JZ, Kelly OJ, Kim Y, Spicer MT. A low-grade chronic inflammation perpetuated by modern diet as a promoter of obesity and osteoporosis. Arch Indust Hygiene Toxicol. 2014;65:139–48.

    CAS  Google Scholar 

  9. Bredella MA, Fazeli PK, Daley SM, Miller KK, Rosen CJ, Klibanski A, Torriani M. Marrow fat composition in anorexia nervosa. Bone. 2014;66:199–204.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Kalyani RR, Corriere M, Ferrucci L. Age-related and disease-related muscle loss: the effect of diabetes, obesity, and other diseases. Lancet. 2014;2:819–29.

    Google Scholar 

  11. Clark BC, Manini TM. Sarcopenia =/= dynapenia. J Gerontol. 2008;63:829–34.

    Google Scholar 

  12. Riggs BL, Melton LJ 3rd, O’Fallon WM. Drug therapy for vertebral fractures in osteoporosis: evidence that decreases in bone turnover and increases in bone mass both determine antifracture efficacy. Bone. 1996;18:197S–201S.

    CAS  PubMed  Google Scholar 

  13. JafariNasabian P, Inglis J, Reilly W, Kelly O, Ilich J. Aging human body: changes in bone, muscle and body fat with consequent changes in nutrient intake. J Endocrinol. 2017;234:R37–51.

    CAS  PubMed  Google Scholar 

  14. Janssen I, Heymsfield SB, Wang ZM, et al. Skeletal muscle mass and distribution in 468 men and women aged 18-88 yr. J Appl Physiol (1985). 2000;89:81–8.

    CAS  Google Scholar 

  15. Cruz-Jentoft AJ, Landi F, Schneider SM, et al. Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS). Age Ageing. 2014;43:748–59.

    PubMed  PubMed Central  Google Scholar 

  16. Gielen E, O’Neill TW, Pye SR, et al. Endocrine determinants of incident sarcopenia in middle-aged and elderly European men. J Cachexia Sarcopenia Muscle. 2015;6:242–52.

    PubMed  PubMed Central  Google Scholar 

  17. Delmonico MJ, Harris TB, Visser M, et al. Longitudinal study of muscle strength, quality, and adipose tissue infiltration. Am J Clin Nutr. 2009;90:1579–85.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Yoo S, No M, Heo J, Park D, Kang J, Kim S, Kwak H. Role of exercise in age-related sarcopenia. J Exercise Rehabilitation. 2018;14(4):551–8.

    Google Scholar 

  19. Heo JW, No MH, Park DH, Kang JH, Kwak HB. Aging-induced sarcopenia and exercise. Asian J Kinesiol. 2017;19:43–59.

    Google Scholar 

  20. Alexeyev MF. Is there more to aging than mitochondrial DNA and reactive oxygen species? FEBS J. 2009;276:5768–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Wanagat J, Cao Z, Pathare P, Aiken JM. Mitochondrial DNA deletion mutations colocalize with segmental electron transport system abnormalities, muscle fiber atrophy, fiber splitting, and oxidative damage in sarcopenia. FASEB J. 2001;15:322–32.

    CAS  PubMed  Google Scholar 

  22. Hiona A, Sanz A, Kujoth GC, Pamplona R, Seo AY, Hofer T, Someya S, Miyakawa T, Nakayama C, Samhan-Arias AK, Servais S, Barger JL, Portero-Otín M, Tanokura M, Prolla TA, Leeuwenburgh C. Mitochondrial DNA mutations induce mitochondrial dysfunction, apoptosis and sarcopenia in skeletal muscle of mitochondrial DNA mutator mice. PLoS One. 2010;5:e11468.

    PubMed  PubMed Central  Google Scholar 

  23. Leeuwenburgh C. Role of apoptosis in sarcopenia. J Gerontol A Biol Sci Med Sci. 2003;58:999–1001.

    PubMed  Google Scholar 

  24. Marzetti E, Leeuwenburgh C. Skeletal muscle apoptosis, sarcopenia and frailty at old age. Exp Gerontol. 2006;41:1234–8.

    CAS  PubMed  Google Scholar 

  25. Song W, Kwak HB, Lawler JM. Exercise training attenuates age-induced changes in apoptotic signaling in rat skeletal muscle. Antioxid Redox Signal. 2006;8:517–28.

    CAS  PubMed  Google Scholar 

  26. Gouspillou G, Sgarioto N, Kapchinsky S, Purves-Smith F, Norris B, Pion CH, Barbat-Artigas S, Lemieux F, Taivassalo T, Morais JA, Aubertin-Leheudre M, Hepple RT. Increased sensitivity to mitochondrial permeability transition and myonuclear translocation of endonuclease G in atrophied muscle of physically active older humans. FASEB J. 2014;28:1621–33.

    CAS  PubMed  Google Scholar 

  27. Siu PM, Pistilli EE, Alway SE. Apoptotic responses to hindlimb suspension in gastrocnemius muscles from young adult and aged rats. Am J Physiol Regul Integr Comp Physiol. 2005;289:R1015–26.

    CAS  PubMed  Google Scholar 

  28. Seo AY, Joseph AM, Dutta D, Hwang JC, Aris JP, Leeuwenburgh C. New insights into the role of mitochondria in aging: mitochondrial dynamics and more. J Cell Sci. 2010a;123(Pt 15):2533–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Ni HM, Williams JA, Ding WX. Mitochondrial dynamics and mitochondrial quality control. Redox Biol. 2015;4:6–13.

    CAS  PubMed  Google Scholar 

  30. Archer SL. Mitochondrial dynamics--mitochondrial fission and fusion in human diseases. N Engl J Med. 2013;369:2236–51.

    CAS  PubMed  Google Scholar 

  31. Westermann B. Mitochondrial fusion and fission in cell life and death. Nat Rev Mol Cell Biol. 2010;11:872–84.

    CAS  PubMed  Google Scholar 

  32. Chen H, Vermulst M, Wang YE, Chomyn A, Prolla TA, McCaffery JM, Chan DC. Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations. Cell. 2010;141:280–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Romanello V, Guadagnin E, Gomes L, Roder I, Sandri C, Petersen Y, Milan G, Masiero E, Del Piccolo P, Foretz M, Scorrano L, Rudolf R, Sandri M. Mitochondrial fission and remodelling contributes to muscle atrophy. EMBO J. 2010;29:1774–85.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Yan Z, Lira VA, Greene NP. Exercise training-induced regulation of mitochondrial quality. Exerc Sport Sci Rev. 2012;40:159–64.

    PubMed  PubMed Central  Google Scholar 

  35. Joseph AM, Adhihetty PJ, Wawrzyniak NR, Wohlgemuth SE, Picca A, Kujoth GC, Prolla TA, Leeuwenburgh C. Dysregulation of mitochondrial quality control processes contribute to sarcopenia in a mouse model of premature aging. PLoS One. 2013;8:e69327.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Pagano TB, Wojcik S, Costagliola A, De Biase D, Iovino S, Iovane V, Russo V, Papparella S, Paciello O. Age related skeletal muscle atrophy and upregulation of autophagy in dogs. Vet J. 2015;206:54–60.

    CAS  PubMed  Google Scholar 

  37. Elkina Y, von Haehling S, Anker SD, Springer J. The role of myostatin in muscle wasting: an overview. J Cachexia Sarcopenia Muscle. 2011;2:143–51.

    PubMed  PubMed Central  Google Scholar 

  38. Yarasheski KE, Bhasin S, Sinha-Hikim I, Pak-Loduca J, Gonzalez-Cadavid NF. Serum myostatin-immunoreactive protein is increased in 60-92 year old women and men with muscle wasting. J Nutr Health Aging. 2002;6:343–8.

    CAS  PubMed  Google Scholar 

  39. White TA, LeBrasseur NK. Myostatin and sarcopenia: opportunities and challenges - a mini-review. Gerontology. 2014;60:289–93.

    CAS  PubMed  Google Scholar 

  40. Siriett V, Salerno MS, Berry C, Nicholas G, Bower R, Kambadur R, Sharma M. Antagonism of myostatin enhances muscle regeneration during sarcopenia. Mol Ther. 2007;15:1463–70.

    CAS  PubMed  Google Scholar 

  41. Budui SL, Rossi AP, Zamboni M. The pathogenetic bases of sarcopenia. Clin Cases Miner Bone Metab. 2015;12:22–6.

    PubMed  PubMed Central  Google Scholar 

  42. Rolland Y, Czerwinski S, Abellan Van Kan G, Morley JE, Cesari M, Onder G, Woo J, Baumgartner R, Pillard F, Boirie Y, Chumlea WM, Vellas B. Sarcopenia: its assessment, etiology, pathogenesis, consequences and future perspectives. J Nutr Health Aging. 2008;12:433–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Maurel D, Jähn K, Lara-Castillo N. Muscle–bone crosstalk, emerging opportunities for novel therapeutic approaches to treat musculoskeletal pathologies. Biomedicine. 2017;5:62. https://doi.org/10.3390/biomedicines5040062.

    Article  CAS  Google Scholar 

  44. Schiessl H, Frost HM, Jee WSS. Estrogen and bone-muscle strength and mass relationships. Bone. 1998;22:1–6.

    CAS  PubMed  Google Scholar 

  45. Mitchell WK, Williams J, Atherton P, Larvin M, Lund J, Narici M. Sarcopenia, dynapenia, and the impact of advancing age on human skeletal muscle size and strength; a quantitative review. Front Physiol. 2012;3:260.

    PubMed  PubMed Central  Google Scholar 

  46. Ducher G, Courteix D, Même S, Magni C, Viala JF, Benhamou CL. Bone geometry in response to long-term tennis playing and its relationship with muscle volume: a quantitative magnetic resonance imaging study in tennis players. Bone. 2005;37:457–66.

    CAS  PubMed  Google Scholar 

  47. Reginster J-Y, Beaudart C, Buckinx F, Bruyère O. Osteoporosis and sarcopenia: two diseases or one? Curr Opin Clin Nutr Metab Care. 2016;19:31–6.

    PubMed  Google Scholar 

  48. Avin KG, Bloomfield SA, Gross TS, Warden SJ. Biomechanical aspects of the muscle-bone interaction. Curr Osteoporos Rep. 2015;13:1–8.

    PubMed  PubMed Central  Google Scholar 

  49. Frost HM. Muscle, bone, and the Utah paradigm: a 1999 overview. Med Sci Sports Exerc. 2000;32:911–7.

    CAS  PubMed  Google Scholar 

  50. Sharir A, Stern T, Rot C, Shahar R, Zelzer E. Muscle force regulates bone shaping for optimal load-bearing capacity during embryogenesis. Development. 2011;138:3247–59.

    CAS  PubMed  Google Scholar 

  51. Rot-Nikcevic I, Reddy T, Downing KJ, Belliveau AC, Hallgrímsson B, Hall BK, Kablar B. Myf5−/−:MyoD−/− amyogenic fetuses reveal the importance of early contraction and static loading by striated muscle in mouse skeletogenesis. Dev Genes Evol. 2006;216:1–9.

    PubMed  Google Scholar 

  52. Gunter KB, Almstedt HC, Janz KF. Physical activity in childhood may be the key to optimizing lifespan skeletal health. Exerc Sport Sci Rev. 2012;40:13–21.

    PubMed  PubMed Central  Google Scholar 

  53. Frost HM. Bone’s mechanostat: a 2003 update. Anat Rec A Discov Mol Cell Evol Biol. 2003;275A:1081–101.

    Google Scholar 

  54. Brotto M, Johnson ML. Endocrine crosstalk between muscle and bone. Curr Osteoporos Rep. 2014;12:135–41.

    PubMed  PubMed Central  Google Scholar 

  55. Steensberg A, van Hall G, Osada T, Sacchetti M, Saltin B, Pedersen BK. Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6. J Physiol. 2000;529:237–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Hiscock N, Chan MHS, Bisucci T, Darby IA, Febbraio MA. Skeletal myocytes are a source of interleukin-6 mRNA expression and protein release during contraction: evidence of fiber type specificity. FASEB J. 2004;18:992–4.

    CAS  PubMed  Google Scholar 

  57. Serrano AL, Baeza-Raja B, Perdiguero E, Jardí M, Muñoz-Cánoves P. Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy. Cell Metab. 2008;7:33–44.

    CAS  PubMed  Google Scholar 

  58. Wallenius V, Wallenius K, Ahrén B, Rudling M, Carlsten H, Dickson SL, Ohlsson C, Jansson J-O. Interleukin-6-deficient mice develop mature-onset obesity. Nat Med. 2002;8:75–9.

    CAS  PubMed  Google Scholar 

  59. Pedersen BK, Åkerström TCA, Nielsen AR, Fischer CP. Role of myokines in exercise and metabolism. J Appl Physiol. 2007;103:1093–8.

    CAS  PubMed  Google Scholar 

  60. Deister C, Schmidt CE. Optimizing neurotrophic factor combinations for neurite outgrowth. J Neural Eng. 2006;3(2):172–9.

    CAS  PubMed  Google Scholar 

  61. Cuppini R, Sartini S, Agostini D, Guescini M, Ambrogini P, Betti M, Bertini L, Vallasciani M, Stocchi V. Bdnf expression in rat skeletal muscle after acute or repeated exercise. Arch Ital Biol. 2007;145:99–110.

    CAS  PubMed  Google Scholar 

  62. Yu T, Chang Y, Gao XL, Li H, Zhao P. Dynamic expression and the role of BDNF in exercise-induced skeletal muscle regeneration. Int J Sports Med. 2017;38:959–66.

    CAS  PubMed  Google Scholar 

  63. Matthews VB, Aström M-B, Chan MHS, Bruce CR, Krabbe KS, Prelovsek O, Akerström T, Yfanti C, Broholm C, Mortensen OH, et al. Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase. Diabetologia. 2009;52:1409–18.

    CAS  PubMed  Google Scholar 

  64. Allen DL, Cleary AS, Speaker KJ, Lindsay SF, Uyenishi J, Reed JM, Madden MC, Mehan RS. Myostatin, activin receptor IIb, and follistatin-like-3 gene expression are altered in adipose tissue and skeletal muscle of obese mice. Am J Physiol Endocrinol Metab. 2008;294:E918–27.

    CAS  PubMed  Google Scholar 

  65. Langley B, Thomas M, Bishop A, Sharma M, Gilmour S, Kambadur R. Myostatin inhibits myoblast differentiation by down-regulating MyoD expression. J Biol Chem. 2002;277:49831–40.

    CAS  PubMed  Google Scholar 

  66. Joulia-Ekaza D, Cabello G. The myostatin gene: physiology and pharmacological relevance. Curr Opin Pharmacol. 2007;7:310–5.

    CAS  PubMed  Google Scholar 

  67. Handschin C, Spiegelman BM. The role of exercise and PGC1alpha in inflammation and chronic disease. Nature. 2008;454:463–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Sandri M, et al. PGC-1alpha protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription. Proc Natl Acad Sci U S A. 2006;103:16260–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Boström EA, Choi JH, Long JZ, et al. A PGC1--dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481:463–8.

    PubMed  PubMed Central  Google Scholar 

  70. Liu S, Zhou J, Tang W, Jiang X, Rowe DW, Quarles LD. Pathogenic role of Fgf23 in Hyp mice. Am J Physiol Endocrinol Metab. 2006;291:E38–49.

    CAS  PubMed  Google Scholar 

  71. Hu MC, Shiizaki K, Kuro-o M, Moe OW. Fibroblast growth factor 23 and klotho: physiology and pathophysiology of an endocrine network of mineral metabolism. Annu Rev Physiol. 2013;75:503–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Quarles LD. Skeletal secretion of FGF-23 regulates phosphate and vitamin D metabolism. Nat Rev Endocrinol. 2012;8:276–86.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Gattineni J, Bates C, Twombley K, Dwarakanath V, Robinson ML, Goetz R, Mohammadi M, Baum M. FGF23 decreases renal NaPi-2a and NaPi-2c expression and induces hypophosphatemia in vivo predominantly via FGF receptor 1. Am J Physiol Renal Physiol. 2009;297:F282–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Faul C, Amaral AP, Oskouei B, Hu M-C, Sloan A, Isakova T, Gutiérrez OM, Aguillon-Prada R, Lincoln J, Hare JM, et al. FGF23 induces left ventricular hypertrophy. J Clin Investig. 2011;121:4393–408.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Nishimoto SK, Price PA. Proof that the gamma-carboxyglutamic acid-containing bone protein is synthesized in calf bone. Comparative synthesis rate and effect of coumadin on synthesis. J Biol Chem. 1979;254:437–41.

    CAS  PubMed  Google Scholar 

  76. Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DY, et al. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007;130:456–69.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Mera P, Laue K, Ferron M, Confavreux C, Wei J, Galán-Díez M, Lacampagne A, Mitchell SJ, Mattison JA, Chen Y, et al. Osteocalcin signaling in myofibers is necessary and sufficient for optimum adaptation to exercise. Cell Metab. 2016;23:1078–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Mera P, Laue K, Wei J, Berger JM, Karsenty G. Osteocalcin is necessary and sufficient to maintain muscle mass in older mice. Mol Metab. 2016;5:1042–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Balemans W, Piters E, Cleiren E, Ai M, VanWesenbeeck L, Warman ML, Van Hul W. The binding between sclerostin and LRP5 is altered by DKK1 and by high-bone mass LRP5 mutations. Calcif Tissue Int. 2008;82:445–53.

    CAS  PubMed  Google Scholar 

  80. Clarke BL, Drake MT. Clinical utility of serum sclerostin measurements. Bonekey Rep. 2013;2:361.

    PubMed  PubMed Central  Google Scholar 

  81. Ardawi M-SM, Rouzi AA, Al-Sibiani SA, Al-Senani NS, Qari MH, Mousa SA. High serum sclerostin predicts the occurrence of osteoporotic fractures in postmenopausal women: the Center of Excellence for Osteoporosis Research Study. J Bone Miner Res. 2012;27:2592–602.

    CAS  PubMed  Google Scholar 

  82. Toyosawa S, Shintani S, Fujiwara T, Ooshima T, Sato A, Ijuhin N, Komori T. Dentin matrix protein 1 is predominantly expressed in chicken and rat osteocytes but not in osteoblasts. J Bone Miner Res. 2001;16:2017–26.

    CAS  PubMed  Google Scholar 

  83. Feng JQ, Ward LM, Liu S, Lu Y, Xie Y, Yuan B, Yu X, Rauch F, Davis SI, Zhang S, et al. Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nat Genet. 2006;38:1310–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Linkhart TA, Mohan S, Baylink DJ. Growth factors for bone growth and repair: IGF, TGF beta and BMP. Bone. 1996;19:S1–S12.

    Google Scholar 

  85. Nikawa T, Ishidoh K, Hirasaka K, Ishihara I, Ikemoto M, Kano M, Kominami E, Nonaka I, Ogawa T, Adams GR, et al. Skeletal muscle gene expression in space-flown rats. FASEB J. 2004;18:522–4.

    CAS  PubMed  Google Scholar 

  86. Hamrick MW, McNeil PL, Patterson SL. Role of muscle-derived growth factors in bone formation. J Musculoskelet Neuronal Interact. 2010;10:64–70.

    CAS  PubMed  Google Scholar 

  87. Lai X, Price C, Lu XL, Wang L. Imaging and quantifying solute transport across periosteum: implications for muscle-bone crosstalk. Bone. 2014;66:82–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Houweling P, Kulkarni RN, Baldock PA. Neuronal control of bone and muscle. Bone. 2015;80:95–100.

    CAS  PubMed  Google Scholar 

  89. Hinkle RT, Hodge KMB, Cody DB, Sheldon RJ, Kobilka BK, Isfort RJ. Skeletal muscle hypertrophy and anti-atrophy effects of clenbuterol are mediated by the beta2-adrenergic receptor. Muscle Nerve. 2002;25:729–34.

    CAS  PubMed  Google Scholar 

  90. Joassard OR, Durieux A-C, Freyssenet DG. 2-Adrenergic agonists and the treatment of skeletal muscle wasting disorders. Int J Biochem Cell Biol. 2013;45:2309–21.

    CAS  PubMed  Google Scholar 

  91. Lynch GS, Ryall JG. Role of -adrenoceptor signaling in skeletal muscle: implications for muscle wasting and disease. Physiol Rev. 2008;88:729–67.

    CAS  PubMed  Google Scholar 

  92. Downie D, Delday MI, Maltin CA, Sneddon AA. Clenbuterol increases muscle fiber size and GATA-2 protein in rat skeletal muscle in utero. Mol Reprod Dev. 2008;75:785–94.

    CAS  PubMed  Google Scholar 

  93. Beitzel F, Sillence MN, Lynch GS. Adrenoceptor signaling in regenerating skeletal muscle after ß-agonist administration. Am J Physiol Endocrinol Metab. 2007;293:E932–40.

    CAS  PubMed  Google Scholar 

  94. Beitzel F, Gregorevic P, Ryall JG, Plant DR, Sillence MN, Lynch GS. ß2-Adrenoceptor agonist fenoterol enhances functional repair of regenerating rat skeletal muscle after injury. J Appl Physiol. 2004;96:1385–92.

    CAS  PubMed  Google Scholar 

  95. 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.

    CAS  PubMed  Google Scholar 

  96. Baldock PA, Sainsbury A, Couzens M, Enriquez RF, Thomas GP, Gardiner EM, Herzog H. Hypothalamic Y2 receptors regulate bone formation. J Clin Investig. 2002;109:915–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Baldock PA, Allison SJ, Lundberg P, Lee NJ, Slack K, Lin E-JD, Enriquez RF, McDonald MM, Zhang L, During MJ, et al. Novel role of Y1 receptors in the coordinated regulation of bone and energy homeostasis. J Biol Chem. 2007;282:19092–102.

    CAS  PubMed  Google Scholar 

  98. Lee NJ, Nguyen AD, Enriquez RF, Doyle KL, Sainsbury A, Baldock PA, Herzog H. Osteoblast specific Y1 receptor deletion enhances bone mass. Bone. 2011;48:461–7.

    CAS  PubMed  Google Scholar 

  99. Bonewald LF, Kiel D, Clemens T, Esser K, Orwoll E, O’Keefe R, Fielding R. Forum on bone and skeletal muscle interactions: summary of the proceedings of an ASBMR workshop. J Bone Miner Res. 2013;28:1857–65.

    PubMed  Google Scholar 

  100. Shah K, Armamento-Villareal R, Parimi N, Chode S, Sinacore DR, Hilton TN, Napoli N, Qualls C, Villareal DT. Exercise training in obese older adults prevents increase in bone turnover and attenuates decrease in hip BMD induced by weight loss despite decline in bone-active hormones. J Bone Miner Res. 2011;26:2851–9.

    CAS  PubMed  Google Scholar 

  101. Villareal DT, Chode S, Parimi N, Sinacore DR, Hilton T, Armamento-Villareal R, Napoli N, Qualls C, Shah K. Weight loss, exercise, or both and physical function in obese older adults. N Engl J Med. 2011;364:1218–29.

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Bermeo S, Gunaratnam K, Duque G. Fat and bone interactions. Curr Osteoporos Rep. 2014;12:235–42.

    PubMed  Google Scholar 

  103. Udagawa N, Takahashi N, Akatsu T, Tanaka H, Sasaki T, Nishihara T, Koga T, Martin TJ, Suda T. Origin of osteoclasts: mature monocytes and macrophages are capable of differentiating into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells. Proc Natl Acad Sci U S A. 1990;87:7260–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Chang MK, Raggatt L-J, Alexander KA, Kuliwaba JS, Fazzalari NL, Schroder K, Maylin ER, Ripoll VM, Hume DA, Pettit AR. Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo. J Immunol. 2008;181:1232–44.

    CAS  PubMed  Google Scholar 

  105. Tidball JG, Villalta SA. Regulatory interactions between muscle and the immune system during muscle regeneration. Am J Physiol Regul Integr Comp Physiol. 2010;298:R1173–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Deng B, Wehling-Henricks M, Villalta SA, Wang Y, Tidball JG. IL-10 triggers changes in macrophage phenotype that promote muscle growth and regeneration. J Immunol. 2012;189:3669–80.

    CAS  PubMed  Google Scholar 

  107. Kohno S, Yamashita Y, Abe T, Hirasaka K, Oarada M, Ohno A, Teshima-Kondo S, Higashibata A, Choi I, Mills EM, et al. Unloading stress disturbs muscle regeneration through perturbed recruitment and function of macrophages. J Appl Physiol. 2012;112:1773–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Riley LA, Esser KA. The role of the molecular clock in skeletal muscle and what it is teaching us about muscle-bone crosstalk. Curr Osteoporos Rep. 2017;15:222–30.

    PubMed  PubMed Central  Google Scholar 

  109. Schroder EA, Harfmann BD, Zhang X, Srikuea R, England JH, Hodge BA, Wen Y, Riley LA, Yu Q, Christie A, et al. Intrinsic muscle clock is necessary for musculoskeletal health. J Physiol. 2015;593:5387–404.

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Hodge BA, Wen Y, Riley LA, Zhang X, England JH, Harfmann BD, Schroder EA, Esser KA. The endogenous molecular clock orchestrates the temporal separation of substrate metabolism in skeletal muscle. Skelet Muscle. 2015;5:17.

    PubMed  PubMed Central  Google Scholar 

  111. Gorski JP, Huffman NT, Vallejo J, Brotto L, Chittur SV, Breggia A, Stern A, Huang J, Mo C, Seidah NG, et al. Deletion of Mbtps1 (Pcsk8, S1p, Ski-1) gene in osteocytes stimulates soleus muscle regeneration and increased size and contractile force with age. J Biol Chem. 2016;291:4308–22.

    CAS  PubMed  Google Scholar 

  112. Gorski JP, Price JL. Bone muscle crosstalk targets muscle regeneration pathway regulated by core circadian transcriptional repressors DEC1 and DEC2. Bonekey Rep. 2016;5:850.

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Cardozo CP, Graham ZA. Muscle-bone interactions: movement in the field of mechano-humoral coupling of muscle and bone. Ann N Y Acad Sci. 2017;1402:10–7.

    CAS  PubMed  Google Scholar 

  114. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European working group on sarcopenia in older people. Age Ageing. 2010;39:412–23.

    PubMed  PubMed Central  Google Scholar 

  115. Schaap LA, van Schoor NM, Lips P, et al. Associations of sarcopenia definitions, and their components, with the incidence of recurrent falling and fractures: the longitudinal aging study Amsterdam. J Gerontol A Biol Sci Med Sci. 2018;73:1199–204.

    PubMed  Google Scholar 

  116. Ibrahim K, May C, Patel HP, et al. A feasibility study of implementing grip strength measurement into routine hospital practice (GRImP): study protocol. Pilot Feasibility Stud. 2016;2:27.

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Leong DP, Teo KK, Rangarajan S, et al. Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study. Lancet. 2015;386:266–73.

    PubMed  Google Scholar 

  118. Schaap LA, Koster A, Visser M. Adiposity, muscle mass, and muscle strength in relation to functional decline in older persons. Epidemiol Rev. 2013;35:51–65.

    PubMed  Google Scholar 

  119. Buckinx F, Landi F, Cesari M, et al. Pitfalls in the measurement of muscle mass: a need for a reference standard. J Cachexia Sarcopenia Muscle. 2018;9:269–78.

    PubMed  PubMed Central  Google Scholar 

  120. Masanes F, Rojano ILX, Salva A, et al. Cut-off points for muscle mass—not grip strength or gait speed—determine variations in sarcopenia prevalence. J Nutr Health Aging. 2017;21:825–9.

    CAS  PubMed  Google Scholar 

  121. Trevino-Aguirre E, Lopez-Teros T, Gutierrez-Robledo L, et al. Availability and use of dual energy X-ray absorptiometry (DXA) and bio-impedance analysis (BIA) for the evaluation of sarcopenia by Belgian and Latin American geriatricians. J Cachexia Sarcopenia Muscle. 2014;5:79–81.

    PubMed  PubMed Central  Google Scholar 

  122. Reginster JY, Cooper C, Rizzoli R, et al. Recommendations for the conduct of clinical trials for drugs to treat or prevent sarcopenia. Aging Clin Exp Res. 2016;28:47–58.

    PubMed  Google Scholar 

  123. Mijnarends DM, Meijers JM, Halfens RJ, et al. Validity and reliability of tools to measure muscle mass, strength, and physical performance in community-dwelling older people: a systematic review. J Am Med Dir Assoc. 2013;14:170–8.

    PubMed  Google Scholar 

  124. Malmstrom TK, Miller DK, Simonsick EM, et al. SARC-F: a symptom score to predict persons with sarcopenia at risk for poor functional outcomes. J Cachexia Sarcopenia Muscle. 2016;7:28–36.

    PubMed  Google Scholar 

  125. Woo J, Leung J, Morley JE. Defining sarcopenia in terms of incident adverse outcomes. J Am Med Dir Assoc. 2015;16:247–52.

    PubMed  Google Scholar 

  126. Bahat G, Yilmazi O, Kilic C, et al. Performance of SARC-F in regard to sarcopenia definitions, muscle mass and functional measures. J Nutr Health Aging. 2018. https://doi.org/10.1007/s12603-018-1067-8. Epub ahead of print.

  127. Bahat G, Yilmaz O, Oren M, et al. Cross-cultural adaptation and validation of the SARC-F to assess sarcopenia: methodological report from European Union Geriatric Medicine Society Sarcopenia Special Interest Group. Eur Geriatr Med. 2018;9:23–8.

    PubMed  Google Scholar 

  128. Locquet M, Beaudart C, Reginster JY, et al. Comparison of the performance of five screening methods for sarcopenia. Clin Epidemiol. 2018;10:71–82.

    PubMed  Google Scholar 

  129. Ishii S, Tanaka T, Shibasaki K, et al. Development of a simple screening test for sarcopenia in older adults. Geriatr Gerontol Int. 2014;14(Suppl 1):93–101.

    PubMed  Google Scholar 

  130. Roberts HC, Denison HJ, Martin HJ, et al. A review of the measurement of grip strength in clinical and epidemiological studies: towards a standardised approach. Age Ageing. 2011;40:423–9.

    PubMed  Google Scholar 

  131. Rossi AP, Fantin F, Micciolo R, et al. Identifying sarcopenia in acute care setting patients. J Am Med Dir Assoc. 2014;15:303.e7–12.

    Google Scholar 

  132. Dodds R, Sayer AA. Sarcopenia and frailty: new challenges for clinical practice. Clin Med (Lond). 2015;15(Suppl 6):s88–91.

    Google Scholar 

  133. Beaudart C, McCloskey E, Bruyere O, et al. Sarcopenia in daily practice: assessment and management. BMC Geriatr. 2016;16:170.

    PubMed  PubMed Central  Google Scholar 

  134. Sipers WM, Verdijk LB, Sipers SJ, et al. The Martin vigorimeter represents a reliable and more practical tool than the Jamar dynamometer to assess handgrip strength in the geriatric patient. J Am Med Dir Assoc. 2016;17:466.e1–7.

    Google Scholar 

  135. Francis P, Toomey C, Mc Cormack W, et al. Measurement of maximal isometric torque and muscle quality of the knee extensors and flexors in healthy 50- to 70-year-old women. Clin Physiol Funct Imaging. 2017;37:448–55.

    PubMed  Google Scholar 

  136. Cesari M, Kritchevsky SB, Newman AB, et al. Added value of physical performance measures in predicting adverse health-related events: results from the Health, Aging and Body Composition Study. J Am Geriatr Soc. 2009;57:251–9.

    PubMed  PubMed Central  Google Scholar 

  137. Jones CJ, Rikli RE, Beam WC. A 30-s chair-stand test as a measure of lower body strength in community-residing older adults. Res Q Exerc Sport. 1999;70:113–9.

    CAS  PubMed  Google Scholar 

  138. Lusardi MM, Fritz S, Middleton A, et al. Determining risk of falls in community dwelling older adults: a systematic review and meta-analysis using posttest probability. J Geriatr Phys Ther. 2017;40(1):1–36.

    PubMed  Google Scholar 

  139. Cooper C, Fielding R, Visser M, et al. Tools in the assessment of sarcopenia. Calcif Tissue Int. 2013;93:201–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Cawthon PM, Peters KW, Shardell MD, et al. Cutpoints for low appendicular lean mass that identify older adults with clinically significant weakness. J Gerontol A Biol Sci Med Sci. 2014;69:567–75.

    PubMed  PubMed Central  Google Scholar 

  141. Hull H, He Q, Thornton J, et al. iDXA, prodigy, and DPXL dual-energy X-ray absorptiometry whole-body scans: a cross-calibration study. J Clin Densitom. 2009;12:95–102.

    PubMed  Google Scholar 

  142. Kim KM, Jang HC, Lim S. Differences among skeletal muscle mass indices derived from height-, weight-, and body mass index-adjusted models in assessing sarcopenia. Korean J Intern Med. 2016;31:643–50.

    PubMed  PubMed Central  Google Scholar 

  143. Newman AB, Haggerty CL, Goodpaster B, et al. Strength and muscle quality in a well-functioning cohort of older adults: the Health, Aging and Body Composition Study. J Am Geriatr Soc. 2003;51:323–30.

    PubMed  Google Scholar 

  144. Sergi G, De Rui M, Veronese N, et al. Assessing appendicular skeletal muscle mass with bioelectrical impedance analysis in free-living Caucasian older adults. Clin Nutr. 2015;34:667–73.

    PubMed  Google Scholar 

  145. Gonzalez MC, Heymsfield SB. Bioelectrical impedance analysis for diagnosing sarcopenia and cachexia: what are we really estimating? J Cachexia Sarcopenia Muscle. 2017;8:187–9.

    PubMed  PubMed Central  Google Scholar 

  146. Yu SC, Powell A, Khow KS, et al. The performance of five bioelectrical impedance analysis prediction equations against dual X-ray absorptiometry in estimating appendicular skeletal muscle mass in an Adult Australian Population. Nutrients. 2016;8:189.

    PubMed  PubMed Central  Google Scholar 

  147. Reiss J, Iglseder B, Kreutzer M, et al. Case finding for sarcopenia in geriatric inpatients: performance of bioimpedance analysis in comparison to dual X-ray absorptiometry. BMC Geriatr. 2016;16:52.

    PubMed  PubMed Central  Google Scholar 

  148. Tosato M, Marzetti E, Cesari M, et al. Measurement of muscle mass in sarcopenia: from imaging to biochemical markers. Aging Clin Exp Res. 2017;29:19–27.

    PubMed  Google Scholar 

  149. Landi F, Onder G, Russo A, et al. Calf circumference, frailty and physical performance among older adults living in the community. Clin Nutr. 2014;33:539–44.

    PubMed  Google Scholar 

  150. Beaudart C, Rolland Y, Cruz-Jentoft A, et al. Assessment of muscle function and physical performance in daily clinical practice. Submitted 2018.

    Google Scholar 

  151. Bruyere O, Beaudart C, Reginster J-V, et al. Assessment of muscle mass, muscle strength and physical performance in clinical practice: an international survey. Eur Geriatr Med. 2016;7:243–6.

    Google Scholar 

  152. Abellan van Kan G, Rolland Y, Andrieu S, et al. Gait speed at usual pace as a predictor of adverse outcomes in community-dwelling older people an International Academy on Nutrition and Aging (IANA) task force. J Nutr Health Aging. 2009;13:881–9.

    CAS  PubMed  Google Scholar 

  153. Peel NM, Kuys SS, Klein K. Gait speed as a measure in geriatric assessment in clinical settings: a systematic review. J Gerontol A Biol Sci Med Sci. 2013;68:39–46.

    PubMed  Google Scholar 

  154. Studenski S, Perera S, Patel K, et al. Gait speed and survival in older adults. JAMA. 2011;305:50–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Guralnik JM, Ferrucci L, Pieper CF, et al. Lower extremity function and subsequent disability: consistency across studies, predictive models, and value of gait speed alone compared with the short physical performance battery. J Gerontol A Biol Sci Med Sci. 2000;55:M221–31.

    CAS  PubMed  Google Scholar 

  156. Maggio M, Ceda GP, Ticinesi A, et al. Instrumental and non-instrumental evaluation of 4-meter walking speed in older individuals. PLoS One. 2016;11:e0153583.

    PubMed  PubMed Central  Google Scholar 

  157. Rydwik E, Bergland A, Forsen L, et al. Investigation into the reliability and validity of the measurement of elderly people’s clinical walking speed: a systematic review. Physiother Theory Pract. 2012;28:238–56.

    CAS  PubMed  Google Scholar 

  158. Short Physical Performance Battery (SPPB). https://www.nia.nih.gov/research/labs/leps/short-physical-performance-battery-sppb [cited 18 June 2019].

  159. Podsiadlo D, Richardson S. The timed ‘Up & Go’: a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc. 1991;39:142–8.

    CAS  PubMed  Google Scholar 

  160. Pavasini R, Guralnik J, Brown JC, et al. Short physical performance battery and all-cause mortality: systematic review and meta-analysis. BMC Med. 2016;14:215.

    PubMed  PubMed Central  Google Scholar 

  161. Vestergaard S, Patel KV, Bandinelli S, et al. Characteristics of 400-meter walk test performance and subsequent mortality in older adults. Rejuvenation Res. 2009;12:177–84.

    PubMed  PubMed Central  Google Scholar 

  162. Bergland A, Jorgensen L, Emaus N, et al. Mobility as a predictor of all-cause mortality in older men and women: 11.8 year follow-up in the Tromso study. BMC Health Serv Res. 2017;17:22.

    PubMed  PubMed Central  Google Scholar 

  163. Heymsfield SB, Gonzalez MC, Lu J, et al. Skeletal muscle mass and quality: evolution of modern measurement concepts in the context of sarcopenia. Proc Nutr Soc. 2015;74:355–66.

    PubMed  Google Scholar 

  164. Mourtzakis M, Prado CM, Lieffers JR, et al. A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care. Appl Physiol Nutr Metab. 2008;33:997–1006.

    PubMed  Google Scholar 

  165. Fearon K, Strasser F, Anker SD, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12:489–95.

    PubMed  Google Scholar 

  166. Kim EY, Kim YS, Park I, et al. Prognostic significance of CT-determined sarcopenia in patients with small-cell lung cancer. J Thorac Oncol. 2015;10:1795–9.

    CAS  PubMed  Google Scholar 

  167. Baracos V, Kazemi-Bajestani SM. Clinical outcomes related to muscle mass in humans with cancer and catabolic illnesses. Int J Biochem Cell Biol. 2013;45:2302–8.

    CAS  PubMed  Google Scholar 

  168. Moisey LL, Mourtzakis M, Cotton BA, et al. Skeletal muscle predicts ventilator-free days, ICU-free days, and mortality in elderly ICU patients. Crit Care. 2013;17:R206.

    PubMed  PubMed Central  Google Scholar 

  169. Montano-Loza AJ, Meza-Junco J, Baracos VE, et al. Severe muscle depletion predicts postoperative length of stay but is not associated with survival after liver transplantation. Liver Transpl. 2014;20:640–8.

    PubMed  Google Scholar 

  170. Baracos VE, Reiman T, Mourtzakis M, et al. Body composition in patients with non-small cell lung cancer: a contemporary view of cancer cachexia with the use of computed tomography image analysis. Am J Clin Nutr. 2010;91:1133S–7S.

    CAS  PubMed  Google Scholar 

  171. Gu DH, Kim MY, Seo YS, et al. Clinical usefulness of psoas muscle thickness for the diagnosis of sarcopenia in patients with liver cirrhosis. Clin Mol Hepatol. 2018;24:319–30.

    PubMed  PubMed Central  Google Scholar 

  172. Hanaoka M, Yasuno M, Ishiguro M, et al. Morphologic change of the psoas muscle as a surrogate marker of sarcopenia and predictor of complications after colorectal cancer surgery. Int J Color Dis. 2017;32:847–56.

    Google Scholar 

  173. Baracos VE. Psoas as a sentinel muscle for sarcopenia: a flawed premise. J Cachexia Sarcopenia Muscle. 2017;8:527–8.

    PubMed  PubMed Central  Google Scholar 

  174. Rutten IJG, Ubachs J, Kruitwagen R, et al. Psoas muscle area is not representative of total skeletal muscle area in the assessment of sarcopenia in ovarian cancer. J Cachexia Sarcopenia Muscle. 2017;8:630–8.

    PubMed  PubMed Central  Google Scholar 

  175. Hamaguchi Y, Kaido T, Okumura S, et al. Impact of skeletal muscle mass index, intramuscular adipose tissue content, and visceral to subcutaneous adipose tissue area ratio on early mortality of living donor liver transplantation. Transplantation. 2017;101:565–74.

    PubMed  Google Scholar 

  176. Lynch NA, Metter EJ, Lindle RS, et al. Muscle quality. I. Age-associated differences between arm and leg muscle groups. J Appl Physiol (1985). 1999;86:188–94.

    CAS  Google Scholar 

  177. Rolland Y, Lauwers-Cances V, Pahor M, et al. Muscle strength in obese elderly women: effect of recreational physical activity in a cross-sectional study. Am J Clin Nutr. 2004;79:552–7.

    CAS  PubMed  Google Scholar 

  178. Tracy BL, Ivey FM, Hurlbut D, et al. Muscle quality. II. Effects of strength training in 65- to 75-yr-old men and women. J Appl Physiol (1985). 1999;86:195–201.

    CAS  Google Scholar 

  179. Shankaran M, Czerwieniec G, Fessler C, et al. Dilution of oral D3-creatine to measure creatine pool size and estimate skeletal muscle mass: development of a correction algorithm. J Cachexia Sarcopenia Muscle. 2018;9:540–6.

    PubMed  PubMed Central  Google Scholar 

  180. Clark RV, Walker AC, Miller RR, et al. Creatine ( methyl-d3) dilution in urine for estimation of total body skeletal muscle mass: accuracy and variability vs. MRI and DXA. J Appl Physiol. 2018;124:1–9. [PMC free article] [PubMed] [Google Scholar].

    CAS  PubMed  Google Scholar 

  181. Buehring B, Siglinsky E, Krueger D, et al. Comparison of muscle/lean mass measurement methods: correlation with functional and biochemical testing. Osteoporos Int. 2018;29:675–83.

    CAS  PubMed  Google Scholar 

  182. Galindo Martin CA, Monares Zepeda E, Lescas Mendez OA. Bedside ultrasound measurement of rectus femoris: a tutorial for the nutrition support clinician. J Nutr Metab. 2017;2017:2767232.

    PubMed  PubMed Central  Google Scholar 

  183. Ticinesi A, Narici MV, Lauretani F, et al. Assessing sarcopenia with vastus lateralis muscle ultrasound: an operative protocol. Aging Clin Exp Res. 2018. https://doi.org/10.1007/s40520-018-0958-1.

  184. SARCUS working group on behalf of the Sarcopenia Special Interest Group of the European Geriatric Medicine Society, Perkisas S, Baudry S, et al. Application of ultrasound for muscle assessment in sarcopenia: towards standardized measurements. Eur J Med 2018. In press. https://doi.org/10.1007/s41999-018-0104-9.

  185. Sipila S, Suominen H. Muscle ultrasonography and computed tomography in elderly trained and untrained women. Muscle Nerve. 1993;16:294–300.

    CAS  PubMed  Google Scholar 

  186. Ismail C, Zabal J, Hernandez HJ, et al. Diagnostic ultrasound estimates of muscle mass and muscle quality discriminate between women with and without sarcopenia. Front Physiol. 2015;6:302.

    PubMed  PubMed Central  Google Scholar 

  187. Nijholt W, Scafoglieri A, Jager-Wittenaar H, et al. The reliability and validity of ultrasound to quantify muscles in older adults: a systematic review. J Cachexia Sarcopenia Muscle. 2017;8:702–12.

    PubMed  PubMed Central  Google Scholar 

  188. Ticinesi A, Meschi T, Narici MV, et al. Muscle ultrasound and sarcopenia in older individuals: a clinical perspective. J Am Med Dir Assoc. 2017;18:290–300.

    PubMed  Google Scholar 

  189. Abe T, Loenneke JP, Young KC, et al. Validity of ultrasound prediction equations for total and regional muscularity in middle-aged and older men and women. Ultrasound Med Biol. 2015;41:557–64.

    PubMed  Google Scholar 

  190. Curcio F, Ferro G, Basile C, et al. Biomarkers in sarcopenia: a multifactorial approach. Exp Gerontol. 2016;85:1–8.

    CAS  PubMed  Google Scholar 

  191. Calvani R, Marini F, Cesari M, et al. Biomarkers for physical frailty and sarcopenia. Aging Clin Exp Res. 2017;29:29–34.

    PubMed  Google Scholar 

  192. Beaudart C, Biver E, Reginster JY, et al. Development of a self-administrated quality of life questionnaire for sarcopenia in elderly subjects: the SarQoL. Age Ageing. 2015;44:960–6.

    PubMed  PubMed Central  Google Scholar 

  193. Beaudart C, Reginster JY, Geerinck A, et al. Current review of the SarQoL(R): a health-related quality of life questionnaire specific to sarcopenia. Expert Rev Pharmacoecon Outcomes Res. 2017;17:335–41.

    PubMed  Google Scholar 

  194. Beaudart C, Locquet M, Reginster JY, et al. Quality of life in sarcopenia measured with the SarQoL(R): impact of the use of different diagnosis definitions. Aging Clin Exp Res. 2018;30:307–13.

    PubMed  Google Scholar 

  195. Beaudart C, Biver E, Reginster JY, et al. Validation of the SarQoL(R), a specific health-related quality of life questionnaire for Sarcopenia. J Cachexia Sarcopenia Muscle. 2017;8:238–44.

    PubMed  Google Scholar 

  196. El Miedany Y, El Gaafary M, Toth M, Palmer D, Ahmed I. Falls risk assessment score (FRAS): time to rethink. J Clin Gerontol Geriatrics. 2011;2(1):21–6.

    Google Scholar 

  197. El Miedany Y, El Gaafary M, Toth M, Hassan W, Mehanna A. Identification and management of patient at increased risk of osteoporotic fracture: implementation of imminent risk factor in standard daily practice for bone mineral density assessment and patient management. Ann Rheum Dis. 2019;78(suppl 2):A184.

    Google Scholar 

  198. El Miedany Y, Toth M. Osteoporosis, fracture prevention and falls risk assessment –closing the gap between treatment guidelines and clinical practice. Eur Musculoskelet Rev. 2011;6(1):14–7.

    Google Scholar 

  199. Hassan E, Duque G. Osteosarcopenia: a new geriatric syndrome. Aust Fam Physician. 2017;46(1):849–53.

    PubMed  Google Scholar 

  200. Johnson K, Suriyaarachchi P, Kakkat M, et al. Yield and cost-effectiveness of laboratory testing to identify metabolic contributors to falls and fractures in older persons. Arch Osteoporos. 2015;10:226.

    PubMed  Google Scholar 

  201. Gomez F, Curcio CL, Suriyaarachchi P, Demontiero O, Duque G. Differing approaches to falls and fracture prevention between Australia and Colombia. Clin Interv Aging. 2013;8:61–7.

    PubMed  PubMed Central  Google Scholar 

  202. The Royal Australian College of General Practitioners. Osteoporosis prevention, diagnosis and management in postmenopausal women and men over 50 years of age. Melbourne: RACGP, 2010. Available at www.racgp.org.au/your-practice/guidelines/musculoskeletal/osteoporosis. Accessed 25th May 2019.

  203. Mijnarends DM, Koster A, Schols JM, et al. Physical activity and incidence of sarcopenia: the population-based AGES-Reykjavik study. Age Ageing. 2016;45:614–20.

    PubMed  PubMed Central  Google Scholar 

  204. Prado CM, Wells JC, Smith SR, et al. Sarcopenic obesity: a critical appraisal of the current evidence. Clin Nutr. 2012;31:583–601.

    CAS  PubMed  Google Scholar 

  205. Binder EF, Yarasheski KE, Steger-May K, et al. Effects of progressive resistance training on body composition in frail older adults: results of a randomized, controlled trial. J Gerontol A Biol Sci Med Sci. 2005;60:1425–31.

    PubMed  Google Scholar 

  206. Bunout D, Barrera G, de la Maza P, et al. The impact of nutritional supplementation and resistance training on the health functioning of free-living Chilean elders: results of 18 months of follow-up. J Nutr. 2001;131:2441S–6S.

    CAS  PubMed  Google Scholar 

  207. Suetta C, Andersen JL, Dalgas U, et al. Resistance training induces qualitative changes in muscle morphology, muscle architecture, and muscle function in elderly postoperative patients. J Appl Physiol. 2008;105:180–6.

    PubMed  Google Scholar 

  208. Kemmler W, von Stengel S, Engelke K, Häberle L, Mayhew JL, Kalender WA. Exercise, body composition, and functional ability a randomized controlled trial. Am J Prev Med. 2010;38:279–87.

    PubMed  Google Scholar 

  209. Rydwik E, Lammes E, Frändin K, Akner G. Effects of a physical and nutritional intervention program for frail elderly individuals over age 75: a randomized controlled pilot treatment trial. Aging Clin Exp Res. 2008;20:159–70.

    PubMed  Google Scholar 

  210. Bonnefoy M, Cornu C, Normand S, et al. The effects of exercise and protein-energy supplements on body composition and muscle function in frail elderly individuals: a long-term controlled randomised study. Br J Nutr. 2003;89:731–9.

    CAS  PubMed  Google Scholar 

  211. Yoshimura Y, Wakabayashi H, Yamada M, Kim H, Harada A, Arai H. Interventions for treating sarcopenia: a systematic review and meta-analysis of randomized controlled studies. J Am Med Dir Assoc. 2017;18:553.e1–553.e16.

    Google Scholar 

  212. Kim HK, Suzuki T, Saito K, et al. Effects of exercise and amino acid supplementation on body composition and physical function in community-dwelling elderly Japanese sarcopenic women: a randomized controlled trial. J Am Geriatr Soc. 2012;60:16–23.

    PubMed  Google Scholar 

  213. Kim H, Suzuki T, Saito K, et al. Effects of exercise and tea catechins on muscle mass, strength and walking ability in community-dwelling elderly Japanese sarcopenic women: a randomized controlled trial. Geriatr Gerontol Int. 2013;13:458–65.

    PubMed  Google Scholar 

  214. Kim H, Kim M, Kojima N, et al. Exercise and nutritional supplementation on community-dwelling elderly Japanese women with sarcopenic obesity: a randomized controlled trial. J Am Med Dir Assoc. 2016;17:1011–9.

    PubMed  Google Scholar 

  215. Wei N, Pang MY, Ng SS, Ng GY. Optimal frequency/ time combination of whole-body vibration training for improving muscle size and strength of individuals with age related muscle loss (sarcopenia): a randomized controlled trial. Geriatr Gerontol Int. 2017;17:1412–20.

    PubMed  Google Scholar 

  216. Johnston AP, De Lisio M, Parise G. Resistance training, sarcopenia, and the mitochondrial theory of aging. Appl Physiol Nutr Metab. 2008;33:191–9.

    CAS  PubMed  Google Scholar 

  217. Lee MY, Jun WS, Lee MG. Effects of a 12-week circuit exercise program on fall-related fitness in elderly women with sarcopenia. Korean J Sports Sci. 2017;26:1123–35.

    Google Scholar 

  218. Takeshima N, Rogers ME, Islam MM, Yamauchi T, Watanabe E, Okada A. Effect of concurrent aerobic and resistance circuit exercise training on fitness in older adults. Eur J Appl Physiol. 2004;93:173–82.

    PubMed  Google Scholar 

  219. Gudlaugsson J, Aspelund T, Gudnason V, Olafsdottir AS, Jonsson PV, Arngrimsson SA, Johannsson E. The effects of 6 months’ multimodal training on functional performance, strength, endurance, and body mass index of older individuals. Are the benefits of training similar among women and men? Laeknabladid. 2013;99:331–7.

    PubMed  Google Scholar 

  220. Paddon-Jones D, Rasmussen BB. Dietary protein recommendations and the prevention of sarcopenia. Curr Opin Clin Nutr Metab Care. 2009;12:86–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  221. Waters DL, Baumgartner RN, Garry PJ, Vellas B. Advantages of dietary, exercise-related, and therapeutic interventions to prevent and treat sarcopenia in adult patients: an update. Clin Interv Aging. 2010;5:259–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  222. Volpi E, Mittendorfer B, Rasmussen BB, Wolfe RR. The response of muscle protein anabolism to combined hyperaminoacidemia and glucose-induced hyperinsulinemia is impaired in the elderly. J Clin Endocrinol Metab. 2000;85:4481–90.

    CAS  PubMed  Google Scholar 

  223. Muscariello E, Nasti G, Siervo M, Di Maro M, Lapi D, D’Addio G, Colantuoni A. Dietary protein intake in sarcopenic obese older women. Clin Interv Aging. 2016;11:133–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  224. Anand I, Chandrashekhan Y, De Giuli F, Pasini E, Mazzoletti A, Confortini R, Ferrari R. Chronic effects of propionyl-L-carnitine on the hemodynamics, exercise capacity, and hormones in patients with congestive heart failure. Cardiovasc Drugs Ther. 1998;12:291–9.

    CAS  PubMed  Google Scholar 

  225. Leenders M, van Loon LJ. Leucine as a pharmaconutrient to prevent and treat sarcopenia and type 2 diabetes. Nutr Rev. 2011;69:675–89.

    PubMed  Google Scholar 

  226. Rieu I, Balage M, Sornet C, Giraudet C, Pujos E, Grizard J, Mosoni L, Dardevet D. Leucine supplementation improves muscle protein synthesis in elderly men independently of hyperaminoacidaemia. J Physiol. 2006;575:305–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  227. Drummond MJ, Rasmussen BB. Leucine-enriched nutrients and the regulation of mammalian target of rapamycin signaling and human skeletal muscle protein synthesis. Curr Opin Clin Nutr Metab Care. 2008;11:222–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  228. Solerte SB, Gazzaruso C, Bonacasa R, Rondanelli M, Zamboni M, Basso C, Locatelli E, Schifino N, Giustina A, Fioravanti M. Nutritional supplements with oral amino acid mixtures increases whole-body lean mass and insulin sensitivity in elderly subjects with sarcopenia. Am J Cardiol. 2008;101:69E–77E.

    CAS  PubMed  Google Scholar 

  229. Rubio-Ruiz ME, El Hafidi M, Pérez-Torres I, Baños G, Guarner V. Medicinal agents and metabolic syndrome. Curr Med Chem. 2013;20:2626–40.

    CAS  PubMed  Google Scholar 

  230. Peredo-Escárcega AE, Guarner-Lans V, Pérez-Torres I, Ortega-Ocampo S, Carreón-Torres E, Castrejón-Tellez V, Díaz-Díaz E, Rubio-Ruiz ME. The combination of resveratrol and quercetin attenuates Metabolic Syndrome in rats by modifying the serum fatty acid composition and by upregulating SIRT 1 and SIRT 2 expression in white adipose tissue. Evid Based Complement Alternat Med. 2015;2015:1–9.

    Google Scholar 

  231. Le NH, Kim CS, Park T, Park JH, Sung MK, Lee DG, Hong SM, Choe SY, Goto T, Kawada T, et al. Quercetin protects against obesity-induced skeletal muscle inflammation and atrophy. Mediat Inflamm. 2014;2014:834294.

    Google Scholar 

  232. Hori YS, Kuno A, Hosoda R, Tanno M, Miura T, Shimamoto K, Horio Y. Resveratrol ameliorates muscular pathology in the dystrophic mdx mouse, a model for Duchenne muscular dystrophy. J Pharmacol Exp Ther. 2011;338:784–94.

    CAS  PubMed  Google Scholar 

  233. Rubio-Ruiz ME, Guarner-Lans V, Pérez-Torres I, Soto ME. Mechanisms underlying metabolic syndrome-related sarcopenia and possible therapeutic measures. Int J Mol Sci. 2019;20(3):647. https://doi.org/10.3390/ijms20030647.

    Article  CAS  PubMed Central  Google Scholar 

  234. Waijers PM, Feskens EJ, Ocké MC. A critical review of predefined diet quality scores. Br J Nutr. 2007;97:219–31.

    CAS  PubMed  Google Scholar 

  235. Hu FB. Dietary pattern analysis: a new direction in nutritional epidemiology. Curr Opin Lipidol. 2002;13:3–9.

    CAS  PubMed  Google Scholar 

  236. Willcox DC, Scapagnini G, Willcox BJ. Healthy aging diets other than the Mediterranean: a focus on the Okinawan diet. Mech Ageing Dev. 2014;136–137:148–62.

    PubMed  PubMed Central  Google Scholar 

  237. Schwingshackl L, Bogensberger B, Hoffmann G. Diet quality as assessed by the healthy eating index, alternate healthy eating index, dietary approaches to stop hypertension score, and health outcomes: an updated systematic review and meta-analysis of cohort studies. J Acad Nutr Diet. 2018;118:74–100.

    PubMed  Google Scholar 

  238. Schwedhelm C, Boeing H, Hoffmann G, Aleksandrova K, Schwingshackl L. Effect of diet on mortality and cancer recurrence among cancer survivors: a systematic review and meta-analysis of cohort studies. Nutr Rev. 2016;74:737–48.

    PubMed  PubMed Central  Google Scholar 

  239. McNaughton SA, Bates CJ, Mishra GD. Diet quality is associated with all-cause mortality in adults aged 65 years and older. J Nutr. 2012;142:320–5.

    CAS  PubMed  Google Scholar 

  240. McNaughton SA, Dunstan DW, Ball K, Shaw J, Crawford D. Dietary quality is associated with diabetes and cardio-metabolic risk factors. J Nutr. 2009;139:734–42.

    CAS  PubMed  Google Scholar 

  241. Bloom I, Shand C, Cooper C, Robinson S, Baird J. Diet quality and sarcopenia in older adults: a systematic review. Nutrients. 2018;10:308–36. https://doi.org/10.3390/nu10030308.

    Article  PubMed Central  Google Scholar 

  242. Robinson SM, Reginster JY, Rizzoli R, Shaw SC, Kanis JA, Bautmans I, Bischoff-Ferrari H, Bruyère O, Cesari M, Dawson-Hughes B, et al. Does nutrition play a role in the prevention and management of sarcopenia? Clin Nutr. 2018;37:1121–32.

    CAS  PubMed  Google Scholar 

  243. Dobs AS, Nguyen T, Pace C, Roberts CP. Differential effects of oral estrogen versus oral estrogen androgen replacement therapy on body composition in postmenopausal women. J Clin Endocrinol Metab. 2002;87:1509–16.

    CAS  PubMed  Google Scholar 

  244. Wang C, Cunningham G, Dobs A, et al. Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab. 2004;89:2085–98.

    CAS  PubMed  Google Scholar 

  245. Cleasby ME, Jamieson PM, Atherton PJ. Insulin resistance and sarcopenia: mechanistic links between common co-morbidities. J Endocrinol. 2016;229:R67–81.

    CAS  PubMed  Google Scholar 

  246. Bouchonville MF, Villareal DT. Sarcopenic obesity: how do we treat it? Curr Opin Endocrinol Diabetes Obes. 2013;20:412–9.

    PubMed  PubMed Central  Google Scholar 

  247. Aryana IGPS, Kuswardhani RAT. Sarcopenia in elderly. Int J GeriatrGerontol: IJGG-109; 2018.

    Google Scholar 

  248. Bates B, Bates C, Prentice P, Swan G. National diet and nutrition survey headline results from years 1 and 2 (combined) of the rolling programme (2008/2009–2009/10); supplementary report: blood analytes; Department of Health and the Food Standards Agency: London, UK, 2011. Available online: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/215348/dh_130788.pdf. Accessed on 22nd June 2019.

  249. Wongwiwatthananukit S, Sansanayudh N, Phetkrajaysang N, Krittiyanunt S. Effects of vitamin D(2) supplementation on insulin sensitivity and metabolic parameters in Metabolic syndrome patients. J Endocrinol Investig. 2013;36:558–63.

    CAS  Google Scholar 

  250. Ceglia L, Niramitmahapanya S, da Silva Morais M, Rivas DA, Harris SS, Bischoff-Ferrari H, Fielding RA, Dawson-Hughes B. A randomized study on the effect of vitamin D (3) supplementation on skeletal muscle morphology and vitamin D receptor concentration in older women. J Clin Endocrinol Metab. 2013;98:E1927–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  251. Beaudart C, Buckinx F, Rabenda V, Gillain S, Cavalier E, Slomian J, Petermans J, Reginster JY, Bruyere O. The effects of vitamin D on skeletal muscle strength, muscle mass, and muscle power: a systematic review and meta-analysis of randomized controlled trials. J Clin Endocrinol Metab. 2014;99:4336–45.

    CAS  PubMed  Google Scholar 

  252. Burne TH, Johnston AN, McGrath JJ, Mackay-Sim A. Swimming behavior and post-swimming activity in vitamin D receptor knockout mice. Brain Res Bull. 2006;69:74–8.

    CAS  PubMed  Google Scholar 

  253. Endo I, Inoue D, Mitsui T, Umaki Y, Akaike M, Yoshizawa T, Kato S, Matsumoto T. Deletion of vitamin D receptor gene in mice results in abnormal skeletal muscle development with deregulated expression of myoregulatory transcription factors. Endocrinology. 2003;144:5138–44.

    CAS  PubMed  Google Scholar 

  254. Narvaez CJ, Matthews D, Broun E, Chan M, Welsh J. Lean phenotype and resistance to diet-induced obesity in vitamin D receptor knockout mice correlates with induction of uncoupling protein-1 in white adipose tissue. Endocrinology. 2009;150:651–61.

    CAS  PubMed  Google Scholar 

  255. Bruyère O, Cavalier E, Buckinx F, Reginster JY. Relevance of vitamin D in the pathogenesis and therapy of frailty. Curr Opin Clin Nutr Metab Care. 2017;20:26–9.

    PubMed  Google Scholar 

  256. Burton LA, Sumukadas D. Optimal management of sarcopenia 5. Clin Interv Aging. 2010;5:217–28.

    CAS  PubMed  PubMed Central  Google Scholar 

  257. Bergera MJ, Dohertya TJ. Sarcopenia: prevalence, Mecha6. nisms, and functional consequences. In: Mobbs CV, Hof PR, editors. Body composition and aging. Interdiscipl Top Gerontol, vol. 37. Basel: Karger; 2010. p. 94–114.

    Google Scholar 

  258. Bhasin S, Woodhouse L, Storer TW. Proof of the effect of testosterone on skeletal muscle. J Endocrinol. 2001;170:27–38.

    CAS  PubMed  Google Scholar 

  259. Allan CA, Strauss BJG, McLachlan RI. Body composition, Metabolic syndrome and testosterone in ageing men. Int J Impot Res. 2007;19:448–57.

    CAS  PubMed  Google Scholar 

  260. Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, Bremner WJ, McKinlay JB. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 2002;87:589–98.

    CAS  PubMed  Google Scholar 

  261. Morley JE, Perry HM. Androgens and women at the menopause and beyond. J Gerontol A Biol Sci Med Sci. 2003;58:M409–16.

    PubMed  Google Scholar 

  262. Schaap LA, Pluijm SMF, Smitt JH, van Schoor NM, Visser M, Gooren LJ, Lips P. The association of sex hormone levels with poor mobility, low muscle strength and incidence of falls among older men and women. Clin Endocrinol. 2005;63:152–60.

    CAS  Google Scholar 

  263. Chu LW, Tam S, Kung AWC, Lo S, Fan S, Wong RL, Morley JE, Lam KS. Serum total and bioavailable testosterone levels, central obesity, and muscle strength changes with aging in healthy Chinese men. J Am Geriatr Soc. 2008;56:1286–91.

    PubMed  Google Scholar 

  264. Brodsky IG, Balagopal P, Nair KS. Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men—a clinical research center study. J Clin Endocrinol Metab. 1996;81:3469–75.

    CAS  PubMed  Google Scholar 

  265. Bhasin S, Woodhouse L, Casaburi R, Singh AB, Bhasin D, Berman N, Chen X, Yarasheski KE, Magliano L, Dzekov C, et al. Testosterone dose-response relationships in healthy young men. Am J Physiol Endocrinol Metab. 2001;281:E1172–81.

    CAS  PubMed  Google Scholar 

  266. Sinha-Hikim I, Cornford M, Gaytan H, Lee ML, Bhasin S. Effects of testosterone supplementation on skeletal muscle fiber hypertrophy and satellite cells in community-dwelling older men. J Clin Endocrinol Metab. 2006;91:3024–33.

    CAS  PubMed  Google Scholar 

  267. Comhaire F. Hormone replacement therapy and longevity. Andrologia. 2016;48:65–8.

    CAS  PubMed  Google Scholar 

  268. Morgentaler A. Words of wisdom. Re: adverse events associated with testosterone administration. Eur Urol. 2011;59:465.

    PubMed  Google Scholar 

  269. Wang X, Smith GI, Patterson BW, Reeds DN, Kampelman J, Magkos F, Mittendorfer B. Testosterone increases the muscle protein synthesis rate but does not affect very-low-density lipoprotein metabolism in obese premenopausal women. Am J Physiol Endocrinol Metab. 2012;302:E740–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  270. Shores MM, Moceri VM, Gruenewald DA, Brodkin KI, Matsumoto AM, Kivlahan DR. Low testosterone is associated with decreased function and increased mortality risk: a preliminary study of men in a geriatric rehabilitation unit. J Am Geriatr Soc. 2004;52:2077–81.

    PubMed  Google Scholar 

  271. Pérez Torres I, El Hafidi M, Zamora-González J, Infante O, Chavira R, Baños G. Modulation of aortic vascular reactivity by sex hormones in a male rat model of Metabolic syndrome. Life Sci. 2007;80:2170–80.

    Google Scholar 

  272. Min L, Yanase T, Tanaka T, Fan W, Nomura M, Kawate H, Okabe T, Takayanagi R, Nawata H. A novel synthetic androgen receptor ligand, S42, works as a selective androgen receptor modulator and possesses metabolic effects with little impact on the prostate. Endocrinology. 2009;150:5606–16.

    CAS  PubMed  Google Scholar 

  273. Clarkson PM, Hubal MJ. Are women less susceptible to exercise-induced muscle damage? Curr Opin Clin Nutr Metab Care. 2001;4:527–31.

    CAS  PubMed  Google Scholar 

  274. Sarwar R, Niclos BB, Rutherford OM. Changes in muscle strength, relaxation rate and fatiguability during the human menstrual cycle. J Physiol. 1996;493:267–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  275. Sørensen MB, Rosenfalck AM, Højgaard L, Ottesen B. Obesity and sarcopenia after menopause are reversed by sex hormone replacement therapy. Obes Res. 2001;9:622–6.

    PubMed  Google Scholar 

  276. Dieli-Conwright CM, Spektor TM, Rice JC, Sattler FR, Schroeder ET. Hormone therapy attenuates exercise-induced skeletal muscle damage in postmenopausal women. J Appl Physiol. 2009;107:853–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  277. Tiidus PM, Lowe DA, Brown M. Estrogen replacement and skeletal muscle: mechanisms and population health. J Appl Physiol. 2013;115:569–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  278. Parkington J, Fielding RA, Kandarian SC, Koncarevic A, Theilhaber J, et al. Identification of a molecular signature of sarcopenia. Physiol Genomics. 2005;21:253–63.

    PubMed  Google Scholar 

  279. Umpleby AM, Russell-Jones DL. The hormonal control of protein metabolism. Bailliere Clin Endocrinol Metab. 1996;10:551–70.

    CAS  Google Scholar 

  280. Cuthbertson D, Smith K, Babraj J, Leese G, Waddell T, Atherton P, Wackerhage H, Taylor PM, Rennie MJ. Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. FASEB J. 2005;19:422–4.

    CAS  PubMed  Google Scholar 

  281. Guillet C, Zangarelli A, Gachon P, Morio B, Giraudet C, Rousset P, Boirie Y. Whole body protein breakdown is less inhibited by insulin, but still responsive to amino acid, in nondiabetic elderly subjects. J Clin Endocrinol Metab. 2004;89:6017–24.

    CAS  PubMed  Google Scholar 

  282. Wilkes EA, Selby AL, Atherton PJ, Patel R, Rankin D, Smith K, Rennie MJ. Blunting of insulin inhibition of proteolysis in legs of older subjects may contribute to age-related sarcopenia. Am J Clin Nutr. 2009;90:1343–50.

    CAS  PubMed  Google Scholar 

  283. Fujita S, Rasmussen BB, Cadenas JG, Grady JJ, Volpi E. Effect of insulin on human skeletal muscle protein synthesis is modulated by insulin-induced changes in muscle blood flow and amino acid availability. Am J Physiol Endocrinol Metab. 2006;291:E745–54.

    CAS  PubMed  Google Scholar 

  284. Guillet C, Delcourt I, Rance M, Giraudet C, Walrand S, Bedu M, Duche P, Boirie Y. Changes in basal and insulin and amino acid response of whole body and skeletal muscle proteins in obese men. J Clin Endocrinol Metab. 2009;94:3044–50.

    CAS  PubMed  Google Scholar 

  285. Nilsson MI, Dobson JP, Greene NP, Wiggs MP, Shimkus KL, Wudeck EV, Davis AR, Laureano ML, Fluckey JD. Abnormal protein turnover and anabolic resistance to exercise in sarcopenic obesity. FASEB J. 2003;27:3905–16.

    Google Scholar 

  286. Murton AJ, Marimuthu K, Mallinson JE, Selby AL, Smith K, Rennie MJ, Greenhaff PL. Obesity appears to be associated with altered muscle protein synthetic and breakdown responses to increased nutrient delivery in older men, but not reduced muscle mass or contractile function. Diabetes. 2015;64:3160–71.

    CAS  PubMed  Google Scholar 

  287. Fujita S, Rasmussen BB, Cadenas JG, Drummond MJ, Glynn EL, Sattler FR, Volpi E. Aerobic exercise overcomes the age-related insulin resistance of muscle protein metabolism by improving endothelial function and Akt/mammalian target of rapamycin signaling. Diabetes. 2007;56:1615–22.

    CAS  PubMed  Google Scholar 

  288. Sandri M, Barberi L, Bijlsma AY, Blaauw B, Dyar KA, Milan G, Mammucari C, Meskers CG, Pallafacchina G, Paoli A, et al. Signalling pathways regulating muscle mass in ageing skeletal muscle: the role of the IGF1-Akt-mTOR-FoxO pathway. Biogerontology. 2013;14:303–23.

    CAS  PubMed  Google Scholar 

  289. Florini JR, Ewton DZ, Coolican SA. Growth hormone and the insulin-like growth factor system in myogenesis. Endocr Rev. 1996;17:481–517.

    CAS  PubMed  Google Scholar 

  290. Hermann M, Berger P. Hormonal changes in aging men: a therapeutic indication? Exp Gerontol. 2001;36:1075–82.

    CAS  PubMed  Google Scholar 

  291. Ryall JG, Schertzer JD, Lynch GS. Cellular and molecular mechanisms underlying age-related skeletal muscle wasting and weakness. Biogerontology. 2008;9:213–28.

    CAS  PubMed  Google Scholar 

  292. Nass R, Johannsson G, Christiansen JS, Kopchick JJ, Thorner MO. The aging population—is there a role for endocrine interventions? Growth Hormon IGF Res. 2009;19:89–100.

    CAS  Google Scholar 

  293. Sakuma K, Yamaguchi A. Molecular mechanisms in aging and current strategies to counteract sarcopenia. Curr Aging Sci. 2010;3:90–101.

    CAS  PubMed  Google Scholar 

  294. van Dam PS, Smid HEC, de Vries WR, Niesink M, Bolscher E, Waasdorp EJ, Dieguez C, Casanueva FF, Koppeschaar HP. Reduction of free fatty acids by acipimox enhances the growth hormone (GH) responses to GH-releasing peptide 2 in elderly men. J Clin Endocrinol Metab. 2000;85:4706–11.

    PubMed  Google Scholar 

  295. Weltman A, Weltman JY, Veldhuis JD, Hartman ML. Body composition, physical exercise, growth hormone and obesity. Eat Weight Disord. 2001;6:28–37.

    CAS  PubMed  Google Scholar 

  296. Waters DL, Qualls CR, Dorin RI, Veldhuis JD, Baumgartner RN. Altered growth hormone, cortisol, and leptin secretion in healthy elderly persons with sarcopenia and mixed body composition phenotypes. J Gerontol A Biol Sci Med Sci. 2008;63:536–41.

    PubMed  Google Scholar 

  297. Makimura H, Feldpausch MN, Rope AM, Hemphill LC, Torriani M, Lee H, Grinspoon SK. Metabolic effects of a growth hormone-releasing factor in obese subjects with reduced growth hormone secretion: a randomized controlled trial. J Clin Endocrinol Metab. 2012;97:4769–79.

    CAS  PubMed  PubMed Central  Google Scholar 

  298. Gabriely I, Ma XH, Yang XM, Atzmon G, Rajala MW, Berg AH, Scherer P, Rossetti L, Barzilai N. Removal of visceral fat prevents insulin resistance and glucose intolerance of aging: an adipokine-mediated process? Diabetes. 2002;51:2951–8.

    CAS  PubMed  Google Scholar 

  299. McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-superfamily member. Nature. 1997;387:83–90.

    CAS  PubMed  Google Scholar 

  300. Guo T, Jou W, Chanturiya T, Portas J, Gavrilova O, McPherron AC. Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity. PLoS One. 2009;4:e4937.

    PubMed  PubMed Central  Google Scholar 

  301. Akpan I, Goncalves MD, Dhir R, Yin X, Pistilli EE, Bogdanovich S, Khurana TS, Ucran J, Lachey J, Ahima RS. The effects of a soluble activin type IIB receptor on obesity and insulin sensitivity. Int J Obes. 2009;33:1265–73.

    CAS  Google Scholar 

  302. Smith RC, Lin BK. Myostatin inhibitors as therapies for muscle wasting associated with cancer and other disorders. Curr Opin Support Palliat Care. 2013;7:352–60.

    PubMed  PubMed Central  Google Scholar 

  303. Zhang C, McFarlane C, Lokireddy S, Bonala S, Ge X, Masuda S, Gluckman PD, Sharma M, Kambadur R. Myostatin-deficient mice exhibit reduced insulin resistance through activating the AMP-activated protein kinase signalling pathway. Diabetologia. 2011;54:1491–501.

    CAS  PubMed  Google Scholar 

  304. Zhang C, McFarlane C, Lokireddy S, Masuda S, Ge X, Gluckman PD, Sharma M, Kambadur R. Inhibition of myostatin protects against diet-induced obesity by enhancing fatty acid oxidation and promoting a brown adipose phenotype in mice. Diabetologia. 2012;55:183–93.

    CAS  PubMed  Google Scholar 

  305. Lu-Nguyen NB, Jarmin SA, Saleh AF, Popplewell L, Gait MJ, Dickson G. Combination antisense treatment for destructive exon skipping of myostatin and open reading frame rescue of dystrophin in neonatal mdx mice. Mol Ther. 2015;23:1341–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  306. Allen DL, Hittel DS, McPherron AC. Expression and function of myostatin in obesity, diabetes, and exercise adaptation. Med Sci Sports Exerc. 2011;43:1828–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  307. Wagner KR, Fleckenstein JL, Amato AA, Barohn RJ, Bushby K, Escolar DM, Flanigan KM, Pestronk A, Tawil R, Wolfe GI, et al. A phase I/IItrial of MYO-029 in adult subjects with muscular dystrophy. Ann Neurol. 2008;63:561–71.

    CAS  PubMed  Google Scholar 

  308. Krivickas LS, Walsh R, Amato AA. Single muscle fiber contractile properties in adults with muscular dystrophy treated with MYO-029. Muscle Nerve. 2009;39:3–9.

    CAS  PubMed  Google Scholar 

  309. Hinkle RT, Donnelly E, Cody DB, Bauer MB, Isfort RJ. Urocortin II treatment reduces skeletal muscle mass and function loss during atrophy and increases nonatrophying skeletal muscle mass and function. Endocrinology. 2003;144:4939–46.

    CAS  PubMed  Google Scholar 

  310. Chen A, Brar B, Choi CS, Rousso D, Vaughan J, Kuperman Y, Kim SN, Donaldson C, Smith SM, Jamieson P, et al. Urocortin 2 modulates glucose utilization and insulin sensitivity in skeletal muscle. Proc Natl Acad Sci U S A. 2006;103:16580–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  311. Bale TL, Anderson KR, Roberts AJ, Lee KF, Nagy TR, Vale WW. Corticotropin-releasing factor receptor-2-deficient mice display abnormal homeostatic responses to challenges of increased dietary fat and cold. Endocrinology. 2003;144:2580–7.

    CAS  PubMed  Google Scholar 

  312. Jamieson PM, Cleasby ME, Kuperman Y, Morton NM, Kelly PA, Brownstein DG, Mustard KJ, Vaughan JM, Carter RN, Hahn CN, et al. Urocortin 3 transgenic mice exhibit a metabolically favourable phenotype resisting obesity and hyperglycaemia on a high-fat diet. Diabetologia. 2011;54:2392–403.

    CAS  PubMed  PubMed Central  Google Scholar 

  313. Roustit MM, Vaughan JM, Jamieson PM, Cleasby ME. Urocortin 3 activates AMPK and Akt pathways and enhances glucose disposal in rat skeletal muscle. J Endocrinol. 2014;223:143–54.

    CAS  PubMed  PubMed Central  Google Scholar 

  314. Simões e Silva S, Silveira KD, Ferreira AJ, Teixeira MM. ACE2, angiotensin-(1-7) and Mas receptor axis in inflammation and fibrosis. Br J Pharmacol. 2013;169(3):477–92.

    PubMed  PubMed Central  Google Scholar 

  315. Cabello-Verrugio C, Morales MG, Rivera JC, Cabrera D, Simon F. Renin-angiotensin system: an old player with novel functions in skeletal muscle. Med Res Rev. 2015;35:437–63.

    CAS  PubMed  Google Scholar 

  316. Ábrigo J, Simon F, Cabrera D, Cabello-Verrugio C. Angiotensin-(1-7) prevents skeletal muscle atrophy induced by transforming growth factor type beta (TGF-ß) via Mas receptor activation. Cell Physiol Biochem. 2016;40:27–38.

    PubMed  Google Scholar 

  317. Morales MG, Abrigo J, Acuña MJ, Santos RA, Bader M, Brandan E, Simon F, Olguin H, Cabrera D, Cabello-Verrugio C. Angiotensin-(1-7) attenuates disuse skeletal muscle atrophy in mice via its receptor. Mas Dis Model Mech. 2016;9:441–9.

    CAS  PubMed  Google Scholar 

  318. Marcus Y, Shefer G, Sasson K, Kohen F, Limor R, Pappo O, Nevo N, Biton I, Bach M, Berkutzki T, et al. Angiotensin 1-7 as means to prevent the metabolic syndrome: lessons from the fructose-fed rat model. Diabetes. 2013;62:1121–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  319. Carter CS, Onder G, Kritchevsky SB, Pahor M. Angiotensin-converting enzyme inhibition intervention in elderly persons: effects on body composition and physical performance. J Gerontol A Biol Sci Med Sci. 2005;60:1437–46.

    PubMed  Google Scholar 

  320. Sartiani L, Spinelli V, Laurino A, Blescia S, Raimondi L, Cerbai E, Mugelli A. Pharmacological perspectives in sarcopenia: a potential role for renin-angiotensin system blockers? Clin Cases Miner Bone Metab. 2015;12:135–8.

    PubMed  PubMed Central  Google Scholar 

  321. Dillon EL, Durham WJ, Urban RJ, Sheffield-Moore M. Hormone treatment and muscle anabolism during aging: androgens. Clin Nutr. 2010;29:697–700.

    CAS  PubMed  PubMed Central  Google Scholar 

  322. Narayanan R, Mohler ML, Bohl CE, Miller DD, Dalton JT. Selective androgen receptor modulators in preclinical and clinical development. Nucl Recept Signal. 2008;6:e010.

    PubMed  PubMed Central  Google Scholar 

  323. Siparsky P, Kirkendall D, Garrett W Jr. Muscle changes in aging: understanding sarcopenia. Sports Health. 2014;6(1):36–40.

    PubMed  PubMed Central  Google Scholar 

  324. Clark AL, Coats AJS, Krum H, et al. Effect of beta-adrenergic blockade with carvedilol on cachexia in severe chronic heart failure: results from the COPERNICUS trial. J Cachexia Sarcopenia Muscle. 2017;8:549–56.

    PubMed  PubMed Central  Google Scholar 

  325. Mochamat H, Cuhls M, Marinova S, et al. A systematic review on the role of vitamins, minerals, proteins, and other supplements for the treatment of cachexia in cancer: a European Palliative Care Research Centre cachexia project. J Cachexia Sarcopenia Muscle. 2017;8:25–39.

    CAS  PubMed  Google Scholar 

  326. Hojan K, Milecki P, Molinska-Glura M, Roszak A, Leszczynski P. Effect of physical activity on bone strength and body composition in breast cancer premenopausal women during endocrine therapy. Eur J Phys Rehabil Med. 2013;49:331–9.

    CAS  PubMed  Google Scholar 

  327. Galvão DA, Taaffe DR, Spry N, Joseph D, Newton RU. Combined resistance and aerobic exercise program reverses muscle loss in men undergoing androgen suppression therapy for prostate cancer without bone metastases: a randomized controlled trial. J Clin Oncol. 2010;28:340–7.

    PubMed  Google Scholar 

  328. Dal Negro RW, Aquilani R, Bertacco S, Boschi F, Micheletto C, Tognella S. Comprehensive effects of supplemented essential amino acids in patients with severe COPD and sarcopenia. Monaldi Arch Chest Dis. 2010;73:25–33.

    CAS  PubMed  Google Scholar 

  329. Moon SJ, Kim TH, Yoon SY, Chung JH, Hwang HJ. Relationship between stage of chronic kidney disease and sarcopenia in Korean aged 40 years and older using the Korea National Health and Nutrition Examination Surveys (KNHANES IV- 2, 3, and V- 1, 2), 2008–2011. PLoS One. 2015;10:e0130740.

    PubMed  PubMed Central  Google Scholar 

  330. Hirai K, Ookawara S, Morishita Y. Sarcopenia and physical inactivity in patients with chronic kidney disease. Nephrourol Mon. 2016;8:e37443.

    PubMed  PubMed Central  Google Scholar 

  331. Rossi AP, Burris DD, Lucas FL, Crocker GA, Wasserman JC. Effects of a renal rehabilitation exercise program in patients with CKD: a randomized, controlled trial. Clin J Am Soc Nephrol. 2014;9:2052–8.

    PubMed  PubMed Central  Google Scholar 

  332. Fülster S, Tacke M, Sandek A, et al. Muscle wasting in patients with chronic heart failure: results from the studies investigating comorbidities aggravating heart failure (SICA-HF). Eur Heart J. 2013;34:512–9.

    PubMed  Google Scholar 

  333. Rozentryt P, von Haehling S, Lainscak M, et al. The effects of a high-caloric protein-rich oral nutritional supplement in patients with chronic heart failure and cachexia on quality of life, body composition, and inflammation markers: a randomized, double-blind pilot study. J Cachexia Sarcopenia Muscle. 2010;1:35–42.

    PubMed  PubMed Central  Google Scholar 

  334. Lenk K, Erbs S, Höllriegel R, et al. Exercise training leads to a reduction of elevated myostatin levels in patients with chronic heart failure. Eur J Prev Cardiol. 2012;19:404–11.

    PubMed  Google Scholar 

  335. Cunha TF, Bacurau AV, Moreira JB, et al. Exercise training prevents oxidative stress and ubiquitin-proteasome system overactivity and reverse skeletal muscle atrophy in heart failure. PLoS One. 2012;7:e41701.

    CAS  PubMed  PubMed Central  Google Scholar 

  336. Caminiti G, Volterrani M, Iellamo F, et al. Effect of long acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study. J Am Coll Cardiol. 2009;54:919–27.

    CAS  PubMed  Google Scholar 

  337. Kenny AM, Kleppinger A, Annis K, et al. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels, low bone mass, and physical frailty. J Am Geriatr Soc. 2010;58:1134–43.

    PubMed  PubMed Central  Google Scholar 

  338. Park JH, Park KH, Cho S, et al. Concomitant increase in muscle strength and bone mineral density with decreasing IL- 6 levels after combination therapy with alendronate and calcitriol in postmenopausal women. Menopause. 2013;20:747–53.

    PubMed  Google Scholar 

  339. Arai H, Wakabayashi H, Yoshimura Y, Yamada M, Kim H, Harada A. Treatment of sarcopenia. Geriatr Gerontol Int. 2018;18(Suppl. 1):28–44.

    PubMed  Google Scholar 

  340. Bohannon RW. Reference values for the five-repetition sit-to-stand test: a descriptive meta-analysis of data from elders. Percept Mot Skills. 2006;103(1):215–22.

    PubMed  Google Scholar 

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  1. Canterbury Christ Church University, Canterbury, Kent, UK

    Yasser El Miedany

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    Yasser El Miedany

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El Miedany, Y. (2022). Osteosarcopenia. In: El Miedany, Y. (eds) New Horizons in Osteoporosis Management. Springer, Cham. https://doi.org/10.1007/978-3-030-87950-1_3

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