Musculoskeletal frailty: A geriatric syndrome at the core of fracture occurrence in older age

Calcified Tissue International

Volumn 91, Issue 3, 2012, Pages 161-177

  Gielen, E ^a   Verschueren, S ^a   O'Neill, T W ^b   Pye, S R ^b   O'Connell, M D L ^b   Lee, D M ^b   Ravindrarajah, R ^b   Claessens, F ^a   Laurent, M ^a   Milisen, K ^a   Tournoy, J ^a   Dejaeger, M ^a   Wu, F C ^b   Vanderschueren, D ^a   Boonen, S ^a  

^a UNIVERSITY OF LEUVEN   (Belgium)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

Author keywords

Comprehensive geriatric assessment; Frailty; Muscle mass; Muscle strength; Osteoporotic fracture; Sarcopenia

Indexed keywords

ANDROGEN; CALCIUM; CAROTENOID; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; GROWTH HORMONE; GROWTH HORMONE SECRETAGOGUE; ICOSAPENTAENOIC ACID; PROTEIN INHIBITOR; SELECTIVE ANDROGEN RECEPTOR MODULATOR; TESTOSTERONE; URSOLIC ACID; VITAMIN D;

AGING; ARTHRALGIA; BONE DENSITY; CARPAL TUNNEL SYNDROME; CLINICAL EFFECTIVENESS; DISEASE COURSE; DOSE RESPONSE; DRUG EFFECT; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; EDEMA; ELDERLY CARE; EVIDENCE BASED MEDICINE; FALL RISK ASSESSMENT; FRAGILITY FRACTURE; FRAIL ELDERLY; GERIATRIC DISORDER; GROWTH HORMONE DEFICIENCY; GYNECOMASTIA; HORMONE SUBSTITUTION; HUMAN; MUSCLE ATROPHY; MUSCLE MASS; MUSCLE STRENGTH; NONHUMAN; OBESITY; PHENOTYPIC VARIATION; PHYSICAL ACTIVITY; PRIORITY JOURNAL; PROTEIN DIET; RESISTANCE TRAINING; REVIEW; SOFT TISSUE DISEASE; TREATMENT PLANNING; UNSPECIFIED SIDE EFFECT; VITAMIN D DEFICIENCY;

AGED; AGED, 80 AND OVER; AGING; FRACTURES, BONE; FRAIL ELDERLY; HUMANS; MUSCLE WEAKNESS; PHENOTYPE; SARCOPENIA; SYNDROME;

EID: 84866042229     PISSN: 0171967X     EISSN: 14320827     Source Type: Journal    
DOI: 10.1007/s00223-012-9622-5     Document Type: Review

References (159)

1. Walston J, Hadley EC, Ferrucci L, Guralnik JM, Newman AB, Studenski SA, Ershler WB, Harris T, Fried LP (2006) Research agenda for frailty in older adults: toward a better understanding of physiology and etiology: summary from the American geriatrics society/national institute on aging research conference on frailty in older adults. J Am Geriatr Soc 54:991-1001
2. Rosenberg IH (1989) Summary comments. Am J Clin Nutr 50:3
3. Baumgartner RN, Koehler KM, Gallagher D, Romero L, Heymsfield SB, Ross RR, Garry PJ, Lindeman RD (1998) Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol 147:755-763
4. Janssen I (2006) Influence of sarcopenia on the development of physical disability: the cardiovascular health study. J Am Geriatr Soc 54:56-62
5. Visser M, Goodpaster BH, Kritchevsky SB, Newman AB, Nevitt M, Rubin SM, Simonsick EM, Harris TB (2005) Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons. J Gerontol A Biol Sci Med Sci 60:324-333
6. Szulc P, Beck TJ, Marchand F, Delmas PD (2005) Low skeletal muscle mass is associated with poor structural parameters of bone and impaired balance in elderly men-the MINOS study. J Bone Miner Res 20:721-729
7. Landi F, Liperoti R, Russo A, Giovannini S, Tosato M, Capoluongo E, Bernabei R, Onder G (2012) Sarcopenia as a risk factor for falls in elderly individuals: results from the ilSIRENTE study. Clin Nutr 96:1150-1163
8. Lang TF, Cauley J, Tylavsky F, Bauer D, Cummings S, Harris T (2010) Computed tomography measurements of thigh muscle cross-sectional area and attenuation coefficient predict hip fracture: the health, aging and body composition study. J Bone Miner Res 25:513-519
9. Landi F, Liperoti R, Fusco D, Mastropaolo S, Quattrociocchi D, Proia A, Tosato M, Bernabei R, Onder G (2012) Sarcopenia and mortality among older nursing home residents. J Am Med Dir Assoc 13:121-126
10. Lang T, Streeper T, Cawthon P, Baldwin K, Taaffe DR, Harris TB (2010) Sarcopenia: etiology, clinical consequences, intervention, and assessment. Osteoporos Int 21:543-559
11. Gallagher D, Visser M, De Meersman RE, Sepulveda D, Baumgartner RN, Pierson RN, Harris T, Heymsfield SB (1997) Appendicular skeletal muscle mass: effects of age, gender, and ethnicity. J Appl Physiol 83:229-239
12. Doherty TJ (2003) Invited review: aging and sarcopenia. J Appl Physiol 95:1717-1727
13. Janssen I, Heymsfield SB, Wang ZM, Ross R (2000) Skeletal muscle mass and distribution in 468 men and women aged 18-88 yr. J Appl Physiol 89:81-88
14. Beyer I, Njemini R, Bautmans I, Demanet C, Bergmann P, Mets T (2012) Inflammation-related muscle weakness and fatigue in geriatric patients. Exp Gerontol 47:52-59
15. Cesari M, Kritchevsky SB, Baumgartner RN, Atkinson HH, Penninx BW, Lenchik L, Palla SL, Ambrosius WT, Tracy RP, Pahor M (2005) Sarcopenia, obesity, and inflammation-results from the trial of angiotensin converting enzyme inhibition and novel cardiovascular risk factors study. Am J Clin Nutr 82: 428-434
16. Szulc P, Duboeuf F, Marchand F, Delmas PD (2004) Hormonal and lifestyle determinants of appendicular skeletal muscle mass in men: the MINOS study. Am J Clin Nutr 80:496-503
17. Araujo AB, Travison TG, Bhasin S, Esche GR, Williams RE, Clark RV, McKinlay JB (2008) Association between testosterone and estradiol and age-related decline in physical function in a diverse sample of men. J Am Geriatr Soc 56:2000-2008
18. Visser M, Deeg DJ, Lips P (2003) Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the longitudinal aging study Amsterdam. J Clin Endocrinol Metab 88:5766-5772
19. Perrini S, Laviola L, Carreira MC, Cignarelli A, Natalicchio A, Giorgino F (2010) The GH/IGF1 axis and signaling pathways in the muscle and bone: mechanisms underlying age-related skeletal muscle wasting and osteoporosis. J Endocrinol 205:201-210
20. Abbatecola AM, Paolisso G, Fattoretti P, Evans WJ, Fiore V, Dicioccio L, Lattanzio F (2011) Discovering pathways of sarcopenia in older adults: a role for insulin resistance on mitochondria dysfunction. J Nutr Health Aging 15:890-895
21. Abbatecola AM, Paolisso G (2008) Is there a relationship between insulin resistance and frailty syndrome? Curr Pharm Des 14:405-410
22. Marzetti E, Leeuwenburgh C (2006) Skeletal muscle apoptosis, sarcopenia and frailty at old age. Exp Gerontol 41:1234-1238
23. Morley JE, Anker SD, Evans WJ (2009) Cachexia and aging: an update based on the fourth international cachexia meeting. J Nutr Health Aging 13:47-55
24. Clark BC, Manini TM (2008) Sarcopenia =/= dynapenia. J Gerontol A Biol Sci Med Sci 63:829-834
25. Manini TM, Clark BC (2012) Dynapenia and aging: an update. J Gerontol A Biol Sci Med Sci 67:28-40
26. Hughes VA, Frontera WR, Wood M, Evans WJ, Dallal GE, Roubenoff R, Singh MAF (2001) Longitudinal muscle strength changes in older adults: influence of muscle mass, physical activity, and health. J Gerontol A Biol Sci Med Sci 56:B209-B217
27. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel JP, Rolland Y, Schneider SM, Topinkova E, Vandewoude M, Zamboni M (2010) Sarcopenia: European consensus on definition and diagnosis: report of the European working group on sarcopenia in older People. Age Ageing 39:412-423
28. Kyle UG, Genton L, Karsegard L, Slosman DO, Pichard C (2001) Single prediction equation for bioelectrical impedance analysis in adults aged 20-94 years. Nutrition 17:248-253
29. Fielding RA, Vellas B, Evans WJ, Bhasin S, Morley JE, Newman AB, van Kan GA, Andrieu S, Bauer J, Breuille D, Cederholm T, Chandler J, De Meynard C, Donini L, Harris T, Kannt A, Guibert FK, Onder G, Papanicolaou D, Rolland Y, Rooks D, Sieber C, Souhami E, Verlaan S, Zamboni M (2011) Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc 12:249-256
30. Muscaritoli M, Anker SD, Argiles J, Aversa Z, Bauer JM, Biolo G, Boirie Y, Bosaeus I, Cederholm T, Costelli P, Fearon KC, Laviano A, Maggio M, Fanelli FR, Schneider SM, Schols A, Sieber CC (2010) Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by special interest groups (SIG) "cachexia-anorexia in chronic wasting diseases" and "nutrition in geriatrics". Clin Nutr 29:154-159
31. Morley JE, Abbatecola AM, Argiles JM, Baracos V, Bauer J, Bhasin S, Cederholm T, Coats AJ, Cummings SR, Evans WJ, Fearon K, Ferrucci L, Fielding RA, Guralnik JM, Harris TB, Inui A, Kalantar-Zadeh K, Kirwan BA, Mantovani G, Muscaritoli M, Newman AB, Rossi-Fanelli F, Rosano GM, Roubenoff R, Schambelan M, Sokol GH, Storer TW, Vellas B, von Haehling S, Yeh SS, Anker SD (2011) Sarcopenia with limited mobility: an international consensus. J Am Med Dir Assoc 12:403-409
32. Newman AB, Kupelian V, Visser M, Simonsick EM, Goodpaster BH, Kritchevsky SB, Tylavsky FA, Rubin SM, Harris TB (2006) Strength, but not muscle mass, is associated with mortality in the health, aging and body composition study cohort. J Gerontol A Biol Sci Med Sci 61:72-77
33. Puthoff ML, Nielsen DH (2007) Relationships among impairments in lower-extremity strength and power, functional limitations, and disability in older adults. Phys Ther 87:1334-1347
34. Foldvari M, Clark M, Laviolette LC, Bernstein MA, Kaliton D, Castaneda C, Pu CT, Hausdorff JM, Fielding RA, Singh MA (2000) Association of muscle power with functional status in community-dwelling elderly women. J Gerontol A Biol Sci Med Sci 55:M192-M199
35. Skelton DA, Greig CA, Davies JM, Young A (1994) Strength, power and related functional ability of healthy people aged 65-89 years. Age Ageing 23:371-377
36. Bean JF, Kiely DK, Herman S, Leveille SG, Mizer K, Frontera WR, Fielding RA (2002) The relationship between leg power and physical performance in mobility-limited older people. J Am Geriatr Soc 50:461-467
37. Bean JF, Leveille SG, Kiely DK, Bandinelli S, Guralnik JM, Ferrucci L (2003) A comparison of leg power and leg strength within the InCHIANTI study: which influences mobility more? J Gerontol A Biol Sci Med Sci 58:728-733
38. Lauretani F, Russo CR, Bandinelli S, Bartali B, Cavazzini C, Di Iorio A, Corsi AM, Rantanen T, Guralnik JM, Ferrucci L (2003) Age-associated changes in skeletal muscles and their effect on mobility: an operational diagnosis of sarcopenia. J Appl Physiol 95:1851-1860
39. Marsh AP, Miller ME, Saikin AM, Rejeski WJ, Hu N, Lauretani F, Bandinelli S, Guralnik JM, Ferrucci L (2006) Lower extremity strength and power are associated with 400-meter walk time in older adults: the InCHIANTI study. J Gerontol A Biol Sci Med Sci 61:1186-1193
40. Fiatarone MA, O'Neill EF, Ryan ND, Clements KM, Solares GR, Nelson ME, Roberts SB, Kehayias JJ, Lipsitz LA, Evans WJ (1994) Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med 330: 1769-1775
41. Bean JF, Kiely DK, LaRose S, O'Neill E, Goldstein R, Frontera WR (2009) Increased velocity exercise specific to task training versus the National institute on aging's strength training program: changes in limb power and mobility. J Gerontol A Biol Sci Med Sci 64:983-991
42. Hedayati KK, Dittmar M (2010) Prevalence of sarcopenia among older community-dwelling people with normal health and nutritional state. Ecol Food Nutr 49:9
43. Iannuzzi-Sucich M, Prestwood KM, Kenny AM (2002) Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women. J Gerontol A Biol Sci Med Sci 57:M772-M777
44. Baumgartner RN (2000) Body composition in healthy aging. Ann N Y Acad Sci 904:437-448
45. Stenholm S, Harris TB, Rantanen T, Visser M, Kritchevsky SB, Ferrucci L (2008) Sarcopenic obesity: definition, cause and consequences. Curr Opin Clin Nutr Metab Care 11:693-700
46. Stenholm S, Rantanen T, Heliovaara M, Koskinen S (2008) The mediating role of C-reactive protein and handgrip strength between obesity and walking limitation. J Am Geriatr Soc 56:462-469
47. Rantanen T, Harris T, Leveille SG, Visser M, Foley D, Masaki K, Guralnik JM (2000) Muscle strength and body mass index as long-term predictors of mortality in initially healthy men. J Gerontol A Biol Sci Med Sci 55:M168-M173
48. National Institute on Aging Baltimore (1958-1998) Longitudinal study of aging. Selected findings from 1978-1998. http://www.grc.nia.nih.gov/branches/ blsa/blsafindings.pdf. Accessed 1 Sep 2005
49. Gondo Y, Hirose N, Arai Y, Inagaki H, Masui Y, Yamamura K, Shimizu K, Takayama M, Ebihara Y, Nakazawa S, Kitagawa K (2006) Functional status of centenarians in Tokyo, Japan: developing better phenotypes of exceptional longevity. J Gerontol A Biol Sci Med Sci 61:305-310
50. Woods NF, LaCroix AZ, Gray SL, Aragaki A, Cochrane BB, Brunner RL, Masaki K, Murray A, Newman AB (2005) Frailty: emergence and consequences in women aged 65 and older in the Women's health initiative observational study. J Am Geriatr Soc. 53:1321-1330
51. Ensrud KE, Ewing SK, Cawthon PM, Fink HA, Taylor BC, Cauley JA, Dam TT, Marshall LM, Orwoll ES, Cummings SR (2009) A comparison of frailty indexes for the prediction of falls, disability, fractures, and mortality in older men. J Am Geriatr Soc 57:492-498
52. Ensrud KE, Ewing SK, Taylor BC, Fink HA, Cawthon PM, Stone KL, Hillier TA, Cauley JA, Hochberg MC, Rodondi N, Tracy JK, Cummings SR (2008) Comparison of 2 frailty indexes for prediction of falls, disability, fractures, and death in older women. Arch Intern Med 168:382-389
53. Rolland Y, Van Kan GA, Gillette-Guyonnet S, Roux C, Boonen S, Vellas B (2011) Strontium ranelate and risk of vertebral fractures in frail osteoporotic women. Bone 48:332-338
54. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA (2001) Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 56:M146-M156
55. Bandeen-Roche K, Xue QL, Ferrucci L, Walston J, Guralnik JM, Chaves P, Zeger SL, Fried LP (2006) Phenotype of frailty: characterization in the women's health and aging studies. J Gerontol A Biol Sci Med Sci 61:262-266
56. Rockwood K, Mitnitski A, Song X, Steen B, Skoog I (2006) Long-term risks of death and institutionalization of elderly people in relation to deficit accumulation at age 70. J Am Geriatr Soc 54:975-979
57. Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G (2004) Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J Gerontol A Biol Sci Med Sci 59:255-263
58. Fried LP, Darer J, Walston J (2003) Frailty. Springer-Verlag, New York
59. Binkley N, Buehring B (2009) Beyond FRAX: it's time to consider "sarco-osteopenia". J Clin Densitom 12:413-416
60. Bortz WM 2nd (2002) A conceptual framework of frailty: a review. J Gerontol A Biol Sci Med Sci 57:M283-M288
61. Haentjens P, Magaziner J, Colon-Emeric CS, Vanderschueren D, Milisen K, Velkeniers B, Boonen S (2010) Meta-analysis: excess mortality after hip fracture among older women and men. Ann Intern Med 152:380-390
62. Boonen S, Autier P, Barette M, Vanderschueren D, Lips P, Haentjens P (2004) Functional outcome and quality of life following hip fracture in elderly women: a prospective controlled study. Osteoporos Int 15:87-94
63. Kanapuru B, Ershler WB (2009) Inflammation, coagulation, and the pathway to frailty. Am J Med 122:605-613
64. Walston J, McBurnie MA, Newman A, Tracy RP, Kop WJ, Hirsch CH, Gottdiener J, Fried LP (2002) Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the cardiovascular health study. Arch Intern Med 162:2333-2341
65. Barzilay JI, Blaum C, Moore T, Xue QL, Hirsch CH, Walston JD, Fried LP (2007) Insulin resistance and inflammation as precursors of frailty: the cardiovascular health study. Arch Intern Med 167:635-641
66. Reiner AP, Aragaki AK, Gray SL, Wactawski-Wende J, Cauley JA, Cochrane BB, Kooperberg CL, Woods NF, LaCroix AZ (2009) Inflammation and thrombosis biomarkers and incident frailty in postmenopausal women. Am J Med 122: 947-954
67. Wu IC, Shiesh SC, Kuo PH, Lin XZ (2009) High oxidative stress is correlated with frailty in elderly Chinese. J Am Geriatr Soc 57:1666-1671
68. Mulero J, Zafrilla P, Martinez-Cacha A (2011) Oxidative stress, frailty and cognitive decline. J Nutr Health Aging 15:756-760
69. Ho YY, Matteini AM, Beamer B, Fried L, Xue QL, Arking DE, Chakravarti A, Fallin MD, Walston J (2011) Exploring biologically relevant pathways in frailty. J Gerontol A Biol Sci Med Sci 66:975-979
70. Mohr BA, Bhasin S, Kupelian V, Araujo AB, O'Donnell AB, McKinlay JB (2007) Testosterone, sex hormone-binding globulin, and frailty in older men. J Am Geriatr Soc 55:548-555
71. Tajar A, O'Connell MD, Mitnitski AB, O'Neill TW, Searle SD, Huhtaniemi IT, Finn JD, Bartfai G, Boonen S, Casanueva FF, Forti G, Giwercman A, Han TS, Kula K, Labrie F, Lean ME, Pendleton N, Punab M, Silman AJ, Vanderschueren D, Rockwood K, Wu FC (2011) Frailty in relation to variations in hormone levels of the hypothalamic-pituitary-testicular axis in older men: results from the European male aging study. J Am Geriatr Soc 59:814-821
72. Hyde Z, Flicker L, Almeida OP, Hankey GJ, McCaul KA, Chubb SA, Yeap BB (2010) Low free testosterone predicts frailty in older men: the health in men study. J Clin Endocrinol Metab 95:3165-3172
73. Travison TG, Nguyen AH, Naganathan V, Stanaway FF, Blyth FM, Cumming RG, Le Couteur DG, Sambrook PN, Handelsman DJ (2011) Changes in reproductive hormone concentrations predict the prevalence and progression of the frailty syndrome in older men: the concord health and ageing in men project. J Clin Endocrinol Metab 96:2464-2474
74. Cawthon PM, Ensrud KE, Laughlin GA, Cauley JA, Dam TT, Barrett-Connor E, Fink HA, Hoffman AR, Lau E, Lane NE, Stefanick ML, Cummings SR, Orwoll ES (2009) Sex hormones and frailty in older men: the osteoporotic fractures in men (MrOS) study. J Clin Endocrinol Metab 94:3806-3815
75. Perez-Lopez FR, Chedraui P, Fernandez-Alonso AM (2011) Vitamin D and aging: beyond calcium and bone metabolism. Maturitas 69:27-36
76. Ensrud KE, Ewing SK, Fredman L, Hochberg MC, Cauley JA, Hillier TA, Cummings SR, Yaffe K, Cawthon PM (2010) Circulating 25-hydroxyvitamin D levels and frailty status in older women. J Clin Endocrinol Metab 95:5266-5273
77. Ensrud KE, Blackwell TL, Cauley JA, Cummings SR, Barrett- Connor E, Dam TT, Hoffman AR, Shikany JM, Lane NE, Stefanick ML, Orwoll ES, Cawthon PM (2011) Circulating 25-hydroxyvitamin D levels and frailty in older men: the osteoporotic fractures in men study. J Am Geriatr Soc 59:101-106
78. Shardell M, Hicks GE, Miller RR, Kritchevsky S, Andersen D, Bandinelli S, Cherubini A, Ferrucci L (2009) Association of low vitamin D levels with the frailty syndrome in men and women. J Gerontol A Biol Sci Med Sci 64:69-75
79. Lips P (2006) Vitamin D physiology. Progr Biophys Mol Biol 92:4-8
80. Blaum CS, Xue QL, Michelon E, Semba RD, Fried LP (2005) The association between obesity and the frailty syndrome in older women: the women's health and aging studies. J Am Geriatr Soc 53:927-934
81. Hubbard RE, Lang IA, Llewellyn DJ, Rockwood K (2010) Frailty, body mass index, and abdominal obesity in older people. J Gerontol A Biol Sci Med Sci 65:377-381
82. Fried LP, Borhani NO, Enright P, Furberg CD, Gardin JM, Kronmal RA, Kuller LH, Manolio TA, Mittelmark MB, Newman A et al (1991) The cardiovascular health study: design and rationale. Ann Epidemiol 1:263-276
83. Cawthon PM, Marshall LM, Michael Y, Dam TT, Ensrud KE, Barrett-Connor E, Orwoll ES (2007) Frailty in older men: prevalence, progression, and relationship with mortality. J Am Geriatr Soc 55:1216-1223
84. Ble A, Cherubini A, Volpato S, Bartali B, Walston JD, Windham BG, Bandinelli S, Lauretani F, Guralnik JM, Ferrucci L (2006) Lower plasma vitamin E levels are associated with the frailty syndrome: the InCHIANTI study. J Gerontol A Biol Sci Med Sci 61:278-283
85. Santos-Eggimann B, Cuenoud P, Spagnoli J, Junod J (2009) Prevalence of frailty in middle-aged and older communitydwelling Europeans living in 10 countries. J Gerontol A Biol Sci Med Sci 64:675-681
86. Romero-Ortuno R, Walsh CD, Lawlor BA, Kenny RA (2010) A frailty instrument for primary care: findings from the survey of health, ageing and retirement in Europe (SHARE). BMC Geriatr 10:57
87. Rolfson DB, Majumdar SR, Tsuyuki RT, Tahir A, Rockwood K (2006) Validity and reliability of the Edmonton frail scale. Age Ageing 35:526-529
88. Bergman H, Béland F, Karunananthan S, Hummel S, Hogan D, Wolfson C (2004) Développement d'un cadre de travail pour comprendre et étudier la fragilité. Gerontol Soc 109:15
89. Strawbridge WJ, Shema SJ, Balfour JL, Higby HR, Kaplan GA (1998) Antecedents of frailty over three decades in an older cohort. J Gerontol B Psychol Sci Soc Sci 53:S9-S16
90. Avila-Funes JA, Amieva H, Barberger-Gateau P, Le Goff M, Raoux N, Ritchie K, Carriere I, Tavernier B, Tzourio C, Gutierrez-Robledo LM, Dartigues JF (2009) Cognitive impairment improves the predictive validity of the phenotype of frailty for adverse health outcomes: the three-city study. J Am Geriatr Soc 57:453-461
91. Rockwood K, Mitnitski A (2007) Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci 62:722-727
92. Searle SD, Mitnitski A, Gahbauer EA, Gill TM, Rockwood K (2008) A standard procedure for creating a frailty index. BMC Geriatr 8:24
93. van Kan GA, Rolland Y, Houles M, Gillette-Guyonnet S, Soto M, Vellas B (2010) The assessment of frailty in older adults. Clin Geriatr Med 26:275-286
94. Rockwood K, Andrew M, Mitnitski A (2007) A comparison of two approaches to measuring frailty in elderly people. J Gerontol A Biol Sci Med Sci 62:738-743
95. Abellan van Kan G, Rolland Y, Bergman H, Morley JE, Kritchevsky SB, Vellas B (2008) The IANA ask force on frailty assessment of older people in clinical practice. J Nutr Health Aging 12:29-37
96. Cigolle CT, Ofstedal MB, Tian Z, Blaum CS (2009) Comparing models of frailty: the health and retirement study. J Am Geriatr Soc 57:830-839
97. van Iersel MB, Rikkert MG (2006) Frailty criteria give heterogenous results when applied in clinical practice. J Am Geriatr Soc 54:728-729
98. Hubbard RE, O'Mahony MS, Woodhouse KW (2009) Characterising frailty in the clinical setting-a comparison of different approaches. Age Ageing 38:115-119
99. Cooper C, Dere W, Evans W, Kanis JA, Rizzoli R, Sayer AA, Sieber CC, Kaufman JM, Abellan van Kan G, Boonen S, Adachi J, Mitlak B, Tsouderos Y, Rolland Y, Reginster JY (2012) Frailty and sarcopenia: definitions and outcome parameters. Osteoporos Int 23(7):1839-1848
100. Rockwood K (2005) What would make a definition of frailty successful? Age Ageing 34:432-434
101. Gobbens RJ, Luijkx KG, Wijnen-Sponselee MT, Schols JM (2010) Toward a conceptual definition of frail community dwelling older people. Nurs Outlook 58:76-86
102. Rolland Y, Abellan van Kan G, Benetos A, Blain H, Bonnefoy M, Chassagne P, Jeandel C, Laroche M, Nourhashemi F, Orcel P, Piette F, Ribot C, Ritz P, Roux C, Taillandier J, Tremollieres F, Weryha G, Vellas B (2008) Frailty, osteoporosis and hip fracture: causes, consequences and therapeutic perspectives. J Nutr Health Aging 12:335-346
103. Gill TM, Gahbauer EA, Allore HG, Han L (2006) Transitions between frailty states among community-living older persons. Arch Intern Med 166:418-423
104. Theou O, Stathokostas L, Roland KP, Jakobi JM, Patterson C, Vandervoort AA, Jones GR (2011) The effectiveness of exercise interventions for the management of frailty: a systematic review. J Aging Res 2011:569194
105. Liu CJ, Latham NK (2009) Progressive resistance strength training for improving physical function in older adults. Cochrane Database Syst Rev 3:CD002759
106. Fielding RA, LeBrasseur NK, Cuoco A, Bean J, Mizer K, Fiatarone Singh MA (2002) High-velocity resistance training increases skeletal muscle peak power in older women. J Am Geriatr Soc 50:655-662
107. Roelants M, Delecluse C, Verschueren SM (2004) Whole-bodyvibration training increases knee-extension strength and speed of movement in older women. J Am Geriatr Soc 52:901-908
108. Bogaerts A, Delecluse C, Claessens AL, Coudyzer W, Boonen S, Verschueren SM (2007) Impact of whole-body vibration training versus fitness training on muscle strength and muscle mass in older men: a 1-year randomized controlled trial. J Gerontol A Biol Sci Med Sci 62:630-635
109. Howe TE, Shea B, Dawson LJ, Downie F, Murray A, Ross C, Harbour RT, Caldwell LM, Creed G (2011) Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database Syst Rev 7:CD000333
110. Whiteford J, Ackland T, Dhaliwal S, James A, Woodhouse J, Price R (2010) Effects of a 1-year randomized controlled trial of resistance training on lower limb bone and muscle structure and function in older men. Osteoporos Int 21:8
111. Wysocki A, Butler M, Shamliyan T, Kane RL (2011) Wholebody vibration therapy for osteoporosis: state of the science. Ann Intern Med 155(680-686):W206-W613
112. Sattler FR, Castaneda-Sceppa C, Binder EF, Schroeder ET, Wang Y, Bhasin S, Kawakubo M, Stewart Y, Yarasheski KE, Ulloor J, Colletti P, Roubenoff R, Azen SP (2009) Testosterone and growth hormone improve body composition and muscle performance in older men. J Clin Endocrinol Metab 94:1991-2001
113. Morley JE (2010) Anabolic steroids and frailty. J Am Med Dir Assoc 11:533-536
114. Srinivas-Shankar U, Roberts SA, Connolly MJ, O'Connell MD, Adams JE, Oldham JA, Wu FC (2010) Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 95:639-650
115. Travison TG, Basaria S, Storer TW, Jette AM, Miciek R, Farwell WR, Choong K, Lakshman K, Mazer NA, Coviello AD, Knapp PE, Ulloor J, Zhang A, Brooks B, Nguyen AH, Eder R, LeBrasseur N, Elmi A, Appleman E, Hede-Brierley L, Bhasin G, Bhatia A, Lazzari A, Davis S, Ni P, Collins L, Bhasin S (2011) Clinical meaningfulness of the changes in muscle performance and physical function associated with testosterone administration in older men with mobility limitation. J Gerontol A Biol Sci Med Sci 66:1090-1099
116. Kenny AM, Kleppinger A, Annis K, Rathier M, Browner B, Judge JO, McGee D (2010) 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 58:1134-1143
117. Kanis JA, Bianchi G, Bilezikian JP, Kaufman JM, Khosla S, Orwoll E, Seeman E (2011) Towards a diagnostic and therapeutic consensus in male osteoporosis. Osteoporos Int 22: 2789-2798
118. Isidori AM, Giannetta E, Greco EA, Gianfrilli D, Bonifacio V, Isidori A, Lenzi A, Fabbri A (2005) Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endicrinol 63:280-293
119. Kaufman JM, Vermeulen A (2005) The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev 26:833-876
120. Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang A, Choong K, Lakshman KM, Mazer NA, Miciek R, Krasnoff J, Elmi A, Knapp PE, Brooks B, Appleman E, Aggarwal S, Bhasin G, Hede-Brierley L, Bhatia A, Collins L, LeBrasseur N, Fiore LD, Bhasin S (2010) Adverse events associated with testosterone administration. N Engl J Med 363:109-122
121. Fernandez-Balsells MM, Murad MH, Lane M, Lampropulos JF, Albuquerque F, Mullan RJ, Agrwal N, Elamin MB, Gallegos-Orozco JF, Wang AT, Erwin PJ, Bhasin S, Montori VM (2010) Clinical review 1. Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab 95:2560-2575
122. Calof OM, Singh AB, Lee ML, Kenny AM, Urban RJ, Tenover JL, Bhasin S (2005) Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol A Biol Sci Med Sci 60:1451-1457
123. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM (2010) Testosterone therapy in men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 95: 2536-2559
124. Annweiler C, Schott AM, Berrut G, Fantino B, Beauchet O (2009) Vitamin D-related changes in physical performance: a systematic review. J Nutr Health Aging 13:893-898
125. Stockton KA, Mengersen K, Paratz JD, Kandiah D, Bennell KL (2011) Effect of vitamin D supplementation on muscle strength: a systematic review and meta-analysis. Osteoporos Int 22: 859-871
126. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, Orav JE, Stuck AE, Theiler R, Wong JB, Egli A, Kiel DP, Henschkowski J (2009) Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. Br Med J 339:b3692
127. Ceglia L (2008) Vitamin D and skeletal muscle tissue and function. Mol Aspects Med 29:407-414
128. Lin R, White JH (2004) The pleiotropic actions of vitamin D. Bioessays 26:21-28
129. Annweiler C, Schott AM, Berrut G, Chauvire V, Le Gall D, Inzitari M, Beauchet O (2010) Vitamin D and ageing: neurological issues. Neuropsychobiology 62:139-150
130. Lyles KW, Colon-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, Hyldstrup L, Recknor C, Nordsletten L, Moore KA, Lavecchia C, Zhang J, Mesenbrink P, Hodgson PK, Abrams K, Orloff JJ, Horowitz Z, Eriksen EF, Boonen S (2007) Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med 357:1799-1809
131. Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A (2007) Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet 370:657-666
132. Hennessey JV, Chromiak JA, DellaVentura S, Reinert SE, Puhl J, Kiel DP, Rosen CJ, Vandenburgh H, MacLean DB (2001) Growth hormone administration and exercise effects on muscle fiber type and diameter in moderately frail older people. J Am Geriatr Soc 49:852-858
133. Merriam GR, Schwartz RS, Vitiello MV (2003) Growth hormone- releasing hormone and growth hormone secretagogues in normal aging. Endocrine 22:41-48
134. Hersch EC, Merriam GR (2008) Growth hormone (GH)- releasing hormone and GH secretagogues in normal aging: fountain of youth or pool of tantalus? Clin Interv Aging 3: 121-129
135. Liu H, Bravata DM, Olkin I, Nayak S, Roberts B, Garber AM, Hoffman AR (2007) Systematic review: the safety and efficacy of growth hormone in the healthy elderly. Ann Intern Med 146:104-115
136. White HK, Petrie CD, Landschulz W, MacLean D, Taylor A, Lyles K, Wei JY, Hoffman AR, Salvatori R, Ettinger MP, Morey MC, Blackman MR, Merriam GR (2009) Effects of an oral growth hormone secretagogue in older adults. J Clin Endocrinol Metab 94:1198-1206
137. Nass R, Pezzoli SS, Oliveri MC, Patrie JT, Harrell FE Jr, Clasey JL, Heymsfield SB, Bach MA, Vance ML, Thorner MO (2008) Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Ann Intern Med 149:601-611
138. Milne AC, Potter J, Avenell A (2005) Protein and energy supplementation in elderly people at risk from malnutrition. Cochrane Database Syst Rev 2:CD003288
139. Seeman E, Vellas B, Benhamou C, Aquino JP, Semler J, Kaufman JM, Hoszowski K, Varela AR, Fiore C, Brixen K, Reginster JY, Boonen S (2006) Strontium ranelate reduces the risk of vertebral and nonvertebral fractures in women eighty years of age and older. J Bone Miner Res 21:1113-1120
140. Colon-Emeric CS, Mesenbrink P, Lyles KW, Pieper CF, Boonen S, Delmas P, Eriksen EF, Magaziner J (2010) Potential mediators of the mortality reduction with zoledronic acid after hip fracture. J Bone Miner Res 25:91-97
141. Cooper C, Atkinson EJ, Jacobsen SJ, O'Fallon WM, Melton LJ 3rd (1993) Population-based study of survival after osteoporotic fractures. Am J Epidemiol 137:1001-1005
142. Chrischilles EA,Butler CD, Davis CS, Wallace RB(1991)Amodel of lifetime osteoporosis impact. Arch Intern Med 151:2026-2032
143. Maggi S, Siviero P, Wetle T, Besdine RW, Saugo M, Crepaldi G (2010) A multicenter survey on profile of care for hip fracture: predictors of mortality and disability. Osteoporos Int 21:223-231
144. Oleksik A, Lips P, Dawson A, Minshall ME, Shen W, Cooper C, Kanis J (2000) Health-related quality of life in postmenopausal women with low BMD with or without prevalent vertebral fractures. J Bone Miner Res 15:1384-1392
145. Morley JE (2009) Developing novel therapeutic approaches to frailty. Curr Pharm Des 15:3384-3395
146. Sakuma K, Yamaguchi A (2012) Novel intriguing strategies attenuating to sarcopenia. J Aging Res 2012:251217
147. Onder G, Penninx BW, Balkrishnan R, Fried LP, Chaves PH, Williamson J, Carter C, Di Bari M, Guralnik JM, Pahor M (2002) Relation between use of angiotensin-converting enzyme inhibitors and muscle strength and physical function in older women: an observational study. Lancet 359:926-930
148. Velloso CP (2008) Regulation of muscle mass by growth hormone and IGF-I. Br J Pharmacol 154:557-568
149. Semba RD, Varadhan R, Bartali B, Ferrucci L, Ricks MO, Blaum C, Fried LP (2007) Low serum carotenoids and development of severe walking disability among older women living in the community: the women's health and aging study I. Age Ageing 36:62-67
150. Boonen S, Milisen K, Gielen E, Meeuwissen J, Dejaeger E, Sermon A,
151. Van Craen K, Braes T, Wellens N, Denhaerynck K, Flamaing J, Moons P, Boonen S, Gosset C, Petermans J, Milisen K (2010) The effectiveness of inpatient geriatric evaluation and management units: a systematic review and meta-analysis. J Am Geriatr Soc 58:83-92
152. Mayer-Davis EJ, D'Agostino R Jr, Karter AJ, Haffner SM, Rewers MJ, Saad M, Bergman RN (1998) Intensity and amount of physical activity in relation to insulin sensitivity: the insulin resistance atherosclerosis study. J Am Med Assoc 279:669-674
153. Walsh NP, Gleeson M, Shephard RJ, Woods JA, Bishop NC, Fleshner M, Green C, Pedersen BK, Hoffman-Goetz L, Rogers CJ, Northoff H, Abbasi A, Simon P (2011) Position statement, part 1. Immune function and exercise. Exerc Immunol Rev 17:6-63
154. De Palo EF, Antonelli G, Gatti R, Chiappin S, Spinella P, Cappellin E (2008) Effects of two different types of exercise on GH/IGF axis in athletes. Is the free/total IGF-I ratio a new investigative approach? Clin Chimica Acta 387:71-74
155. Tremblay MS, Copeland JL, Van Helder W (2004) Effect of training status and exercise mode on endogenous steroid hormones in men. J Appl Physiol 96:531-539
156. Li J, Siegrist J (2012) Physical activity and risk of cardiovascular disease-a meta-analysis of prospective cohort studies. Int J Environ Res Public Health 9:391-407
157. Tan EJ, Xue QL, Li T, Carlson MC, Fried LP (2006) Volunteering: a physical activity intervention for older adults-the experience corps program in Baltimore. J Urban Health 83: 954-969
158. Kenny AM, Bellantonio S, Gruman CA, Acosta RD, Prestwood KM (2002) Effects of transdermal testosterone on cognitive function and health perception in older men with low bioavailable testosterone levels. J Gerontol A Biol Sci Med Sci 57:M321-M325
159. Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, Nicholson GC (2010) Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. J Am Med Assoc 303:1815-1822