[en] The co-existence of impaired bone health (osteopenia/osteoporosis), reduced muscle mass and strength (sarcopenia), and increased adiposity (obesity) in middle-aged and older people has been identified in recent studies, leading to a proposal for the existence of “osteosarcopenic obesity” as a distinct entity. Evidence for the pathophysiological overlap of these conditions is mounting, although a causal relationship is yet to be established. Each component condition occurs frequently with increasing age, and with shared risk factors in many instances, thus, an overlap of these three conditions is not surprising. However, whether the concurrent existence of sarcopenia, osteoporosis and obesity leads to an increased risk of adverse musculoskeletal outcomes and mortality above and beyond the risks associated with the sum of the component parts remains
to be proven and is a question of research interest. In this article, we review evidence for the existence of osteosarcopenic obesity including the current operational definition of osteosarcopenic obesity, prevalence, pathophysiology, outcomes and exploratory approaches to the management of components. We conclude that, there is insufficient evidence to support a discrete clinical entity of osteosarcopenic obesity at this time. To expand knowledge and understanding in this area, there is a need for consensus on a definition of osteosarcopenic obesity which will allow for identification, further epidemiological studies and comparisons between studies. Additionally, studies should assess whether the clinical outcomes associated with osteosarcopenic obesity are worse than the mere addition of those linked with its components. This will help to determine
whether defining a person as having this triad will eventually result in a more effective treatment than addressing each of the three conditions separately.
Disciplines :
General & internal medicine Public health, health care sciences & services
Author, co-author :
Bauer, J. M.; Center for Geriatric Medicine, University of Heidelberg, AGAPLESION Bethanien Krankenhaus Heidelberg, Heidelberg, Germany
Cruz-Jentoft, A. J.; Servicio de Geriatría, Hospital Universitario Ramón y Cajal (IRYCIS), Madrid, Spain
Fielding, R. A.; Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, United States
Kanis, J. A.; Mary McKillop Health Institute, Australian Catholic University, Melbourne, Australia, Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, United Kingdom
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé
Bruyère, Olivier ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé
Cesari, M.; Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
Chapurlat, R.; INSERM, UMR 1033, Université de Lyon, Hôpital E Herriot, Lyon Cedex 03, 69437, France
Al-Daghri, N.; Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia
Dennison, E.; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, United Kingdom
Kaufman, J.-M.; Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
Landi, F.; Department of Geriatrics, Neurosciences and Orthopaedics, Orthogeriatric Unit, Teaching Hospital “Agostino Gemelli”, Catholic University of the Sacred Heart School of Medicine, Rome, Italy
Laslop, A.; Scientific Office, Federal Office for Safety in Health Care, Austrian Agency for Health and Food Safety, Vienna, Austria
Locquet, Médéa ; Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie clinique
Maggi, S.; Aging Program, National Research Council, Padua, Italy
McCloskey, E.; Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, United Kingdom, Mellanby Centre for Bone Research and Centre for Integrated Research in Musculoskeletal Ageing, University of Sheffield, Sheffield, United Kingdom
Perna, S.; Department of Biology, College of Science, University of Bahrain, Sakhir Campus, P.O. Box 32038, Zallaq, Bahrain
Rolland, Y.; CHU Toulouse, Médecine Gériatrie Gérontopôle, Cité de la Santé, 20 Rue du Pont Saint Pierre, Inserm 1027, Toulouse, 31059, France
Rondanelli, M.; IRCCS Mondino Foundation, Pavia, Department of Public Health, Experimental and Forensic Medicine, Unit of Human Nutrition, University of Pavia, Pavia, Italy
Szulc, P.; INSERM, UMR 1033, University of Lyon, Hôpital Edouard Herriot, Lyon, France
Vellas, B.; CHU Toulouse, Médecine Gériatrie Gérontopôle, Cité de la Santé, 20 Rue du Pont Saint Pierre, Inserm 1027, Toulouse, 31059, France
Vlaskovska, M.; Medical Faculty, Department of Pharmacology, Medical University Sofia, 2, Zdrave Str, Sofia, 1431, Bulgaria
FMedSci, C. C.; WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium, MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, United Kingdom, NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, United Kingdom
von Ruesten A, Steffen A, Floegel A, van der Daphne A, Masala G, Tjonneland A, Halkjaer J, Palli D, Wareham NJ, Loos RJ, Sorensen TI, Boeing H (2011) Trend in obesity prevalence in European adult cohort populations during follow-up since 1996 and their predictions to 2015. PLoS ONE 6(11):e27455. 10.1371/journal.pone.0027455
Mathus-Vliegen EM (2012) Prevalence, pathophysiology, health consequences and treatment options of obesity in the elderly: a guideline. Obes Facts 5(3):460–483. 10.1159/000341193
Ilich JZ (2017) Another impairment in older age: what does osteosarcopenic obesity syndrome mean for middle-aged and older women? J Am Med Dir Assoc 18(8):648–650. 10.1016/j.jamda.2017.05.001
Davison MJ, Maly MR, Adachi JD, Noseworthy MD, Beattie KA (2017) Relationships between fatty infiltration in the thigh and calf in women with knee osteoarthritis. Aging Clin Exp Res 29(2):291–299. 10.1007/s40520-016-0556-z
Barazzoni R, Bischoff SC, Boirie Y, Busetto L, Cederholm T, Dicker D, Toplak H, Van Gossum A, Yumuk V, Vettor R (2018) Sarcopenic obesity: time to meet the challenge. Clin Nutr. 10.1016/j.clnu.2018.04.018
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, European Working Group on Sarcopenia in Older P (2010) Sarcopenia: European consensus on definition and diagnosis: report of the european working group on sarcopenia in older people. Age Ageing 39(4):412–423. 10.1093/ageing/afq034
Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M (2018) Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 10.1093/ageing/afy169
Reid KF, Doros G, Clark DJ, Patten C, Carabello RJ, Cloutier GJ, Phillips EM, Krivickas LS, Frontera WR, Fielding RA (2012) Muscle power failure in mobility-limited older adults: preserved single fiber function despite lower whole muscle size, quality and rate of neuromuscular activation. Eur J Appl Physiol 112(6):2289–2301. 10.1007/s00421-011-2200-0
Kalinkovich A, Livshits G (2017) Sarcopenic obesity or obese sarcopenia: a cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis. Ageing Res Rev 35:200–221. 10.1016/j.arr.2016.09.008
Marzetti E, Calvani R, Tosato M, Cesari M, Di Bari M, Cherubini A, Collamati A, D’Angelo E, Pahor M, Bernabei R, Landi F (2017) Sarcopenia: an overview. Aging Clin Exp Res 29(1):11–17. 10.1007/s40520-016-0704-5
Baumgartner RN, Wayne SJ, Waters DL, Janssen I, Gallagher D, Morley JE (2004) Sarcopenic obesity predicts instrumental activities of daily living disability in the elderly. Obes Res 12(12):1995–2004. 10.1038/oby.2004.250
Kanis JA, Johnell O, Oden A, Sembo I, Redlund-Johnell I, Dawson A, De Laet C, Jonsson B (2000) Long-term risk of osteoporotic fracture in Malmo. Osteoporos Int 11(8):669–674
Hirschfeld HP, Kinsella R, Duque G (2017) Osteosarcopenia: where bone, muscle, and fat collide. Osteoporos Int 28(10):2781–2790. 10.1007/s00198-017-4151-8
Kaplan SJ, Pham TN, Arbabi S, Gross JA, Damodarasamy M, Bentov I, Taitsman LA, Mitchell SH, Reed MJ (2017) Association of radiologic indicators of frailty with 1-year mortality in older trauma patients: opportunistic screening for sarcopenia and osteopenia. JAMA Surg 152(2):e164604. 10.1001/jamasurg.2016.4604
Nielsen BR, Abdulla J, Andersen HE, Schwarz P, Suetta C (2018) Sarcopenia and osteoporosis in older people: a systematic review and meta-analysis. Eur Geriatr Med 9(4):419–434. 10.1007/s41999-018-0079-6
Yoo JI, Kim H, Ha YC, Kwon HB, Koo KH (2018) Osteosarcopenia in patients with hip fracture is related with high mortality. J Korean Med Sci 33(4):e27. 10.3346/jkms.2018.33.e27
Drey M, Sieber CC, Bertsch T, Bauer JM, Schmidmaier R (2016) Osteosarcopenia is more than sarcopenia and osteopenia alone. Aging Clin Exp Res 28(5):895–899. 10.1007/s40520-015-0494-1
Chalhoub D, Cawthon PM, Ensrud KE, Stefanick ML, Kado DM, Boudreau R, Greenspan S, Newman AB, Zmuda J, Orwoll ES, Cauley JA (2015) Risk of nonspine fractures in older adults with sarcopenia, low bone mass, or both. J Am Geriatr Soc 63(9):1733–1740. 10.1111/jgs.13605
Scott D, Seibel M, Cumming R, Naganathan V, Blyth F, Le Couteur DG, Handelsman DJ, Waite LM, Hirani V (2018) Does combined osteopenia/osteoporosis and sarcopenia confer greater risk of falls and fracture than either condition alone in older men? The Concord health and ageing in men project. J Gerontol A Biol Sci Med Sci. 10.1093/gerona/gly162
Harris R, Chang Y, Beavers K, Laddu-Patel D, Bea J, Johnson K, LeBoff M, Womack C, Wallace R, Li W, Crandall C, Cauley J (2017) Risk of fracture in women with sarcopenia, low bone mass, or both. J Am Geriatr Soc 65(12):2673–2678. 10.1111/jgs.15050
Zaslavsky O, Li W, Going S, Datta M, Snetselaar L, Zelber-Sagi S (2017) Association between body composition and hip fractures in older women with physical frailty. Geriatr Gerontol Int 17(6):898–904. 10.1111/ggi.12798
Trajanoska K, Schoufour JD, Darweesh SK, Benz E, Medina-Gomez C, Alferink LJ, Lahousse L, Brusselle G, Stricker B, Darwish Murad S, Zillikens MC, Uitterlinden AG, Ikram MA, Franco OH, Rivadeneira F (2018) Sarcopenia and its clinical correlates in the general population: the Rotterdam study. J Bone Miner Res 33(7):1209–1218. 10.1002/jbmr.3416
Ilich JZ, Kelly OJ, Inglis JE (2016) Osteosarcopenic obesity syndrome: what is it and how can it be identified and diagnosed? Curr Gerontol Geriatr Res 2016:7325973. 10.1155/2016/7325973
Szlejf C, Parra-Rodriguez L, Rosas-Carrasco O (2017) Osteosarcopenic obesity: prevalence and relation with frailty and physical performance in middle-aged and older women. J Am Med Dir Assoc 18(8):733 e731–733 e735. 10.1016/j.jamda.2017.02.023
Chung JH, Hwang HJ, Shin HY, Han CH (2016) Association between sarcopenic obesity and bone mineral density in middle-aged and elderly Korean. Ann Nutr Metab 68(2):77–84. 10.1159/000442004
Ilich JZ, Inglis JE, Kelly OJ, McGee DL (2015) Osteosarcopenic obesity is associated with reduced handgrip strength, walking abilities, and balance in postmenopausal women. Osteoporos Int 26(11):2587–2595. 10.1007/s00198-015-3186-y
WHO (2000) World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 894:1–253
Shah NR, Braverman ER (2012) Measuring adiposity in patients: the utility of body mass index (BMI), percent body fat, and leptin. PLoS ONE 7(4):e33308. 10.1371/journal.pone.0033308
WHO (1995) World health organization. Physical status: the use and interpretation of anthropometry. Report of a WHO expert committee. World Health Organ Tech Rep Ser 854(1):e452
Dufour AB, Hannan MT, Murabito JM, Kiel DP, McLean RR (2013) Sarcopenia definitions considering body size and fat mass are associated with mobility limitations: the Framingham study. J Gerontol A Biol Sci Med Sci 68(2):168–174. 10.1093/gerona/gls109
Studenski SA, Peters KW, Alley DE, Cawthon PM, McLean RR, Harris TB, Ferrucci L, Guralnik JM, Fragala MS, Kenny AM, Kiel DP, Kritchevsky SB, Shardell MD, Dam TT, Vassileva MT (2014) The FNIH sarcopenia project: rationale, study description, conference recommendations, and final estimates. J Gerontol A Biol Sci Med Sci 69(5):547–558. 10.1093/gerona/glu010
Janssen I, Heymsfield SB, Ross R (2002) Low relative skeletal muscle mass (sarcopenia) in older persons is associated with functional impairment and physical disability. J Am Geriatr Soc 50(5):889–896
Bischoff-Ferrari HA, Orav JE, Kanis JA, Rizzoli R, Schlogl M, Staehelin HB, Willett WC, Dawson-Hughes B (2015) Comparative performance of current definitions of sarcopenia against the prospective incidence of falls among community-dwelling seniors age 65 and older. Osteoporos Int 26(12):2793–2802. 10.1007/s00198-015-3194-y
Batsis JA, Barre LK, Mackenzie TA, Pratt SI, Lopez-Jimenez F, Bartels SJ (2013) Variation in the prevalence of sarcopenia and sarcopenic obesity in older adults associated with different research definitions: dual-energy X-ray absorptiometry data from the National Health and Nutrition Examination Survey 1999-2004. J Am Geriatr Soc 61(6):974–980. 10.1111/jgs.12260
Beaudart C, Reginster JY, Slomian J, Buckinx F, Locquet M, Bruyere O (2014) Prevalence of sarcopenia: the impact of different diagnostic cut-off limits. J Musculoskelet Neuronal Interact 14(4):425–431
Kanis JA, Melton LJ 3rd, Christiansen C, Johnston CC, Khaltaev N (1994) The diagnosis of osteoporosis. J Bone Miner Res 9(8):1137–1141. 10.1002/jbmr.5650090802
Kanis JA, McCloskey EV, Johansson H, Oden A, Melton LJ 3rd, Khaltaev N (2008) A reference standard for the description of osteoporosis. Bone 42(3):467–475. 10.1016/j.bone.2007.11.001
Beaudart C, McCloskey E, Bruyere O, Cesari M, Rolland Y, Rizzoli R, Araujo de Carvalho I, Amuthavalli Thiyagarajan J, Bautmans I, Bertiere MC, Brandi ML, Al-Daghri NM, Burlet N, Cavalier E, Cerreta F, Cherubini A, Fielding R, Gielen E, Landi F, Petermans J, Reginster JY, Visser M, Kanis J, Cooper C (2016) Sarcopenia in daily practice: assessment and management. BMC Geriatr 16(1):170. 10.1186/s12877-016-0349-4
Stefanaki C, Peppa M, Boschiero D, Chrousos GP (2016) Healthy overweight/obese youth: early osteosarcopenic obesity features. Eur J Clin Invest 46(9):767–778. 10.1111/eci.12659
Ormsbee MJ, Prado CM, Ilich JZ, Purcell S, Siervo M, Folsom A, Panton L (2014) Osteosarcopenic obesity: the role of bone, muscle, and fat on health. J Cachexia Sarcopenia Muscle 5(3):183–192. 10.1007/s13539-014-0146-x
Picca A, Calvani R, Manes-Gravina E, Spaziani L, Landi F, Bernabei R, Marzetti E (2017) Bone-muscle crosstalk: unraveling new therapeutic targets for osteoporosis. Curr Pharm Des 23(41):6256–6263. 10.2174/1381612823666170526112300
Ilich JZ, Kelly OJ, Inglis JE, Panton LB, Duque G, Ormsbee MJ (2014) Interrelationship among muscle, fat, and bone: connecting the dots on cellular, hormonal, and whole body levels. Ageing Res Rev 15:51–60. 10.1016/j.arr.2014.02.007
Bhasin S, Woodhouse L, Casaburi R, Singh AB, Mac RP, Lee M, Yarasheski KE, Sinha-Hikim I, Dzekov C, Dzekov J, Magliano L, Storer TW (2005) Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle. J Clin Endocrinol Metab 90(2):678–688. 10.1210/jc.2004-1184
Wu FC, Tajar A, Pye SR, Silman AJ, Finn JD, O’Neill TW, Bartfai G, Casanueva F, Forti G, Giwercman A, Huhtaniemi IT, Kula K, Punab M, Boonen S, Vanderschueren D, European Male Aging Study G (2008) Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European male aging study. J Clin Endocrinol Metab 93(7):2737–2745. 10.1210/jc.2007-1972
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(7):3165–3172. 10.1210/jc.2009-2754
Vandenput L, Mellstrom D, Laughlin GA, Cawthon PM, Cauley JA, Hoffman AR, Karlsson MK, Rosengren BE, Ljunggren O, Nethander M, Eriksson AL, Lorentzon M, Leung J, Kwok T, Orwoll ES, Ohlsson C (2017) Low testosterone, but not estradiol, is associated with incident falls in older men: the international MrOS study. J Bone Miner Res 32(6):1174–1181. 10.1002/jbmr.3088
Swiecicka A, Lunt M, Ahern T, O’Neill TW, Bartfai G, Casanueva FF, Forti G, Giwercman A, Han TS, Lean MEJ, Pendleton N, Punab M, Slowikowska-Hilczer J, Vanderschueren D, Huhtaniemi IT, Wu FCW, Rutter MK, Group ES (2017) Nonandrogenic anabolic hormones predict risk of frailty: European male ageing study prospective data. J Clin Endocrinol Metab 102(8):2798–2806. 10.1210/jc.2017-00090
Vermeulen A, Kaufman JM, Giagulli VA (1996) Influence of some biological indexes on sex hormone-binding globulin and androgen levels in aging or obese males. J Clin Endocrinol Metab 81(5):1821–1826. 10.1210/jcem.81.5.8626841
Davison SL, Bell R, Donath S, Montalto JG, Davis SR (2005) Androgen levels in adult females: changes with age, menopause, and oophorectomy. J Clin Endocrinol Metab 90(7):3847–3853. 10.1210/jc.2005-0212
Varadhan R, Walston J, Cappola AR, Carlson MC, Wand GS, Fried LP (2008) Higher levels and blunted diurnal variation of cortisol in frail older women. J Gerontol A Biol Sci Med Sci 63(2):190–195
Zadik Z, Chalew SA, McCarter RJ Jr, Meistas M, Kowarski AA (1985) The influence of age on the 24-hour integrated concentration of growth hormone in normal individuals. J Clin Endocrinol Metab 60(3):513–516. 10.1210/jcem-60-3-513
Sinclair AJ, Abdelhafiz AH, Rodriguez-Manas L (2017) Frailty and sarcopenia - newly emerging and high impact complications of diabetes. J Diabetes Complications 31(9):1465–1473. 10.1016/j.jdiacomp.2017.05.003
Srikanthan P, Karlamangla AS (2011) Relative muscle mass is inversely associated with insulin resistance and prediabetes. Findings from the third National Health and Nutrition Examination Survey. J Clin Endocrinol Metab 96(9):2898–2903. 10.1210/jc.2011-0435
Kalyani RR, Metter EJ, Egan J, Golden SH, Ferrucci L (2015) Hyperglycemia predicts persistently lower muscle strength with aging. Diabetes Care 38(1):82–90. 10.2337/dc14-1166
Park SW, Goodpaster BH, Lee JS, Kuller LH, Boudreau R, de Rekeneire N, Harris TB, Kritchevsky S, Tylavsky FA, Nevitt M, Cho YW, Newman AB, Health A, Body Composition S (2009) Excessive loss of skeletal muscle mass in older adults with type 2 diabetes. Diabetes Care 32(11):1993–1997. 10.2337/dc09-0264
Kim J, Lee Y, Kye S, Chung YS, Kim JH, Chon D, Lee KE (2017) Diet quality and osteosarcopenic obesity in community-dwelling adults 50 years and older. Maturitas 104:73–79. 10.1016/j.maturitas.2017.08.007
JafariNasabian P, Inglis JE, Kelly OJ, Ilich JZ (2017) Osteosarcopenic obesity in women: impact, prevalence, and management challenges. Int J Womens Health 9:33–42. 10.2147/IJWH.S106107
Veronese N, Stubbs B, Koyanagi A, Hebert JR, Cooper C, Caruso MG, Guglielmi G, Reginster JY, Rizzoli R, Maggi S, Shivappa N (2018) Pro-inflammatory dietary pattern is associated with fractures in women: an eight-year longitudinal cohort study. Osteoporos Int 29(1):143–151. 10.1007/s00198-017-4251-5
Shivappa N, Stubbs B, Hebert JR, Cesari M, Schofield P, Soysal P, Maggi S, Veronese N (2018) The relationship between the dietary inflammatory index and incident frailty: a longitudinal cohort study. J Am Med Dir Assoc 19(1):77–82. 10.1016/j.jamda.2017.08.006
Mohseni R, Aliakbar S, Abdollahi A, Yekaninejad MS, Maghbooli Z, Mirzaei K (2017) Relationship between major dietary patterns and sarcopenia among menopausal women. Aging Clin Exp Res 29(6):1241–1248. 10.1007/s40520-016-0721-4
Isanejad M, Sirola J, Mursu J, Rikkonen T, Kroger H, Tuppurainen M, Erkkila AT (2018) Association of the Baltic sea and mediterranean diets with indices of sarcopenia in elderly women. OSPTRE-FPS study. Eur J Nutr 57(4):1435–1448. 10.1007/s00394-017-1422-2
Alvarez-Perez J, Sanchez-Villegas A, Diaz-Benitez EM, Ruano-Rodriguez C, Corella D, Martinez-Gonzalez MA, Estruch R, Salas-Salvado J, Serra-Majem L (2016) Influence of a mediterranean dietary pattern on body fat distribution: results of the predimed-canarias intervention randomized trial. J Am Coll Nutr 35(6):568–580. 10.1080/07315724.2015.1102102
Veronese N, Stubbs B, Noale M, Solmi M, Rizzoli R, Vaona A, Demurtas J, Crepaldi G, Maggi S (2017) Adherence to a mediterranean diet is associated with lower incidence of frailty: a longitudinal cohort study. Clin Nutr. 10.1016/j.clnu.2017.08.028
Kelly OJ, Gilman JC, Kim Y, Ilich JZ (2017) Macronutrient intake and distribution in the etiology, prevention and treatment of osteosarcopenic obesity. Curr Aging Sci 10(2):83–105. 10.2174/1874609809666160509122558
Houston DK, Nicklas BJ, Ding J, Harris TB, Tylavsky FA, Newman AB, Lee JS, Sahyoun NR, Visser M, Kritchevsky SB, Health ABCS (2008) Dietary protein intake is associated with lean mass change in older, community-dwelling adults: the health, aging, and body composition (Health ABC) study. Am J Clin Nutr 87(1):150–155. 10.1093/ajcn/87.1.150
Houston DK, Tooze JA, Garcia K, Visser M, Rubin S, Harris TB, Newman AB, Kritchevsky SB, Health ABCS (2017) Protein intake and mobility limitation in community-dwelling older adults: the Health ABC study. J Am Geriatr Soc 65(8):1705–1711. 10.1111/jgs.14856
Kelly OJ, Gilman JC, Kim Y, Ilich JZ (2016) Micronutrient intake in the etiology, prevention and treatment of osteosarcopenic obesity. Curr Aging Sci 9(4):260–278
Agarwal S, Reider C, Brooks JR, Fulgoni VL 3rd (2015) Comparison of prevalence of inadequate nutrient intake based on body weight status of adults in the united states: an analysis of NHANES 2001-2008. J Am Coll Nutr 34(2):126–134. 10.1080/07315724.2014.901196
Kim J, Lee Y, Kye S, Chung YS, Lee O (2017) Association of serum vitamin d with osteosarcopenic obesity: Korea National Health and Nutrition Examination Survey 2008–2010. J Cachexia Sarcopenia Muscle 8(2):259–266. 10.1002/jcsm.12154
Curtis E, Litwic A, Cooper C, Dennison E (2015) Determinants of muscle and bone aging. J Cell Physiol 230(11):2618–2625. 10.1002/jcp.25001
Wang YJ, Wang Y, Zhan JK, Tang ZY, He JY, Tan P, Deng HQ, Huang W, Liu YS (2015) Sarco-osteoporosis: prevalence and association with frailty in Chinese community-dwelling older adults. Int J Endocrinol 2015:482940. 10.1155/2015/482940
Bauer JM, Sieber CC (2008) Sarcopenia and frailty: a clinician’s controversial point of view. Exp Gerontol 43(7):674–678. 10.1016/j.exger.2008.03.007
Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA, Cardiovascular Health Study Collaborative Research G (2001) Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 56(3):M146–M156
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. 10.1007/s00198-012-1913-1
Li G, Thabane L, Papaioannou A, Ioannidis G, Levine MA, Adachi JD (2017) An overview of osteoporosis and frailty in the elderly. BMC Musculoskelet Disord 18(1):46. 10.1186/s12891-017-1403-x
Liao Q, Zheng Z, Xiu S, Chan P (2018) Waist circumference is a better predictor of risk for frailty than BMI in the community-dwelling elderly in Beijing. Aging Clin Exp Res. 10.1007/s40520-018-0933-x
Perna S, Spadaccini D, Nichetti M, Avanzato I, Faliva MA, Rondanelli M (2018) Osteosarcopenic visceral obesity and osteosarcopenic subcutaneous obesity, two new phenotypes of sarcopenia: prevalence, metabolic profile, and risk factors. J Aging Res 2018:6147426. 10.1155/2018/6147426
Fielding RA, Travison TG, Kirn DR, Koochek A, Reid KF, von Berens A, Zhu H, Folta SC, Sacheck JM, Nelson ME, Liu CK, Aberg AC, Nydahl M, Lilja M, Gustafsson T, Cederholm T (2017) Effect of structured physical activity and nutritional supplementation on physical function in mobility-limited older adults: results from the VIVE2 randomized trial. J Nutr Health Aging 21(9):936–942. 10.1007/s12603-017-0936-x
Pahor M, Guralnik JM, Ambrosius WT, Blair S, Bonds DE, Church TS, Espeland MA, Fielding RA, Gill TM, Groessl EJ, King AC, Kritchevsky SB, Manini TM, McDermott MM, Miller ME, Newman AB, Rejeski WJ, Sink KM, Williamson JD (2014) Effect of structured physical activity on prevention of major mobility disability in older adults: the life study randomized clinical trial. JAMA 311(23):2387–2396. 10.1001/jama.2014.5616
Moreira LD, Oliveira ML, Lirani-Galvao AP, Marin-Mio RV, Santos RN, Lazaretti-Castro M (2014) Physical exercise and osteoporosis: effects of different types of exercises on bone and physical function of postmenopausal women. Arq Bras Endocrinol Metabol 58(5):514–522
Bauer J, Biolo G, Cederholm T, Cesari M, Cruz-Jentoft AJ, Morley JE, Phillips S, Sieber C, Stehle P, Teta D, Visvanathan R, Volpi E, Boirie Y (2013) Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the prot-age study group. J Am Med Dir Assoc 14(8):542–559. 10.1016/j.jamda.2013.05.021
Wall BT, Gorissen SH, Pennings B, Koopman R, Groen BB, Verdijk LB, van Loon LJ (2015) Aging is accompanied by a blunted muscle protein synthetic response to protein ingestion. PLoS ONE 10(11):e0140903. 10.1371/journal.pone.0140903
Moore DR, Churchward-Venne TA, Witard O, Breen L, Burd NA, Tipton KD, Phillips SM (2015) Protein ingestion to stimulate myofibrillar protein synthesis requires greater relative protein intakes in healthy older versus younger men. J Gerontol A Biol Sci Med Sci 70(1):57–62. 10.1093/gerona/glu103
Murphy CH, Saddler NI, Devries MC, McGlory C, Baker SK, Phillips SM (2016) Leucine supplementation enhances integrative myofibrillar protein synthesis in free-living older men consuming lower- and higher-protein diets: a parallel-group crossover study. Am J Clin Nutr 104(6):1594–1606. 10.3945/ajcn.116.136424
Rizzoli R, Biver E, Bonjour JP, Coxam V, Goltzman D, Kanis JA, Lappe J, Rejnmark L, Sahni S, Weaver C, Weiler H, Reginster JY (2018) Benefits and safety of dietary protein for bone health-an expert consensus paper endorsed by the European Society for Clinical and Economical aspects of Osteopororosis, Osteoarthritis, and Musculoskeletal diseases and by the International Osteoporosis Foundation. Osteoporos Int. 10.1007/s00198-018-4534-5
Pereira-Santos M, Costa PR, Assis AM, Santos CA, Santos DB (2015) Obesity and vitamin D deficiency: a systematic review and meta-analysis. Obes Rev 16(4):341–349. 10.1111/obr.12239
Bauer JM, Verlaan S, Bautmans I, Brandt K, Donini LM, Maggio M, McMurdo ME, Mets T, Seal C, Wijers SL, Ceda GP, De Vito G, Donders G, Drey M, Greig C, Holmback U, Narici M, McPhee J, Poggiogalle E, Power D, Scafoglieri A, Schultz R, Sieber CC, Cederholm T (2015) Effects of a vitamin D and leucine-enriched whey protein nutritional supplement on measures of sarcopenia in older adults, the provide study: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc 16(9):740–747. 10.1016/j.jamda.2015.05.021
Verlaan S, Aspray TJ, Bauer JM, Cederholm T, Hemsworth J, Hill TR, McPhee JS, Piasecki M, Seal C, Sieber CC, Ter Borg S, Wijers SL, Brandt K (2017) Nutritional status, body composition, and quality of life in community-dwelling sarcopenic and non-sarcopenic older adults: a case-control study. Clin Nutr 36(1):267–274. 10.1016/j.clnu.2015.11.013
Jeromson S, Gallagher IJ, Galloway SD, Hamilton DL (2015) Omega-3 fatty acids and skeletal muscle health. Mar Drugs 13(11):6977–7004. 10.3390/md13116977
Rousseau JH, Kleppinger A, Kenny AM (2009) Self-reported dietary intake of omega-3 fatty acids. JAGS 57(10):1781–1788
Smith GI, Atherton P, Reeds DN, Mohammed BS, Rankin D, Rennie MJ, Mittendorfer B (2011) Dietary omega-3 fatty acid supplementation increases the rate of muscle protein synthesis in older adults: a randomized controlled trial. Am J Clin Nutr 93(2):402–412. 10.3945/ajcn.110.005611
Rondanelli M, Klersy C, Terracol G, Talluri J, Maugeri R, Guido D, Faliva MA, Solerte BS, Fioravanti M, Lukaski H, Perna S (2016) Whey protein, amino acids, and vitamin D supplementation with physical activity increases fat-free mass and strength, functionality, and quality of life and decreases inflammation in sarcopenic elderly. Am J Clin Nutr 103(3):830–840. 10.3945/ajcn.115.113357
Kirn DR, Koochek A, Reid KF, von Berens Å, Travison TG, Folta S, Sacheck J, Nelson M, Liu C, Phillips E, Åberg AC, Nydahl M, Gustafsson T, Cederholm T, Fielding RA (2015) The vitality, independence, and vigor in the elderly 2 study (VIVE2): design and methods. Contemp Clin Trials 43:164–171. 10.1016/j.cct.2015.06.001
Englund DA, Kirn DR, Koochek A, Zhu H, Travison TG, Reid KF, von Berens A, Melin M, Cederholm T, Gustafsson T, Fielding RA (2017) Nutritional supplementation with physical activity improves muscle composition in mobility-limited older adults, the VIVE2 study: a randomized, double-blind, placebo-controlled trial. J Gerontol A Biol Sci Med Sci 73(1):95–101. 10.1093/gerona/glx141
Inglis JE, Ilich JZ (2015) The microbiome and osteosarcopenic obesity in older individuals in long-term care facilities. Curr Osteoporos Rep 13(5):358–362. 10.1007/s11914-015-0287-7
Bindels LB, Delzenne NM (2013) Muscle wasting: the gut microbiota as a new therapeutic target? Int J Biochem Cell Biol 45(10):2186–2190. 10.1016/j.biocel.2013.06.021
Puiman P, Stoll B, Molbak L, de Bruijn A, Schierbeek H, Boye M, Boehm G, Renes I, van Goudoever J, Burrin D (2013) Modulation of the gut microbiota with antibiotic treatment suppresses whole body urea production in neonatal pigs. Am J Physiol Gastrointest Liver Physiol 304(3):G300–G310. 10.1152/ajpgi.00229.2011
Kakkar AK, Dahiya N (2015) Drug treatment of obesity: current status and future prospects. Eur J Intern Med 26(2):89–94. 10.1016/j.ejim.2015.01.005
Martin KA, Mani MV, Mani A (2015) New targets to treat obesity and the metabolic syndrome. Eur J Pharmacol 763(Pt A):64–74. 10.1016/j.ejphar.2015.03.093
Tella SH, Gallagher JC (2014) Prevention and treatment of postmenopausal osteoporosis. J Steroid Biochem Mol Biol 142:155–170. 10.1016/j.jsbmb.2013.09.008
Reginster JY, Neuprez A, Beaudart C, Lecart MP, Sarlet N, Bernard D, Disteche S, Bruyere O (2014) Antiresorptive drugs beyond bisphosphonates and selective oestrogen receptor modulators for the management of postmenopausal osteoporosis. Drugs Aging 31(6):413–424. 10.1007/s40266-014-0179-z
Morley JE (2016) Pharmacologic options for the treatment of sarcopenia. Calcif Tissue Int 98(4):319–333. 10.1007/s00223-015-0022-5
De Spiegeleer A, Beckwee D, Bautmans I, Petrovic M, Sarcopenia Guidelines Development group of the Belgian Society of Geriatrics (2018) Pharmacological interventions to improve muscle mass, muscle strength and physical performance in older people: an umbrella review of systematic reviews and meta-analyses. Drugs Aging 35(8):719–734. 10.1007/s40266-018-0566-y
Girgis CM, Mokbel N, Digirolamo DJ (2014) Therapies for musculoskeletal disease: can we treat two birds with one stone? Curr Osteoporos Rep 12(2):142–153. 10.1007/s11914-014-0204-5
Reginster JY, Cooper C, Rizzoli R, Kanis JA, Appelboom G, Bautmans I, Bischoff-Ferrari HA, Boers M, Brandi ML, Bruyere O, Cherubini A, Flamion B, Fielding RA, Gasparik AI, Van Loon L, McCloskey E, Mitlak BH, Pilotto A, Reiter-Niesert S, Rolland Y, Tsouderos Y, Visser M, Cruz-Jentoft AJ (2016) Recommendations for the conduct of clinical trials for drugs to treat or prevent sarcopenia. Aging Clin Exp Res 28(1):47–58. 10.1007/s40520-015-0517-y
Bahat G, Tufan A, Tufan F, Karan MA (2016) Suggestions on sarcopenia-related trials. Aging Clin Exp Res 28(5):1029–1030. 10.1007/s40520-016-0601-y
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 Endocrinol (Oxf) 63(3):280–293. 10.1111/j.1365-2265.2005.02339.x
Storer TW, Basaria S, Traustadottir T, Harman SM, Pencina K, Li Z, Travison TG, Miciek R, Tsitouras P, Hally K, Huang G, Bhasin S (2017) Effects of testosterone supplementation for 3 years on muscle performance and physical function in older men. J Clin Endocrinol Metab 102(2):583–593. 10.1210/jc.2016-2771
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(2):639–650. 10.1210/jc.2009-1251
Ottenbacher KJ, Ottenbacher ME, Ottenbacher AJ, Acha AA, Ostir GV (2006) Androgen treatment and muscle strength in elderly men: a meta-analysis. J Am Geriatr Soc 54(11):1666–1673. 10.1111/j.1532-5415.2006.00938.x
Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, Gill TM, Barrett-Connor E, Swerdloff RS, Wang C, Ensrud KE, Lewis CE, Farrar JT, Cella D, Rosen RC, Pahor M, Crandall JP, Molitch ME, Cifelli D, Dougar D, Fluharty L, Resnick SM, Storer TW, Anton S, Basaria S, Diem SJ, Hou X, Mohler ER 3rd, Parsons JK, Wenger NK, Zeldow B, Landis JR, Ellenberg SS, Testosterone Trials I (2016) Effects of testosterone treatment in older men. N Engl J Med 374(7):611–624. 10.1056/NEJMoa1506119
Pierorazio PM, Ferrucci L, Kettermann A, Longo DL, Metter EJ, Carter HB (2010) Serum testosterone is associated with aggressive prostate cancer in older men: results from the Baltimore longitudinal study of aging. BJU Int 105(6):824–829. 10.1111/j.1464-410X.2009.08853.x
Spitzer M, Huang G, Basaria S, Travison TG, Bhasin S (2013) Risks and benefits of testosterone therapy in older men. Nat Rev Endocrinol 9(7):414–424. 10.1038/nrendo.2013.73
Bhasin S, Brito JP, Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM, Snyder PJ, Swerdloff RS, Wu FC, Yialamas MA (2018) Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 103(5):1715–1744. 10.1210/jc.2018-00229
Dalton JT, Barnette KG, Bohl CE, Hancock ML, Rodriguez D, Dodson ST, Morton RA, Steiner MS (2011) The selective androgen receptor modulator gtx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase ii trial. J Cachexia Sarcopenia Muscle 2(3):153–161. 10.1007/s13539-011-0034-6
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(2):104–115
Rudman D, Feller AG, Nagraj HS, Gergans GA, Lalitha PY, Goldberg AF, Schlenker RA, Cohn L, Rudman IW, Mattson DE (1990) Effects of human growth hormone in men over 60 years old. N Engl J Med 323(1):1–6. 10.1056/NEJM199007053230101
Papadakis MA, Grady D, Black D, Tierney MJ, Gooding GA, Schambelan M, Grunfeld C (1996) Growth hormone replacement in healthy older men improves body composition but not functional ability. Ann Intern Med 124(8):708–716
Blackman MR, Sorkin JD, Munzer T, Bellantoni MF, Busby-Whitehead J, Stevens TE, Jayme J, O’Connor KG, Christmas C, Tobin JD, Stewart KJ, Cottrell E, St Clair C, Pabst KM, Harman SM (2002) Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial. JAMA 288(18):2282–2292
Nass R, Pezzoli S, Clancy Oliveri M, Patrie J, Harrell F, Clasey J, Heymsfield S, Bach M, Lee Vance M, Thorner M (2008) Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults a randomized trial. Ann Intern Med 149(9):601–611
Adunsky A, Chandler J, Heyden N, Lutkiewicz J, Scott BB, Berd Y, Liu N, Papanicolaou DA (2011) Mk-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study. Arch Gerontol Geriatr 53(2):183–189. 10.1016/j.archger.2010.10.004
Bach MA, Rockwood K, Zetterberg C, Thamsborg G, Hebert R, Devogelaer JP, Christiansen JS, Rizzoli R, Ochsner JL, Beisaw N, Gluck O, Yu L, Schwab T, Farrington J, Taylor AM, Ng J, Fuh V, Group MKHFS (2004) The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture. J Am Geriatr Soc 52(4):516–523. 10.1111/j.1532-5415.2004.52156.x
Guo B, Zhang ZK, Liang C, Li J, Liu J, Lu A, Zhang BT, Zhang G (2017) Molecular communication from skeletal muscle to bone: a review for muscle-derived myokines regulating bone metabolism. Calcif Tissue Int 100(2):184–192. 10.1007/s00223-016-0209-4
Rooks DS, Laurent D, Praestgaard J, Rasmussen S, Bartlett M, Tanko LB (2017) Effect of bimagrumab on thigh muscle volume and composition in men with casting-induced atrophy. J Cachexia Sarcopenia Muscle 8(5):727–734. 10.1002/jcsm.12205
Rooks D, Praestgaard J, Hariry S, Laurent D, Petricoul O, Perry RG, Lach-Trifilieff E, Roubenoff R (2017) Treatment of sarcopenia with bimagrumab: results from a phase II, randomized, controlled, proof-of-concept study. J Am Geriatr Soc 65(9):1988–1995. 10.1111/jgs.14927
Garito T, Roubenoff R, Hompesch M, Morrow L, Gomez K, Rooks D, Meyers C, Buchsbaum MS, Neelakantham S, Swan T, Filosa LA, Laurent D, Petricoul O, Zakaria M (2018) Bimagrumab improves body composition and insulin sensitivity in insulin-resistant individuals. Diabetes Obes Metab 20(1):94–102. 10.1111/dom.13042
Sumukadas D, Witham MD, Struthers AD, McMurdo ME (2007) Effect of perindopril on physical function in elderly people with functional impairment: a randomized controlled trial. CMAJ 177(8):867–874. 10.1503/cmaj.061339
Cesari M, Pedone C, Incalzi RA, Pahor M (2010) Ace-inhibition and physical function: results from the trial of angiotensin-converting enzyme inhibition and novel cardiovascular risk factors (train) study. J Am Med Dir Assoc 11(1):26–32. 10.1016/j.jamda.2009.09.014
Band MM, Sumukadas D, Struthers AD, Avenell A, Donnan PT, Kemp PR, Smith KT, Hume CL, Hapca A, Witham MD (2018) Leucine and ACE inhibitors as therapies for sarcopenia (LACE trial): study protocol for a randomised controlled trial. Trials 19(1):6. 10.1186/s13063-017-2390-9
