Research Article| Volume 101, P42-50, July 2017

Effectiveness of nutritional supplementation on sarcopenia and recovery in hip fracture patients. A multi-centre randomized trial

  • Vincenzo Malafarina
    Corresponding author at:. Depratment of Geriatrics Complejo Hospitalario de Navarra, Calle Irunlarrea, 31008 Pamplona, Spain.
    Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain

    Department of Geriatrics, Complejo Hospitalario de Navarra, Pamplona, Spain
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  • Francisco Uriz-Otano
    Department of Geriatrics, Hospital San Juan de Dios, Pamplona, Spain
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  • Concetta Malafarina
    Department of Radiology, Complejo Hospitalario de Navarra, Pamplona, Spain
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  • J. Alfredo Martinez
    Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain

    CIBERobn, Physiopathology of Obesity and Nutrition, Instituto de Salud Carlos III, Madrid, Spain

    Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain

    Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
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  • M. Angeles Zulet
    Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain

    CIBERobn, Physiopathology of Obesity and Nutrition, Instituto de Salud Carlos III, Madrid, Spain

    Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain

    Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
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      • Oral nutritional supplementation improves functional recovery and body composition.
      • β-Hydroxy-β-methylbutyrate preserves muscle mass in elderly patients who have had a hip fracture.
      • Oral nutritional supplementation improves nutritional aspects during rehabilitation.
      • High-protein supplements and β-hydroxy-β-methylbutyrate may prevent the onset of sarcopenic obesity.


      Background and objectives

      Functional deterioration and reduced mobility in elderly patients with a hip fracture are associated with a loss of both muscle mass and function (sarcopenia). The aim of this study was to assess whether oral nutritional supplementation (ONS) improves muscle mass and nutritional markers (BMI, proteins) in elderly patients with hip fracture.


      Patients aged 65 years and over with hip fractures admitted to either of two rehabilitation facilities were included. Patients with diabetes, with Barthel index scores <40 prior to the fracture or with pathological fractures were excluded. A random-numbers generator was used to randomly allocate patients to the intervention group (IG) or the control group (CG). Those in the IG received a standard diet plus ONS in the form of two bottles a day of β-hydroxy-β-methylbutyrate (HMB), while those in the CG received a standard diet only. The intervention was not blinded.
      In order to assess changes in body mass index (BMI), anthropometric parameters were recorded at both admission and discharge. Patients’ functional situation was evaluated using the Barthel index (BI) and the Functional Ambulation Categories (FAC) score. Muscle mass was assessed using bioelectrical impedance analysis, which allowed us to calculate appendicular lean mass (aLM). The outcome variable was the difference between aLM upon discharge, minus aLM upon admission (Δ-aLM).


      Of the 107 randomised patients (IG n55, CG n52), 49 finished the study in the IG and 43 in the CG. BMI and aLM were stable in IG patients, whilst these parametres decreased in the CG. A significant difference was observed between the two groups (p < 0.001, and p = 0.020 respectively). The predictive factors for Δ-aLM were ONS (p = 0.006), FAC prior to fracture (p < 0.001) and BI prior to fracture (p = 0.007).
      The concentration of proteins (p = 0.007) and vitamin D (p.001) had increased more in the IG than in the CG.


      A diet enriched in HMB improves muscle mass, prevents the onset of sarcopenia and is associated with functional improvement in elderly patients with hip fractures. Orally administered nutritional supplements can help to prevent the onset of sarcopenic obesity.
      Trial registration: identifier: NCT01404195, registered 22 July 2011, HYPERPROT-GER Study.


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        • Ensrud K.E.
        Epidemiology of fracture risk with advancing age.
        J. Gerontol. A. Biol. Sci. Med. Sci. 2013; 68: 1236-1242
        • Alvarez-Nebreda M.L.
        • Jimenez A.B.
        • Rodriguez P.
        • Serra J.A.
        Epidemiology of hip fracture in the elderly in Spain.
        Bone. 2008; 42: 278-285
        • Wakabayashi H.
        • Sashika H.
        Malnutrition is associated with poor rehabilitation outcome in elderly inpatients with hospital-associated deconditioning a prospective cohort study.
        J. Rehabil. Med. 2014; 46: 277-282
        • Uriz-Otano F.
        • Uriz-Otano J.I.
        • Malafarina V.
        Factors associated with short-term functional recovery in elderly people with a hip fracture. Influence of cognitive impairment.
        J. Am. Med. Dir. Assoc. 2015; 16: 215-220
        • Uriz-Otano F.
        • Pla-Vidal J.
        • Tiberio-Lopez G.
        • Malafarina V.
        Factors associated to institutionalization and mortality over three years, in elderly people with a hip fracture-an observational study.
        Maturitas. 2016; 89: 9-15
        • Vellas B.
        • Fielding R.
        • Miller R.
        • Rolland Y.
        • Bhasin S.
        • Magaziner J.
        • Bischoff-Ferrari H.
        Designing drug trials for sarcopenia in older adults with hip fracture − a task force from the International Conference on Frailty and Sarcopenia Research (ICFSR).
        J. Frailty Aging. 2014; 3: 199-204
        • Hida T.
        • Ishiguro N.
        • Shimokata H.
        • Sakai Y.
        • Matsui Y.
        • Takemura M.
        • Terabe Y.
        • Harada A.
        High prevalence of sarcopenia and reduced leg muscle mass in Japanese patients immediately after a hip fracture.
        Geriatr. Gerontol. Int. 2013; 13: 413-420
        • Di Monaco M.
        • Castiglioni C.
        • Vallero F.
        • Di Monaco R.
        • Tappero R.
        Sarcopenia is more prevalent in men than in women after hip fracture: a cross-sectional study of 591 inpatients.
        Arch. Gerontol. Geriatr. 2012; 55: e48-e52
        • Kuhls D.A.
        • Rathmacher J.A.
        • Musngi M.D.
        • Frisch D.A.
        • Nielson J.
        • Barber A.
        • MacIntyre A.D.
        • Coates J.E.
        • Fildes J.J.
        Beta-hydroxy-beta-methylbutyrate supplementation in critically ill trauma patients.
        J. Trauma. 2007; 62 (discussion 131-2): 125-131
        • Malafarina V.
        • Uriz-Otano F.
        • Gil-Guerrero L.
        • Iniesta R.
        The anorexia of ageing: physiopathology, prevalence, associated comorbidity and mortality. A systematic review.
        Maturitas. 2013; 74: 293-302
        • Malafarina V.
        • Uriz-Otano F.
        • Iniesta R.
        • Gil-Guerrero L.
        Effectiveness of nutritional supplementation on muscle mass in treatment of sarcopenia in old age: a systematic review.
        J. Am. Med. Dir. Assoc. 2013; 14: 10-17
        • Marshall S.
        Protein-energy malnutrition in the rehabilitation setting: evidence to improve identification.
        Maturitas. 2016; 86: 77-85
        • Koren-Hakim T.
        • Weiss A.
        • Hershkovitz A.
        • Otzrateni I.
        • Grosman B.
        • Frishman S.
        • Salai M.
        • Beloosesky Y.
        The relationship between nutritional status of hip fracture operated elderly patients and their functioning, comorbidity and outcome.
        Clin. Nutr. 2012; 31: 917-921
        • Gumieiro D.N.
        • Rafacho B.P.
        • Goncalves A.F.
        • Tanni S.E.
        • Azevedo P.S.
        • Sakane D.T.
        • Carneiro C.A.
        • Gaspardo D.
        • Zornoff L.A.
        • Pereira G.J.
        • Paiva S.A.
        • Minicucci M.F.
        Mini nutritional assessment predicts gait status and mortality 6 months after hip fracture.
        Br. J. Nutr. 2013; 109: 1657-1661
        • Agarwal E.
        • Miller M.
        • Yaxley A.
        • Isenring E.
        Malnutrition in the elderly: a narrative review.
        Maturitas. 2013; 76: 296-302
        • Fitschen P.J.
        • Wilson G.J.
        • Wilson J.M.
        • Wilund K.R.
        Efficacy of beta-hydroxy-beta-methylbutyrate supplementation in elderly and clinical populations.
        Nutrition. 2013; 29: 29-36
        • Kuriyan R.
        • Lokesh D.P.
        • Selvam S.
        • Jayakumar J.
        • Philip M.G.
        • Shreeram S.
        • Kurpad A.V.
        The relationship of endogenous plasma concentrations of beta-hydroxy beta-methyl butyrate (HMB) to age and total appendicular lean mass in humans.
        Exp. Gerontol. 2016; 81: 13-18
        • Rizzoli R.
        • Stevenson J.C.
        • Bauer J.M.
        • van Loon L.J.
        • Walrand S.
        • Kanis J.A.
        • Cooper C.
        • Brandi M.L.
        • Diez-Perez A.
        • Reginster J.Y.
        • ESCEO Task Force
        The role of dietary protein and vitamin D in maintaining musculoskeletal health in postmenopausal women: a consensus statement from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO).
        Maturitas. 2014; 79: 122-132
        • Espaulella J.
        • Guyer H.
        • Diaz-Escriu F.
        • Mellado-Navas J.A.
        • Castells M.
        • Pladevall M.
        Nutritional supplementation of elderly hip fracture patients. A randomized, double-blind, placebo-controlled trial.
        Age Ageing. 2000; 29: 425-431
        • Anbar R.
        • Beloosesky Y.
        • Cohen J.
        • Madar Z.
        • Weiss A.
        • Theilla M.
        • Koren Hakim T.
        • Frishman S.
        • Singer P.
        Tight calorie control in geriatric patients following hip fracture decreases complications: a randomized, controlled study.
        Clin. Nutr. 2014; 33: 23-28
        • Myint M.W.
        • Wu J.
        • Wong E.
        • Chan S.P.
        • To T.S.
        • Chau M.W.
        • Ting K.H.
        • Fung P.M.
        • Au K.S.
        Clinical benefits of oral nutritional supplementation for elderly hip fracture patients: a single blind randomised controlled trial.
        Age Ageing. 2013; 42: 39-45
        • Malafarina V.
        • Uriz-Otano F.
        • Gil-Guerrero L.
        • Iniesta R.
        • Zulet M.A.
        • Martinez J.A.
        Study protocol: high-protein nutritional intervention based on beta-hydroxy-beta-methylbutirate, vitamin D3 and calcium on obese and lean aged patients with hip fractures and sarcopenia. the HIPERPROT-GER study.
        Maturitas. 2013; 76: 123-128
        • Roberts H.C.
        • Denison H.J.
        • Martin H.J.
        • Patel H.P.
        • Syddall H.
        • Cooper C.
        • Sayer A.A.
        A review of the measurement of grip strength in clinical and epidemiological studies: towards a standardised approach.
        Age Ageing. 2011; 40: 423-429
        • Bautmans I.
        • Onyema O.
        • Van Puyvelde K.
        • Pleck S.
        • Mets T.
        Grip work estimation during sustained maximal contraction: validity and relationship with dependency and inflammation in elderly persons.
        J. Nutr. Health Aging. 2011; 15: 731-736
        • Sergi G.
        • De Rui M.
        • Veronese N.
        • Bolzetta F.
        • Berton L.
        • Carraro S.
        • Bano G.
        • Coin A.
        • Manzato E.
        • Perissinotto E.
        Assessing appendicular skeletal muscle mass with bioelectrical impedance analysis in free-living Caucasian older adults.
        Clin. Nutr. 2015; 34: 667-673
        • Kim J.
        • Heshka S.
        • Gallagher D.
        • Kotler D.P.
        • Mayer L.
        • Albu J.
        • Shen W.
        • Freda P.U.
        • Heymsfield S.B.
        Intermuscular adipose tissue-free skeletal muscle mass: estimation by dual-energy X-ray absorptiometry in adults.
        J. Appl. Physiol (1985). 2004; 97: 655-660
        • Cruz-Jentoft A.J.
        • Baeyens J.P.
        • Bauer J.M.
        • Boirie Y.
        • Cederholm T.
        • Landi F.
        • Martin F.C.
        • Michel J.P.
        • Rolland Y.
        • Schneider S.M.
        • Topinkova E.
        • Vandewoude M.
        • Zamboni M.
        European working group on sarcopenia in older people, sarcopenia: european consensus on definition and diagnosis: report of the European working group on sarcopenia in older people.
        Age Ageing. 2010; 39: 412-423
        • Rubenstein L.Z.
        • Harker J.O.
        • Salva A.
        • Guigoz Y.
        • Vellas B.
        Screening for undernutrition in geriatric practice: developing the short-form mini-nutritional assessment (MNA-SF).
        J. Gerontol. A. Biol. Sci. Med. Sci. 2001; 56: M366-72
        • Mahoney F.I.
        • Barthel D.W.
        Functional evaluation: the barthel index.
        Md. State Med. J. 1965; 14: 61-65
        • Viosca E.
        • Martinez J.L.
        • Almagro P.L.
        • Gracia A.
        • Gonzalez C.
        Proposal and validation of a new functional ambulation classification scale for clinical use.
        Arch. Phys. Med. Rehabil. 2005; 86: 1234-1238
        • Folstein M.F.
        • Folstein S.E.
        • McHugh P.R.
        Mini-mental state. A practical method for grading the cognitive state of patients for the clinician.
        J. Psychiatr. Res. 1975; 12: 189-198
        • Charlson M.E.
        • Pompei P.
        • Ales K.L.
        • MacKenzie C.R.
        A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.
        J. Chronic Dis. 1987; 40: 373-383
        • Matthews D.R.
        • Hosker J.P.
        • Rudenski A.S.
        • Naylor B.A.
        • Treacher D.F.
        • Turner R.C.
        Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.
        Diabetologia. 1985; 28: 412-419
        • Diaz Palacios M.E.
        • Dominguez Puente O.
        • Toyos Garcia G.
        Results of the application of a scale of a scale of sociofamily values in primary attention.
        Revista Espanola de Geriatria y Gerontologia. 1994; 29: 239-245
        • Landi F.
        • Liperoti R.
        • Russo A.
        • Giovannini S.
        • Tosato M.
        • Capoluongo E.
        • Bernabei R.
        • Onder G.
        Sarcopenia as a risk factor for falls in elderly individuals: results from the ilSIRENTE study.
        Clin. Nutr. 2012; 31: 652-658
        • Rossi A.P.
        • Fantin F.
        • Micciolo R.
        • Bertocchi M.
        • Bertassello P.
        • Zanandrea V.
        • Zivelonghi A.
        • Bissoli L.
        • Zamboni M.
        Identifying sarcopenia in acute care setting patients.
        J. Am. Med. Dir. Assoc. 2014; 15 (303.e7–303.12)
        • Senior H.E.
        • Henwood T.R.
        • Beller E.M.
        • Mitchell G.K.
        • Keogh J.W.
        Prevalence and risk factors of sarcopenia among adults living in nursing homes.
        Maturitas. 2015; 82: 418-423
        • Malafarina V.
        • Uriz-Otano F.
        • Iniesta R.
        • Gil-Guerrero L.
        Sarcopenia in the elderly: diagnosis, physiopathology and treatment.
        Maturitas. 2012; 71: 109-114
        • Vidan M.
        • Serra J.A.
        • Moreno C.
        • Riquelme G.
        • Ortiz J.
        Efficacy of a comprehensive geriatric intervention in older patients hospitalized for hip fracture: a randomized, controlled trial.
        J. Am. Geriatr. Soc. 2005; 53: 1476-1482
        • Ortiz-Alonso F.J.
        • Vidan-Astiz M.
        • Alonso-Armesto M.
        • Toledano-Iglesias M.
        • Alvarez-Nebreda L.
        • Branas-Baztan F.
        • Serra-Rexach J.A.
        The pattern of recovery of ambulation after hip fracture differs with age in elderly patients.
        J. Gerontol. A. Biol. Sci. Med. Sci. 2012; 67: 690-697
        • Camina-Martin M.A.
        • de Mateo-Silleras B.
        • Malafarina V.
        • Lopez-Mongil R.
        • Nino-Martin V.
        • Lopez-Trigo J.A.
        • Redondo-del-Rio M.P.
        Nutritional status assessment in geriatrics: consensus declaration by the spanish society of geriatrics and gerontology nutrition work group.
        Maturitas. 2015; 81: 414-419
        • Steihaug O.M.
        • Gjesdal C.G.
        • Bogen B.
        • Ranhoff A.H.
        Identifying low muscle mass in patients with hip fracture: validation of biolectrical impedance analysis and anthropometry compared to dual energy X-ray absorptiometry.
        J. Nutr. Health Aging. 2016; 20: 685-690
        • Paz Redondo-del-Rio M.
        • Alicia Camina-Martin M.
        • Moya-Gago L.
        • de-la-Cruz-Marcos S.
        • Malafarina V.
        • de-Mateo-Silleras B.
        Vector bioimpedance detects situations of malnutrition not identified by the indicators commonly used in geriatric nutritional assessment: a pilot study.
        Exp. Gerontol. 2016; 85: 108-111
        • Argiles J.M.
        • Campos N.
        • Lopez-Pedrosa J.M.
        • Rueda R.
        • Rodriguez-Manas L.
        Skeletal muscle regulates metabolism via interorgan crosstalk: roles in health and disease.
        J. Am. Med. Dir. Assoc. 2016; 17: 789-796
        • Hita-Contreras F.
        • Martinez-Amat A.
        • Cruz-Diaz D.
        • Perez-Lopez F.R.
        Osteosarcopenic obesity and fall prevention strategies.
        Maturitas. 2015; 80: 126-132
        • Prado C.M.
        • Gonzalez M.C.
        • Heymsfield S.B.
        Body composition phenotypes and obesity paradox.
        Curr. Opin. Clin. Nutr. Metab. Care. 2015; 18: 535-551
        • Artaza-Artabe I.
        • Saez-Lopez P.
        • Sanchez-Hernandez N.
        • Fernandez-Gutierrez N.
        • Malafarina V.
        The relationship between nutrition and frailty: effects of protein intake, nutritional supplementation, vitamin D and exercise on muscle metabolism in the elderly. A systematic review.
        Maturitas. 2016; 93: 89-99
        • Raschke S.
        • Eckel J.
        Adipo-myokines: two sides of the same coin–mediators of inflammation and mediators of exercise.
        Mediators Inflamm. 2013; 2013: 320724
        • Fischer C.P.
        Interleukin-6 in acute exercise and training: what is the biological relevance.
        Exerc. Immunol. Rev. 2006; 12: 6-33