Advertisement

The health economics burden of sarcopenia: a systematic review

  • Olivier Bruyère
    Correspondence
    Corresponding author at: World Health Organization Collaborating Center for the Public Health Aspects of Musculoskeletal Health and Aging Department of Public Health, Epidemiology and Health Economics, CHU - Sart Tilman, Quartier Hôpital, Avenue Hippocrate 13 (Bât. B23), 4000, Liège, Belgium.
    Affiliations
    World Health Organization Collaborating Center for the Public Health Aspects of Musculoskeletal Health and Aging, Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
    Search for articles by this author
  • Charlotte Beaudart
    Affiliations
    World Health Organization Collaborating Center for the Public Health Aspects of Musculoskeletal Health and Aging, Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
    Search for articles by this author
  • Olivier Ethgen
    Affiliations
    World Health Organization Collaborating Center for the Public Health Aspects of Musculoskeletal Health and Aging, Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
    Search for articles by this author
  • Jean-Yves Reginster
    Affiliations
    World Health Organization Collaborating Center for the Public Health Aspects of Musculoskeletal Health and Aging, Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
    Search for articles by this author
  • Médéa Locquet
    Affiliations
    World Health Organization Collaborating Center for the Public Health Aspects of Musculoskeletal Health and Aging, Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
    Search for articles by this author
Open AccessPublished:November 12, 2018DOI:https://doi.org/10.1016/j.maturitas.2018.11.003

      Highlights

      • Our systematic review found 14 studies that compared the healthcare costs of treating sarcopenic and non-sarcopenic patients.
      • Eleven of these studies showed higher healthcare costs for sarcopenic patients than for non-sarcopenic patients.
      • These studies were very heterogeneous regarding populations and settings, the assessment of sarcopenia and the type of costs evaluated.
      • Most of the included studies showed methodological bias, especially the absence of adjustment for important confounding variables.
      • More well designed studies are needed before it can be concluded that sarcopenia increases healthcare costs.

      Abstract

      Despite of better knowledge about sarcopenia, an optimal understanding of its consequences from a public health perspective remains a challenge. Specifically, the economic burden of the illness is unclear. As a support for the public health policy makers and other health actors, our objective was to perform a systematic review of the literature comparing healthcare costs between sarcopenic and non-sarcopenic patients (under the registration number CRD42018099291). A search for relevant articles was conducted on the Medline and Scopus databases. Rigorous eligibility criteria were established (e.g., subjects with sarcopenia, both men and women, mean age of the sarcopenic population) and applied by two investigators to identify suitable studies. The first screening phase, performed by 2 independent reviewers, covered 455 references. Fourteen relevant studies were included in the final analysis. Overall, we noted an important heterogeneity between studies in the way of assessing sarcopenia (i.e. operational definitions, tools and cut-offs used). There were also large variations between studies in their cost analysis settings (i.e., discrepancies in time horizon, types and sources of economic data). Most of the studies focused on hospitalization costs following surgery for a specific disease such as cancer. Finally, 11 out of the 14 studies reported higher healthcare costs for sarcopenic patients. However, most of the included studies have important methodological bias (e.g. potential confusion factors rarely taken into account), and low to moderate quality scores. More standardized research, taking into account all the limitations of the published studies, should be conducted to assess the true impact of sarcopenia on healthcare consumption.

      Keywords

      1. Introduction

      Sarcopenia, defined as a loss of muscle mass and function, is increasingly considered to be a major public health problem in the older population and in a range of clinical settings [
      • Beaudart C.
      • Rizzoli R.
      • Bruyère O.
      • et al.
      Sarcopenia: burden and challenges for public health.
      ,
      • Ryan A.M.
      • Power D.G.
      • Daly L.
      • et al.
      Cancer-associated malnutrition, cachexia and sarcopenia: the skeleton in the hospital closet 40 years later.
      ]. Indeed, the health consequences of sarcopenia include death, falls, new or prolonged hospitalizations, fractures, loss of mobility and physical function, a reduced quality of life [
      • Beaudart C.
      • Zaaria M.
      • Pasleau F.
      • et al.
      Health Outcomes of Sarcopenia: A Systematic Review and Meta-Analysis.
      ,
      • Shen Y.
      • Hao Q.
      • Zhou J.
      • Dong B.
      The impact of frailty and sarcopenia on postoperative outcomes in older patients undergoing gastrectomy surgery: a systematic review and meta-analysis.
      ,
      • Pamoukdjian F.
      • Bouillet T.
      • Lévy V.
      • et al.
      Prevalence and predictive value of pre-therapeutic sarcopenia in cancer patients: A systematic review.
      ,
      • Zhao Y.
      • Zhang Y.
      • Hao Q.
      • et al.
      Sarcopenia and hospital-related outcomes in the old people: a systematic review and meta-analysis.
      ]. Interestingly, most of these outcomes have potential direct or indirect costs, both for the patient and the society. If a lot of studies assessing the clinical outcomes of sarcopenia have been published, far less studies assessing the costs of sarcopenia are available. The economic burden-of-illness due to its engendered costs is acutely under-explored but however essential for public health policies makers. At the population level, probably the most cited paper on the economic burden of sarcopenia suggested that, in the United States, the direct health care cost attributable to this disease was estimated, for the year 2000, at $18.5 billion (i.e. 1.5% of the total healthcare expenditure) [
      • Janssen I.
      • Shepard D.S.
      • Katzmarzyk P.T.
      • Roubenoff R.
      The healthcare costs of sarcopenia in the United States.
      ]. It should be acknowledged that, in this particular study, no direct individual assessment of healthcare costs was made. However, since a couple of years, some studies have been published to assess, at the individual level, the economic burden of sarcopenia.
      The objective of the present paper is then to summarize, through a systematic review of the literature, all available information in observational studies regarding the healthcare costs of sarcopenia compared to those of individuals without the disease.

      2. Methods

      The research protocol has been published in July 2018 in PROSPERO under the registration number CRD42018099291 (https://www.crd.york.ac.uk/prospero/export_record_pdf.php).
      For the present analysis, the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement has been rigorously followed through all steps of the research [
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • et al.
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement.
      ]. Our issue of interest was first correctly identified and defined using the following PICOS strategy: Population or disease – sarcopenic subjects; Intervention – not applicable; Comparator – subjects without sarcopenia if studied; Outcomes – health care costs; Study design - observational.

      2.1 Literature search

      The electronic databases MEDLINE (via Ovid) and Scopus were searched on May 2018 for cross-sectional, prospective and case-control studies, published in English or in French, reporting on an economic analysis (i.e., monetary value) in sarcopenic individuals. No date limitation was applied. The search strategy (applied on MEDLINE, via Ovid) and search terms, both indexed and free text, used for this research are detailed through Table 1. Additional relevant studies were identified through a manual search of the bibliographic references of relevant articles and existing reviews.
      Table 1Search strategy applied on Medline (via Ovid).
      1 SARCOPENIA/

      2 sarcopenia.ti,ab,kf.

      3 1 or 2

      4 Health Care Costs/

      5 costs.ti,ab,kf.

      6 Health Expenditures/

      7 expense*.ti,ab,kf.

      8 expenditure*.ti,ab,kf.

      9 payment*.ti,ab,kf.

      10 out-of-pocket.ti,ab,kf.

      11 (care adj2 consumption).ti,ab,kf.

      12 economic*.ti,ab,kf.

      13 "cost of illness".ti,ab,kf.

      14 budget*.ti,ab,kf.

      15 monetary.ti,ab,kf.

      16 ((resource* or drug*) adj2 (utili?ation or allocat* or use*)).ti,ab,kf.

      17 ((health or healthcare or direct service* or indirect service* or hospital* or drug*) adj2 (cost or use* or

      utili?ation or resource* or consumption)).ti,ab,kf.

      18 financial.ti,ab,kf.

      19 reimbursement.ti,ab,kf.

      20 ((health* or care) adj2 service).ti,ab,kf.

      21 (burden adj2 (illness or disease* or health*)).ti,ab,kf.

      22 "informal care".ti,ab,kf.

      23 ((patient or societal or health or institutional) adj2 perspective).ti,ab,kf.

      24 (cost* adj2 analys*).ti,ab,kf.

      25 "cost effective".ti,ab,kf.

      26 "health policy".ti,ab,kf.

      27 qalys.ti,ab,kf.

      28 dalys.ti,ab,kf.

      29 "quality-adjusted life years".ti,ab,kf.

      30 "disability-adjusted life years".ti,ab,kf.

      31 or/4-30

      32 and/3,31

      2.2 Study selection

      In the initial screening stage, two investigators independently reviewed the title and abstract of each of the references to exclude articles irrelevant to the systematic review, according to predefined inclusion criteria (Table 2). In the second step, the two investigators independently read the full texts of the articles that were not excluded in the initial stage and relevant selected studies that truly met all the inclusion criteria. If there was any doubt or discrepancies about the inclusion of an article, the final decision was undertaken through discussion and when needed, through the intervention of a third reviewer.
      Table 2Inclusion criteria.
      DesignCross-sectional studies, prospective studies and case-control studies.
      ParticipantsSubjects with sarcopenia, both men and women, mean age of a sarcopenic population, no restriction regarding ethnicity or living environment (i.e., community-dwelling, institutionalized, hospitalized).
      Diagnosis of sarcopeniaAny diagnosis criteria
      OutcomeHealth care costs/expenditures: expenditure on health care to be expressed in terms of monetary units, regardless of the manner by which it has been reported (e.g. based on care certificates, questionnaires, self-reports, medical records, etc.).
      LanguageFrench or English

      2.3 Data extraction

      Data were extracted by one reviewer according to a standardized data extraction form, previously pre-tested on a sample of 3 studies. All extracted data were double checked by the second reviewer and any differences in point of view were discussed in order to achieve consensus. The following data were extracted: authors; journal name; year of publication; country; objective of the study; socio-demographic data (country, type of population, sex ratio, mean age); sample size; design (number of groups, description of groups); tools and cut-offs used to assess sarcopenia (muscle mass, muscle strength and physical performance); health economic outcome(s) in monetary value; source and method of data collection ; perspective of cost ; time horizon of cost data collection ; adjustment factors ; conclusion; potential conflicts of interest and funding. When data of interest were missing, we systematically contacted authors or co-authors when information was missing in the full-text article.

      2.4 Study quality assessment

      All included studies were appraised for methodological quality by two independent reviewers using the Joanna Briggs Institute critical appraisal tools [
      • The Joanna Briggs Institute
      Checklist for systematic reviews and research syntheses.
      ]. The two reviewers critically assessed the studies independently from each other, answering “Yes’’, “No’’, “Unclear’’, or “Not applicable’’ to 8 questions (for cross-sectional studies), 10 questions (for case-control studies) or 11 questions (for cohort studies) about methodological main concerns. After these two independent reviews, the results were confronted and and any discrepancies discussed with a third reviewer experienced in systematic reviews. Each study was displayed with its total points, and the number of “Yes” responses was summed for each study. We considered every study that met the inclusion criteria, independent of their quality.

      2.5 Data synthesis

      A descriptive analysis of the included studies has been performed under the format of a narrative report. Results have been structured according to a primary description of their general characteristics, followed by the evaluation of the intrinsic methodological quality of studies to conclude with a description of the cost comparison analyzes of each included references.

      3. Results

      3.1 Literature Search

      The initial databases search yielded 450 references to systematically assess. An additional 5 studies, identified through a manual research, were also eligible. After the process of selection based on abstract and title and after on the full-text article review (Fig. 1), we finally included 14 studies assessing the difference in health care costs between individuals with or without sarcopenia[
      • Antunes A.C.
      • Araújo D.A.
      • Veríssimo M.T.
      • Amaral T.F.
      Sarcopenia and hospitalisation costs in older adults: a cross-sectional study.
      ,
      • Bokshan S.L.
      • Han A.
      • DePasse J.M.
      • et al.
      Inpatient costs and blood  transfusion rates of sarcopenic patients following thoracolumbar spine surgery.
      ,
      • Chen W.-Z.
      • Chen X.-D.
      • Ma L.-L.
      • et al.
      Impact of Visceral Obesity and Sarcopenia on Short-Term Outcomes After Colorectal Cancer Surgery.
      ,
      • Gani F.
      • Buettner S.
      • Margonis G.A.
      • et al.
      Sarcopenia predicts costs among patients undergoing major abdominal operations.
      ,
      • Huang D.D.
      • Zhou C.J.
      • Wang S.L.
      • et al.
      Impact of different sarcopenia stages on the postoperative outcomes after radical gastrectomy for gastric cancer.
      ,
      • Kirk P.S.
      • Friedman J.F.
      • Cron D.C.
      • et al.
      One-year postoperative resource utilization in sarcopenic patients.
      ,
      • Kaplan S.J.
      • Pham T.N.
      • Arbabi S.
      • et al.
      Association of radiologic indicators of frailty with 1-year mortality in older trauma patients: Opportunistic screening for sarcopenia and osteopenia.
      ,
      • Lo Y.T.C.
      • Wahlqvist M.L.
      • Huang Y.C.
      • et al.
      Medical costs of a low skeletal muscle mass are modulated by dietary diversity and physical activity in community-dwelling older Taiwanese: A longitudinal study.
      ,
      • Lou N.
      • Chi C.H.
      • Chen X.D.
      • et al.
      Sarcopenia in overweight and obese patients is a predictive factor for postoperative complication in gastric cancer: A prospective study.
      ,
      • Mijnarends D.M.
      • Schols J.M.G.A.
      • Halfens R.J.G.
      • et al.
      Burden-of-illness of Dutch community-dwelling older adults with sarcopenia: Health related outcomes and costs.
      ,
      • Sheetz K.H.
      • Waits S.A.
      • Terjimanian M.N.
      • et al.
      Cost of major surgery in the sarcopenic patient.
      ,
      • Sousa A.S.
      • Guerra R.S.
      • Fonseca I.
      • et al.
      Financial impact of sarcopenia on hospitalization costs.
      ,
      • van Vugt J.L.A.
      • Buettner S.
      • Alferink L.J.M.
      • et al.
      Low skeletal muscle mass is associated with increased hospital costs in patients with cirrhosis listed for liver transplantation-a retrospective study.
      ,
      • Wang S.L.
      • Zhuang C.
      • Le
      • Huang D.D.
      • et al.
      Sarcopenia Adversely Impacts Postoperative Clinical Outcomes Following Gastrectomy in Patients with Gastric Cancer: A Prospective Study.
      ]. Sixteen studies were rejected because of duplicate (n = 2) [
      • Bokshan S.L.
      • Han A.
      • DePasse J.M.
      • et al.
      Inpatient costs and blood  transfusion rates of sarcopenic patients following thoracolumbar spine surgery.
      ,
      • Sheetz K.H.
      • Waits S.A.
      • Terjimanian M.N.
      • et al.
      Cost of major surgery in the sarcopenic patient.
      ], wrong outcomes (n = 13) [
      • Tan L.F.
      • Lim Z.Y.
      • Choe R.
      • et al.
      Screening for Frailty and Sarcopenia Among Older Persons in Medical Outpatient Clinics and its Associations With Healthcare Burden.
      ,
      • Coto Montes A.
      • Boga J.A.
      • Bermejo Millo C.
      • et al.
      Potential early biomarkers of sarcopenia among independent older adults.
      ,
      • Wu T.-Y.
      • Liaw C.-K.
      • Chen F.-C.
      • et al.
      Sarcopenia Screened With SARC-F Questionnaire Is Associated With Quality of Life and 4-Year Mortality.
      ,
      • Cawthon P.M.
      • Fox K.M.
      • Gandra S.R.
      • et al.
      Do Muscle Mass, Muscle Density, Strength, and Physical Function Similarly Influence Risk of Hospitalization in Older Adults?.
      ,
      • König M.
      • Spira D.
      • Demuth I.
      • et al.
      Polypharmacy as a Risk Factor for Clinically Relevant Sarcopenia: Results From the Berlin Aging Study II.
      ,
      • Perna S.
      • Francis M.D.
      • Bologna C.
      • et al.
      Performance of Edmonton Frail Scale on frailty assessment: its association with multi-dimensional geriatric conditions assessed with specific screening tools.
      ,
      • Cawthon P.M.
      • Lui L.-Y.
      • McCulloch C.E.
      • et al.
      Sarcopenia and Health Care Utilization in Older Women.
      ,
      • Beaudart C.
      • Reginster J.Y.
      • Petermans J.
      • et al.
      Quality of life and physical components linked to sarcopenia: The SarcoPhAge study.
      ,
      • Du Y.
      • Karvellas C.J.
      • Baracos V.
      • et al.
      Sarcopenia is a predictor of outcomes in very elderly patients undergoing emergency surgery.
      ,
      • Næss G.
      • Kirkevold M.
      • Hammer W.
      • et al.
      Nursing care needs and services utilised by home-dwelling elderly with complex health problems: observational study.
      ,
      • Kilavuz A.
      • Meseri R.
      • Savas S.
      • et al.
      Association of sarcopenia with depressive symptoms and functional status among ambulatory community-dwelling elderly.
      ,
      • Gao L.
      • Jiang J.
      • Yang M.
      • et al.
      Prevalence of Sarcopenia and Associated Factors in Chinese Community-Dwelling Elderly: Comparison Between Rural and Urban Areas.
      ,
      • van Vugt J.L.A.
      • Buettner S.
      • Levolger S.
      • et al.
      Low skeletal muscle mass is associated with increased hospital expenditure in patients undergoing cancer surgery of the alimentary tract.
      ] or wrong exposure factor (n = 1) [
      • Friedman J.
      • Lussiez A.
      • Sullivan J.
      • et al.
      Implications of Sarcopenia in Major Surgery.
      ].
      Fig. 1
      Fig. 1Detailed literature search flow diagram.

      3.2 Characteristics of the included studies

      A complete presentation of the characteristics and design of the 14 included studies [
      • Antunes A.C.
      • Araújo D.A.
      • Veríssimo M.T.
      • Amaral T.F.
      Sarcopenia and hospitalisation costs in older adults: a cross-sectional study.
      ,
      • Bokshan S.L.
      • Han A.
      • DePasse J.M.
      • et al.
      Inpatient costs and blood  transfusion rates of sarcopenic patients following thoracolumbar spine surgery.
      ,
      • Chen W.-Z.
      • Chen X.-D.
      • Ma L.-L.
      • et al.
      Impact of Visceral Obesity and Sarcopenia on Short-Term Outcomes After Colorectal Cancer Surgery.
      ,
      • Gani F.
      • Buettner S.
      • Margonis G.A.
      • et al.
      Sarcopenia predicts costs among patients undergoing major abdominal operations.
      ,
      • Huang D.D.
      • Zhou C.J.
      • Wang S.L.
      • et al.
      Impact of different sarcopenia stages on the postoperative outcomes after radical gastrectomy for gastric cancer.
      ,
      • Kirk P.S.
      • Friedman J.F.
      • Cron D.C.
      • et al.
      One-year postoperative resource utilization in sarcopenic patients.
      ,
      • Kaplan S.J.
      • Pham T.N.
      • Arbabi S.
      • et al.
      Association of radiologic indicators of frailty with 1-year mortality in older trauma patients: Opportunistic screening for sarcopenia and osteopenia.
      ,
      • Lo Y.T.C.
      • Wahlqvist M.L.
      • Huang Y.C.
      • et al.
      Medical costs of a low skeletal muscle mass are modulated by dietary diversity and physical activity in community-dwelling older Taiwanese: A longitudinal study.
      ,
      • Lou N.
      • Chi C.H.
      • Chen X.D.
      • et al.
      Sarcopenia in overweight and obese patients is a predictive factor for postoperative complication in gastric cancer: A prospective study.
      ,
      • Mijnarends D.M.
      • Schols J.M.G.A.
      • Halfens R.J.G.
      • et al.
      Burden-of-illness of Dutch community-dwelling older adults with sarcopenia: Health related outcomes and costs.
      ,
      • Sheetz K.H.
      • Waits S.A.
      • Terjimanian M.N.
      • et al.
      Cost of major surgery in the sarcopenic patient.
      ,
      • Sousa A.S.
      • Guerra R.S.
      • Fonseca I.
      • et al.
      Financial impact of sarcopenia on hospitalization costs.
      ,
      • van Vugt J.L.A.
      • Buettner S.
      • Alferink L.J.M.
      • et al.
      Low skeletal muscle mass is associated with increased hospital costs in patients with cirrhosis listed for liver transplantation-a retrospective study.
      ,
      • Wang S.L.
      • Zhuang C.
      • Le
      • Huang D.D.
      • et al.
      Sarcopenia Adversely Impacts Postoperative Clinical Outcomes Following Gastrectomy in Patients with Gastric Cancer: A Prospective Study.
      ] is accessible in Table 3. All studies, specifically regarding their analysis of sarcopenia-related costs, followed a cross-sectional design and was comprised of 50 to 1593 participants. All were interested in both sex, with the male gender more represented (i.e., over 50% of the general population), whose median age varied from 48.5 to 83 years. The type of population studied differed a little between studies : most were carried out on hospitalized individuals (10 studies out of 14, 71%), after surgery (8 studies out of 14, 57%) or not, but two studies [
      • Lo Y.T.C.
      • Wahlqvist M.L.
      • Huang Y.C.
      • et al.
      Medical costs of a low skeletal muscle mass are modulated by dietary diversity and physical activity in community-dwelling older Taiwanese: A longitudinal study.
      ,
      • Mijnarends D.M.
      • Schols J.M.G.A.
      • Halfens R.J.G.
      • et al.
      Burden-of-illness of Dutch community-dwelling older adults with sarcopenia: Health related outcomes and costs.
      ] related to healthy community-dwelling older adults and one to patients living in the community, but presenting a disease (i.e., cirrhosis) [
      • van Vugt J.L.A.
      • Buettner S.
      • Alferink L.J.M.
      • et al.
      Low skeletal muscle mass is associated with increased hospital costs in patients with cirrhosis listed for liver transplantation-a retrospective study.
      ]. Regarding diagnosis of sarcopenia, only half of the included studies reported using a definition of the disease recommended by scientific societies [
      • Antunes A.C.
      • Araújo D.A.
      • Veríssimo M.T.
      • Amaral T.F.
      Sarcopenia and hospitalisation costs in older adults: a cross-sectional study.
      ,
      • Chen W.-Z.
      • Chen X.-D.
      • Ma L.-L.
      • et al.
      Impact of Visceral Obesity and Sarcopenia on Short-Term Outcomes After Colorectal Cancer Surgery.
      ,
      • Lo Y.T.C.
      • Wahlqvist M.L.
      • Huang Y.C.
      • et al.
      Medical costs of a low skeletal muscle mass are modulated by dietary diversity and physical activity in community-dwelling older Taiwanese: A longitudinal study.
      ,
      • Lou N.
      • Chi C.H.
      • Chen X.D.
      • et al.
      Sarcopenia in overweight and obese patients is a predictive factor for postoperative complication in gastric cancer: A prospective study.
      ,
      • Mijnarends D.M.
      • Schols J.M.G.A.
      • Halfens R.J.G.
      • et al.
      Burden-of-illness of Dutch community-dwelling older adults with sarcopenia: Health related outcomes and costs.
      ,
      • Sousa A.S.
      • Guerra R.S.
      • Fonseca I.
      • et al.
      Financial impact of sarcopenia on hospitalization costs.
      ,
      • Wang S.L.
      • Zhuang C.
      • Le
      • Huang D.D.
      • et al.
      Sarcopenia Adversely Impacts Postoperative Clinical Outcomes Following Gastrectomy in Patients with Gastric Cancer: A Prospective Study.
      ].
      Table 3Characteristics of the 14 included studies.
      Authors, yearPopulation

      “n” and type of population

      Sex ratio
      Groups

      Definition

      N

      Age
      Diagnosis of sarcopeniaHealth care costs recording

      Source or method of data collection
      DefinitionMuscle mass

      Tool

      Cut-off
      Muscle strength

      Tool

      Cut-off
      Physical Performance

      Tool

      Cut-off
      Sousa, 2016656 hospitalized adult patients with an expected hospital stay longer than 24h

      354 (53.9%) male
      Two groups:

      Sarcopenia, n = 159, median age: 64 (IQR 19.0) years

      No sarcopenia, n = 497, median age: 54 (IQR 24) years
      EWGSOPBIA

      SMI <10.75 kg/m² for men, <6.75 kg/m² for women
      Hydraulic hand dynamometer

      < 30 kg for men, <20 kg for women
      Not applicableDischarge diagnosis-related group codes and determined on the basis of a relative weight value
      Huang, 2016470 adult patients who underwent a radical gastrectomy for gastric cancer

      364 (77.4%) male
      Four groups:

      Sarcopenia, n = 47, median age: 74 (IQR 10) years

      Pre-sarcopenia, n = 97, median age: 65 (IQR 4) years

      Severe sarcopenia, n = 32, median age: 76 (IQR 9.5) years

      Normal, n = 294, median age: 63 (IQR 4) years
      EWGSOP AWGSCT scan

      L3 SMI ≤ 40.8 cm²/m² in men, ≤34.9 cm²/m² in women
      Electronic hand dynamometer

      <26 kg for men, <18 kg for women
      6-meter gait speed

      ≤0.8 m/s
      Not reported
      Gani, 20161169 adult patients undergoing major abdominal operation

      608 (52.0%) male
      Two groups:

      Sarcopenia, n = 293, median age: 68 (IQR 59-75) years

      No sarcopenia, n = 876, median age: 60 (IQR 50-68) years
      /CT scan

      Lowest sex-specific quartile for L3 total psoas volume
      //Institutional cost accounting system.
      Lo, 20171337 healthy Taiwanese people aged 65 years and older

      689 (51.5%) male
      Two groups:

      Sarcopenia, n = 330, 65-69 years: 22.1% / 70-74 years 33.0%, 75-79 years 23.6%, >80 years: 21.2%

      No sarcopenia, n = 1007, 65-69 years: 44.8% / 70-74 years 33.9%, 75-79 years 15.4%, >80 years: 5.96%
      /BIA

      Lowest SMI quartile: < 11.4 kg/m² for men, <8.5 kg/m² for women
      //National Health Institute research database
      Kaplan, 2016450 patients aged 65 years and older admitted to an intensive care unit

      269 (59.8%) male
      Four groups:

      Sarcopenia only, n = 167, median age: 75 (IQR 69-83) years

      Osteopenia only, n = 48, median age: 78.5 (IQR 72-83) years

      Both sarcopenia and osteopenia, n = 74, median age: 83 (IQR 75-89) years

      No sarcopenia or osteopenia, n = 161, median age: 72 (IQR 68-78) years
      /CT scan

      L3 SMI ≤ 52.4 cm²/m² in men and ≤38.5 cm²/m² in women
      //Institution’s finance office
      Lou, 2017206 overweight and obese gastric cancer patients who underwent surgery

      161 (78.2%) male
      Two groups:

      Sarcopenia, n = 14, median age: 74.8 (IQR 5.1) years

      No sarcopenia, n = 192, median age: 63.3 (IQR 9.93) years
      EWGSOP AWGSCT scan

      L3 SMI ≤ 40.8 cm²/m² in men, ≤34.9 cm²/m² in women
      Electronic hand dynamometer

      <26 kg for men, <18 kg for women
      6-meter gait speed

      ≤0.8 m/s
      Not reported
      Wang, 2016255 patients with gastric cancer who underwent curative gastrectomy

      190 (74.5%) male
      Two groups:

      Sarcopenia, n = 32, median age: 74.7 (IQR 6.8) years

      No sarcopenia, n = 223, median age: 63.8 (10.7) years
      EWGSOP AWGSCT scan

      L3 SMI ≤ 36.0 cm²/m² in men, ≤29.0 cm²/m² in women
      Electronic hand dynamometer

      <26 kg for men, <18 kg for women
      6-meter gait speed

      ≤0.8 m/s
      Not reported
      Kirk, 20151279 patients undergoing elective major general or vascular surgery

      51.3% of male in sarcopenic patients, 51.2% of mal in non-sarcopenic patients
      Two groups:

      Sarcopenia, n = not reported, median age: 66.1 (IQR 14.0) years

      No sarcopenia, n = not reported, median age: 49.8 (13.9) years
      /CT scan

      L4 SMI < to the first tertile
      //Internal cost-accounting database
      Sheetz, 20131593 patients undergoing elective major general or vascular surgery

      52.3% of male in sarcopenic patients, 52.4% of mal in non-sarcopenic patients
      Two groups:

      Sarcopenia, n = not reported, median age: 64.4 (IQR 14.4) years

      No sarcopenia, n = not reported, median age: 48.5 (14.8) years
      /CT scan

      L4 SMI < first tertile
      //Internal cost-accounting database
      Antunes, 2017201 hospitalised older adults

      66.7% of male in sarcopenic patients, 37.8% of mal in non-sarcopenic patients
      Two groups:

      Sarcopenia, n = 21, >75 years: 2(9.5%), ≤75 years: 19 (90.5%)

      No sarcopenia, n = 180, >75 years: 74(41.1%), ≤75 years: 106 (58.9%)
      EWGSOPMid-arm circumference, triceps skin-fold thickness

      ≤ 2 standard deviations from the mean value of the muscle mass of young adults of the same gender and ethnic group
      Handheld grip

      ≤ 29 kg and BMI ≤ 24 kg/m², ≤ 30 and BMI between 24.1 and 28 kg/m², ≤ 32 and BMI > 28 kg/m² for men, ≤ 17 kg and BMI ≤ 24 kg/m², ≤ 17.3 kg and BMI between 24.1 and 26 kg/m², ≤ 18 kg and BMI between 26.1 and 29 kg/m², ≤ 21 and BMI > 29 kg/m² for women
      Time Up and Go test

      >20 seconds
      Patients’ destination and diagnosis related group code after patients discharge.
      Bokshan, 201750 patients older than 55 years having undergone thoracolumbar decompression

      8 (50.0%) male in sarcopenic patients, 18 (52.9%) male in non-sarcopenic patients
      Two groups:

      Sarcopenia, n = 16, mean age : 76.6 (SD 2.2) years

      No sarcopenia, n = 34, 70.8 (SD 1.4) years
      /CT scan

      Total psoas area < sex-specific lowest tertile
      //Hospital charge centre
      Chen, 2018185 patients aged over 18 who underwent colorectal surgery for cancer

      34 (66.7%) male in sarcopenic patients, 90 (67.2%) male in non sarcopenic patients
      Two groups:

      Sarcopenia, n = 51, mean age: 70.7 (SD 12.6)

      No sarcopenia, n = 134, mean age: 59.2 (SD 13.0)
      EWGSOPCT scan

      L3 SMI ≤ 40.8 cm²/m² in men, ≤34.9 cm²/m² in women
      Handheld dynamometer

      <26 kg for men, <18 kg for women
      6-meter gait speed

      ≤0.8 m/s
      Not reported
      Mijnarends, 2016227 community-dwelling older adults

      117 (51.5%) male
      Three groups:

      Sarcopenia, n = 53, mean age: 80.4 (SD 7.1) years

      No sarcopenia, age and sex matched, n = 53, mean age: 79.7 (SD 7.0) years

      No sarcopenia, n = 174, mean age: 73.3 (SD 6.4) years
      EWGSOPBIA

      SMI ≤10,75 kg/m² in men, ≤6,75 kg/m² in women
      Handheld dynamometer

      <30 kg in men and <20 kg in women
      4-meter gait speed

      ≤0.8 m/s
      Questionnaire (interview face-to-face) developed for this purpose.
      van Vugt, 2017224 patients with cirrhosis listed for liver transplantation

      149 (66.5%) of male
      Two groups:

      Sarcopenia, n = 55, mean age: 56 (IQR 48-69) years

      No sarcopenia, n = 169, mean age: 56 (IQR 49-61) years
      /CT scan

      Total psoas area < sex-specific lowest quartile
      //Hospital's electronic accounting system
      * BIA = Bioelectrical Impedance Analysis; IQR = Inter Quartile Range; CT = Computed Tomography; SMI = skeletal muscle mass index; EWGSOP = European Working Group on Sarcopenia in Older People; AWGS = Asian Working group on Sarcopenia; L3= lumbar vertebrae 3; L4= lumbar vertebrae 4; SD = standard deviation.
      * BIA = Bioelectrical Impedance Analysis; IQR = Inter Quartile Range; CT = Computed Tomography; SMI = skeletal muscle mass index; EWGSOP = European Working Group on Sarcopenia in Older People; AWGS = Asian Working group on Sarcopenia; L4= lumbar vertebrae 4; SD = standard deviation.
      The way to diagnose sarcopenia was indeed very heterogeneous, the diagnostic thresholds being also arbitrarily placed for the majority of the included studies. For instance, 11 studies out of 14 [
      • Bokshan S.L.
      • Han A.
      • DePasse J.M.
      • et al.
      Inpatient costs and blood  transfusion rates of sarcopenic patients following thoracolumbar spine surgery.
      ,
      • Chen W.-Z.
      • Chen X.-D.
      • Ma L.-L.
      • et al.
      Impact of Visceral Obesity and Sarcopenia on Short-Term Outcomes After Colorectal Cancer Surgery.
      ,
      • Gani F.
      • Buettner S.
      • Margonis G.A.
      • et al.
      Sarcopenia predicts costs among patients undergoing major abdominal operations.
      ,
      • Huang D.D.
      • Zhou C.J.
      • Wang S.L.
      • et al.
      Impact of different sarcopenia stages on the postoperative outcomes after radical gastrectomy for gastric cancer.
      ,
      • Kirk P.S.
      • Friedman J.F.
      • Cron D.C.
      • et al.
      One-year postoperative resource utilization in sarcopenic patients.
      ,
      • Kaplan S.J.
      • Pham T.N.
      • Arbabi S.
      • et al.
      Association of radiologic indicators of frailty with 1-year mortality in older trauma patients: Opportunistic screening for sarcopenia and osteopenia.
      ,
      • Lo Y.T.C.
      • Wahlqvist M.L.
      • Huang Y.C.
      • et al.
      Medical costs of a low skeletal muscle mass are modulated by dietary diversity and physical activity in community-dwelling older Taiwanese: A longitudinal study.
      ,
      • Lou N.
      • Chi C.H.
      • Chen X.D.
      • et al.
      Sarcopenia in overweight and obese patients is a predictive factor for postoperative complication in gastric cancer: A prospective study.
      ,
      • Sheetz K.H.
      • Waits S.A.
      • Terjimanian M.N.
      • et al.
      Cost of major surgery in the sarcopenic patient.
      ,
      • van Vugt J.L.A.
      • Buettner S.
      • Alferink L.J.M.
      • et al.
      Low skeletal muscle mass is associated with increased hospital costs in patients with cirrhosis listed for liver transplantation-a retrospective study.
      ,
      • Wang S.L.
      • Zhuang C.
      • Le
      • Huang D.D.
      • et al.
      Sarcopenia Adversely Impacts Postoperative Clinical Outcomes Following Gastrectomy in Patients with Gastric Cancer: A Prospective Study.
      ] applied diagnostic thresholds according to the results intrinsic to their own study and population (i.e., lowest tertile or quartile) and not based on data validated and recognized in the scientific literature, as used by the three other studies [
      • Antunes A.C.
      • Araújo D.A.
      • Veríssimo M.T.
      • Amaral T.F.
      Sarcopenia and hospitalisation costs in older adults: a cross-sectional study.
      ,
      • Mijnarends D.M.
      • Schols J.M.G.A.
      • Halfens R.J.G.
      • et al.
      Burden-of-illness of Dutch community-dwelling older adults with sarcopenia: Health related outcomes and costs.
      ,
      • Sousa A.S.
      • Guerra R.S.
      • Fonseca I.
      • et al.
      Financial impact of sarcopenia on hospitalization costs.
      ]. However, when applicable, the cut-offs used to measure muscle strength and physical performance were all based on more robust scientific evidence. In terms of sarcopenia costing, we observed generally fairly robust methods of data collection (i.e., use of the institution's financial accounting system). Only one study [
      • Mijnarends D.M.
      • Schols J.M.G.A.
      • Halfens R.J.G.
      • et al.
      Burden-of-illness of Dutch community-dwelling older adults with sarcopenia: Health related outcomes and costs.
      ] collected data on the patient's self-report via a face-to-face questionnaire and four studies [
      • Chen W.-Z.
      • Chen X.-D.
      • Ma L.-L.
      • et al.
      Impact of Visceral Obesity and Sarcopenia on Short-Term Outcomes After Colorectal Cancer Surgery.
      ,
      • Huang D.D.
      • Zhou C.J.
      • Wang S.L.
      • et al.
      Impact of different sarcopenia stages on the postoperative outcomes after radical gastrectomy for gastric cancer.
      ,
      • Lo Y.T.C.
      • Wahlqvist M.L.
      • Huang Y.C.
      • et al.
      Medical costs of a low skeletal muscle mass are modulated by dietary diversity and physical activity in community-dwelling older Taiwanese: A longitudinal study.
      ,
      • Lou N.
      • Chi C.H.
      • Chen X.D.
      • et al.
      Sarcopenia in overweight and obese patients is a predictive factor for postoperative complication in gastric cancer: A prospective study.
      ] did not reported at all the method of collecting cost data.

      3.3 Quality assessment of the included studies

      All publications included were assessed for their methodological quality by means of the Joanna Briggs Institute tool for cross-sectional studies. The scores varied from 3 to 8 points (i.e., number summed of “yes”). Even if one study [
      • Sousa A.S.
      • Guerra R.S.
      • Fonseca I.
      • et al.
      Financial impact of sarcopenia on hospitalization costs.
      ] obtained the maximum score (8 points), the other assessed studies received a moderate-quality score (around 4 points). The details of scoring are transcribed in Table 4, but, globally, two criteria of a good methodological quality were not met for most of the researches:
      Table 4Quality of studies (Joanna Briggs Institute - Cross-sectional studies).
      Authors, year1. Clear inclusion criteria2. Subjects and setting described3. Sarcopenia assessment valid and reliable4. Standard criteria for sarcopenia5. Confounding factors identified6. Deal of confounding factors7. Outcomes valid and reliable8. Appropriate statisticsTotal of yes
      Sousa, 2016YesYesYesYesYesYesYesYes8
      Huang, 2016YesYesYesYesNoNoUnclearYes5
      Gani, 2016NoYesNiNoYesYesYesYes5
      Lo, 2017NoYesYesNoNoNoYesYes4
      Kaplan, 2016YesYesYesNoNoNoYesYes4
      Lou, 2017YesYesYesNoNoNoUnclearYes4
      Wang, 2016YesYesYesNoNoNoUnclearYes4
      Kirk, 2015NoYesNoNoUnclearYesYesYes4
      Sheetz, 2013YesYesNoNoUnclearYesYesYes5
      Antunes, 2017YesYesNoNoNoNoYesYes4
      Bokshan, 2017YesYesNoNoYesNoYesYes5
      Chen, 2018YesYesNoNoNoNoNoYes3
      Mijnarends, 2016YesYesYesYesYesNoNoYes6
      van Vugt, 2017YesYesNoNoNoNoYesYes4
      The other quality criteria (i.e., inclusion, study settings, outcome, and statistics) were usually well respected by the articles included in this analysis.

      3.4 Health cost comparison between individuals with or without sarcopenia

      Through Table 5, a complete picture of cost comparison analyses of the 14 included studies is available. We first noticed that the type of health care cost was diverse: some researches were interested in the total costs during the hospital stay [
      • Antunes A.C.
      • Araújo D.A.
      • Veríssimo M.T.
      • Amaral T.F.
      Sarcopenia and hospitalisation costs in older adults: a cross-sectional study.
      ,
      • Gani F.
      • Buettner S.
      • Margonis G.A.
      • et al.
      Sarcopenia predicts costs among patients undergoing major abdominal operations.
      ,
      • Huang D.D.
      • Zhou C.J.
      • Wang S.L.
      • et al.
      Impact of different sarcopenia stages on the postoperative outcomes after radical gastrectomy for gastric cancer.
      ,
      • Kirk P.S.
      • Friedman J.F.
      • Cron D.C.
      • et al.
      One-year postoperative resource utilization in sarcopenic patients.
      ,
      • Kaplan S.J.
      • Pham T.N.
      • Arbabi S.
      • et al.
      Association of radiologic indicators of frailty with 1-year mortality in older trauma patients: Opportunistic screening for sarcopenia and osteopenia.
      ,
      • Lou N.
      • Chi C.H.
      • Chen X.D.
      • et al.
      Sarcopenia in overweight and obese patients is a predictive factor for postoperative complication in gastric cancer: A prospective study.
      ,
      • Sousa A.S.
      • Guerra R.S.
      • Fonseca I.
      • et al.
      Financial impact of sarcopenia on hospitalization costs.
      ,
      • van Vugt J.L.A.
      • Buettner S.
      • Alferink L.J.M.
      • et al.
      Low skeletal muscle mass is associated with increased hospital costs in patients with cirrhosis listed for liver transplantation-a retrospective study.
      ,
      • Wang S.L.
      • Zhuang C.
      • Le
      • Huang D.D.
      • et al.
      Sarcopenia Adversely Impacts Postoperative Clinical Outcomes Following Gastrectomy in Patients with Gastric Cancer: A Prospective Study.
      ], others at the hospitalization cost only [
      • Chen W.-Z.
      • Chen X.-D.
      • Ma L.-L.
      • et al.
      Impact of Visceral Obesity and Sarcopenia on Short-Term Outcomes After Colorectal Cancer Surgery.
      ,
      • Lo Y.T.C.
      • Wahlqvist M.L.
      • Huang Y.C.
      • et al.
      Medical costs of a low skeletal muscle mass are modulated by dietary diversity and physical activity in community-dwelling older Taiwanese: A longitudinal study.
      ], and others to general health care costs for community-dwelling individuals [
      • Mijnarends D.M.
      • Schols J.M.G.A.
      • Halfens R.J.G.
      • et al.
      Burden-of-illness of Dutch community-dwelling older adults with sarcopenia: Health related outcomes and costs.
      ,
      • Sheetz K.H.
      • Waits S.A.
      • Terjimanian M.N.
      • et al.
      Cost of major surgery in the sarcopenic patient.
      ]. Most studies reported compared costs in terms of differences in monetary value. Only one expressed this difference in percentages [
      • Antunes A.C.
      • Araújo D.A.
      • Veríssimo M.T.
      • Amaral T.F.
      Sarcopenia and hospitalisation costs in older adults: a cross-sectional study.
      ].
      Table 5Synthesis of cost analyses among the 14 included studies.
      Authors, yearCost 1Cost 2Time horizon for cost-related data collectionAdjustment factors for cost comparison analysis
      Type of health care costCost for sarcopenicCost for non-sarcopenicP-valueType of health care costCost for sarcopenicCost for non-sarcopenicP-value
      Sousa, 2016Median total hospital costs during hospital stay€3151 (IQR €4175)€2170 (IQR €2515)<0.001////Median days of hospital stay: Sarcopenia: 9.0 (IQR 10.0) days; No sarcopenia: 6.0 (IQR 6.0) daysAge, marital status, hospital ward, length of hospital stay, nutritional status
      Huang, 2016Median hospital costs¥63 995.8

      (IQR ¥31 449.0)
      ¥54 395.3

      (IQR ¥17 625.7)
      0.001////Not reportedNone
      Gani, 2016Median hospital costs (health system)$38,804

      (IQR $25,027-$43,462)
      $24,482

      (IQR $22,573-$38,025)
      <0.001Median total net payments

      (patient)
      $37 335

      (IQR $28 640-$55 717)
      $32,680

      (IQR $24 326-$45 756)
      <0.001Median days of hospital stay:

      whole sample: 8 (IQR 6-12)
      Patient and disease characteristics (only for total hospital costs)
      Lo, 2017Median cost of hospitalisationNT $77 500NT $ 38 700<0.001Median total medical expenditureNT $102 000NT $ 67 400<0.0018 yearsNone
      Kaplan, 2016Median hospital costs$ 31600

      (IQR $17 100-$57 100)
      $ 33600

      (IQR $18 500-$62 600)
      0.82////Median days of hospital stay:

      Sarcopenia: 7 (IQR 4-12); No sarcopenia: 7 (IQR 5-11)
      None
      Lou, 2017Median hospital costs¥68 026 (IQR ¥41 132)¥ 55 316 (IQR 18 003)0.003////Not reportedNone
      Wang, 2016Median hospital costs¥ 70 627 (IQR ¥29 961)¥ 54 348 (IQR ¥ 21 181)<0.001////Not reportedNone
      Kirk, 2015Median in-hospital costs$67 525$39 720<0.0011 yearAdjusted but factors not reported
      Sheetz, 201390-day post operation procedural costs and facility fees$ 34 796.37$ 21 380.07<0.001Median hospital cost$ 35 056.30$ 18 488.48<0.001From 2 days before operation to 90 days postoperativelyNone
      Antunes, 2017Difference in hospital costs deviation99% had cost deviation (superior the mean - i.e., €2 396,24)84,4% had cost deviation (superior the mean - i.e., €2 396,24)>0.05////Median days of hospital stay:

      8 days (IQR 8)
      None
      Bokshan, 2017Median total inpatient cost$53 128

      (SEM: ± $10 612)
      $30 292

      (SEM: ± $6 535)
      0.04////Period following spine surgery: a median of 4,6 years (IQR 6 days - 12,7 years)None
      Chen, 2018Median hospitalization costs¥ 52 793.4

      (SD: ¥ 21 421.0)
      ¥ 45 347.6

      (SD: ¥ 20 734.9)
      0.01////30 days post-surgeryNone
      Mijnarends, 2016Average costs of health care per person per 3 months€4 325

      (95%CI: €3 198-€5 471)
      €2 768

      (95%CI: €1 914-€3 743)
      >0.05////3 monthsSarcopenic matched for age and sex
      van Vugt, 2017Median total hospital costs€11 294

      (IQR €3570–€46 469)
      €6 878

      (IQR €1305–€20 683)
      0.01Median cost per day€68 (IQR €16–€503)€40 (IQR €10–€108)0.01Median days during listed for transplantation: 176 days (IQR 51-306)None
      *IQR = Inter Quartile Range; NT$ = New Taiwan Dollar; SEM = standard error of mean; 95%CI = 95% confidence interval.
      For the majority of studies included, we find that health care costs were significantly higher for people with sarcopenia compared to people without the disease. However, there are only two studies [
      • Gani F.
      • Buettner S.
      • Margonis G.A.
      • et al.
      Sarcopenia predicts costs among patients undergoing major abdominal operations.
      ,
      • Sousa A.S.
      • Guerra R.S.
      • Fonseca I.
      • et al.
      Financial impact of sarcopenia on hospitalization costs.
      ] which have taken into account some confounding factors, clearly recognized as having a significant impact on the consumption of health care, quite independently from the sarcopenic status, such as age, sex, number of comorbidities and nutritional status for example. Next, three studies [
      • Antunes A.C.
      • Araújo D.A.
      • Veríssimo M.T.
      • Amaral T.F.
      Sarcopenia and hospitalisation costs in older adults: a cross-sectional study.
      ,
      • Kaplan S.J.
      • Pham T.N.
      • Arbabi S.
      • et al.
      Association of radiologic indicators of frailty with 1-year mortality in older trauma patients: Opportunistic screening for sarcopenia and osteopenia.
      ,
      • Mijnarends D.M.
      • Schols J.M.G.A.
      • Halfens R.J.G.
      • et al.
      Burden-of-illness of Dutch community-dwelling older adults with sarcopenia: Health related outcomes and costs.
      ] out of 14 have different conclusions: there is no significant difference in spending on health care between sarcopenic and non-sarcopenic populations (p-values> 0.05). It should also be noted that the time period during which the costs are collected in the different studies (i.e., time horizon) varied very strongly from one study to another, ranging from 7 days [
      • Kaplan S.J.
      • Pham T.N.
      • Arbabi S.
      • et al.
      Association of radiologic indicators of frailty with 1-year mortality in older trauma patients: Opportunistic screening for sarcopenia and osteopenia.
      ] to 8 years [
      • Lo Y.T.C.
      • Wahlqvist M.L.
      • Huang Y.C.
      • et al.
      Medical costs of a low skeletal muscle mass are modulated by dietary diversity and physical activity in community-dwelling older Taiwanese: A longitudinal study.
      ].

      4. Discussion

      At a first glance, from this systematic review, a trend toward an economic burden of sarcopenia is observed. However, a critical appraisal of the available data reduces the scope of the results:
      • 1
        Some definitions used to assess sarcopenia were not satisfactory and aligned with recent guidelines or recommendations for the operational definition of sarcopenia [
        • Chen L.-K.
        • Liu L.-K.
        • Woo J.
        • et al.
        Sarcopenia in Asia: Consensus Report of the Asian Working Group for Sarcopenia.
        ,
        • Studenski S.A.
        • Peters K.W.
        • Alley D.E.
        • et al.
        The FNIH Sarcopenia Project: Rationale, Study Description, Conference Recommendations, and Final Estimates.
        ]. Indeed, half of the included studies only assessed muscle mass and, consequently, forgot the importance of muscle strength or physical function in sarcopenia.
      • 2
        Different tools are used to assess muscle mass and they do not have the same scientific value [
        • Beaudart C.
        • McCloskey E.
        • Bruyère O.
        • et al.
        Sarcopenia in daily practice: assessment and management.
        ,
        • Buckinx F.
        • Landi F.
        • Cesari M.
        • et al.
        Pitfalls in the measurement of muscle mass: a need for a reference standard.
        ]. If, albeit not totally optimal, the DEXA is widely used and considered as the gold standard for the diagnosis of sarcopenia, the BIA is less reliable and accurate [
        • Buckinx F.
        • Landi F.
        • Cesari M.
        • et al.
        Pitfalls in the measurement of muscle mass: a need for a reference standard.
        ]. More importantly, the CT scan, used in the majority of the included studies, is still considered as a tool “under investigation” for the diagnosis of sarcopenia [
        • Buckinx F.
        • Landi F.
        • Cesari M.
        • et al.
        Pitfalls in the measurement of muscle mass: a need for a reference standard.
        ].
      • 3
        The cut-offs used, both for muscle mass and muscle strength, were heterogeneous. For the latter, this is not a major issue [
        • Masanés F.
        • Rojano i Luque X.
        • Salvà A.
        • et al.
        Cut-off points for muscle mass — not grip strength or gait speed — determine variations in sarcopenia prevalence.
        ] since all these threshold values come from published recommendations of respectable scientific organizations [
        • Chen L.-K.
        • Liu L.-K.
        • Woo J.
        • et al.
        Sarcopenia in Asia: Consensus Report of the Asian Working Group for Sarcopenia.
        ,
        • Studenski S.A.
        • Peters K.W.
        • Alley D.E.
        • et al.
        The FNIH Sarcopenia Project: Rationale, Study Description, Conference Recommendations, and Final Estimates.
        ,
        • Cruz-Jentoft A.J.
        • Baeyens J.P.
        • Bauer J.M.
        • et al.
        Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People.
        ]. The problem is more important for some cut-offs related to muscle mass assessed by CT scan that are not published or recommended by scientific societies. Two options are then available. The first is the use of threshold based on predictive value (i.e. a value below which subjects have an increased risk of adverse outcomes). These kind of cut-off, albeit not fully validated, could make sense. The second is the use of threshold based on stratification of the studied population by quartiles, tiertiles of other percentiles. This is much more an issue since, it that case, the cut-off are very different from one study to another and subject considered as sarcopenic in one study could not be considered as such in the others. Unfortunately, most of the cut-off values for CT scan are based on stratification of the studies population, making the observed results of limited interest. For BIA, one selected study also used this approach making again the interpretation quite complex.
      • 4
        The populations in the selected papers were also heterogeneous but a substantial proportion included subjects experiencing major surgeries for major diseases such as cancer. Consequently, our summary results could hardly be extrapolated to older subject.
      • 5
        In the majority of the included papers (12 studies out of 14, 86%), the group having sarcopenia and the group who do not were not balanced according to demographic or clinical characteristics. For example, age could be very different among groups and this is, obviously, a major confounding factors when comparing the healthcare costs between two groups. Unfortunately, adjustment for all these potential confounding variables were rarely performed in the included studies.
      • 6
        The costs were, in the majority of the studies, limited to those occurred at the hospital immediately after the surgery. When having in mind the long-term potential consequences of sarcopenia on fractures, fall or loss of autonomy, the time frame and the setting is probably too limited to have a global view of the economic burden of the disease.
      • 7
        At last, the quality of most of the included studies were low to moderate, and in a substantial proportion of them, few information were available regarding the collection of cost data, the confounding variables or the statistical analysis performed. It should be acknowledged that most of the papers does not have the economic burden as primary outcome and, consequently, less information were available when presenting these data.
      This work of systematic review is, to our knowledge, the first carried out on this theme, but, however, presents certain limitations. First, we searched for relevant manuscripts in two databases, as recommended, but some relevant databases were not investigated (e.g. EMBASE) due to logistical constraints. However, manual search of other relevant articles were performed and we do not believe that many papers were missing. Second, we included, as discussed before, studies having used non-validated and potentially irrelevant cut-off for the assessment of muscle mass. Maybe that other studies using these kinds of cut-offs but without claiming that they diagnosed sarcopenia with it have been missed with our search strategy. Third, because of the heterogeneous nature of the selected papers, no meta-analysis has been performed and it was not possible to assess publication bias. Lastly, we decided to avoid transformation of all monetary units into a single one. It can be discussed and challenged but our idea was to avoid (by us but mostly by others) making some kind of “global summary cost of sarcopenia” that would have been false given all limitations of the selected papers.

      5. Conclusion

      In conclusion, our systematic review found a large heterogeneity between studies regarding the selected population, the time horizon, the type and source of economic data but, globally, shows some trends toward a more important use of healthcare resources in the sarcopenic population. However, the heterogeneity in the tools to measure of sarcopenia, the use of non-validated thresholds to define sarcopenia, and the moderate or even poor methodological quality of most of the studies, do not allow to make definitive conclusion regarding the economic burden of sarcopenia. There is a clear need for well conducted studies in the field of sarcopenia regarding economic analysis.

      Contributors

      Olivier Bruyère screened the results of the search, assessed titles and abstracts for eligibility, performed full-text screening, data extraction, quality assessment and drafted the paper.
      Charlotte Beaudart screened the results of the search, assessed titles and abstracts for eligibility, performed full-text screening, data extraction, quality assessment and drafted the paper.
      Olivier Ethgen acted as an independent reviewer where needed.
      Jean-Yves Reginster acted as an independent reviewer where needed.
      Médéa Locquet ran the searches, screened the results of the search, assessed titles and abstracts for eligibility, performed full-text screening, data extraction, quality assessment and drafted the paper.
      All authors were responsible for the study concept and design, and participated in the development of the search strategy and the critical appraisal of the results.
      They were all responsible for editing and reviewing the manuscript, and all saw approved the final version.

      Conflict of interest

      The authors declare that they have no conflict of interest.

      Funding

      No funding was received for the preparation of this review.

      Provenance and peer review

      This article has undergone peer review.

      Acknowledgments

      We warmly thank Dr. Teresa Amaral for providing us with additional information for a detailed analysis of her article in our systematic review.

      References

        • Beaudart C.
        • Rizzoli R.
        • Bruyère O.
        • et al.
        Sarcopenia: burden and challenges for public health.
        Arch Public Heal. 2014; 72https://doi.org/10.1186/2049-3258-72-45
        • Ryan A.M.
        • Power D.G.
        • Daly L.
        • et al.
        Cancer-associated malnutrition, cachexia and sarcopenia: the skeleton in the hospital closet 40 years later.
        Proc Nutr Soc. 2016; 75: 199-211https://doi.org/10.1017/S002966511500419X
        • Beaudart C.
        • Zaaria M.
        • Pasleau F.
        • et al.
        Health Outcomes of Sarcopenia: A Systematic Review and Meta-Analysis.
        PLoS One. 2017; 12 (e0169548)https://doi.org/10.1371/journal.pone.0169548
        • Shen Y.
        • Hao Q.
        • Zhou J.
        • Dong B.
        The impact of frailty and sarcopenia on postoperative outcomes in older patients undergoing gastrectomy surgery: a systematic review and meta-analysis.
        BMC Geriatr. 2017; 17https://doi.org/10.1186/s12877-017-0569-2
        • Pamoukdjian F.
        • Bouillet T.
        • Lévy V.
        • et al.
        Prevalence and predictive value of pre-therapeutic sarcopenia in cancer patients: A systematic review.
        Clin Nutr. 2018; 37: 1101-1113https://doi.org/10.1016/j.clnu.2017.07.010
        • Zhao Y.
        • Zhang Y.
        • Hao Q.
        • et al.
        Sarcopenia and hospital-related outcomes in the old people: a systematic review and meta-analysis.
        Aging Clin Exp Res. 2018; : 1-10https://doi.org/10.1007/s40520-018-0931-z
        • Janssen I.
        • Shepard D.S.
        • Katzmarzyk P.T.
        • Roubenoff R.
        The healthcare costs of sarcopenia in the United States.
        J Am Geriatr Soc. 2004; 52: 80-85
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • et al.
        Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement.
        PLoS Med. 2009; 6 (e1000097)https://doi.org/10.1371/journal.pmed.1000097
        • The Joanna Briggs Institute
        Checklist for systematic reviews and research syntheses.
        2017
        • Antunes A.C.
        • Araújo D.A.
        • Veríssimo M.T.
        • Amaral T.F.
        Sarcopenia and hospitalisation costs in older adults: a cross-sectional study.
        Nutr Diet. 2017; 74: 46-50https://doi.org/10.1111/1747-0080.12287
        • Bokshan S.L.
        • Han A.
        • DePasse J.M.
        • et al.
        Inpatient costs and blood  transfusion rates of sarcopenic patients following thoracolumbar spine surgery.
        J Neurosurg Spine. 2017; 27: 676-680https://doi.org/10.3171/2017.5.SPINE17171
        • Chen W.-Z.
        • Chen X.-D.
        • Ma L.-L.
        • et al.
        Impact of Visceral Obesity and Sarcopenia on Short-Term Outcomes After Colorectal Cancer Surgery.
        Dig Dis Sci. 2018; 63: 1620-1630https://doi.org/10.1007/s10620-018-5019-2
        • Gani F.
        • Buettner S.
        • Margonis G.A.
        • et al.
        Sarcopenia predicts costs among patients undergoing major abdominal operations.
        Surg (United States). 2016; 160: 1162-1171https://doi.org/10.1016/j.surg.2016.05.002
        • Huang D.D.
        • Zhou C.J.
        • Wang S.L.
        • et al.
        Impact of different sarcopenia stages on the postoperative outcomes after radical gastrectomy for gastric cancer.
        Surg (United States). 2017; 161: 680-693https://doi.org/10.1016/j.surg.2016.08.030
        • Kirk P.S.
        • Friedman J.F.
        • Cron D.C.
        • et al.
        One-year postoperative resource utilization in sarcopenic patients.
        J Surg Res. 2015; 199: 51-55https://doi.org/10.1016/j.jss.2015.04.074
        • Kaplan S.J.
        • Pham T.N.
        • Arbabi S.
        • et al.
        Association of radiologic indicators of frailty with 1-year mortality in older trauma patients: Opportunistic screening for sarcopenia and osteopenia.
        JAMA Surg. 2017; 152: 1-8https://doi.org/10.1001/jamasurg.2016.4604
        • Lo Y.T.C.
        • Wahlqvist M.L.
        • Huang Y.C.
        • et al.
        Medical costs of a low skeletal muscle mass are modulated by dietary diversity and physical activity in community-dwelling older Taiwanese: A longitudinal study.
        Int J Behav Nutr Phys Act. 2017; 14: 1-12https://doi.org/10.1186/s12966-017-0487-x
        • Lou N.
        • Chi C.H.
        • Chen X.D.
        • et al.
        Sarcopenia in overweight and obese patients is a predictive factor for postoperative complication in gastric cancer: A prospective study.
        Eur J Surg Oncol. 2017; 43: 188-195https://doi.org/10.1016/j.ejso.2016.09.006
        • Mijnarends D.M.
        • Schols J.M.G.A.
        • Halfens R.J.G.
        • et al.
        Burden-of-illness of Dutch community-dwelling older adults with sarcopenia: Health related outcomes and costs.
        Eur Geriatr Med. 2016; 7: 276-284https://doi.org/10.1016/j.eurger.2015.12.011
        • Sheetz K.H.
        • Waits S.A.
        • Terjimanian M.N.
        • et al.
        Cost of major surgery in the sarcopenic patient.
        J  Am Coll Surg. 2013; 217: 813-818https://doi.org/10.1016/j.jamcollsurg.2013.04.042
        • Sousa A.S.
        • Guerra R.S.
        • Fonseca I.
        • et al.
        Financial impact of sarcopenia on hospitalization costs.
        Eur J Clin Nutr. 2016; 70: 1046-1051https://doi.org/10.1038/ejcn.2016.73
        • van Vugt J.L.A.
        • Buettner S.
        • Alferink L.J.M.
        • et al.
        Low skeletal muscle mass is associated with increased hospital costs in patients with cirrhosis listed for liver transplantation-a retrospective study.
        Transpl Int. 2018; 31: 165-174https://doi.org/10.1111/tri.13048
        • Wang S.L.
        • Zhuang C.
        • Le
        • Huang D.D.
        • et al.
        Sarcopenia Adversely Impacts Postoperative Clinical Outcomes Following Gastrectomy in Patients with Gastric Cancer: A Prospective Study.
        Ann Surg Oncol. 2016; 23: 556-564https://doi.org/10.1245/s10434-015-4887-3
        • Tan L.F.
        • Lim Z.Y.
        • Choe R.
        • et al.
        Screening for Frailty and Sarcopenia Among Older Persons in Medical Outpatient Clinics and its Associations With Healthcare Burden.
        J Am Med Dir Assoc. 2017; 18: 583-587https://doi.org/10.1016/j.jamda.2017.01.004
        • Coto Montes A.
        • Boga J.A.
        • Bermejo Millo C.
        • et al.
        Potential early biomarkers of sarcopenia among independent older adults.
        Maturitas. 2017; 104: 117-122https://doi.org/10.1016/j.maturitas.2017.08.009
        • Wu T.-Y.
        • Liaw C.-K.
        • Chen F.-C.
        • et al.
        Sarcopenia Screened With SARC-F Questionnaire Is Associated With Quality of Life and 4-Year Mortality.
        J Am Med Dir Assoc. 2016; 17: 1129-1135https://doi.org/10.1016/j.jamda.2016.07.029
        • Cawthon P.M.
        • Fox K.M.
        • Gandra S.R.
        • et al.
        Do Muscle Mass, Muscle Density, Strength, and Physical Function Similarly Influence Risk of Hospitalization in Older Adults?.
        J Am Geriatr Soc. 2009; 57: 1411-1419https://doi.org/10.1111/j.1532-5415.2009.02366.x
        • König M.
        • Spira D.
        • Demuth I.
        • et al.
        Polypharmacy as a Risk Factor for Clinically Relevant Sarcopenia: Results From the Berlin Aging Study II.
        Journals Gerontol Ser A. 2018; 73: 117-122https://doi.org/10.1093/gerona/glx074
        • Perna S.
        • Francis M.D.
        • Bologna C.
        • et al.
        Performance of Edmonton Frail Scale on frailty assessment: its association with multi-dimensional geriatric conditions assessed with specific screening tools.
        BMC Geriatr. 2017; 17https://doi.org/10.1186/s12877-016-0382-3
        • Cawthon P.M.
        • Lui L.-Y.
        • McCulloch C.E.
        • et al.
        Sarcopenia and Health Care Utilization in Older Women.
        Journals Gerontol Ser A Biol Sci Med Sci. 2017; 72: 95-101https://doi.org/10.1093/gerona/glw118
        • Beaudart C.
        • Reginster J.Y.
        • Petermans J.
        • et al.
        Quality of life and physical components linked to sarcopenia: The SarcoPhAge study.
        Exp Gerontol. 2015; 69: 103-110https://doi.org/10.1016/j.exger.2015.05.003
        • Du Y.
        • Karvellas C.J.
        • Baracos V.
        • et al.
        Sarcopenia is a predictor of outcomes in very elderly patients undergoing emergency surgery.
        Surgery. 2014; 156: 521-527https://doi.org/10.1016/j.surg.2014.04.027
        • Næss G.
        • Kirkevold M.
        • Hammer W.
        • et al.
        Nursing care needs and services utilised by home-dwelling elderly with complex health problems: observational study.
        BMC Health Serv Res. 2017; 17https://doi.org/10.1186/s12913-017-2600-x
        • Kilavuz A.
        • Meseri R.
        • Savas S.
        • et al.
        Association of sarcopenia with depressive symptoms and functional status among ambulatory community-dwelling elderly.
        Arch Gerontol Geriatr. 2018; 76: 196-201https://doi.org/10.1016/j.archger.2018.03.003
        • Gao L.
        • Jiang J.
        • Yang M.
        • et al.
        Prevalence of Sarcopenia and Associated Factors in Chinese Community-Dwelling Elderly: Comparison Between Rural and Urban Areas.
        J Am Med Dir Assoc. 2015; 16 (e1-1003.e6)https://doi.org/10.1016/j.jamda.2015.07.020
        • van Vugt J.L.A.
        • Buettner S.
        • Levolger S.
        • et al.
        Low skeletal muscle mass is associated with increased hospital expenditure in patients undergoing cancer surgery of the alimentary tract.
        PLoS One. 2017; 12 (e0186547)https://doi.org/10.1371/journal.pone.0186547
        • Friedman J.
        • Lussiez A.
        • Sullivan J.
        • et al.
        Implications of Sarcopenia in Major Surgery.
        Nutr Clin Pract. 2015; 30: 175-179https://doi.org/10.1177/0884533615569888
        • Chen L.-K.
        • Liu L.-K.
        • Woo J.
        • et al.
        Sarcopenia in Asia: Consensus Report of the Asian Working Group for Sarcopenia.
        J Am Med Dir Assoc. 2014; 15: 95-101https://doi.org/10.1016/j.jamda.2013.11.025
        • Studenski S.A.
        • Peters K.W.
        • Alley D.E.
        • et al.
        The FNIH Sarcopenia Project: Rationale, Study Description, Conference Recommendations, and Final Estimates.
        Journals Gerontol Ser A Biol Sci Med Sci. 2014; 69: 547-558https://doi.org/10.1093/gerona/glu010
        • Beaudart C.
        • McCloskey E.
        • Bruyère O.
        • et al.
        Sarcopenia in daily practice: assessment and management.
        BMC Geriatr. 2016; 16: 170https://doi.org/10.1186/s12877-016-0349-4
        • Buckinx F.
        • Landi F.
        • Cesari M.
        • et al.
        Pitfalls in the measurement of muscle mass: a need for a reference standard.
        J Cachexia Sarcopenia Muscle. 2018; 9: 269-278https://doi.org/10.1002/jcsm.12268
        • Masanés F.
        • Rojano i Luque X.
        • Salvà A.
        • et al.
        Cut-off points for muscle mass — not grip strength or gait speed — determine variations in sarcopenia prevalence.
        J Nutr Health Aging. 2017; 21: 825-829https://doi.org/10.1007/s12603-016-0844-5
        • Cruz-Jentoft A.J.
        • Baeyens J.P.
        • Bauer J.M.
        • et al.
        Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People.
        Age Ageing. 2010; 39: 412-423https://doi.org/10.1093/ageing/afq034