The Journal of Nutrition, Health and Aging 28 (2024) 100257
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Editorial
Implementing clinical operationalization of sarcopenia: the contribution of WHO ICOPE program
In 2016, sarcopenia was recognized as a disease with an ICD-code
M62.84 [1] in the same as did previously other body composition changes
such as obesity (ICD-code E66.9) or osteoporosis (ICD-code M81.0). This
important advance followed nearly 30 years of mainly epidemiological
work and foreshadowed significant therapeutic drug advances as well as
the adoption by clinicians of a more systematic diagnostic approach to
sarcopenia [1]. In 2024, we must recognize that the enthusiasm generated
by the recognition of sarcopenia as a disease has not translated into an
increase in the diagnostic approach among clinicians nor by the hoped-for
acceleration of clinical trials evaluating the effectiveness of innovative
molecules for sarcopenia (Fig. 1). To date, no drug has an indication for
treating sarcopenia [2]. A quick assessment on PubMed Medline of the
current published randomized trials shows that therapeutic research is
not in the expected dynamic (Fig. 1). To date, 3 pharmacological
molecules (excluding nutritional trials and vitamin D trials) have been
tested in patients meeting the usual criteria for sarcopenia (EWGOS,
ASWGOS, FNIH): The Selective Androgen Receptor Modulator (MK-
0773) in 2013, Bimagrumab (BYM338) in 2017 and 2020 and an
Angiotensin Converting Enzyme inhibitor (Perindopril) in 2022. In total,
the cumulative number of sarcopenic patients having been included in a
randomized drug trial is only 535 patients to date. Likewise, the
therapeutic perspectives recorded on the Clinicaltrial.gov site demon-
strate that very few RCTs include subjects meeting the sarcopenic criteria.
Only 3 ongoing phase 2 randomized controlled trials include sarcopenic
subjects. Two focus on sarcopenic patients in specific medical condition
(cirrhosis or inflammatory context) (2). Only the SARA-Int study
evaluates the effects of 20-hydroxyecdysone, an activator of the Mas
receptor (MasR) in sarcopenic patients. Upstream, a multitude of
molecules targeting various muscle biological pathways are in the
preclinical phase, demonstrating that fundamental research on sarcope-
nia is dynamic and that therapeutic advances are possible.
This concern was the subject of a symposium at the ICFSR
(International Conference on Frailty & Sarcopenia Research) 2024 in
Albuquerque (NM, US) [3]. If the Global Leadership Initiative in
Sarcopenia (GLIS) [4] made an important step forward by stating a
conceptual definition of sarcopenia (the concurrent combination of
reduced muscle mass and muscle strength), the clinical operationaliza-
tion of sarcopenia remains to be established for the clinical practice as
well as the clinical trials [4]. Torn between multiple clinical definitions
based on an evaluation of lean mass by DEXA [5] and new approaches
(such D3-Creatine Dilution Method [6]) quantifying muscle mass,
sarcopenia struggles to impose an operational approach both in care
and in research.
How have other geriatric diseases or syndromes became operational in
care and research? The example of dementia and Mild Cognitive
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Impairment (MCI) are interesting. Dementia is a pathology which, like
sarcopenia, has multiple etiologies, is very prevalent in geriatrics, impairs
performance, impacts function and independence, and is associated with
anatomical changes of an organ (hippocampal atrophy, amyloid plaque,
and or vascular lesions for vascular and mixed dementia). After several
decades of very active research, the diagnosis of dementia remains
primarily clinical, both in care and in research, and is based on history,
examination, and appropriate clinical assessments, using standard
criteria such as DSM-5 [7]. In a clinical context, the association of
abnormalities in psychometric clinical tests and functional impact are the
two cardinal components of the DSM diagnostic criteria for dementia. Of
course, clinical sense first makes it possible to ensure that cognitive
abnormalities are not explained by confusion, psychiatric pathology,
refusal or any other differential diagnoses. Additional biological and
imaging tests (first and foremost brain MRI) make it possible to clarify the
etiology (Alzheimer's disease, vascular dementia or others). Certain more
sophisticated examinations, used in the clinic or in research, such as
amyloid PET or specific biomarkers (Protein Tau, Ab42, and others) make
it possible to increase the certainty of the etiological diagnosis. Note that
according to the DSM-5, brain imaging is not required to make the
diagnosis of dementia.
According to the same clinical DSM approach for dementia, and
following the GLIS conclusion [4], the “reduced muscle mass and the
reduced muscle strength or just two measures (muscle mass and strength)
or just one (muscle-specific strength)” will be the cardinal components of
an operational definition of sarcopenia [4]. As previously for dementia,
clinical sense would prevail and would ensure that motor abnormalities
are not explained by pain, rheumatic pathology, refusal or any other
differential diagnoses. Quantification of muscle mass or quality
assessment with devices (DXA, BIA, RMI), are currently a prerequisite
for the diagnosis of confirmed sarcopenia in the case finding of the
EWGOS or AGWS) [8–11] but the poor relevance of DEXA or the BIA to
assess muscle mass, and the low accessibility and high cost of MRI in
clinical practice are important limitation. On the other hand, reduced
muscle mass is a clinical sign, easy to see at the clinical exam (wasting,
thinness of the limbs) by an experienced clinician or a nurse assistant.
Many clinical trials on anthropometric measures such as the calf
circumference [12] can be helpful to define cutoff. Normative values of
calf circumference across ages and in large cohort are available [13].
None of the anthropometric measures is perfect (as it is with BMI for
adiposity) but a pragmatical clinical test, easy to implement in practice is
expected.
The assessment of reduced muscle strength or reduced muscle-specific
strength does not belong to clinical practice currently and devices such as
the hand grip dynamometer has not yet found its common place in general
Y. Rolland et al.
Fig. 1. Number of RCT published in Pub Med.
practice [14,15]. Family doctors and geriatrician are however experienc-
ing an accelerated development of new approaches aimed at preventing
mobility disability. The Integrated Care for Older People (ICOPE)
program developed by the World Health Organization (WHO) is currently
implemented in community dwelling older adults living in France [16],
and several other countries [17–21]. For example, more than 50,000
individuals aged 60+ are currently followed around Toulouse (France)
using this approach [16]. The aim of ICOPE is to prevent functional
decline by following the trajectory of older adult’s intrinsic capacity (IC)
(including by a digital device) and intervene early on functional domains
including locomotion. Mobility is part of the first step screening of ICOPE
and is measured by the 5 times chair rise test (5CRT; time needed to rise 5
consecutive times from a chair as fast as possible). A 5CRT performed in
14 s or more (or 16 s or more at ages 80+) is considered abnormal [22,23]
and results in a more in-deep comprehensive geriatric assessment. The
5CRT was chosen by the WHO both for its ability to predict mobility
disability and is simplicity. Unlike the grip strength, the 5CRT assess
lower extremity strength without requiring adjustment to the subject's
anthropometry. Family doctors will not multiply the muscle strength
assessment tests and the implementation of the WHO ICOPE program
worldwide, with the systematic screening of mobility with the 5CRT, for
all older adult 60+, is certainly a great opportunity to raise awareness
among the medical community about sarcopenia and implementing
prevention strategies targeting sarcopenia. The integrated care offered by
ICOPE [16] is also relevant for the management of sarcopenic subjects
because all determinants of IC (vision, cognition, mood, hearing,
nutrition) interact with physical performances, a major outcome [4] in
the management of sarcopenic subjects.
The updated versions of the operational definitions and “case
findings” of the EWGOS [8] and the AWGS [9] in 2019, proposing the
diagnosis of “probable” sarcopenia (when the Handgrip strength, or Chair
rise test is low; EWGOS) or “possible” sarcopenia (when the strength or
performance are reduced; AWGS) or more recently the Sarcopenia
Definition and Outcomes Consortium (SDOC) that identified grip strength
has a main contributor to the diagnostic of sarcopenia [24], were already
important steps in making diagnosis and treatment possible in clinics for
as many people as possible. The GLIS [4], is another step forward to
overcome the difficulties encountered to operationalize sarcopenia in
research and in the clinic, and so that the greatest number of patients can
access the diagnosis and treatment of sarcopenia. As for other geriatric
diseases and syndromes, clinical symptoms, and physical exam should be
the core of the clinical operationalization of sarcopenia. The on-going
worldwide implementation of ICOPE in the community by WHO, with the
5CRT as a screening tool for abnormal mobility could be an important
contribution to diagnose sarcopenia and to implement preventive
intervention to a large number of sarcopenic patients. Considering an
operational definition of sarcopenia in harmonization with the WHO
ICOPE program seems relevant.
2
The Journal of nutrition, health and aging 28 (2024) 100257
Declaration of competing interest
Y.R. reports support from CHU Toulouse, University Paul Sabatier and
INSERM CERPOP1295 (employee), to be a shareholder of SARQOL SPRL,
a spin-off of the University of Liege, consultancy fees from Longeveron,
Biophytis, and honoraria for lectures for Pfizer.
R.A.F. is partially supported by the US Department of Agriculture
(USDA), under agreement No. 58-8050-9-004, by NIH Boston Claude D.
Pepper Center (OAIC; 1P30AG031679). Any opinions, findings, con-
clusions, or recommendations expressed in this publication are those of
the authors and do not necessarily reflect the view of the USDA.
F.L. is partially supported by the Italian Ministry of Health—Ricerca
Corrente 2024 and European Union – Next Generation EU (AGE-IT).
B.V. reports support from CHU Toulouse, University Paul Sabatier and
INSERM CERPOP1295 (employee), grant from Pfizer, Pierre Fabre.
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Yves Rollanda,*, Roger Fieldingb
Francesco Landic
Bruno Vellasa
a
IHU HealthAge, CERPOP UMR 1295, CHU Toulouse, France
b
Nutrition, Exercise Physiology and Sarcopenia Laboratory, Jean Mayer
USDA Human Nutrition Research Center on Aging, Tufts University, 711
Washington Street, Boston, MA, USA
c
Department of Geriatrics, Orthopedics and Rheumatology, Università
Cattolica del Sacro Cuore, Fondazione Policlinico Universitario "Agostino
Gemelli" IRCCS, 00168 Rome, Italy