Biochemical Markers of Musculoskeletal Health and Aging to be Assessed in Clinical Trials of Drugs Aiming at the Treatment of Sarcopenia: Consensus Paper from an Expert Group Meeting Organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the Centre Académique de Recherche et d'Expérimentation en Santé (CARES SPRL), Under the Auspices of the World Health Organization Collaborating Center for the Epidemiology of Musculoskeletal Conditions and Aging

Aurélie Ladang^#¹, Charlotte Beaudart^#², Jean-Yves Reginster^{2

3}, Nasser Al-Daghri³, Olivier Bruyère², Nansa Burlet², Matteo Cesari^{4

5}, Antonio Cherubini⁶, Mario Coelho da Silva⁷, Cyrus Cooper⁸, Alfonso J Cruz-Jentoft⁹, Francesco Landi¹⁰, Andrea Laslop¹¹, Stefania Maggi¹², Ali Mobasheri^{2

13

14

15}, Sif Ormarsdottir¹⁶, Régis Radermecker¹⁷, Marjolein Visser¹⁸, Maria Concepcion Prieto Yerro¹⁹, René Rizzoli^#²⁰, Etienne Cavalier^#²¹

Affiliations

¹ Department of Clinical Chemistry, CHU de Liège, University of Liège, Liège, Belgium. aladang@chuliege.be.
² Division of Public Health, Epidemiology and Health Economics, WHO Collaborating Center for Public Health Aspects of Musculo-Skeletal Health and Ageing,, University of Liège, Liège, Belgium.
³ Biochemistry Department, College of Science, Chair for Biomarkers of Chronic Diseases, King Saud University, Riyadh, 11451, Saudi Arabia.
⁴ Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
⁵ Geriatric Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
⁶ Geriatric Unit, IRCCS Istituti Clinici Scientifici Maugeri, Milan, Italy.
⁷ Laboratory of Clinical and Therapeutical Pharmacology, Lisbon, Portugal.
⁸ MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
⁹ Servicio de Geriatría. Hospital Universitario Ramón Y Cajal (IRYCIS), Madrid, Spain.
¹⁰ Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart, Rome, Italy.
¹¹ Scientific Office, Federal Office for Safety in Health Care, Vienna, Austria.
¹² CNR Aging Branch-IN, Padua, Italy.
¹³ State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania.
¹⁴ Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland.
¹⁵ Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
¹⁶ Landspitali, University Hospital of Iceland, Reykjavik, Iceland.
¹⁷ Department of Diabetes, Nutrition and Metabolic Disorders, Clinical Pharmacology, University of Liege, CHU de Liège, Liège, Belgium.
¹⁸ Department of Health Sciences, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
¹⁹ Agencia Española de Medicamentos Y Productos Sanitarios, Madrid, Spain.
²⁰ Faculty of Medicine, Service of Bone Diseases, Geneva University Hospitals, Geneva, Switzerland.
²¹ Department of Clinical Chemistry, CHU de Liège, University of Liège, Liège, Belgium.

^# Contributed equally.

PMID: 36633611
PMCID: PMC9859913
DOI: 10.1007/s00223-022-01054-z

Review

Biochemical Markers of Musculoskeletal Health and Aging to be Assessed in Clinical Trials of Drugs Aiming at the Treatment of Sarcopenia: Consensus Paper from an Expert Group Meeting Organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the Centre Académique de Recherche et d'Expérimentation en Santé (CARES SPRL), Under the Auspices of the World Health Organization Collaborating Center for the Epidemiology of Musculoskeletal Conditions and Aging

Aurélie Ladang et al. Calcif Tissue Int. 2023 Feb.

. 2023 Feb;112(2):197-217.

doi: 10.1007/s00223-022-01054-z. Epub 2023 Jan 12.

Authors

Affiliations

¹ Department of Clinical Chemistry, CHU de Liège, University of Liège, Liège, Belgium. aladang@chuliege.be.
² Division of Public Health, Epidemiology and Health Economics, WHO Collaborating Center for Public Health Aspects of Musculo-Skeletal Health and Ageing,, University of Liège, Liège, Belgium.
³ Biochemistry Department, College of Science, Chair for Biomarkers of Chronic Diseases, King Saud University, Riyadh, 11451, Saudi Arabia.
⁴ Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
⁵ Geriatric Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
⁶ Geriatric Unit, IRCCS Istituti Clinici Scientifici Maugeri, Milan, Italy.
⁷ Laboratory of Clinical and Therapeutical Pharmacology, Lisbon, Portugal.
⁸ MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
⁹ Servicio de Geriatría. Hospital Universitario Ramón Y Cajal (IRYCIS), Madrid, Spain.
¹⁰ Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart, Rome, Italy.
¹¹ Scientific Office, Federal Office for Safety in Health Care, Vienna, Austria.
¹² CNR Aging Branch-IN, Padua, Italy.
¹³ State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania.
¹⁴ Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland.
¹⁵ Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
¹⁶ Landspitali, University Hospital of Iceland, Reykjavik, Iceland.
¹⁷ Department of Diabetes, Nutrition and Metabolic Disorders, Clinical Pharmacology, University of Liege, CHU de Liège, Liège, Belgium.
¹⁸ Department of Health Sciences, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
¹⁹ Agencia Española de Medicamentos Y Productos Sanitarios, Madrid, Spain.
²⁰ Faculty of Medicine, Service of Bone Diseases, Geneva University Hospitals, Geneva, Switzerland.
²¹ Department of Clinical Chemistry, CHU de Liège, University of Liège, Liège, Belgium.

^# Contributed equally.

PMID: 36633611
PMCID: PMC9859913
DOI: 10.1007/s00223-022-01054-z

Erratum in

Correction: Biochemical Markers of Musculoskeletal Health and Aging to be Assessed in Clinical Trials of Drugs Aiming at the Treatment of Sarcopenia: Consensus Paper from an Expert Group Meeting Organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the Centre Académique de Recherche et d'Expérimentation en Santé (CARES SPRL), Under the Auspices of the World Health Organization Collaborating Center for the Epidemiology of Musculoskeletal Conditions and Aging.
Ladang A, Beaudart C, Reginster JY, Al-Daghri N, Bruyère O, Burlet N, Cesari M, Cherubini A, da Silva MC, Cooper C, Cruz-Jentoft AJ, Landi F, Laslop A, Maggi S, Mobasheri A, Ormarsdottir S, Radermecker R, Visser M, Yerro MCP, Rizzoli R, Cavalier E. Ladang A, et al. Calcif Tissue Int. 2023 Sep;113(3):357-358. doi: 10.1007/s00223-023-01114-y. Epub 2023 Jul 24. Calcif Tissue Int. 2023. PMID: 37488204 Free PMC article. No abstract available.

Abstract

In clinical trials, biochemical markers provide useful information on the drug's mode of action, therapeutic response and side effect monitoring and can act as surrogate endpoints. In pharmacological intervention development for sarcopenia management, there is an urgent need to identify biomarkers to measure in clinical trials and that could be used in the future in clinical practice. The objective of the current consensus paper is to provide a clear list of biochemical markers of musculoskeletal health and aging that can be recommended to be measured in Phase II and Phase III clinical trials evaluating new chemical entities for sarcopenia treatment. A working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) proposed classifying biochemical markers into 2 series: biochemical markers evaluating musculoskeletal status and biochemical markers evaluating causal factors. For series 1, the group agreed on 4 biochemical markers that should be assessed in Phase II or Phase III trials (i.e., Myostatin-Follistatin, Brain Derived Neurotrophic Factor, N-terminal Type III Procollagen and Serum Creatinine to Serum Cystatin C Ratio - or the Sarcopenia Index). For series 2, the group agreed on 6 biochemical markers that should be assessed in Phase II trials (i.e., the hormones insulin-like growth factor-1 (IGF-I), dehydroepiandrosterone sulphate, and cortisol, and the inflammatory markers C-reactive protein (CRP), interleukin-6 and tumor necrosis factor-α), and 2 in Phase III trials (i.e., IGF-I and CRP). The group also proposed optional biochemical markers that may provide insights into the mode of action of pharmacological therapies. Further research and development of new methods for biochemical marker assays may lead to the evolution of these recommendations.

Keywords: Biochemical markers; Biomarkers; Clinical trial; Pharmacological drugs; Recommendations; Sarcopenia.

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Conflict of interest statement

The views expressed in this article are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the agencies or organizations with which the authors are affiliated. C. Beaudart reports to be a shareholder of SARQOL SRL, a spin-off of the University of Liege O. Bruyere reports grants or fees from AMGEN, APTISSEN, BIOPHYTIS, IBSA, MEDA, SANOFI, SERVIER, SMB, THERAMEX and UCB outside the submitted work. He also a shareholder of SARQOL SRL, a spin-off of the University of Liege. J-Y. Reginster reports consulting fees or paid advisory boards (IBSA-GENEVRIER, MYLAN, RADIUS HEALTH, PIERRE FABRE, ECHOLIGHT, TEVA), lecture fees when speaking at the invitation of sponsor (IBSA-GENEVRIER, MYLAN, CNIEL, DAIRY RESEARCH COUNCIL (DRC), TEVA), grant Support from Industry (All through Institution) (IBSA-GENEVRIER, MYLAN, CNIEL, RADIUS HEALTH). He also a shareholder of SARQOL SRL, a spin-off of the University of Liege as well as the CARES SRL, former spin-off of the University of Liège. AJ Cruz-Jentoft reports consulting fees or paid advisory boards from REJUVENATE BIOMED, RENEO PHARMACEUTICASL and AKROS PHARMA on the development of drugs to treat sarcopenia. Other authors reported no conflicts of interest in relation to this work.

References

1. Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48:16–31. doi: 10.1093/ageing/afy169. - DOI - PMC - PubMed
1. Bruyère O, Beaudart C, Ethgen O, et al. The health economics burden of sarcopenia: a systematic review. Maturitas. 2019;119:61–69. doi: 10.1016/j.maturitas.2018.11.003. - DOI - PubMed
1. Beaudart C, Zaaria M, Pasleau F, et al. Health outcomes of sarcopenia: a systematic review and meta-analysis. PLoS ONE. 2017 doi: 10.1371/journal.pone.0169548. - DOI - PMC - PubMed
1. Veronese N, Demurtas J, Soysal P, et al. Sarcopenia and health-related outcomes: an umbrella review of observational studies. Eur Geriatr Med. 2019;10:853–862. doi: 10.1007/s41999-019-00233-w. - DOI - PubMed
1. Fernandes LV, Paiva AEG, Silva ACB, et al. Prevalence of sarcopenia according to EWGSOP1 and EWGSOP2 in older adults and their associations with unfavorable health outcomes: a systematic review. Aging Clin Exp Res. 2022;34:505–514. doi: 10.1007/s40520-021-01951-7. - DOI - PubMed

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