Novel approaches to the stratified management of knee osteoarthritis

Nicholas R Fuggle¹, Roland Chapurlat², Andrea Laslop³, Nasser Al-Daghri⁴, Majed Alokail⁵, Jotheeswaran Amuthavalli Thiyagarajan⁶, Ewa Balkowiec-Iskra⁷, Francis Berenbaum⁸, Angie Botto-van Bemden⁹, John-Joseph Borg¹⁰, Olivier Bruyère¹¹, Nansa Burlet¹¹, Etienne Cavalier¹², Mario M Rosa¹³, Philip G Conaghan¹⁴, Cyrus Cooper^{1

15

16}, Elaine M Dennison¹, Martin Englund¹⁷, Gun-Il Im¹⁸, Ida K Haugen¹⁹, Mickaël Hiligsmann²⁰, Andreas Kurth²¹, Nancy Lane²², Rik Lories²³, Stefan Marlovits²⁴, Radmila Matijevic²⁵, Ali Mobasheri^{26

27

28}, Sif Ormarsdóttir²⁹, Maria C Prieto Yerro³⁰, Régis P Radermecker³¹, François Rannou³², Bruno Sepodes^{33

34}, Stuart Silverman³⁵, Carla Torre^{33

34}, Nicola Veronese³⁶, René Rizzoli³⁷, Jean-Yves Reginster^#⁵, Nicholas C Harvey^#^{38

39}

Affiliations

¹ MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK.
² INSERM UMR 1033, Université Claude Bernard-Lyon 1, Hôpital Edouard-Herriot, Lyon, France.
³ Scientific Office, Federal Office for Safety in Health Care, Vienna, Austria.
⁴ Biomarkers of Chronic Disease Chair, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.
⁵ Protein Research Chair, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.
⁶ Ageing and Health Unit, World Health Organization, Geneva, Switzerland.
⁷ Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland.
⁸ Sorbonne University, INSERM, AP-HP Saint-Antoine Hospital, Paris, France.
⁹ Musculoskeletal Research International, Key Biscayne, FL, USA.
¹⁰ Malta Medicines Authority, San Ġwann, Malta.
¹¹ Research Unit in Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.
¹² Department of Clinical Chemistry, University of Liège, CIRM, CHU de Liège, Liège, Belgium.
¹³ Laboratory of Clinical and Therapeutical Pharmacology, University of Lisbon, Lisbon, Portugal.
¹⁴ Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
¹⁵ NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, UK.
¹⁶ NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
¹⁷ Clinical Epidemiology Unit, Orthopedics, Faculty of Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
¹⁸ Department of Orthopedics, Dongguk University Ilsan Hospital, Goyang Gyeonggi-Do, Republic of Korea.
¹⁹ Center for Treatment of Rheumatic and Musculoskeletal Diseases, Diakonhjemmet Hospital, Oslo, Norway.
²⁰ Department of Health Services Research, CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, the Netherlands.
²¹ Johann Wolfgang Goethe University, Frankfurt, Germany.
²² Department of Medicine, University of California Davis, Sacramento, CA, USA.
²³ Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven and Division of Rheumatology, UZ Leuven, Leuven, Belgium.
²⁴ Centre for Cartilage Regeneration, Orthobiologics and Joint Preservation, Vienna, Austria.
²⁵ University of Novi Sad, Faculty of Medicine, Clinic for Orthopedic Surgery and Traumatology, Clinical Center of Vojvodina, Novi Sad, Serbia.
²⁶ Research Unit of Health Sciences and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland.
²⁷ Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania.
²⁸ Department of Joint Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
²⁹ Medicine Assessment and Licencing, Icelandic Medicines Agency, Reykjavik, Iceland.
³⁰ Agencia Española de Medicamentos Y Productos Sanitarios, Madrid, Spain.
³¹ Department of Diabetes, Nutrition and Metabolic Disorders, Clinical Pharmacology, University of Liège, Liège, Belgium.
³² Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France.
³³ Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal.
³⁴ Laboratory of Systems Integration Pharmacology, Clinical and Regulatory Science, Research Institute for Medicines of the University of Lisbon, Lisbon, Portugal.
³⁵ Cedars-Sinai Medical Center, Los Angeles, CA, USA.
³⁶ Saint Camillus International University of Health Sciences, Rome, Italy.
³⁷ Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
³⁸ MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK. nch@mrc.soton.ac.uk.
³⁹ NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, UK. nch@mrc.soton.ac.uk.

^# Contributed equally.

PMID: 41044417
DOI: 10.1038/s41584-025-01305-x

Review

Novel approaches to the stratified management of knee osteoarthritis

Nicholas R Fuggle et al. Nat Rev Rheumatol. 2025 Nov.

. 2025 Nov;21(11):684-695.

doi: 10.1038/s41584-025-01305-x. Epub 2025 Oct 3.

Authors

Affiliations

¹ MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK.
² INSERM UMR 1033, Université Claude Bernard-Lyon 1, Hôpital Edouard-Herriot, Lyon, France.
³ Scientific Office, Federal Office for Safety in Health Care, Vienna, Austria.
⁴ Biomarkers of Chronic Disease Chair, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.
⁵ Protein Research Chair, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.
⁶ Ageing and Health Unit, World Health Organization, Geneva, Switzerland.
⁷ Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland.
⁸ Sorbonne University, INSERM, AP-HP Saint-Antoine Hospital, Paris, France.
⁹ Musculoskeletal Research International, Key Biscayne, FL, USA.
¹⁰ Malta Medicines Authority, San Ġwann, Malta.
¹¹ Research Unit in Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.
¹² Department of Clinical Chemistry, University of Liège, CIRM, CHU de Liège, Liège, Belgium.
¹³ Laboratory of Clinical and Therapeutical Pharmacology, University of Lisbon, Lisbon, Portugal.
¹⁴ Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
¹⁵ NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, UK.
¹⁶ NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
¹⁷ Clinical Epidemiology Unit, Orthopedics, Faculty of Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
¹⁸ Department of Orthopedics, Dongguk University Ilsan Hospital, Goyang Gyeonggi-Do, Republic of Korea.
¹⁹ Center for Treatment of Rheumatic and Musculoskeletal Diseases, Diakonhjemmet Hospital, Oslo, Norway.
²⁰ Department of Health Services Research, CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, the Netherlands.
²¹ Johann Wolfgang Goethe University, Frankfurt, Germany.
²² Department of Medicine, University of California Davis, Sacramento, CA, USA.
²³ Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven and Division of Rheumatology, UZ Leuven, Leuven, Belgium.
²⁴ Centre for Cartilage Regeneration, Orthobiologics and Joint Preservation, Vienna, Austria.
²⁵ University of Novi Sad, Faculty of Medicine, Clinic for Orthopedic Surgery and Traumatology, Clinical Center of Vojvodina, Novi Sad, Serbia.
²⁶ Research Unit of Health Sciences and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland.
²⁷ Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania.
²⁸ Department of Joint Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
²⁹ Medicine Assessment and Licencing, Icelandic Medicines Agency, Reykjavik, Iceland.
³⁰ Agencia Española de Medicamentos Y Productos Sanitarios, Madrid, Spain.
³¹ Department of Diabetes, Nutrition and Metabolic Disorders, Clinical Pharmacology, University of Liège, Liège, Belgium.
³² Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France.
³³ Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal.
³⁴ Laboratory of Systems Integration Pharmacology, Clinical and Regulatory Science, Research Institute for Medicines of the University of Lisbon, Lisbon, Portugal.
³⁵ Cedars-Sinai Medical Center, Los Angeles, CA, USA.
³⁶ Saint Camillus International University of Health Sciences, Rome, Italy.
³⁷ Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
³⁸ MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK. nch@mrc.soton.ac.uk.
³⁹ NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, UK. nch@mrc.soton.ac.uk.

^# Contributed equally.

PMID: 41044417
DOI: 10.1038/s41584-025-01305-x

Abstract

Knee osteoarthritis is a highly prevalent whole-joint disease that is associated with substantial morbidity. If step changes are to be made in the management of knee osteoarthritis, novel patient stratification approaches are needed to identify the most effective treatment for individual patients. Numerous methods for stratifying patients with knee osteoarthritis can be employed; clinical presentation, including co-morbidity and pain phenotype, can influence treatment decisions, and there is a rich history of imaging biomarker use, both from conventional radiographs and, since its development, via MRI, in identifying patients at risk of disease progression, and the latter facilitates the detection of synovitis. The development of novel biochemical biomarkers and the rapid growth of '-omics' technologies provide fresh opportunities to deploy these advances in the stratification of patients with knee osteoarthritis. The health economic landscape in this area is developing, and scoping work has highlighted the need for further studies.

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Conflict of interest statement

Competing interests: R.C., N.A-D., M.A., J.A.T., J.-J.B., N.B., E.C., M.M.R, C.C., G.I.I., A.K., N.L., S.M., R.M., S.O., M.C.P.Y., R.P.R., F.R., B.S., S.S., C.T., A.L. and E.B.I. declare no competing interests. N.R.F. has received speaker fees and honoraria from UCB and Viatris and travel bursaries from Pfizer and Eli Lilly. F.B. reports personal fees from 4 P Pharma, 4Moving Biotech, Grunenthal, GSK, Heel, Nordic Bioscience, Novartis, Servier, TRB Chemedica and Viatris. O.B. has received consulting or lecture fees from Amgen, Aptissen, Biophytis, IBSA, Mylan, Novartis, Nutricia, Orifarm, Sanofi, UCB and Viatris. P.G.C. has performed consultancies or speakers bureaus for Eli Lilly, Eupraxia, Formation Bio, Galapagos, Genascence, GSK, Grunenthal, Janssen, Kolon TissueGene, Levicept, Medipost, Moebius, Novartis, Pacira, Sandoz and Stryker & Takeda. E.M.D. reports honoraria from UCB, Viatris and Pfizer. M.E. reports consultancy for Grünenthal Sweden AB and Key2Compliance. I.K.H. reports personal fees from Novartis, AbbVie, Grünenthal and GSK during the past 36 months. M.H. reports in the past 36 months research grants (paid to institution) from Radius Heath and Angelini Pharma, as well as lecture or consulting fees (all paid to institution) from Grunenthal, Pfizer, Mylan Pharmaceuticals and IBSA. Leuven R&D and the valorization division of KU Leuven, and has received speaker fees and honoraria from AbbVie, Amgen, Galapagos, Biosplice (formerly Samumed), Biocon (formerly Viatris), Eli-Lilly, Novartis and UCB on behalf of R.L. A.M. has received speaker fees and honoraria from HALEON, Grünenthal, Kolon TissueGene, Kolon Life Science Cluster, Aptissen SA, California Institute for Regenerative Medicine (CIRM), Sanofi, Sanofi Consumer Healthcare, GSK, Novartis, Pfizer, Viatris, Contura, Enlivex, Orion Corporation, Pluri, Pacira Biosciences, Laboratoires Expanscience and Synartro Ampio Pharmaceuticals. N.V. reports personal fees from IBSA, Mylan, Viatris, Sanofi, Nestlè and Fidia outside of the submitted work. R.R. has received fees for advisory board or lectures from Abiogen, Effryx and Theramex. J-Y.R. reports consulting fees or paid advisory boards for IBSA-Genevrier, Mylan, Radius Health, Pierre Fabre, Faes Pharma, Rejuvenate Biomed, Samumed, Teva, Theramex, Pfizer and Mithra Pharmaceuticals, lecture fees when speaking at the invitation of sponsor for IBSA-Genevrier, Mylan, Cniel, Dairy Research Council, Nutricia, Danone and Agnovos, and grant support from IBSA-Genevrier, Mylan, Cniel, Radius Health and TRB. N.C.H reports personal fees, consultancy, lecture fees and honoraria from Alliance for Better Bone Health, AMGEN, MSD, Eli Lilly, UCB, Kyowa Kirin, Servier, Shire, Consilient Healthcare, Theramex and Internis Pharma.

References

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Novel approaches to the stratified management of knee osteoarthritis

Affiliations

Novel approaches to the stratified management of knee osteoarthritis

Authors

Affiliations

Abstract

Conflict of interest statement

References

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