[en] [en] OBJECTIVES: Osteoarthritis (OA), a prevalent and disabling condition, significantly burdens individuals and healthcare systems worldwide. It is characterized by joint pain, stiffness, and structural changes in cartilage, bone, and synovium. The clinical manifestations of OA vary widely, reflecting complex interactions among genetic, metabolic, biomechanical, and environmental factors. Despite progress in identifying OA clinical phenotypes, inconsistent terminology, including "phenotypes," "subtypes," and "subgroups," hinders effective communication and research translation. This review aims to synthesize existing literature on clinical OA phenotypes, terminology, and definitions and propose a research agenda.
METHOD: This scoping review followed PRISMA-ScR guidelines, focusing on publications from 2010 to 2023 investigating clinical phenotypes in adult OA patients. Searches were conducted in MEDLINE, SCOPUS, and EBSCOhost using combinations of terms related to clinical phenotypes in OA. Studies were screened, duplicates removed, and relevant data were charted and analyzed by two independent reviewers.
RESULTS: From 196 identified studies, 50 were included in the final analysis. Eight clinical phenotypes were categorized, including inflammatory, biomechanical, metabolic, and pain-sensitization. minimal joint disease, psychologically driven, menopause, severe radiographic. Most studies focused on knee OA, with limited exploration of hand, midfoot, and hip OA. Phenotype-based management strategies demonstrated potential for improving treatment outcomes and guiding research.
CONCLUSION: Standardizing terminology and leveraging phenotype-based frameworks hold promise for advancing personalized OA care and research. Future efforts should focus on validating criteria, developing accessible diagnostic tools, and addressing understudied OA phenotypes. This work highlights the value of tailoring interventions to specific OA phenotypes for improved patient outcomes.
CLINICAL TRIAL NUMBER: Not applicable.
Disciplines :
Rheumatology
Author, co-author :
Gijon-Nogueron, Gabriel; Department Nursing and Podiatry, University of Malaga, Malaga, Spain. gagijon@uma.es
Balint, Peter; Musculoskeletal Radiology Group, Semmelweis University, Budapest, Hungary
Batalov, Anastas; Faculty of Medicine, Clinic of Rheumatology, Medical University of Plovdiv, University Hospital "Kaspela", Plovdiv, Bulgaria
Ostojic, Predrag; Institute of Rheumatology, School of Medicine, University of Belgrade, Belgrade, Serbia
Sollmann, Nico; Department of Diagnostic and Interventional Radiology, University Hospital Ulm, Ulm, Germany ; Department of Diagnostic and Interventional Neuroradiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany ; TUM-Neuroimaging Center, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
van Middelkoop, Marienke; Department of General Practice, Erasmus MC Medical University Center Rotterdam, Rotterdam, The Netherlands
Agricola, Rintje; Erasmus Medical Center, Rotterdam, The Netherlands
Naili, Josefine E; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden ; Motion Analysis Lab, Karolinska University Hospital, Stockholm, Sweden
Milovanovic, Darko; Faculty of Medicine, Clinic for Orthopaedic Surgery and Traumatology, University of Belgrade, University Clinical Centre of Serbia, Belgrade, 11000, Serbia
Popova, Stanislava; Medical University of Plovdiv, Plovdiv, Bulgaria
Kazakova, Maria; Department of Medical Biology, Research Institute, Medical University-Plovdiv, Plovdiv, Bulgaria
Nuernberger, Sylvia; Department of Trauma Surgery, General Hospital, Medical University of Vienna, Vienna, Austria ; Austrian Cluster for Tissue Regeneration, Vienna, Austria
Aulin, Cecilia; Department of Medicine Solna, Division of Rheumatology, Centre for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
Karalilova, Rositsa; Faculty of Medicine, Clinic of Rheumatology, Medical University of Plovdiv, University Hospital "Kaspela", Plovdiv, Bulgaria
Henrotin, Yves ; Université de Liège - ULiège > Département des Sciences de l'activité physique et de la réadaptation > Pathologie générale et physiopathologie - Techniques particulières de kinésithérapie
Hunter DJ, Bierma-Zeinstra S, Osteoarthritis. The Lancet. 2019;393(10182).
Schulze TG, McMahon FJ. Defining the phenotype in human genetic studies: Forward genetics and reverse phenotyping. In: Human Heredity. 2004.
Zhang Y, Jordan JM. Epidemiology of osteoarthritis. Clin Geriatr Med. 2010;26(3).
Castaneda S, Roman-Blas JA, Largo R, Herrero-Beaumont G. Osteoarthritis: a progressive disease with changing phenotypes. Rheumatology. 2014;53(1).
Glyn-Jones S, Palmer AJR, Agricola R, Price AJ, Vincent TL, Weinans H et al. Osteoarthr Lancet. 2015;386(9991).
Mobasheri A, Rayman MP, Gualillo O, Sellam J, van der Kraan P, Fearon U. The role of metabolism in the pathogenesis of osteoarthritis. Nat Rev Rheumatol. 2017;13(5).
Bannuru RR, Osani MC, Vaysbrot EE, Arden NK, Bennell K, Bierma-Zeinstra SMA et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019;27(11).
Iijima H, Fukutani N, Aoyama T, Fukumoto T, Uritani D, Kaneda E et al. Clinical phenotype classifications based on static varus alignment and varus thrust in Japanese patients with medial knee osteoarthritis. Arthritis Rheumatol. 2015;67(9).
Tricco AC, Lillie E, Zarin W, O’Brien KK, Colquhoun H, Levac D et al. PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med. 2018;169(7).
A. Stang Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses Eur J Epidemiol 25 9 603 5 10.1007/s10654-010-9491-z 20652370
Knoop J, van der Leeden M, Thorstensson CA, Roorda LD, Lems WF, Knol DL et al. Identification of phenotypes with different clinical outcomes in knee osteoarthritis: data from the osteoarthritis initiative. Arthritis Care Res (Hoboken). 2011;63(11).
Castañeda S, Roman-Blas JA, Largo R, Herrero-Beaumont G. Subchondral bone as a key target for osteoarthritis treatment. Biochemical Pharmacology. 2012 Elsevier Inc. 83:315–23.
Finan PH, Buenaver LF, Bounds SC, Hussain S, Park RJ, Haque UJ et al. Discordance between pain and radiographic severity in knee osteoarthritis: findings from quantitative sensory testing of central sensitization. Arthritis Rheum. 2013;65(2).
Hawker GA, Stanaitis I. Osteoarthritis year in review 2014: clinical. Osteoarthritis Cartilage. 2014;22(12).
Thomas MJ, Peat G, Rathod T, Marshall M, Moore A, Menz HB et al. The epidemiology of symptomatic midfoot osteoarthritis in community-dwelling older adults: Cross-sectional findings from the clinical assessment study of the foot. Arthritis Res Ther. 2015;17(1).
M. Van der Esch J. Knoop M. van der Leeden L.D. Roorda W.F. Lems D.L. Knol et al. Clinical phenotypes in patients with knee osteoarthritis: A study in the Amsterdam osteoarthritis cohort Osteoarthritis Cartilage 23 4 544 9 10.1016/j.joca.2015.01.006 25596322
J.H. Waarsing S.M.A. Bierma-Zeinstra H. Weinans Distinct subtypes of knee osteoarthritis: data from the osteoarthritis initiative Rheumatol (United Kingdom) 54 9 1650 8
Wesseling J, Bastick AN, ten Wolde S, Kloppenburg M, Lafeber FPJG, Bierma-Zeinstra SMA et al. Identifying trajectories of pain severity in early symptomatic knee osteoarthritis: A 5-year followup of the cohort hip and cohort knee (CHECK) study. J Rheumatol. 2015;42(8).
Raynauld J, Pelletier J, Roubille C, Dorais M, Abram F, Li W et al. Magnetic resonance Imaging–Assessed Vastus medialis muscle fat content and risk for knee osteoarthritis progression: relevance from a clinical trial. Arthritis Care Res (Hoboken). 2015;67(10).
Eymard F, Parsons C, Edwards MH, Petit-Dop F, Reginster JY, Bruyère O et al. Diabetes is a risk factor for knee osteoarthritis progression. Osteoarthritis Cartilage. 2015;23(6).
Dell’Isola A, Allan R, Smith SL, Marreiros SSP, Steultjens M. Identification of clinical phenotypes in knee osteoarthritis: a systematic review of the literature. BMC Musculoskelet Disord 2016;17(1).
Kittelson AJ, Stevens-Lapsley JE, Schmiege SJ. Determination of pain phenotypes in knee osteoarthritis: A latent class analysis using data from the osteoarthritis initiative. Arthritis Care Res (Hoboken). 2016;68(5).
Cardoso JS, Riley JL, Glover T, Sibille KT, Bartley EJ, Goodin BR et al. Experimental pain phenotyping in community-dwelling individuals with knee osteoarthritis. Pain. 2016;157(9).
Frey-Law LA, Bohr NL, Sluka KA, Herr K, Clark CR, Noiseux NO et al. Pain sensitivity profiles in patients with advanced knee osteoarthritis. Pain. 2016;157(9).
Messier SP, Beavers DP, Herman C, Hunter DJ, DeVita P. Are unilateral and bilateral knee osteoarthritis patients unique subsets of knee osteoarthritis? A Biomechanical perspective. Osteoarthritis Cartilage. 2016;24(5).
Deveza LA, Melo L, Yamato TP, Mills K, Ravi V, Hunter DJ. Knee osteoarthritis phenotypes and their relevance for outcomes: a systematic review. Osteoarthritis Cartilage. 2017;25(12).
Herrero-Beaumont G, Roman-Blas JA, Bruyère O, Cooper C, Kanis J, Maggi S et al. Clinical settings in knee osteoarthritis: pathophysiology guides treatment. Maturitas. 2017;96.
Dell’Isola A, Steultjens M. Classification of patients with knee osteoarthritis in clinical phenotypes: data from the osteoarthritis initiative. PLoS ONE. 2018;13(1).
Bay-Jensen AC, Thudium CS, Gualillo O, Mobasheri A. Biochemical marker discovery, testing and evaluation for facilitating OA drug discovery and development. Drug Discov Today. 2018;23(2).
Büchele G, Günther KP, Brenner H, Puhl W, Stürmer T, Rothenbacher D et al. Osteoarthritis-patterns, cardio-metabolic risk factors and risk of all-cause mortality: 20 years follow-up in patients after hip or knee replacement. Sci Rep. 2018;8(1).
Mobasheri A, Saarakkala S, Finnilä M, Karsdal MA, Bay-Jensen AC, van Spil WE. Recent advances in Understanding the phenotypes of osteoarthritis. F1000Res. 2019;8.
Teixeira PEP, Zehry HI, Chaudhari S, Dipietro L, Fregni F. Pain perception in chronic knee osteoarthritis with varying levels of pain inhibitory control: an exploratory study. Scand J Pain. 2020;20(4).
Miles C, Greene A. The effect of treatment with a non-invasive foot worn Biomechanical device on subjective and objective measures in patients with knee osteoarthritis- a retrospective analysis on a UK population. BMC Musculoskelet Disord. 2020;21(1).
Bennell KL, Nelligan RK, Kimp AJ, Schwartz S, Kasza J, Wrigley TV et al. What type of exercise is most effective for people with knee osteoarthritis and co-morbid obesity? The TARGET randomized controlled trial. Osteoarthritis Cartilage. 2020;28(6).
Munugoda IP, Pan F, Wills K, Mattap SM, Cicuttini F, Graves SE et al. Identifying subgroups of community-dwelling older adults and their prospective associations with long-term knee osteoarthritis outcomes. Clin Rheumatol. 2020;39(5).
A.J. Kittelson S.J. Schmiege K. Maluf S.Z. George J.E. Stevens-Lapsley Determination of pain phenotypes in knee osteoarthritis using latent profile analysis Pain Med (United States) 22 3 653 62 10.1093/pm/pnaa398
Xu T, Jia X, Chen S, Xie Y, Tong KK, Iezzi T et al. Physical activity and sleep differences between osteoarthritis, rheumatoid arthritis and non-arthritic people in China: objective versus self report comparisons. BMC Public Health. 2021;21(1).
Knoop J, Ostelo RWJG, van der Esch M, de Zwart A, Bennell KL, van der Leeden M et al. Construct validity of the OCTOPuS stratification algorithm for allocating patients with knee osteoarthritis into subgroups. BMC Musculoskelet Disord. 2021;22(1).
Berna Güzel Mehmet Derya Demirağ, Düriye Sıla Karagöz Özen, Nizamettin Güzel, mukadder Erdem, Berna Göker. Associations between the radiographic phenotypes and the presence of metabolic syndrome in patients with knee osteoarthritis Turk J Med Sci 51 5 2461 6
Guehring H, Moreau F, Daelken B, Ladel C, Guenther O, Bihlet AR et al. The effects of sprifermin on symptoms and structure in a subgroup at risk of progression in the FORWARD knee osteoarthritis trial. Semin Arthritis Rheum. 2021;51(2).
Fawole H, Felson D, Frey-Law L, Jafarzadeh S, Dell’Isola A, Steultjens M et al. Is the association between physical activity and fatigue mediated by physical function or depressive symptoms in symptomatic knee osteoarthritis? The multicenter osteoarthritis study. Scand J Rheumatol. 2021;50(5).
Zhu Z, Hu G, Jin F, Yao X. Correlation of osteoarthritis or rheumatoid arthritis with bone mineral density in adults aged 20–59 years. J Orthop Surg Res. 2021;16(1).
Nishigami T, Tanaka S, Mibu A, Imai R, Wand BM. Knee-related disability was largely influenced by cognitive factors and disturbed body perception in knee osteoarthritis. Sci Rep. 2021;11(1).
Duarte-Salazar C, Marín-Arriaga N, Miranda-Duarte A. The high clinical burden of erosive hand osteoarthritis is associated with clinical findings, pain, and radiographic severity. Reumatología Clínica (English Edition). 2022;18(6).
Hess S, Moser LB, Robertson EL, Behrend H, Amsler F, Iordache E et al. Osteoarthritic and non-osteoarthritic patients show comparable coronal knee joint line orientations in a cross-sectional study based on 3D reconstructed CT images. Knee Surgery, Sports Traumatology, Arthroscopy. 2022;30(2).
Knoop J, de Joode JW, Brandt H, Dekker J, Ostelo RWJG. Patients’ and clinicians’ experiences with stratified exercise therapy in knee osteoarthritis: a qualitative study. BMC Musculoskelet Disord. 2022;23(1).
Nelson AE, Keefe TH, Schwartz TA, Callahan LF, Loeser RF, Golightly YM et al. Biclustering reveals potential knee OA phenotypes in exploratory analyses: data from the osteoarthritis initiative. PLoS ONE. 2022;17(5).
Hangaard S, Boesen M, Bliddal H, Wirth W. Do Ahlbäck scores identify subgroups with different magnitudes of cartilage thickness loss in patients with moderate to severe radiographic osteoarthritis? One-year follow-up data from the osteoarthritis initiative. Skeletal Radiol. 2022;51(4).
Pihl K, Roos EM, Taylor RS, Grønne DT, Skou ST. Prognostic factors for health outcomes after exercise therapy and education in individuals with knee and hip osteoarthritis with or without comorbidities: A study of 37,576 patients treated in primary care. Arthritis Care Res (Hoboken). 2022;74(11).
Stamenkovic BN, Rancic NK, Bojanovic MR, Stojanovic SK, Zivkovic VG, Djordjevic DB et al. Is osteoarthritis always associated with low bone mineral density in elderly patients?? Med (B Aires). 2022;58(9).
T.-N. Cao K.-N. Huynh H.-T. Tran Nguyen. Association between asymptomatic hyperuricemia and knee osteoarthritis in older outpatients Eur Rev Med Pharmacol Sci 26 18 6600 7 36196710
Binvignat M, Pires G, Tchitchek N, Costantino F, Courties A, Klatzmann D et al. Identification of symptom phenotypes of hand osteoarthritis using hierarchical clustering: results from the DIGICOD cohort. Arthritis Care Res (Hoboken). 2023;75(7).
Copp G, Robb KP, Viswanathan S. Culture-expanded mesenchymal stromal cell therapy: does it work in knee osteoarthritis? A pathway to clinical success. Cell Mol Immunol. 2023;20(6).
N.E.J. Jansen E. Molendijk D. Schiphof J.B.J. van Meurs E.H.G. Oei M. van Middelkoop et al. Metabolic syndrome and the progression of knee osteoarthritis on MRI Osteoarthritis Cartilage 31 5 647 55 1:STN:280:DC%2BB28fltVGqsg%3D%3D 10.1016/j.joca.2023.02.003 36801367
Demanse D, Saxer F, Lustenberger P, Tankó LB, Nikolaus P, Rasin I et al. Unsupervised machine-learning algorithms for the identification of clinical phenotypes in the osteoarthritis initiative database. Semin Arthritis Rheum. 2023;58.
Feng Jling, Ma R, han, Sun L, li, Zhao Jru, Zhao Y ping, Li G. Quantitative assessment of condylar bone resorption using fused CBCT images: differentiating and diagnosing three distinct groups based on volume and thickness decrease. Dentomaxillofacial Radiology. 2023;52(8).
Gonzalez FF, Leporace G, Franciozi C, Cockrane M, Metsavaht L, Carpes FP et al. Clinical and radiographic characterization of three-dimensional gait profiles of patients with knee osteoarthritis. Knee. 2023;44.
Sharma K, Eckstein F, Maschek S, Roth M, Hunter DJ, Wirth W. Association of quantitative measures of medial meniscal extrusion with structural and symptomatic knee osteoarthritis progression– Data from the OAI FNIH biomarker study. Osteoarthritis Cartilage. 2023;31(10).
Hart HF, Birmingham TB, Sritharan P, Primeau C, King MG, Fischer LK. Sex-related differences in gait characteristics and their associations with symptoms in individuals with patellofemoral osteoarthritis. Gait Posture. 2024;107.
Deveza LA, Melo L, Yamato TP, Mills K, Ravi V, Hunter DJ. Knee osteoarthritis phenotypes and their relevance for outcomes: a systematic review. Osteoarthritis and Cartilage. 2017 W.B. Saunders Ltd; 25:1926–41.
