The 2024 International Osteoarthritis Research Society (OARSI) conference concluded last week, offering valuable exchange and information. What insights could we gather from these dynamic four days? One of the most interesting themes was the relationship between patients’ osteoarthritis (OA), pain, and psychosocial state – a crucial but often overlooked topic. Indeed, OA studies typically assess patients based on radiological criteria or pain but rarely consider psychosocial states such as fatigue, anxiety, depression, and isolation. However, the number of interventions, abstracts, and posters presented on this topic suggests that it deserves a more significant role in the management of OA patients and clinical trials.

Firstly, what are we talking about? Alongside pain, which is always the primary characteristic for evaluating the condition of an OA patient, numerous psychosocial factors may evolve following the onset of OA. During his presentation titled “(Bio) Psychological Network Models of Chronic Joint Pain”, Professor R. Geenen from Utrecht University provided a non-exhaustive list of these factors, including fatigue and sleep problems, psychological issues (anxiety, depression, stress), inactivity (physical and social), dietary issues, among others. As discussed in numerous abstracts presented at the conference, these parameters will play an important role, particularly in the progression of the disease. For example, patients suffering from anxiety, stress, or depression tend to experience more pain (1,2), less physical functioning (3), more healthcare consultations (4), and weak improvement after surgical intervention (5). Likewise, patients with sleep problems report more pain (6-8). In fact, insomnia and associated fatigue are significant characteristics of OA patients. In (6), 66% of patients with knee or hip OA experienced sleep problems, with 20% of them suffering from insomnia.

While several abstracts presented at the conference attempted to provide mechanistic explanations for the onset and progression of these symptoms (9-12), their understanding remains complex. In particular, as emphasized by Professor Geenen, it is important not to view these issues of anxiety, fatigue, etc., simply as a cause or consequence of pain. Indeed, chronic stress and sleep disorders can be both the cause and result of pain and the development of OA (2,7). Moreover, these psychosocial symptoms are themselves entangled (13,14). It is, therefore, essential to fully map the patient’s profile to understand the underlying network model. This is precisely the aim of the NET-RMDs study (15), some results of which were presented by Professor Geenen. One of the significant findings of these analyses is that while most of these symptoms (pain, fatigue, sleep problems, psychological problems, unhealthy diet, etc.) are interconnected, pain is not the central primary factor; instead, fatigue takes precedence. Furthermore, as associations between symptoms are sometimes weak, they can characterize different patient profiles. This brings us back to the main problem of an indication such as OA: the heterogeneity of patients. By focusing solely on their pain, we overlook a portion of the variability of symptoms they suffer from.

This is also why, within the framework of the GO-PAIN project, a working group composed of experts from different backgrounds, a place was made for OA patients to directly characterize, verbatim, what this indication represented to them. Also presented by Professor Geenen at the conference, this work has allowed for a better mapping of all the problems encountered by patients: the multitude of symptoms, the impact on their social, professional, and economic life, their relationship with their doctor, their way of managing this disease, etc. The variety of responses received highlights, once again, the diversity of patients and the need for an individual approach.

From a clinical perspective, since the patient’s disease status, and personal and social factors differ, it is essential that patient management also differs. As emphasized in (16), this begins with a diagnosis provided with tailored information, adapting to the patient’s feelings, experiences, and beliefs. Subsequently, it may be helpful to propose combined treatments to manage multiple symptoms (3,17). Similarly, developing solutions that may not be medication-based (as in (18)) can help align with the patient’s beliefs, particularly regarding the use of painkillers.

From the perspective of clinical trials, it is essential also to consider this significant variability in patient profiles. It has long been known that this is the leading cause of the considerable heterogeneity of outcomes in RCTs and their low assay sensitivity. Pain alone cannot characterize a patient. This is why some propose complementary evaluations (19, 20). These evaluations can firstly allow for the definition of new outcomes in RCTs. Indeed, increasing the importance given to these other psychosocial symptoms in evaluating treatments could be relevant. However, the key is primarily to understand what differentiates patients at the beginning of the study. Indeed, as demonstrated by Professor Geenen through his two examples, all these psychosocial factors and symptoms are intertwined, and it is impossible to understand a symptom’s evolution without taking the complete picture into account. And even though pain remains and will remain the main point of interest in clinical studies on OA, we need to zoom out and look at the forest of other symptoms (anxiety, stress, depression, fatigue, etc.) and characteristics (beliefs, experiences, social isolation, etc.) of the patient. Only through such work can we explain the heterogeneity of the response measured in RCTs and thus improve the assay sensitivity and statistical power of clinical studies.

Bibliography

1. Biomechanical & Psychological Factors Associated with Hip Pain in Aging Adults, Samaan, Michael A. et al., Osteoarthritis and Cartilage, Volume 32, S158, DOI:https://doi.org/10.1016/j.joca.2024.02.225

2. Chronic Stress in Osteoarthritis: Cause or Effect?, Rösch, Gundula et al., Osteoarthritis and Cartilage, Volume 32, S441, DOI:https://doi.org/10.1016/j.joca.2024.02.650

3. Pain Severity Mediates the Longitudinal Relationship Between Depressive Symptoms and Physical Function in Knee Osteoarthritis, Rathbun, Alan M. et al., Osteoarthritis and Cartilage, Volume 32, S506 – S507, DOI:https://doi.org/10.1016/j.joca.2024.02.753

4. Anxiety, depression and healthcare consultations/inpatient days in people with osteoarthritis: A register-based matched cohort study, Kiadaliri, Ali et al., Osteoarthritis and Cartilage, Volume 32, S325 – S326, DOI:https://doi.org/10.1016/j.joca.2024.02.480

5. Association Between Depression and Outcome Regarding Pain after Participation in a First-Line Intervention Program for Knee and Hip Osteoarthritis. A Study from the Swedish Osteoarthritis Register, Gustafsson, Kristin et al., Osteoarthritis and Cartilage, Volume 32, S217 – S218, DOI:https://doi.org/10.1016/j.joca.2024.02.314

6. How Common is Insomnia Among Patients with Knee and Hip Osteoarthritis? A Cross-Sectional Study Using Data From the Good Life with Osteoarthritis in Denmark (GLA:D®) Register, Thorlund, Jonas B. et al., Osteoarthritis and Cartilage, Volume 32, S194, DOI:https://doi.org/10.1016/j.joca.2024.02.276

7. Do Sleep Disorders Have a Role in the Development of Osteoarthritis and in the Symptoms of this Disease? – A Systematic Review, Pinheiro, Grazielle P. et al., Osteoarthritis and Cartilage, Volume 32, S223 – S224, DOI:https://doi.org/10.1016/j.joca.2024.02.323

8. Sleep Problems are Associated with Higher Pain Itensity in a Longitudinal Study of People with Hand Osteoarthritis: Data from the Nor-Hand Study, Bordvik, Daniel H. et al., Osteoarthritis and Cartilage, Volume 32, S99 – S100, DOI:https://doi.org/10.1016/j.joca.2024.02.141

9. Association Between Sleep Quality and Peripheral and Central Pain Sensitization in People with Knee Osteoarthritis, Venturini, Paula et al., Osteoarthritis and Cartilage, Volume 32, S228, DOI:https://doi.org/10.1016/j.joca.2024.02.330

10. Impaired Sleep and Hippocampal Neuroplasticity in an Inflammatory Knee Pain Model, Villegas, Angel Rose L. et al., Osteoarthritis and Cartilage, Volume 32, S515, DOI:https://doi.org/10.1016/j.joca.2024.02.766

11. Physical Activity, Pain, Function, and QoL in People with the Comorbidity of Knee OA and Diabetes: Data from the Osteoarthritis Initiative, Hart, Harvi F. et al., Osteoarthritis and Cartilage, Volume 32, S183 – S184, DOI:https://doi.org/10.1016/j.joca.2024.02.261

12. Obesity Subtypes and Relationship with Physical Function, Pain, and Quality of Life: the Multicenter Osteoarthritis (MOST) Study, Godziuk, Kristine et al., Osteoarthritis and Cartilage, Volume 32, S202, DOI:https://doi.org/10.1016/j.joca.2024.02.288

13. Pain Sensitivity, Physical Activity, Pain Intensity or Depression and Anxiety: Which Factors are Most Associated to Sleep Quality in Knee Osteoarthritis?, Venturini, Paula et al., Osteoarthritis and Cartilage, Volume 32, S226 – S227, DOI:https://doi.org/10.1016/j.joca.2024.02.328

14. Insomnia Symptoms Among Individuals with Osteoarthritis and with Symptoms Indicative of Osteoarthritis: a Population-Based Study, Cavallo, Melissa et al., Osteoarthritis and Cartilage, Volume 32, S327 – S328, DOI:https://doi.org/10.1016/j.joca.2024.02.483

15. NET-RMDs Study: Networks of Fatigue and Pain in Rheumatic and Musculoskeletal Diseases – Protocol for an International Cross-Sectional Study, Gavilán-Carrera B et al., BMJ Open 2022;12:e061099, DOI: 10.1136/bmjopen-2022-061099

16. What Do People Think and Feel about Diagnostic Information for Hip Pain?: A Qualitative Study, Haber, Travis S. et al., Osteoarthritis and Cartilage, Volume 32, S196, DOI:https://doi.org/10.1016/j.joca.2024.02.279

17. Sleep Efficiency among Patients with Knee Osteoarthritis Receiving a Total Knee Arthroplasty: a 12-Month Longitudinal Observation Study, Na, Annalisa et al., Osteoarthritis and Cartilage, Volume 32, S214, DOI:https://doi.org/10.1016/j.joca.2024.02.308

18. Effect of Exercise on Sleep in People with Knee Osteoarthritis, Yang, Yiwen et al., Osteoarthritis and Cartilage, Volume 32, S568, DOI:https://doi.org/10.1016/j.joca.2024.02.840

19. Pain Scores on a 0-10 Visual Numeric Scale in Osteoarthritis Patients Reflect Polyarthritis and Comorbidities Beyond Joint Involvement: Pragmatic Recognition Using a Multidimensional Health Assessment Questionnaire (MDHAQ), Schmukler, Juan et al., Osteoarthritis and Cartilage, Volume 32, S501 – S502, DOI:https://doi.org/10.1016/j.joca.2024.02.745

20. Psychometric Properties of the EQ-5D-5L in Patients with Knee or Hip Osteoarthritis: Confirmatory Factor Analysis and Item Response Theory, Kiadaliri, Ali, Osteoarthritis and Cartilage, Volume 32, S196 – S197, DOI:https://doi.org/10.1016/j.joca.2024.02.280