How are patient-reported pain outcomes associated with biomarker and structural pathology subtypes in knee osteoarthritis? An explorative evaluation in the IMI-APPROACH cohort
Jansen MP, Mastbergen SC, Wirth W, Roemer FW, Bacardit J, Bay-Jensen AC, Kloppenburg M, Blanco FJ, Haugen IK, Berenbaum F, Eijkelkamp N, Jarraya M (2026)
Publication Type: Journal article
Publication year: 2026
Journal
Book Volume: 8
Article Number: 100726
Journal Issue: 1
DOI: 10.1016/j.ocarto.2025.100726
Abstract
Objective: To explore associations between patient-reported pain outcomes and knee osteoarthritis (OA) subtypes based on systemic biochemical markers and joint structural pathology as defined by MRI. Methods: Data were obtained from 297 knee OA patients from the IMI-APPROACH study. Pain outcomes were assessed using the KOOS, WOMAC, ICOAP, NRS, PainDETECT, and a pain diary. Biochemical markers in serum and urine were used to classify patients into systemic biomarker subtypes (low tissue turnover, structural damage, and systemic inflammation) via k-means clustering. Structural pathology subtypes were determined using MRI into an inflammatory, meniscus/cartilage damage, and subchondral bone pathology subtype. Associations between pain measures and subtypes were analyzed using multivariable regression models adjusted for age, sex, and BMI. Results: The systemic inflammation biomarker subtype was significantly associated with higher KOOS pain, WOMAC weight-bearing pain, NRS knee pain, and PainDETECT scores (all p ≤ 0.042 and β ≥ 0.12). The low tissue turnover subtype negatively associated with lower KOOS, WOMAC, and ICOAP constant pain (all p ≤ 0.22 and β ≤ −0.13), and the structural damage subtype with lower PainDETECT scores (more nociceptive-like pain; p = 0.046 and β = −0.12). Among MRI subtypes, meniscus/cartilage damage was significantly associated with lower PainDETECT scores (p = 0.005 and β = −0.16). No significant associations were found for the subchondral bone subtype or pain diary outcomes. Conclusion: For commonly used pain questionnaires, pain severity seems linked with inflammatory activity more than structural damage. Structural damage is primarily associated with nociceptive-like pain according to PainDETECT, which might be valuable for patient selection to clinical trials and observational studies.
Involved external institutions
University Medical Centre Utrecht (UMC Utrecht)
Netherlands (NL)
Paracelsus Medizinische Privatuniversität
Austria (AT)
Boston University
United States (USA) (US)
Newcastle University
United Kingdom (GB)
Nordic Bioscience A/S
Denmark (DK)
Leiden University Medical Center
Netherlands (NL)
Coruña University Hospital / Complexo Hospitalario Universitario A Coruña (CHUAC)
Spain (ES)
Diakonhjemmet Hospital
Norway (NO)
Hôpital Saint-Antoine
France (FR)
Harvard University
United States (USA) (US)
Netherlands (NL)
Paracelsus Medizinische Privatuniversität
Austria (AT)
Boston University
United States (USA) (US)
Newcastle University
United Kingdom (GB)
Nordic Bioscience A/S
Denmark (DK)
Leiden University Medical Center
Netherlands (NL)
Coruña University Hospital / Complexo Hospitalario Universitario A Coruña (CHUAC)
Spain (ES)
Diakonhjemmet Hospital
Norway (NO)
Hôpital Saint-Antoine
France (FR)
Harvard University
United States (USA) (US)
How to cite
APA:
Jansen, M.P., Mastbergen, S.C., Wirth, W., Roemer, F.W., Bacardit, J., Bay-Jensen, A.C.,... Jarraya, M. (2026). How are patient-reported pain outcomes associated with biomarker and structural pathology subtypes in knee osteoarthritis? An explorative evaluation in the IMI-APPROACH cohort. Osteoarthritis and Cartilage Open, 8(1). https://doi.org/10.1016/j.ocarto.2025.100726
MLA:
Jansen, M. P., et al. "How are patient-reported pain outcomes associated with biomarker and structural pathology subtypes in knee osteoarthritis? An explorative evaluation in the IMI-APPROACH cohort." Osteoarthritis and Cartilage Open 8.1 (2026).
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