Exploring longitudinal associations of histologically assessed inflammation with symptoms and radiographic damage in knee osteoarthritis: combined results of three prospective cohort studies

M J M Minten; A Blom; G F Snijders; M Kloppenburg; F H J van den Hoogen; A A den Broeder; P M van der Kraan; C H M van den Ende

doi:10.1016/j.joca.2018.10.014

Exploring longitudinal associations of histologically assessed inflammation with symptoms and radiographic damage in knee osteoarthritis: combined results of three prospective cohort studies

Osteoarthritis Cartilage. 2019 Jan;27(1):71-79. doi: 10.1016/j.joca.2018.10.014. Epub 2018 Nov 16.

Authors

M J M Minten¹, A Blom², G F Snijders², M Kloppenburg³, F H J van den Hoogen⁴, A A den Broeder⁴, P M van der Kraan², C H M van den Ende⁴

Affiliations

¹ Department of Rheumatology, Sint Maartenskliniek, Nijmegen, Netherlands. Electronic address: m.minten@maartenskliniek.nl.
² Department of Rheumatology, Radboud University Medical Center, Nijmegen, Netherlands.
³ Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands.
⁴ Department of Rheumatology, Sint Maartenskliniek, Nijmegen, Netherlands; Department of Rheumatology, Radboud University Medical Center, Nijmegen, Netherlands.

PMID: 30448532
DOI: 10.1016/j.joca.2018.10.014

Abstract

Objective: To explore the associations between different histologically assessed, inflammatory synovial characteristics and subsequent clinical and structural aspects in knee osteoarthritis (OA).

Design: Knee OA patients, ranging in stage from early to advanced, were recruited from three different ongoing studies. Synovial tissue biopsies were taken and histologically assessed for six features (four inflammatory related aspects, fibrosis and fibrin deposition). Clinical aspects (WOMAC pain, functioning and stiffness and SF-36 vitality) and structural aspects (Kellgren and Lawrence (KL)-grade, joint space narrowing (JSN; 0-3) and osteophytes (0-3), and reception of total knee replacement (TKR)) were repeatedly assessed during follow-up. Associations between histology and clinical and structural aspects were analysed using linear mixed model analyses and cox proportional hazards analysis.

Results: Biopsies of 83 patients (median complaint duration: 5 [2-8] years) were analysed. Follow-up was a median of 1.4 [0.8-2.7] years for clinical and 1.8 [0.2-5.2] years for structural aspects. Fibrosis and fibrin deposition were inversely correlated with the inflammatory features. A higher fibrosis score was associated with a lower scores for KL-grade, JSN and osteophytes, while higher scores for perivascular oedema, synovial lining thickness and vascularisation were associated with higher scores for structural aspects during follow-up. No associations were found between each of the histological features and any of the clinical aspects or the chance for TKR during follow-up.

Conclusions: Inflammatory related histological aspects are associated with subsequent increased radiological severity in knee OA, while fibrosis seems to protect against this, providing a potential therapeutic target for OA treatment.

Keywords: Histology; Inflammation; Knee osteoarthritis; Radiographic severity/progression; Symptoms; Synovitis.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Arthroplasty, Replacement, Knee / statistics & numerical data
Arthroscopy
Biopsy
Disease Progression
Female
Fibrosis
Humans
Knee Joint / diagnostic imaging
Knee Joint / pathology*
Longitudinal Studies
Male
Middle Aged
Osteoarthritis, Knee / diagnostic imaging
Osteoarthritis, Knee / pathology*
Osteoarthritis, Knee / surgery
Prospective Studies
Radiography
Severity of Illness Index
Synovial Membrane / pathology