Evolution of synovitis in osteoarthritic knees and its association with clinical features

Lange-Brokaar, B.J.E. de; Ioan‐Facsinay, Andreea; Yusuf, Erlangga; Kroon, Herman M.; Zuurmond, A.-M.; Stojanovic-Susulic, V.; Nelissen, Rob G H H; Bloem, Johan L.; Kloppenburg, Margreet

doi:10.1016/j.joca.2016.05.021

Cited by 44 publications

(34 citation statements)

References 32 publications

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“…However statistical significance was only reached for BML worsening in the medial PFJ. On the other hand, we found statistically significant associations between Hoffa-synovitis and widespread structural damage both cross-sectionally and longitudinally, which is in line with previous publications 9–12 . To the best of our knowledge this is the first large scale epidemiologic study to report the prevalence of SHFP hyperintensity and its relation to the presence of site-specific structural damage in the knee.…”

Section: Discussionsupporting

confidence: 93%

“…For instance, we recently reported in a longitudinal study that knees that develop both PFJ and TFJ structural damage after 7 years of follow-up often start with isolated PFJ involvement at baseline 32 . In a similar fashion to Hoffa-synovitis, which is a recognized surrogate of widespread cartilage damage 9,11,12 , SHFP hyperintensity may potentially represent a site-specific surrogate of cartilage damage earlier in the disease process.…”

Section: Discussionmentioning

confidence: 96%

“…Hoffa-synovitis, on the other hand, is detected in a more central location. Hoffa-synovitis, a non-specific, albeit sensitive marker of whole knee synovitis has been used as a surrogate marker for a long time and has proven to show cross-sectional associations with structural features of OA and to be predictive of structural progression and OA incidence particularly in the tibiofemoral joint (TFJ) but also in the patellofemoral joint (PFJ) 9–12 . However, previous publications have not addressed whether SHFP hyperintensity is associated with prevalent local structural joint damage in the PFJ.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Is superolateral Hoffa's fat pad hyperintensity a marker of local patellofemoral joint disease? – The MOST study

Jarraya

Guermazi

Felson

et al. 2017

Osteoarthritis and Cartilage

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Purpose To determine the relation of superolateral Hoffa's fat pad (SHFP) hyperintensity to cartilage damage and bone marrow lesions (BMLs) in the patellofemoral joint (PFJ) and tibiofemoral joint (TFJ). Methods We used data from the 60 and 84-month study visits from the Multicenter Osteoarthritis (MOST) study. SHFP hyperintensity and Hoffa-synovitis were graded from 0 to 3. Cartilage damage and BMLs were scored in the PFJ and TFJ. Structural damage was defined as: any cartilage damage, full-thickness cartilage damage and any BML. Worsening structural damage was defined as any increase in cartilage and BML scores. Logistic regression was used to determine the relation of SHFP hyperintensity and Hoffa-synovitis (>0) to structural damage, adjusting for age, sex and body mass index (BMI). Results 1,094 knees were included in the study. Compared to knees without SHFP hyperintensity, those with SHFP hyperintensity had 1.2 (95% Confidence Interval (CI), 1.1–1.4), 1.7 (1.3–2.3) and 1.6 (1.3–1.9) times the prevalence of any cartilage damage, full-thickness cartilage damage, and BMLs in the lateral PFJ respectively, and 1.1 (1.0–1.2), 1.3 (1.0–1.8), and 1.2 (1.0–1.4) times the prevalence of any cartilage damage, full-thickness cartilage damage, and BMLs in the medial PFJ. SHFP hyperintensity was associated with worsening BMLs in the medial PFJ (RR: 1.4 (1.0–1.9)). In general, there was no relation between SHFP hyperintensity and TFJ outcomes. Hoffa-synovitis was associated both cross-sectionally and longitudinally with structural damage, regardless of definition, in all compartments. Conclusion SHFP hyperintensity may be a local marker of PFJ structural damage.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Is superolateral Hoffa's fat pad hyperintensity a marker of local patellofemoral joint disease? – The MOST study

Jarraya

Guermazi

Felson

et al. 2017

Osteoarthritis and Cartilage

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“…Nevertheless, other studies, using imaging modalities for synovitis assessment, have shown associations between inflammation and clinical outcomes 7,11 . Furthermore, synovitis is known to fluctuate, and this fluctuation has shown correlations to fluctuations in clinical outcomes 25,26 , although conflicting evidence exists 27,28 . The discrepancy with our results may be caused by the fact that inflammation was only assessed once, while clinical aspects were assessed multiple times during follow-up.…”

Section: Discussionmentioning

confidence: 99%

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

Minten

Blom

Snijders

et al. 2019

Osteoarthritis and Cartilage

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s u m m a r yObjective: 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; 0e3) and osteophytes (0e3), 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 [2e8] years) were analysed. Follow-up was a median of 1.4 [0.8e2.7] years for clinical and 1.8 [0.2e5.2] 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.

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“…In addition to its relationship with knee pain, synovitis is also strongly associated with more rapid progression of cartilage loss in OA joints and initiation of cartilage loss in joints without OA [7][8][9][10]. This suggests that synovial inflammation can occur upstream of cartilage erosive mechanisms and could therefore not only be a therapeutically accessible symptom-but also diseasemodifying target.…”

Section: Introductionmentioning

confidence: 99%

The relationship between synovial inflammation, structural pathology, and pain in post-traumatic osteoarthritis: differential effect of stem cell and hyaluronan treatment

et al. 2020

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Background: Synovitis is implicated in the severity and progression of pain and structural pathology of osteoarthritis (OA). Increases in inflammatory or immune cell subpopulations including macrophages and lymphocytes have been reported in OA synovium, but how the particular subpopulations influence symptomatic or structural OA disease progression is unclear. Two therapies, hyaluronan (HA) and mesenchymal stem cells (MSCs), have demonstrated efficacy in some clinical settings: HA acting as device to improve joint function and provide pain relief, while MSCs may have immunomodulatory and disease-modifying effects. We used these agents to investigate whether changes in pain sensitization or structural damage were linked to modulation of the synovial inflammatory response in post-traumatic OA. Methods: Skeletally mature C57BL6 male mice underwent medial-meniscal destabilisation (DMM) surgery followed by intra-articular injection of saline, a hyaluronan hexadecylamide derivative (Hymovis), bone marrow-derived stem cells (MSCs), or MSC + Hymovis. We quantified the progression of OA-related cartilage, subchondral bone and synovial histopathology, and associated pain sensitization (tactile allodynia). Synovial lymphocytes, monocyte/ macrophages and their subpopulations were quantified by fluorescent-activated cell sorting (FACS), and the expression of key inflammatory mediators and catabolic enzyme genes quantified by real-time polymerase chain reaction (PCR). Results: MSC but not Hymovis significantly reduced late-stage (12-week post-DMM) cartilage proteoglycan loss and structural damage. Allodynia was initially reduced by both treatments but significantly better at 8 and 12 weeks by Hymovis. Chondroprotection by MSCs was not associated with specific changes in synovial inflammatory cell populations but rather regulation of post-injury synovial Adamts4, Adamts5, Mmp3, and Mmp9 expression. Reduced acute post-injury allodynia with all treatments coincided with decreased synovial macrophage and T cell numbers, while longer-term effect on pain sensitization with Hymovis was associated with increased M2c macrophages. Conclusions: This therapeutic study in mice demonstrated a poor correlation between cartilage, bone or synovium (histo)pathology, and pain sensitization. Changes in the specific synovial inflammatory cell subpopulations may be associated with chronic OA pain sensitization, and a novel target for symptomatic treatment.

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Evolution of synovitis in osteoarthritic knees and its association with clinical features

Abstract: In individual patients synovitis fluctuates during disease course. Synovitis change was not associated with change in pain. Increase in synovitis is associated with cartilage deterioration, suggesting a role for synovitis as a target for disease-modifying treatment.

Cited by 44 publications

References 32 publications

Is superolateral Hoffa's fat pad hyperintensity a marker of local patellofemoral joint disease? – The MOST study

Is superolateral Hoffa's fat pad hyperintensity a marker of local patellofemoral joint disease? – The MOST study

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

The relationship between synovial inflammation, structural pathology, and pain in post-traumatic osteoarthritis: differential effect of stem cell and hyaluronan treatment

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