scholarly journals FRI0416 COMBINATION OF SERUM ADIPOKINES/RELATED INFLAMMATORY FACTORS AND RATIOS AS PREDICTORS OF INFRAPATELLAR FAT PAD VOLUME IN KNEE OSTEOARTHRITIS PATIENTS: USAGE OF A COMPREHENSIVE MACHINE LEARNING APPROACH

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 806.1-807
Author(s):  
H. Bonakdari ◽  
G. Tardif ◽  
F. Abram ◽  
J. P. Pelletier ◽  
J. Martel-Pelletier
Keyword(s):  
Risk Factors ◽  
Serum Levels ◽  
Infrapatellar Fat Pad ◽  
Inflammatory Factors ◽  
Fat Pad ◽  
Research Support ◽  
Knee Oa ◽  
Total Cohort ◽  
Low Bmi ◽  
The University

Background:One of the hurdles in osteoarthritis (OA) drug discovery and the improvement of therapeutic approaches is the early identification of patients who will progress. It is therefore crucial to find efficient and reliable means of screening OA progressors. Although the main risk factors, age, gender and body mass index (BMI), are important, they alone are poor predictors. However, serum factors could be potential biomarkers for early prediction of knee OA progression.Objectives:In a first step toward finding early reliable predictors of OA progressors, this study aimed to determine, in OA individuals, the optimum combination of serum levels of adipokines/related inflammatory factors, their ratios, and the three main OA risk factors for predicting knee OA infrapatellar fat pad (IPFP) volume, as this tissue has been associated with knee OA onset and progression.Methods:Serum and magnetic resonance images (MRI) were from the Osteoarthritis Initiative at baseline. Variables (48) comprised the 3 main OA risk factors (age, gender, BMI), 6 adipokines, 3 inflammatory factors, and their 36 ratios. IPFP volume was assessed on MRI with a neural network methodology. The best variables and models were identified in Total cohort (n=678), High-BMI (n=341) and Low-BMI (n=337), using an artificial intelligence selection approach: the adaptive neuro-fuzzy inference system embedded with fuzzy c-means clustering (ANFIS-FCM). Performance was validated using uncertainty analyses and statistical indices. Reproducibility was done using 80 OA patients from a clinical trial (female, n=57; male, n=23).Results:For the three groups, 8.44E+14 sub-variables were investigated and 48 models were selected. The best model for each group included five variables: the three risk factors and adipsin/C-reactive protein combined for Total cohort, adipsin/chemerin; High-BMI, chemerin/adiponectin high molecular weight; and Low-BMI, interleukin-8. Data also revealed that the main form of the ratio used for the model was justified, as the use of the inverse form slightly decreased the performance of the model in both training and testing stages. Further investigation indicated that gender improved (13-16%) the prediction results compared to the BMI-based models. For each gender, we then generated a pseudocode (an evolutionary computation equation) with the 5 variables for predicting IPFP volume. Reproducibility experiments were excellent (correlation coefficient: female 0.83, male 0.95).Conclusion:This study demonstrates, for the first time, that the combination of the serum levels of adipokines/inflammatory factors and the three main risk factors of OA could predict IPFP volume with high reproducibility, and superior performance with gender separation. By using the models for each gender and the pseudocodes for OA patients provided in this study, the next step will be to develop a predictive model for OA progressors.Acknowledgments:This work was funded by the Chair in Osteoarthritis of the University of Montreal, the Osteoarthritis Research Unit of the University of Montreal Hospital Research Centre, the Groupe de recherches des maladies rhumatismales du Québec and by ArthroLab Inc., all from Montreal, Quebec, Canada.Disclosure of Interests:Hossein Bonakdari: None declared, Ginette Tardif: None declared, François Abram Employee of: ArthroLab Inc., Jean-Pierre Pelletier Shareholder of: ArthroLab Inc., Grant/research support from: TRB Chemedica, Speakers bureau: TRB Chemedica and Mylan, Johanne Martel-Pelletier Shareholder of: ArthroLab Inc., Grant/research support from: TRB Chemedica

scholarly journals POS1002 BASELINE CALPROTECTIN AND VISFATIN LEVELS PREDICT RADIOGRAPHIC SPINAL PROGRESSION AFTER 2 YEARS IN ANKYLOSING SPONDYLITIS PATIENTS ON TNF INHIBITOR THERAPY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 769.2-770
Author(s):  
J. Rademacher ◽  
M. Siderius ◽  
L. Gellert ◽  
F. Wink ◽  
M. Verba ◽  
...  
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Ankylosing Spondylitis ◽  
Bone Formation ◽  
Bone Turnover ◽  
Radiographic Progression ◽  
Serum Levels ◽  
Tnf Inhibitor ◽  
Research Support

Background:Radiographic spinal progression determinates functional status and mobility in ankylosing spondylitis (AS)1.Objectives:To analyse whether biomarker of inflammation, bone turnover and adipokines at baseline or their change after 3 months or 2 years can predict spinal radiographic progression after 2 years in AS patients treated with TNF-α inhibitors (TNFi).Methods:Consecutive AS patients from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort2 starting TNFi between 2004 and 2012 were included. The following serum biomarkers were measured at baseline, 3 months and 2 years of follow-up with ELISA: - Markers of inflammation: calprotectin, matrix metalloproteinase-3 (MMP-3), vascular endothelial growth factor (VEGF) - Markers of bone turnover: bone-specific alkaline phosphatase (BALP), serum C-terminal telopeptide (sCTX), osteocalcin (OC), osteoprotegerin (OPG), procollagen typ I and II N-terminal propeptide (PINP; PIINP), sclerostin. - Adipokines: high molecular weight (HMW) adiponectin, leptin, visfatinTwo independent readers assessed spinal radiographs at baseline and 2 years of follow-up according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Radiographic spinal progression was defined as mSASSS change ≥2 units or the formation of ≥1 new syndesmophyte over 2 years. Logistic regression was performed to examine the association between biomarker values at baseline, their change after 3 months and 2 years and radiographic spinal progression. Multivariable models for each biomarker were adjusted for mSASSS or syndesmophytes at baseline, elevated CRP (≥5mg/l), smoking status, male gender, symptom duration, BMI, and baseline biomarker level (the latter only in models with biomarker change).Results:Of the 137 included AS patients, 72% were male, 79% HLAB27+; mean age at baseline was 42 years (SD 10.8), ASDAScrp 3.8 (0.8) and mSASSS 10.6 (16.1). After 2 years of follow-up, 33% showed mSASSS change ≥2 units and 24% had developed ≥1 new syndesmophyte. Serum levels of biomarkers of inflammation and bone formation showed significant changes under TNFi therapy, whereas adipokine levels were not altered from baseline (Figure 1).Univariable logistic regression revealed a significant association of baseline visfatin (odds ratio OR [95% confidence interval] 1.106 [1.007-1.215]) and sclerostin serum levels (OR 1.006 [1.001-1.011]) with mSASSS progression after 2 years. Baseline sclerostin levels were also associated with syndesmophyte progression (OR 1.007 [1.001-1.013]). In multivariable logistic analysis, only baseline visfatin level remained significantly associated (OR 1.465 [1.137-1.889]) with mSASSS progression. Furthermore, baseline calprotectin showed a positive association with both, mSASSS (OR 1.195 [1.055-1.355]) and syndesmophyte progression (OR 1.107 [1.001-1.225]) when adjusting for known risk factors for radiographic progression.Univariable logistic regression showed that change of sclerostin after 3 months was associated with syndesmophytes progression (OR 1.007 [1.000-1.015), change of PINP level after 2 years was associated with mSASSS progression (OR 1.027 [1.003-1.052]) and change of visfatin after 2 years was associated with both measures of radiographic progression – mSASSS (OR 1.108 [1.004-1.224]) and syndesmophyte formation (OR 1.115; [1.002-1.24]). However, those associations were lost in multivariable analysis.Conclusion:Independent of known risk factors, baseline calprotectin and visfatin levels were associated with radiographic spinal progression after 2 years of TNFi. Although biomarkers of inflammation and bone formation showed significant changes under TNFi therapy, these changes were not significantly related to radiographic spinal progression in our cohort of AS patients.References:[1]Poddubnyy et al 2018[2]Maas et al 2019Acknowledgements:Dr. Judith Rademacher is participant in the BIH-Charité Clinician Scientist Program funded by the Charité –Universitätsmedizin Berlin and the Berlin Institute of Health.Disclosure of Interests:Judith Rademacher: None declared, Mark Siderius: None declared, Laura Gellert: None declared, Freke Wink Consultant of: AbbVie, Maryna Verba: None declared, Fiona Maas: None declared, Lorraine M Tietz: None declared, Denis Poddubnyy: None declared, Anneke Spoorenberg Consultant of: Abbvie, Pfizer, MSD, UCB, Lilly and Novartis, Grant/research support from: Abbvie, Pfizer, UCB, Novartis, Suzanne Arends Grant/research support from: Pfizer.

scholarly journals Infrapatellar fat pad induces an inflammatory and catabolic phenotype on autologous fibroblast-like synoviocytes from severe knee oa patients

2014 ◽  
Vol 22 ◽  
pp. S448 ◽  
Author(s):  
F. Eymard ◽  
A. Pigenet ◽  
D. Citadelle ◽  
C-H. Flouzat Lachaniette ◽  
A. Poignard ◽  
...  
Keyword(s):  
Infrapatellar Fat Pad ◽  
Fat Pad ◽  
Knee Oa ◽  
Fibroblast Like Synoviocytes

Effects of Conditioned Medium From Osteoarthritic Cartilage Fragments on Donor-Matched Infrapatellar Fat Pad–Derived Mesenchymal Stromal Cells

2019 ◽  
Vol 47 (12) ◽  
pp. 2927-2936 ◽  
Author(s):  
Zhenlan Fu ◽  
Xiongbo Song ◽  
Lin Guo ◽  
Liu Yang ◽  
Cheng Chen
Keyword(s):  
Conditioned Medium ◽  
Chondrogenic Differentiation ◽  
Infrapatellar Fat Pad ◽  
Control Medium ◽  
Fat Pad ◽  
Negative Effects ◽  
Osteoarthritic Cartilage ◽  
Chondrogenic Medium ◽  
Knee Oa

Background: Mesenchymal stromal cell (MSC)–based therapies have emerged as a promising strategy for osteoarthritis (OA) treatment. In particular, infrapatellar fat pad (IPFP)–derived MSCs have become a good option to treat knee OA. Purpose: To investigate the influence of the local microenvironment of the knee joint, especially OA cartilage, on the bioactivities of injected/implanted IPFP MSCs. Study Design: Controlled laboratory study. Methods: Conditioned medium (CM) derived from OA cartilage fragments was collected and characterized. Donor-matched IPFP MSCs were treated with control medium (Dulbecco’s modified Eagle medium (DMEM)/F-12 or chondrogenic medium), control medium + CM, or CM alone; and a series of behaviors including the viability, migration, chondrogenic and hypertrophic differentiation, and catabolic activity of IPFP MSCs were evaluated among groups. Results: There were 14 cytokines detected in CM. CM treatment improved the viability of IPFP MSCs. CM hindered the migration of IPFP MSCs. In chondrogenic differentiation, the presence of CM increased the expression of chondrogenic markers but also enhanced the state of hypertrophy and catabolism. Conclusion: OA cartilage–secreted factors could induce chondrogenic differentiation but also resulted in negative effects including the weakened migration, increased hypertrophy, and catabolism of IPFP MSCs in vitro. Clinical Relevance: These findings provide an insight on the fate of IPFP MSCs after intra-articular injections.

Association Between Infrapatellar Fat Pad Volume and Knee Structural Changes in Patients with Knee Osteoarthritis

2015 ◽  
Vol 42 (10) ◽  
pp. 1878-1884 ◽  
Author(s):  
Jingyu Cai ◽  
Jianhua Xu ◽  
Kang Wang ◽  
Shuang Zheng ◽  
Fan He ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Structural Changes ◽  
Spin Echo ◽  
Cartilage Volume ◽  
Infrapatellar Fat Pad ◽  
Fast Spin Echo ◽  
Cartilage Defects ◽  
Fat Pad ◽  
Cross Sectional ◽  
Knee Oa

Objective.The function of the infrapatellar fat pad (IPFP) in knee osteoarthritis (OA) remains uncertain. This study aimed to examine cross-sectional associations between IPFP volume and knee structures in patients with knee OA.Methods.The study included 174 patients with clinical knee OA (mean age, 55.5 yrs). Fat-suppressed 3-D T1-weighted spoiled gradient recall magnetic resonance imaging (MRI) was used to measure the IPFP and cartilage volume. T2-weighted fast spin echo MRI was used to assess cartilage defects and bone marrow lesions (BML). Radiographic knee osteophytes and joint space narrowing (JSN) were assessed using the Osteoarthritis Research Society International atlas.Results.After adjustment for potential confounders, greater IPFP volume was associated with greater tibial and patellar cartilage volume (all p < 0.05), and fewer cartilage defects at all sites (OR 0.88–0.91, all p < 0.05). IPFP volume was associated with presence of BML at lateral tibial and medial femoral sites (OR 0.88–0.91, all p < 0.05) and osteophytes at lateral tibiofemoral compartment (OR 0.88, p < 0.05). IPFP volume was not significantly associated with JSN.Conclusion.Greater IPFP volume was associated with greater knee cartilage volume and fewer structural abnormalities, suggesting a protective role of IPFP size in knee OA.

scholarly journals Infrapatellar fat pad area on knee MRI: does it correlate with the extent of knee osteoarthritis?

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Eman Ragab ◽  
Dena Serag
Keyword(s):  
Large Scale ◽  
Cartilage Damage ◽  
Surrogate Marker ◽  
Joint Space ◽  
Protective Role ◽  
Infrapatellar Fat Pad ◽  
Cartilage Defects ◽  
Fat Pad ◽  
Knee Oa ◽  
Maximal Area

Abstract Background Osteoarthritis (OA) of the knee joint is a common cause of chronic disability in older adults. During the past 10 years, the infrapatellar fat pad (IPFP) has emerged as a new player in the pathogenesis of knee OA. Its exact role in the pathogenesis of knee OA remains uncertain. While many studies focused on the detrimental effect of the chemical mediators released by IPFP and their role in the accentuation of the development of OA, only few studies elucidated the beneficial effect of IPFP maximal area as a local shock absorber protecting the adjacent articular structures from progressive damage. The aim of this study was to evaluate the relation between the IPFP maximal area and the prevalence of OA manifestations. We also studied the relation between the subcutaneous (SC) fat thicknesses on the medial aspect of the knee as a surrogate marker of body obesity and the IPFP area. Results A total of 216 knee scans for 188 adult patients (64 males and 124 females) who met the inclusion criteria were examined. They were between 45 and 66 years (mean 52.5 years). The mean IPFP area for all patients was 6.9 cm2 (± 1.6 SD) (ranged from 4.5 to 11 cm2). After adjustment for potential confounders, there was a significant negative association between IPFP area and radiographic manifestations of OA (osteophites, joint space narrowing, and grade of OA) (P value < 0.001 for each), as well as MRI manifestations of OA (cartilage defects and subchondral bone marrow lesions) (P value < 0.001 and < 0.003, respectively). There was a negative but non-significant association between IPFP area and SC fat thickness. Conclusion In our study, we found supportive evidence that IPFP maximal area is associated with fewer osteoarthritic knee changes and less cartilage damage, suggesting that it plays a protective role against the development and progression of OA. Further large-scale clinical studies are awaited to confirm the obtained results. Based on our findings, it would be recommended to avoid IPFP resection during surgery in order to maintain its protective effect.

Pathophysiology of obesity on knee joint homeostasis: contributions of the infrapatellar fat pad

2016 ◽  
Vol 26 (2) ◽  
Author(s):  
Kelly S. Santangelo ◽  
Lauren B. Radakovich ◽  
Josie Fouts ◽  
Michelle T. Foster
Keyword(s):  
Knee Joint ◽  
Weight Bearing ◽  
Epidemiological Studies ◽  
Metabolic Effects ◽  
Infrapatellar Fat Pad ◽  
Inflammatory Factors ◽  
Bone Homeostasis ◽  
Fat Pad ◽  
Local Factors ◽  
Adipose Depot

AbstractOsteoarthritis (OA) is a debilitating condition characterized by inflammation, breakdown, and consequent loss of cartilage of the joints. Epidemiological studies indicate obesity is an important risk factor involved in OA initiation and progression. Traditional views propose OA to be a biomechanical consequence of excess weight on weight-bearing joints; however, emerging data demonstrates that systemic and local factors released from white adipose depots play a role. Hence, current views characterize OA as a condition exacerbated by a metabolic link related to adipose tissue, and not solely related to redistributed/altered weight load. Factors demonstrated to influence cartilage and bone homeostasis include adipocyte-derived hormones (“adipokines”) and adipose depot released cytokines. Epidemiological studies demonstrate a positive relation between systemic circulating cytokines, leptin, and resistin with OA types, while the association with adiponectin is controversial. Local factors in joints have also been shown to play a role in OA. In particular, this includes the knee, a weight-bearing joint that encloses a relatively large adipose depot, the infrapatellar fat pad (IFP), which serves as a source of local inflammatory factors. This review summarizes the relation of obesity and OA as it specifically relates to the IFP and other integral supporting structures. Overall, studies support the concept that metabolic effects associated with systemic obesity also extend to the IFP, which promotes inflammation, pain, and cartilage destruction within the local knee joint environment, thus contributing to development and progression of OA.

scholarly journals Contribution of Infrapatellar Fat Pad and Synovial Membrane to Knee Osteoarthritis Pain

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Elisa Belluzzi ◽  
Elena Stocco ◽  
Assunta Pozzuoli ◽  
Marnie Granzotto ◽  
Andrea Porzionato ◽  
...  
Keyword(s):  
Synovial Membrane ◽  
Adult Population ◽  
Joint Damage ◽  
Joint Disease ◽  
Infrapatellar Fat Pad ◽  
Fat Pad ◽  
Pain Mechanisms ◽  
Knee Oa ◽  
New Findings

Osteoarthritis (OA) is the most common form of joint disease and a major cause of pain and disability in the adult population. Interestingly, there are patients with symptomatic OA displaying pain, while patients with asymptomatic OA that do not experience pain but show radiographic signs of joint damage. Pain is a complex experience integrating sensory, affective, and cognitive processes related to several peripheral and central nociceptive factors besides inflammation. During the last years, the role of infrapatellar fat pad (IFP), other than the synovial membrane, has been investigated as a potential source of pain in OA. Interestingly, new findings suggest that IFP and synovial membrane might act as a functional unit in OA pathogenesis and pain. The present review discuss the role of IFP and synovial membrane in the development of OA, with a particular focus on pain onset and the possible involved mediators that may play a role in OA pathology and pain mechanisms. Inflammation of IFP and synovial membrane may drive peripheral and central sensitization in KOA. Since sensitization is associated with pain severity in knee OA and may potentially contribute to the transition from acute to chronic, persistent pain in knee OA, preventing sensitization would be a potentially effective and novel means of preventing worsening of pain in knee OA.

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