Predictive validity of biochemical biomarkers in knee osteoarthritis: data from the FNIH OA Biomarkers Consortium

ObjectiveTo investigate a targeted set of biochemical biomarkers as predictors of clinically relevant osteoarthritis (OA) progression.MethodsEighteen biomarkers were measured at baseline, 12 months (M) and 24 M in serum (s) and/or urine (u) of cases (n=194) from the OA initiative cohort with knee OA and radiographic and persistent pain worsening from 24 to 48 M and controls (n=406) not meeting both end point criteria. Primary analyses used multivariable regression models to evaluate the association between biomarkers (baseline and time-integrated concentrations (TICs) over 12 and 24 M, transposed to z values) and case status, adjusted for age, sex, body mass index, race, baseline radiographic joint space width, Kellgren-Lawrence grade, pain and pain medication use. For biomarkers with adjusted p<0.1, the c-statistic (area under the curve (AUC)), net reclassification index and the integrated discrimination improvement index were used to further select for hierarchical multivariable discriminative analysis and to determine the most predictive and parsimonious model.ResultsThe 24 M TIC of eight biomarkers significantly predicted case status (ORs per 1 SD change in biomarker): sCTXI 1.28, sHA 1.22, sNTXI 1.25, uC2C-HUSA 1.27, uCTXII, 1.37, uNTXI 1.29, uCTXIα 1.32, uCTXIβ 1.27. 24 M TIC of uCTXII (1.47–1.72) and uC2C-Human Urine Sandwich Assay (HUSA) (1.36–1.50) both predicted individual group status (pain worsening, joint space loss and their combination). The most predictive and parsimonious combinatorial model for case status consisted of 24 M TIC uCTXII, sHA and sNTXI (AUC 0.667 adjusted). Baseline uCTXII and uCTXIα both significantly predicted case status (OR 1.29 and 1.20, respectively).ConclusionsSeveral systemic candidate biomarkers hold promise as predictors of pain and structural worsening of OA.

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Association between disease progression and depression onset in persons with radiographic knee osteoarthritis

Rheumatology ◽

10.1093/rheumatology/keaa141 ◽

2020 ◽

Vol 59 (11) ◽

pp. 3390-3399

Author(s):

Alan M Rathbun ◽

Michelle D Shardell ◽

Alice S Ryan ◽

Michelle S Yau ◽

Joseph J Gallo ◽

...

Keyword(s):

Disease Progression ◽

Disease Severity ◽

Gait Speed ◽

Joint Space Width ◽

Joint Space ◽

Knee Oa ◽

Increased Risk ◽

Pain Subscale ◽

Space Width

Abstract Objectives Osteoarthritis (OA) disease progression may lead to deteriorating psychosocial function, but it is unclear what aspects of disease severity are related to the onset of depression. This study assessed which components of OA disease progression cumulatively contribute to depression onset in persons with radiographic knee OA. Methods Osteoarthritis Initiative participants (n = 1651) with radiographic disease (Kellgren-Lawrence grade ≥2) in one or both knees and below the screening threshold for probable depression [Center for Epidemiological Studies Depression (CES-D) scale <16] at baseline were included. Disease severity was measured from baseline to the third annual follow-up visit using joint space width, 20-meter gait speed, and the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale, each categorized into quintiles. Depression onset (CES-D ≥ 16) was assessed annually at four follow-up visits. Marginal structural models that account for time-dependent confounding and attrition evaluated the association between each time-varying disease severity measure and depression onset. Results Each disease severity measure exhibited a non-linear relationship concerning the probability of depression onset, with the higher quintiles generally being associated with a larger risk. The highest quintile (relative to the lowest) of joint space width and gait speed were both significantly associated with depression onset. By contrast, none of the higher pain quintiles compared with the lowest were significantly associated with the onset of depression. Conclusion Faster disease progression as measured by either worsening structural severity or decreasing physical performance corresponds to an increased risk of depression among individuals with radiographic knee OA.

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Baseline clinical characteristics of predicted structural and pain progressors in the IMI-APPROACH knee OA cohort

RMD Open ◽

10.1136/rmdopen-2021-001759 ◽

2021 ◽

Vol 7 (3) ◽

pp. e001759

Author(s):

Eefje Martine van Helvoort ◽

Christoph Ladel ◽

Simon Mastbergen ◽

Margreet Kloppenburg ◽

Francisco J Blanco ◽

...

Keyword(s):

Structural Damage ◽

Clinical Characteristics ◽

Rating Scale ◽

Pearson Correlation ◽

Joint Space Width ◽

Correlation Coefficients ◽

Joint Space ◽

Numeric Rating Scale ◽

Knee Oa ◽

Private Research

ObjectivesTo describe the relations between baseline clinical characteristics of the Applied Public-Private Research enabling OsteoArthritis Clinical Headway (IMI-APPROACH) participants and their predicted probabilities for knee osteoarthritis (OA) structural (S) progression and/or pain (P) progression.MethodsBaseline clinical characteristics of the IMI-APPROACH participants were used for this study. Radiographs were evaluated according to Kellgren and Lawrence (K&L grade) and Knee Image Digital Analysis. Knee Injury and Osteoarthritis Outcome Score (KOOS) and Numeric Rating Scale (NRS) were used to evaluate pain. Predicted progression scores for each individual were determined using machine learning models. Pearson correlation coefficients were used to evaluate correlations between scores for predicted progression and baseline characteristics. T-tests and χ2 tests were used to evaluate differences between participants with high versus low progression scores.ResultsParticipants with high S progressions score were found to have statistically significantly less structural damage compared with participants with low S progression scores (minimum Joint Space Width, minJSW 3.56 mm vs 1.63 mm; p<0.001, K&L grade; p=0.028). Participants with high P progression scores had statistically significantly more pain compared with participants with low P progression scores (KOOS pain 51.71 vs 82.11; p<0.001, NRS pain 6.7 vs 2.4; p<0.001).ConclusionsThe baseline minJSW of the IMI-APPROACH participants contradicts the idea that the (predicted) course of knee OA follows a pattern of inertia, where patients who have progressed previously are more likely to display further progression. In contrast, for pain progressors the pattern of inertia seems valid, since participants with high P score already have more pain at baseline compared with participants with a low P score.

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High Kellgren-Lawrence Grade and Bone Marrow Lesions Predict Worsening Rates of Radiographic Joint Space Narrowing; The SEKOIA Study

The Journal of Rheumatology ◽

10.3899/jrheum.150053 ◽

2016 ◽

Vol 43 (3) ◽

pp. 657-665 ◽

Cited By ~ 10

Author(s):

Mark H. Edwards ◽

Camille Parsons ◽

Olivier Bruyère ◽

Forence Petit Dop ◽

Roland Chapurlat ◽

...

Keyword(s):

Bone Marrow ◽

Plain Radiograph ◽

Joint Space Width ◽

Joint Space ◽

Rate Of Change ◽

Mri Findings ◽

Men And Women ◽

Tibiofemoral Joint ◽

Knee Oa ◽

Knee Mri

Objective.Determinants of radiographic progression in osteoarthritis (OA) are poorly understood. We investigated which features on baseline magnetic resonance imaging (MRI) acted as predictors of change in joint space width (JSW).Methods.A total of 559 men and women over the age of 50 years with clinical knee OA [Kellgren-Lawrence (KL) grade 2–3] were recruited to the placebo arm of the SEKOIA study (98 centers; 18 countries). Minimal tibiofemoral joint space and KL grade on plain radiograph of the knee were assessed at baseline and at yearly followup up to 3 years. In a subset, serial knee MRI examinations were performed. Individuals with a bone marrow lesion (BML) ≥ grade 2 at the tibiofemoral joint at baseline were classified as BML-positive. Relationships between change in JSW and risk factors were assessed using linear regression.Results.The mean age of study participants was 62.8 (SD 7.5) years and 73% were female; 38.6% had BML. Mean baseline JSW was 3.65 mm. This reduced by 0.18 (0.30) mm/year in men and 0.13 (0.23) mm/year in women. Those with BML had a significantly higher rate of annualized change in JSW; this relationship remained robust after adjustment for age, sex, and baseline KL grade [β = −0.10 (95% CI −0.18, −0.02) mm/yr]. Age, sex, baseline KL grade, and other MRI findings did not influence the rate of change in JSW.Conclusion.The rate of change in JSW was similar in men and women. BML on knee MRI predicted the rate of radiographic change in JSW. This relationship was independent of age, sex, and baseline KL grade.

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Identifying Phenotypes of Knee Osteoarthritis by Separate Quantitative Radiographic Features May Improve Patient Selection for More Targeted Treatment

The Journal of Rheumatology ◽

10.3899/jrheum.121004 ◽

2013 ◽

Vol 40 (6) ◽

pp. 891-902 ◽

Cited By ~ 19

Author(s):

Margot B. Kinds ◽

Anne C.A. Marijnissen ◽

Max A. Viergever ◽

Pieter J. Emans ◽

Floris P.J.G. Lafeber ◽

...

Keyword(s):

Bone Density ◽

Clinical Characteristics ◽

Joint Space Width ◽

Specific Treatment ◽

Joint Space ◽

Radiographic Features ◽

Knee Oa ◽

Improve Patient Selection ◽

Space Width ◽

Varus Angle

Objective.Expression of osteoarthritis (OA) varies significantly between individuals, and over time, suggesting the existence of different phenotypes, possibly with specific etiology and targets for treatment. Our objective was to identify phenotypes of progression of radiographic knee OA using separate quantitative features.Methods.Separate radiographic features of OA were measured by Knee Images Digital Analysis (KIDA) in individuals with early knee OA (the CHECK cohort: Cohort Hip & Cohort Knee), at baseline and at 2-year and 5-year followup. Hierarchical clustering was performed to identify phenotypes of radiographic knee OA progression. The phenotypes identified were compared for changes in joint space width (JSW), varus angle, osteophyte area, eminence height, bone density, for Kellgren-Lawrence (K-L) grade, and for clinical characteristics. Logistic regression analysis evaluated whether baseline radiographic features and demographic/clinical characteristics were associated with each of the specific phenotypes.Results.The 5 clusters identified were interpreted as “Severe” or “No,” “Early” or “Late” progression of the radiographic features, or specific involvement of “Bone density.” Medial JSW, varus angle, osteophyte area, eminence height, and bone density at baseline were associated with the Severe and Bone density phenotypes. Lesser eminence height and bone density were associated with Early and Late progression. Larger varus angle and smaller osteophyte area were associated with No progression.Conclusion.Five phenotypes of radiographic progression of early knee OA were identified using separate quantitative features, which were associated with baseline radiographic features. Such phenotypes might require specific treatment and represent relevant subgroups for clinical trials.

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OP0185 KNEE JOINT DISTRACTION IS MORE EFFICIENT IN RESTORING CARTILAGE THICKNESS THAN HIGH TIBIAL OSTEOTOMY IN PATIENTS WITH SEVERE KNEE OSTEOARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1319 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 114.2-115

Author(s):

M. Jansen ◽

S. Maschek ◽

R. Van Heerwaarden ◽

S. Mastbergen ◽

W. Wirth ◽

...

Keyword(s):

Stock Options ◽

Joint Space Width ◽

Joint Space ◽

Cartilage Thickness ◽

Tibial Osteotomy ◽

Knee Oa ◽

Leg Axis ◽

Cartilage Restoration ◽

Joint Distraction ◽

Space Width

Background:Both high tibial osteotomy (HTO) and knee joint distraction (KJD) are joint preserving surgical techniques unloading the affected femorotibial compartment in patients with knee osteoarthritis (OA). While HTO permanently unloads the more affected compartment (MAC) by overcorrecting the leg axis, KJD temporarily unloads the whole joint by separating the tibia and femur for 5 mm for 6 weeks. In a previous randomized controlled trial (RCT), comparable clinical benefit and radiographic joint space width (JSW) increase over 2 years follow-up were demonstrated for both treatments1. Yet, comparison of JSW before and after HTO may be unreliable, as pseudo-widening of the unloaded compartment may occur due to the induced leg axis change. Therefore, direct cartilage thickness measurements need to be compared between KJD and HTO, to accurately evaluate the efficacy of both treatment options on cartilage structure.Objectives:To compare two-year cartilage thickness changes after treatment with KJDvsHTO and identify factors predicting cartilage thickness restoration.Methods:Patients indicated for HTO were randomized to KJD (KJDHTO) or HTO treatment. Patients indicated for total knee arthroplasty received KJD (KJDTKA). Standardized semi-flexed weight-bearing radiographs and 3T MRIs with 3D spoiled gradient recalled imaging sequence with fat suppression (SPGR-fs) were acquired before and two years after surgical treatment. Cartilage thickness in the knee was measured using Chondrometrics Works 3.0 software. On the radiographs the mean JSW in the MAC were measured with KIDA software. Readers were blinded to the type of intervention and acquisition order. The primary and secondary outcomes were the mean MAC cartilage thickness (ThCtAB) and percentage of denuded bone area (dABp) change before and two years after treatment (MRI), with radiographic joint space width (JSW) used as a reference.Results:No statistically significant differences in the baseline characteristics were seen between KJDHTO(n=18) and HTO (n=33). The KJDTKAgroup (n=18) had a higher age and Kellgren-Lawrence grade (KLG) than the HTO and KJDHTOgroups.KJDHTOpatients did not show significant changes in MAC cartilage thickness, dABp, or JSW over time (all p>0.10; figure 1). HTO patients displayed a decrease in MAC cartilage thickness and an increase in dABp (both p<0.03), but an increase in JSW (p=0.006). KJDTKAshowed a significant increase in MAC cartilage thickness and JSW and decrease in dABp (all p<0.01). Baseline OA severity was the strongest predictor of cartilage restoration. KJD patients with severe OA (KJDsevere; KLG ≥3) showed significant restoration (all p<0.01; figure 2); mild OA patients (KJDmild; KLG ≤2) showed a slight deterioration. KJDsevereshowed a significantly greater cartilage restoration response in the MAC than HTOseverefor cartilage thickness (p=0.005) and dABp (p=0.003), but not JSW change (p=0.521). The changes in all three parameters did not differ significantly between KJDmildand HTOmild(all p>0.08).Conclusion:In patients with severe knee OA, KJD is more efficient in restoring cartilage thickness than HTO is. In these patients, KJD causes significant cartilage restoration while HTO, despite shifting the leg axis and demonstrating radiographic joint space widening, shows loss of cartilage as measured on MRI. In patients with mild knee OA, neither HTO nor KJD treatment results in significant cartilage restoration and both treatments show a slight deterioration that is likely the result of natural OA progression. As such, this research promotes the choice KJD as joint-preserving surgery in case of knee OA patients with more severe structural damage.References:[1]MP Jansenet al, Cartilage 2019.Disclosure of Interests:Mylène Jansen: None declared, Susanne Maschek Shareholder of: Stock/stock options at Condrometrics GmbH, Employee of: Employment at Condrometrics GmbH, Ronald Van Heerwaarden: None declared, Simon Mastbergen: None declared, Wolfgang Wirth Shareholder of: Stock/stock options at Condrometrics GmbH, Consultant of: Consultancy to Galapagos NV, Employee of: Employment at Condrometrics GmbH, Floris Lafeber Shareholder of: Co-founder and shareholder of ArthroSave BV, Felix Eckstein Shareholder of: Stock/stock options at Condrometrics GmbH, Consultant of: Consultancy at Merck KGaA, Samumed, Bioclinica, Galapagos, Servier, Novartis, Employee of: Employment at Condrometrics GmbH, Speakers bureau: Development of educational presentations for Medtronic

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Clinical Efficacy of a Single-dose of Platelet Rich Plasma in the Management of Early Knee Osteoarthritis: A Randomized Controlled Study With Mri Assessment and Evaluation of Optimal Dose

10.21203/rs.3.rs-33058/v1 ◽

2020 ◽

Author(s):

Himanshu Bansal ◽

Jerry Leon ◽

Jeremy L. Pont ◽

David A. Wilson ◽

Sathya Meonah ST ◽

...

Keyword(s):

Single Dose ◽

Clinical Efficacy ◽

Platelet Rich Plasma ◽

Joint Space Width ◽

Joint Space ◽

Trial Registration ◽

Controlled Study ◽

Absolute Count ◽

Knee Oa ◽

Space Width

Abstract Background: Osteoarthritis (OA) causes substantial physical disability that limits a person's ability to indulge in daily activities. Non-steroidal anti-inflammatory drugs provide only minimal symptomatic benefit and are associated with mild to severe side effects, thus limiting its continuous use. This being the case, new alternate healing strategies with minimal adverse effects are being explored scientifically. In our study we have attempted to evaluate the clinical efficacy of a single dose of Platelet Rich Plasma (PRP) in treating osteoarthritis. Our primary objectives are:i) To optimise the correct dose of PRP preparation to achieve therapeutic relief in knee OAii) To identify the therapeutic efficacy of PRP in selected patients suffering from symptomatic primary knee OA through Randomized Clinical Trials and analyse the possible outcome using MRI analysis.Methods: A randomized, double-blind, 12-month, placebo-controlled study was conducted in 100 outpatients. PRP was prepared from the blood drawn from the subjects and administered intra-articularly guided by ultrasound. The degree of pain was assessed using WOMAC scores, the International Knee Documentation Committee score (IKDC) and six-minute pain free walking distance. The joint space width and articular cartilage thickness was evaluated through x-ray, ultrasonagraphy and MRI.Result: PRP with absolute count of approximately 100 billion platelets brings out significant therapeutic relief. The WOMAC scores showed reduction from 54.7 at baseline to 28.8 at one month, and 29.9 at 3 months showing efficacy of PRP over placebo. Improvement was evident in one month scores of IKDC tests (Baseline- 53.6; 1 month - 76.9) and VAS (Baseline - 5.8; 1 month - 2.46) followed by slight decline at 3, 6-month and one-year scores. Similarly, the pain-free distance covered during a 6-min walk was significantly improved at one month in both the groups (PRP-146 ft.; placebo-122 ft; p value <0.001). No change is seen on MRI and Joint space width.Conclusion: 7 times Concentration and absolute count of 100 billion platelets is crucial in a PRP formulation to be therapeutically effective in alleviating symptoms in moderate knee OA. The results indicate prevention of structural modification in the PRP group and better chondroprotective effects compared to placebo group.Trial Registration: This study has been registered in the US Clinical Trial Registry (U.S. National Library of Medicine) with Trial registration no. 04198467. Date of registration: December 13, 2019. (Retrospectively registered) URL - https://clinicaltrials.gov/ct2/show/NCT04198467?term=04198467&draw=2&rank=1

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Association between current medication use and progression of radiographic knee osteoarthritis: data from the osteoarthritis initiative

Rheumatology ◽

10.1093/rheumatology/keab059 ◽

2021 ◽

Author(s):

Thomas A Perry ◽

Xia Wang ◽

Michael Nevitt ◽

Christina Abdelshaheed ◽

Nigel Arden ◽

...

Keyword(s):

Reference Group ◽

Medication Use ◽

Joint Space Width ◽

Joint Space ◽

Knee Oa ◽

Current Medication ◽

History Of ◽

Osteoarthritis Initiative ◽

Space Width

Abstract Objective Use of specific medications may accelerate the progression of radiographic knee OA (RKOA). Our aim was to examine the effect of medication use on the progression of RKOA. Methods We used longitudinal data from the Osteoarthritis Initiative (OAI), an observational study of risk factors for knee OA. At baseline, we selected participants with RKOA (Kellgren–Lawrence grade ≥2) and excluded those with a history of knee-related injury/surgery and other musculoskeletal disorders. Current medication use (use/non-use in the previous 30 days) and radiographic medial minimum joint space width (mJSW) data were available at baseline and annually up to 96 months follow-up. We used random effects, panel regression to assess the association between current medication use (non-users as reference group) and change in mJSW. Results Of 2054 eligible participants, 2003 participants with baseline mJSW data were included [55.7% female, mean age 63.3 (s.d. 8.98) years]. Of seven medication classes, at baseline NSAIDs were the most frequently used analgesia (14.7%), anti-histamine (10.4%) use was frequent and the following comorbidity medications were used most frequently: statins (27.4%), anti-hypertensives (up to 15.0%), anti-depressant/anxiolytics/psychotropics (14.0%), osteoporosis-related medication (10.9%) and diabetes-related medication (6.9%). Compared with current non-users, current use of NSAIDs was associated with a loss of mJSW (b = −0.042, 95% CI −0.08, −0.0004). No other associations were observed. Conclusions In current users of NSAIDs, mJSW loss was increased compared with current non-users in participants with RKOA. Clinical trials are required to assess the potential disease-modifying effects of these medications.

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Clinicians’ heuristic assessments of radiographs compared with Kellgren-Lawrence and Ahlbäck ordinal grading: an exploratory study of knee radiographs using paired comparisons

BMJ Open ◽

10.1136/bmjopen-2020-041793 ◽

2021 ◽

Vol 11 (3) ◽

pp. e041793

Author(s):

Mads Møller Pedersen ◽

Kristian Breds Geoffroy Mongelard ◽

Anne Mørup-Petersen ◽

Karl Bang Christensen ◽

Anders Odgaard

Keyword(s):

Cognitive Biases ◽

Good Description ◽

Joint Space Width ◽

Area Under The Curve ◽

Joint Space ◽

Morphological Features ◽

Strength Parameter ◽

Characteristic Analysis ◽

Grading Systems ◽

Ordinal Scales

ObjectivesOrdinal scales provide means for communicating the severity of a condition, but they are affected by cognitive biases, they introduce statistical problems and they sacrifice resolution. Clinicians discern more details than contained in scales, for example, when assessing radiographs, but clinicians’ distinctions are often based on experience-based rules of thumb, that is, heuristics. The objectives of this study are to compare clinicians’ heuristic assessments to ordinal grading, to identify case elements that influence clinicians’ judgements and to present a method for quantifying heuristic assessments.DesignClinicians were presented with 17 207 random pairs from a set of 1087 knee radiographs. For each pair, the radiograph with more severe osteoarthritis was selected. The Bradley-Terry model was used to calculate an osteoarthritis strength parameter for each radiograph. Similarly, strength parameters were determined for 12 morphological features with five additional features being considered either present or absent. All radiographs were also graded according to conventional ordinal systems (Kellgren-Lawrence and Ahlbäck). Relations between clinicians’ judgements and (1) the heuristics-based osteoarthritis strength, (2) conventional ordinal systems and (3) morphological features were investigated.ResultsReceiver operating characteristic analysis showed that the Bradley-Terry model provided a good description of clinicians’ assessments (area under the curve (AUC)=0.97, 95% CI 0.968 to 0.972). Morphological features (AUC=0.90, 95% CI 0.900 to 0.908) provided a superior description of clinicians’ choices compared with conventional ordinal systems (AUC=0.88, 95% CI 0.878 to 0.887 and AUC=0.80, 95% CI 0.796 to 0.809) for Ahlbäck and Kellgren-Lawrence, respectively). The features most strongly associated with osteoarthritis strength were medial joint space width, flattening of the medial femoral and tibial condyles, medial osteophytes and alignment.ConclusionsHeuristics-based assessments give a better distinction than conventional grading systems of knee osteoarthritis. The example presents a general approach to evaluate which features are part of experts’ heuristics. The data suggest that experts discern more details than included in conventional ordinal grading systems. Quantitative heuristic assessments may replace ordinal scales.

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Identification of early response to hypertonic dextrose prolotherapy markers in knee osteoarthritis patients by an inflammation-related cytokine array

10.21203/rs.3.rs-30677/v1 ◽

2020 ◽

Author(s):

Hsing-Chun Kuo ◽

Po-Jung Pan ◽

Jia-Chi Wang ◽

Chih-Chun Tsai

Keyword(s):

Synovial Fluid ◽

Knee Joint ◽

Protein Expression ◽

Joint Space Width ◽

Joint Space ◽

Knee Oa ◽

Womac Index ◽

Minimum Joint Space Width ◽

Space Width ◽

Hypertonic Dextrose

Abstract BACKGROUND/AIMOsteoarthritis (OA) is one of the most common forms of arthritis, and hypertonic dextrose prolotherapy has long been used clinically to treat knee OA. The aim of this study was to investigate the inflammation-related protein-expression profile characterizing the efficacy of the hypertonic dextrose prolotherapy in knee OA as prognostic markers.METHODSOA patients over the age of 65 were recruited for Western Ontario McMaster University Osteoarthritis (WOMAC) index, knee X ray evaluation and knee joint synovial fluid analysis before and after hypertonic dextrose prolotherapy. The expressions of inflammation-related factors were measured using a novel cytokine antibody array methodology. The cytokine levels were quantified by quantitative protein expression and analyzed by ELISA using the patients’ knee-joint synovial fluid. The WOMAC Index and minimum joint space width prior to receiving the intra-articular injection and at 2-week intervals were compared.RESULTS12 patients who received OA intervention were enrolled and finally a clinical evaluation of 12 knee joints and knee synovial fluid samples were analyzed. In this study, after receiving hypertonic dextrose prolotherapy, the OA patients clearly demonstrated a significant improvement in WOMAC index and increasing tendency in the medial minimum joint space width after intervention. Meanwhile, we observed a significantly associated tendency between the high-glucose treatment of knee OA and the upregulation of MMP2, TIMP-1, EGF, CXCL9 and IL-22. These findings provide knee OA patients receiving hypertonic dextrose prolotherapy, which accompanying with the improvement of knee pain, stiffness, and function and increasing tendency in the medial minimum joint space width.

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