ORCID Profile
0000-0003-3913-2564
Current Organisations
Menzies Research Institute Tasmania
,
Southern Medical University
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Springer Science and Business Media LLC
Date: 03-08-2019
DOI: 10.1007/S10067-019-04718-8
Abstract: The aim of this study was to investigate cross-sectional associations between serum levels of IL-8 and the above outcomes in patients with knee osteoarthritis (OA). A total of 160 subjects with clinical knee OA were included. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and Lequesne index were used to assess the joint symptom. Magnetic resonance imaging was used to measure knee structural abnormalities including infrapatellar fat pad (IPFP) signal intensity alternation. Knee radiographic OA was assessed by radiography using the Kellgren-Lawrence (K-L) grading system. Enzyme-linked immunosorbent assay was used to measure the serum levels of IL-8 and cartilage or bone biomarkers. In multivariable analyses, serum IL-8 was positively associated with WOMAC weight-bearing pain (β 2.85, P = 0.028), WOMAC physical dysfunction (β 12.71, P = 0.048), and Lequesne index (β 1.65, P = 0.015), and had positive associations with IPFP signal intensity alteration (OR 3.18, P = 0.011) and serum levels of N-telopeptide of type I collagen (NTXI), N-terminal procollagen III propeptide (PIIINP), matrix metalloproteinase (MMP)3, and MMP13 (β 0.24-1.44, all P < 0.05) in patients with clinical knee OA. Furthermore, there were positive associations between IL-8 and WOMAC score (β 22.49, P = 0.037), K-L grades (OR 3.88, P = 0.013), and IPFP signal intensity alteration (OR 3.20, P = 0.033) in patients with radiographic OA. Serum levels of IL-8 were positively associated with increased knee symptoms, IPFP signal intensity alteration, and serum levels of bone and/or cartilage biomarkers, suggesting that IL-8 may have a role to play in knee OA.Key Point• This study systemically investigates the associations between serum IL 8 and knee symptoms, joint structures, and cartilage or bone biomarkers in patients with knee osteoarthritis, and some significant associations have been found, suggesting that IL 8 may have a role to play in knee OA.
Publisher: Springer Science and Business Media LLC
Date: 23-10-2018
Publisher: Springer Science and Business Media LLC
Date: 17-04-2018
Publisher: Wiley
Date: 29-05-2020
DOI: 10.1111/ECI.13266
Publisher: Elsevier BV
Date: 04-2020
Publisher: Springer Science and Business Media LLC
Date: 12-10-2016
Publisher: Wiley
Date: 28-03-2016
DOI: 10.1002/ART.39526
Abstract: To describe the natural history of quantitatively measured knee effusion-synovitis and the longitudinal associations between effusion-synovitis and knee structural factors, including cartilage defects, cartilage volume, subchondral bone marrow lesions, and meniscal pathology, in older adults. A total of 406 subjects (with a mean age of 63 years, 50% women) were randomly selected at baseline and followed up 2.7 years later. T2- or T1-weighted fat saturation magnetic resonance imaging was used to assess knee effusion-synovitis maximal area, cartilage defects, cartilage volume, bone marrow lesions, and meniscal pathology at baseline and follow-up. Multivariable generalized linear regression was performed to analyze the associations between the maximal area of effusion-synovitis and other joint structural factors after adjustment for age, sex, body mass index, tibial bone area, and/or radiographic osteoarthritis (OA). Over 2.7 years of follow-up, the size of effusion-synovitis increased in 29%, remained stable in 50%, and decreased in 22% of the participants. Baseline effusion-synovitis maximal area was significantly associated with changes in knee cartilage defects (β = 0.18 [95% confidence interval (95% CI)] 0.07, 0.29), bone marrow lesions (β = 0.17 [95% CI 0.05, 0.30]), and cartilage volume (β = -0.40 [95% CI -0.71, -0.09]) but not with change in meniscal pathology. In contrast, baseline structural measures were not associated with change or increase in effusion-synovitis maximal area. Our findings indicate that knee effusion-synovitis is not static in older adults. It is predictive of, but not predicted by, other structural abnormalities, suggesting a potential role in early knee OA changes.
Publisher: Wiley
Date: 25-04-2019
DOI: 10.1002/ACR.23713
Abstract: To describe the cross-sectional and longitudinal associations between quantitative measures of infrapatellar fat pad (IPFP) signal-intensity alteration and knee structural abnormalities in patients with symptomatic knee osteoarthritis (OA). A total of 261 patients (mean ± SD age 63.0 ± 7.2 years) with symptomatic knee OA were selected from a randomized controlled trial with a follow-up of 2 years. IPFP signal-intensity alterations at baseline were quantitatively measured on T2-weighted fat-saturated magnetic resonance imaging using MATLAB. These quantitative measures included the SD of whole IPFP signal intensity measurement, the upper quartile value of high signal intensity (UQ Higher baseline SD of the IPFP, UQ Quantitative measures of increased signal intensity in the IPFP were associated with knee structural abnormalities in the tibiofemoral compartment, suggesting that these measurements could be used as an additional entry criterion to enrich studies for faster progressors of knee OA.
Publisher: Wiley
Date: 20-02-2023
DOI: 10.1002/ACR.24964
Abstract: To investigate associations of dietary vitamin K intake with changes in knee symptoms and structures in patients with knee OA. Participants with symptomatic knee OA were enrolled (n=259) and followed up for 2 years (n=212). Baseline dietary vitamin K intake was calculated from a validated food frequency questionnaire. Knee symptoms were assessed by using the Western Ontario and McMaster University Index of osteoarthritis (WOMAC) scores. Knee cartilage defects, bone marrow lesions and effusion-synovitis volume were measured from MRI scans. Univariable and multivariable linear regressions were used for analyses. Higher vitamin K intake quartile was significantly associated with greater decrease in total WOMAC score and dysfunction score over 24 months. The subgroup analyses showed in patients with severe baseline VAS pain, higher vitamin K intake quartile was associated with more improvement in all WOMAC scores. There were no overall significant associations between vitamin K intake and changes in MRI features. In sub-group analysis, vitamin K intake was negatively associated with changes in tibiofemoral, patellar and total cartilage defects in participants with severe baseline radiographic grade, and was negatively associated with change in total and patellar cartilage defects in participants with severe baseline VAS pain and in female patients. The association of higher vitamin K intake with decreased knee symptoms over 24 months in patients with knee OA suggests that clinical trials examining the effect of vitamin K supplementation for knee OA symptoms are warranted. Whether there is an effect on knee structure is unclear. This article is protected by copyright. All rights reserved.
Publisher: Elsevier BV
Date: 11-2022
DOI: 10.1016/J.JOCA.2022.06.010
Abstract: To provide some causal evidence concerning the effects of metformin on osteoarthritis (OA) using two metformin targets, namely AMP-activated protein kinase (AMPK) and growth differentiation factor 15 (GDF-15) as metformin proxies. This is a 2-s le Mendelian randomization design. We constructed 44 AMPK-related variants genetically predicted in HbA1c (%) as instruments for AMPK and five variants strongly predicted GDF-15 as instruments for GDF-15. Summary-level data for three OA phenotypes, including OA at any site, knee OA, and hip OA were obtained from the largest genome-wide meta-analysis across the UK Biobank and arcOGEN with 455,211 Europeans. Main analyses were conducted using the inverse-variance weighted method. Weighted median and MR-Egger were conducted as sensitivity analyses to assess the robustness of our results. Genetically predicted AMPK were negatively associated with OA at any site (OR: 0.60 95% CI: 0.43-0.83) and hip OA (OR: 0.42 95% CI: 0.22-0.80), but with not knee OA (OR: 0.85 95% CI: 0.49-1.50). Higher levels of genetically predicted GDF-15 reduced the risk of hip OA (OR: 0.95 95% CI: 0.90-0.99), but not OA at any site (OR: 1.00 95% CI: 0.98-1.02) and knee OA (OR: 1.02 95% CI: 0.98-1.07). This study indicates that AMPK and GDF-15 can be potential therapeutic targets for OA, especially for hip OA, and metformin would be repurposed for OA therapy which needs to be verified in randomized controlled trials.
Publisher: Oxford University Press (OUP)
Date: 11-06-2021
DOI: 10.1093/RHEUMATOLOGY/KEAB479
Abstract: To investigate the longitudinal associations of serum inflammatory markers and adipokines with joint symptoms and structures in participants with knee OA. Two hundred participants (46.5% female, mean age 63.1 years, mean BMI 29.5 kg/m2) from Tasmania, part of the VIDEO (Vitamin D Effect on OA) study, were randomly selected in the current study. Serum levels of 19 biomarkers, scores of WOMAC and MRI-assessed knee structures were evaluated at baseline and month 24. The patterns of biomarkers were derived from principal component analysis and their association with knee symptoms and structures were examined using adjusted generalized estimating equations. Five components explained 78% of the total variance. IL-1β, -2, -4, -6, -8, -17 A, -17 F, -21, -22 and -23 loaded the highest on the first component, which was associated with increased bone marrow lesions (BMLs) and WOMAC dysfunction score. IL-10, -12 and GM-CSF loaded on the second component, which was associated with increased cartilage volume, and decreased effusion synovitis and WOMAC scores. Leptin, adipsin and CRP loaded on the third component, which was positively associated with WOMAC scores. Resistin loaded on the fourth component, which was associated with increased BMLs and cartilage defects. Apelin-36 and adiponectin loaded on the fifth component, which was associated with increased BMLs. Various inflammatory and metabolic components were associated differently with joint symptoms and structural changes in knee OA, suggesting a complex inflammatory and metabolic interrelationship in the pathogenesis of knee OA.
Publisher: American Medical Association (AMA)
Date: 03-05-2022
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.JOCA.2018.12.023
Abstract: To investigate the longitudinal association between objectively measured ambulatory activity (AA) and knee MRI-detected osteophytes (OPs), and to test whether this relationship was modified by common risk factors for OA including sex, obesity, disease severity and knee injury history. 408 community-dwelling adults aged 51-81 years were assessed at baseline and 2.7 years. T1-weighted fat-suppressed MRI was used to evaluate knee OPs at both time points. AA was assessed at baseline by pedometers and categorized as: less active (≤7499 steps per day), moderately active (7500-9999 steps per day) and highly active (≥10,000 steps per day). Statistically significant interactions were detected between knee OA risk factors and AA on increases in MRI-detected OPs (all P < 0.05). In stratified analyses, being moderately active, compared to being less active, was protective against an increase in MRI-detected OPs (score change of ≥1) in females (relative risk (RR) = 0.42, 95%CI, 0.25-0.70, P < 0.01), those who were obese (RR = 0.50, 95%CI, 0.30-0.83, P < 0.01), those with radiographic OA (ROA) (RR = 0.68, 95%CI, 0.47-0.97, P = 0.02) and those with a history of knee injury (RR = 0.27, 95%CI, 0.08-0.88, P = 0.02) in almost every knee compartment, after adjustment for confounders. No statistically significant associations were found in males, non-obese, non-ROA or non-injury groups. Being moderately active is protective against an increase in MRI-detected OPs in females, those with ROA, those who are obese and those with a history of knee injury. These findings suggest that being moderately active is beneficial for in iduals who are at higher risk of knee OA.
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.JOCA.2017.01.015
Abstract: To investigate the longitudinal association between endogenous sex hormones and knee osteoarthritis (OA) structures and pain. We examined 200 participants (mean age 63.0 ± 7.3 years) from a clinical trial of vitamin D supplement for symptomatic knee OA. Serum levels of estradiol, progesterone, testosterone and sex hormone binding globulin (SHBG) were analyzed at baseline and 24 months later. Magnetic resonance imaging (MRI) scans of selected knee were obtained at both baseline and follow-up for the measurement of cartilage volume, cartilage defects, bone marrow lesions (BMLs) and effusion-synovitis volume. Knee pain was assessed using a 100 mm visual analogue scale (VAS). Longitudinal data were analyzed using linear mixed-effects model. One hundred and seven males and 93 females were included in this study. For females, after adjustment for age, body mass index (BMI), and vitamin D level, progesterone was positively associated with cartilage volume (β = 0.12 mm In women but not men, low serum levels of endogenous estradiol, progesterone and testosterone are associated with increased knee effusion-synovitis and possibly other OA-related structural changes. This may contribute to observed sex differences in knee OA.
Publisher: Springer Science and Business Media LLC
Date: 07-01-2021
DOI: 10.1186/S12891-020-03875-1
Abstract: To describe demographic and clinical factors associated with the presence and incidence of depression and explore the temporal relationship between depression and joint symptoms in patients with symptomatic knee osteoarthritis (OA). Three hundred ninety-seven participants were selected from a randomized controlled trial in people with symptomatic knee OA and vitamin D deficiency (age 63.3 ± 7.1 year, 48.6% female). Depression severity and knee joint symptoms were assessed using the patient health questionnaire (PHQ-9) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), respectively, at baseline and 24 months. The presence and incidence of depression was 25.4 and 11.2%, respectively. At baseline, having younger age, a higher body mass index (BMI), greater scores of WOMAC pain (PR: 1.05, 95%CI:1.03, 1.07), dysfunction (PR: 1.02, 95%CI:1.01, 1.02) and stiffness (PR: 1.05, 95%CI: 1.02, 1.09), lower education level, having more than one comorbidity and having two or more painful body sites were significantly associated with a higher presence of depression. Over 24 months, being female, having a higher WOMAC pain (RR: 1.05, 95%CI: 1.02, 1.09) and dysfunction score (RR: 1.02, 95%CI: 1.01, 1.03) at baseline and having two or more painful sites were significantly associated with a higher incidence of depression. In contrast, baseline depression was not associated with changes in knee joint symptoms over 24 months. Knee OA risk factors and joint symptoms, along with co-existing multi-site pain are associated with the presence and development of depression. This suggests that managing common OA risk factors and joint symptoms may be important for prevention and treatment depression in patients with knee OA. ClinicalTrials.gov identifier: NCT01176344 . Anzctr.org.au identifier: ACTRN12610000495022 .
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.JAMDA.2018.09.006
Abstract: To determine the effect of vitamin D supplementation and maintaining sufficient serum vitamin D on depressive symptoms in patients with knee osteoarthritis (OA) and vitamin D deficiency. A prespecified secondary analysis of a multicentre, randomized, double-blind, placebo-controlled trial. Participants were randomly assigned to receive oral vitamin D This clinical trial was conducted in participants with symptomatic knee OA and vitamin D deficiency from June 2010 to December 2013 in Tasmania and Victoria, Australia. The primary outcome was the depressive symptoms change over 24 months, which was measured using the Patient Health Questionnaire (PHQ-9, 0-27). Of 599 participants who were screened for eligibility, 413 participants were enrolled (mean age: 63.2 years 50.3% female) and 340 participants (intervention n = 181, placebo n = 159, 82.3% retention rate) completed the study. The baseline prevalence of depression (PHQ-9 score ≥5) was 25.4%. Depressive symptoms improved more in the vitamin D supplementation group compared to the placebo group [β: -0.66, 95% confidence interval (CI): -1.22 to -0.11, P for difference = .02] and in the participants who maintained vitamin D sufficiency compared to those who did not (β: -0.73, 95% CI: -1.41 to -0.05, P for difference = .04) over 24 months. These findings suggest that vitamin D supplementation and maintaining adequate vitamin D levels over 24 months may be beneficial for depressive symptoms in patients with knee OA.
Publisher: Informa UK Limited
Date: 02-09-2021
Publisher: MDPI AG
Date: 17-08-2022
DOI: 10.3390/JCM11164796
Abstract: Objectives: We aimed to examine whether metformin (MET) use is associated with a reduced risk of total knee arthroplasty (TKA) and low severity of knee pain in patients with knee osteoarthritis (OA) and diabetes and/or obesity. Methods: Participants diagnosed with knee OA and diabetes and/or obesity from June 2000 to July 2019 were selected from the information system of a local hospital. Regular MET users were defined as those with recorded prescriptions of MET or self-reported regular MET use for at least 6 months. TKA information was extracted from patients’ surgical records. Knee pain was assessed using the numeric rating scale. Log-binomial regression, linear regression, and propensity score weighting (PSW) were performed for statistical analyses. Results: A total of 862 participants were included in the analyses. After excluding missing data, there were 346 MET non-users and 362 MET users. MET use was significantly associated with a reduced risk of TKA (prevalence ratio: 0.26, 95% CI: 0.15 to 0.45, p 0.001), after adjustment for age, gender, body mass index, various analgesics, and insurance status. MET use was significantly associated with a reduced degree of knee pain after being adjusted for the above covariates (β: −0.48, 95% CI: −0.91 to −0.05, p = 0.029). There was a significantly accumulative effect of MET use on the reduced risk of TKA. Conclusion: MET can be a potential therapeutic option for OA. Further clinical trials are needed to determine if MET can reduce the risk of TKA and the severity of knee pain in metabolic-associated OA patients.
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.JOCA.2017.09.005
Abstract: To describe prevalence of osteophytes (OPs) detected only by magnetic resonance imaging (MRI) but not by standard X-ray in older adults and to evaluate longitudinal associations with knee structural changes. 837 participants were randomly selected from the local community and had MRI scans to assess knee OPs and other structures. OPs detected only by MRI but not by standard X-ray were defined as MRI-detected early OPs (MRI-OPs for short). OPs detected by both MRI and X-ray were defined as established-OPs. The prevalence of MRI-OPs was 50% while the prevalence of established-OPs was 10% and no-OPs was 40% at total tibiofemoral (TF) compartment at baseline. Compared with no-OPs, participants with MRI-OPs had greater risks of increased cartilage defects in all TF compartments (RR 1.37, 95%CI 1.07-1.74) and bone marrow lesions (BMLs) only in medial TF compartment (RR 1.49, 95%CI 1.06-2.11), after adjustment for age, sex, BMI, cartilage defects, BMLs and/or joint space narrowing participants with established-OPs had greater cartilage volume loss at total (β -2.02, 95%CI -3.86, -0.17) and lateral tibial sites (β -5.63, 95%CI -9.93, -1.32), greater risks of increased cartilage defects in total (RR 1.66, 95%CI 1.15-2.40) and medial TF compartments (RR 1.49, 95%CI 1.20-1.69) and BMLs in all TF compartments (RR 1.88, 95%CI 1.22-2.89), after adjustment for covariates. MRI-OPs were associated with changes in knee structures, and the associations were similar but not as prominent as those for established-OPs. These suggest MRI-OPs may have a role to play in knee early-stage osteoarthritic progression.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Elsevier BV
Date: 09-2021
DOI: 10.1016/J.JOCA.2021.06.008
Abstract: To investigate the longitudinal association between MRI-detected osteophyte scores and progression of knee symptoms, and whether the association was modified in the presence of bone marrow lesions (BMLs) or effusion-synovitis. Data from Vitamin D Effects on Osteoarthritis (VIDEO) study, a randomized, double-blinded and placebo-controlled clinical trial in symptomatic knee osteoarthritis (OA) patients, were analyzed as an exploratory study. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to assess knee symptoms. Osteophytes, BMLs and effusion-synovitis were measured using MRI. 334 participants with MRI information and WOMAC score (baseline and follow-up) were included in the analyses, with 24.3% of them having knee pain increased 2 years later. Statistically significant interactions were found between MRI-detected osteophytes and BMLs or effusion-synovitis on increased knee symptoms. In participants with BMLs, higher baseline scores of MRI-detected osteophytes in most compartments were significantly associated with increased total knee pain, weight-bearing pain, stiffness, and physical dysfunction, after adjustment for age, sex, body mass index, intervention and effusion-synovitis. In participants with effusion-synovitis, higher baseline scores of MRI-detected osteophytes in almost all the compartments were significantly associated with increased total knee pain, weight-bearing pain, stiffness, and physical dysfunction, after adjustment for age, sex, body mass index, intervention and BMLs. In contrast, MRI-detected osteophyte scores were generally not associated with knee symptom progression in participants without baseline BMLs or effusion-synovitis. MRI-detected OPs are associated with increased total knee pain, weight-bearing knee pain, stiffness and physical dysfunction in participants presenting BMLs or effusion-synovitis, but not in participants lacking BMLs or effusion-synovitis. This suggests they could interact with bone or synovial abnormalities to induce symptoms in knee OA.
Publisher: Springer Science and Business Media LLC
Date: 27-01-2022
DOI: 10.1186/S13075-022-02719-8
Abstract: To describe the longitudinal associations between the morphological parameters of proximal tibiofibular joint (PTFJ) and joint structural changes in tibiofemoral compartments in patients with knee osteoarthritis (OA). The participants were selected from the Vitamin D Effects on Osteoarthritis (VIDEO) study. PTFJ morphological parameters were measured on coronal and sagittal MRI. The contacting area (S) of PTFJ and its projection areas onto the horizontal (load-bearing area, Sτ), sagittal (lateral stress-bolstering area, Sφ), and coronal plane (posterior stress-bolstering area, Sυ) were assessed. Knee structural abnormalities, including cartilage defects, bone marrow lesions (BMLs), and cartilage volume, were evaluated at baseline and after 2 years. Log binominal regression models and linear regression models were used to assess the associations between PTFJ morphological parameters and osteoarthritic structural changes. In the longitudinal analyses, the S (RR: 1.45) and Sτ (RR: 1.55) of PTFJ were significantly and positively associated with an increase in medial tibial (MT) cartilage defects. The Sτ (β: − 0.07), Sυ (β: − 0.07), and S (β: − 0.06) of PTFJ were significantly and negatively associated with changes in MT cartilage volume. The Sτ (RR: 1.55) of PTFJ was positively associated with an increase in MT BMLs, and Sφ (RR: 0.35) was negatively associated with an increase in medial femoral BMLs. This longitudinal study suggests that higher load-bearing area of PTFJ could be a risk factor for structural changes in medial tibiofemoral (MTF) compartment in knee OA. Clinicaltrials.gov Identifier: NCT01176344 Anzctr.org.au Identifier: ACTRN12610000495022 Date of registration: 7 May 2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 31-03-2023
DOI: 10.1097/JS9.0000000000000337
Abstract: While platelet rich plasma (PRP) has been extensively studied in treating osteoarthritis (OA), there has been an ongoing debate regarding the efficacy of PRP and the optimal subpopulation for PRP treatment remains unknown. The authors hereby aim to establish a pharmacodynamic model-based meta-analysis to quantitatively evaluate PRP efficacy, comparing with hyaluronic acid (HA) and identify relevant factors that significantly affect the efficacy of PRP treatment for OA. The authors searched for PubMed and the Cochrane Library Central Register of Controlled Trials of PRP randomized controlled trials (RCTs) for the treatment of symptomatic or radiographic OA from the inception dates to 15 July 2022. Participants’ clinical and demographic characteristics and efficacy data, defined as Western Ontario and McMaster Universities Osteoarthritis Index and visual analog scale pain scores at each time point were extracted. A total of 45 RCTs (3829 participants) involving 1805 participants injected with PRP were included in the analysis. PRP reached a peak efficacy at ~ 2–3 months after injection in patients with OA. Both conventional meta-analysis and pharmacodynamic maximal effect models showed that PRP was significantly more effective than HA for joint pain and function impairment (additional decrease of 1.1, 0.5, 4.3, and 1.1 scores compared to HA treatment at 12 months for Western Ontario and McMaster Universities Osteoarthritis Index pain, stiffness, function, and visual analog scale pain scores, respectively). Higher baseline symptom scores, older age (≥60 years), higher BMI (≥30), lower Kellgren–Lawrence grade (≤2) and shorter OA duration ( months) were significantly associated with greater efficacy of PRP treatment. These findings sugges t that PRP is a more effective treatment for OA than the more well-known HA treatment. The authors also determined the time when the PRP injection reaches peak efficacy and optimized the targeting subpopulation of OA. Further high-quality RCTs are required to confirm the optimal population of PRP in the treatment of OA.
Publisher: MDPI AG
Date: 07-07-2022
DOI: 10.3390/JCM11143958
Abstract: Previous studies have consistently revealed that both local and systemic inflammations are the key to the onset and progression of osteoarthritis (OA). Thus, anti-inflammatory biologic agents could potentially attenuate the progression of OA. We conducted this meta-analysis to examine the efficacy and safety of ant-inflammatory biologic agents among OA patients. Methods: Five databases were searched for randomized controlled trials (RCTs) comparing biologics with placebo or each other in OA patients. Data of pain, physical function, stiffness, and adverse events (AEs) were extracted for a conventional and a Bayesian network meta-analysis. Results: 15 studies with data for 1566 patients were analyzed. In the conventional meta-analysis, etanercept (SMD −0.47 95% CI −0.89, −0.05) and infliximab (SMD −2.04 CI −2.56, −1.52) were superior to placebo for knee pain. In the network meta-analysis, infliximab was superior to all the other biologic agents in improving pain (vs. hyaluronic acid (SMD −22.95 CI −34.21, −10.43), vs. adalimumab (SMD −21.71 CI −32.65, −11.00), vs. anakinra (SMD −24.63 CI −38.79, −10.05), vs. canakinumab (SMD −32.83 CI −44.45, −20.68), vs. etanercept (SMD −18.40 CI −29.93, −5.73), vs. lutikizumab (SMD −25.11 CI −36.47, −14.78), vs. naproxen (SMD −30.16 CI −41.78, −17.38), vs. tocilizumab (SMD −24.02 CI −35.63, −11.86) and vs. placebo (SMD −25.88 CI −34.87, −16.60)). No significant differences were observed between biologics and placebo regarding physical function, stiffness, and risk of AEs. Conclusions: The findings suggest that infliximab may relieve pain more than other biological agents in OA patients. No significant differences were observed between biologics and placebo regarding physical function, stiffness, and risk of AEs. The results must be interpreted cautiously therefore, further randomized controlled trials are warranted.
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.JOCA.2016.06.008
Abstract: To assess reliability and validity of a semi-automated quantitative method to measure infrapatellar fat pad (IPFP) signal intensity in patients with knee osteoarthritis (OA). Hundred patients with knee OA were selected. Sagittal planes of fat-saturated T2-weighted images obtained on 1.5-T magnetic resonance imaging (MRI) were utilized to assess IPFP signal intensity using MATLAB. Knee structural abnormalities including cartilage defects, bone marrow lesions (BML) and radiographic OA (ROA) were evaluated. Clinical construct validity and concurrent validity were examined through describing associations of IPFP measurements with knee structural abnormalities and a semi-quantitative scoring method, respectively. The reliability was examined by calculating the intra- and inter-observer correlation coefficients. Significantly positive associations were found between standard deviation of IPFP signal intensity [sDev (IPFP)], clustering factor (H) and all knee structural abnormalities. The volume of high signal intensity regions [Volume (H)] and the ratio of Volume (H) to volume of whole IPFP [Percentage (H)] were positively associated with cartilage defects and ROA, but not with BMLs. The median value [Median (H)] and upper quartile value [UQ (H)] of high signal intensity were only significantly associated with quartiles of cartilage defect score. Significant correlations were found between all quantitative measurements and semi-quantitative scores (All P 0.90). A novel and efficient method to segment IPFP and calculate its signal intensity on T2-weighted MRI images is documented. This method is reproducible, and has concurrent and clinical construct validity, but its predictive validity needs to be examined by future longitudinal studies.
Publisher: Springer Science and Business Media LLC
Date: 17-08-2022
DOI: 10.1186/S12891-022-05635-9
Abstract: The aim of this study was to explore the longitudinal associations between baseline quadriceps strength and knee joint structural abnormalities in knee osteoarthritis (KOA). This study is a longitudinally observational study based on Osteoarthritis Initiative (OAI) cohort, including men and women aged 45–79. Quadriceps strength was measured by isometric knee extension testing at baseline. Knee joint structural abnormalities, including cartilage damage, bone marrow lesions (BMLs), effusion-synovitis and Hoffa-synovitis, were evaluated by Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS) at baseline and 1-year follow-up. Generalized estimating equations were employed to examine the associations between quadriceps strength and knee structural abnormalities. All analyses were stratified by sex. One thousand three hundred thirty-eight participants (523 men and 815 women) with a mean age of 61.8 years and a mean BMI of 29.4 kg/m 2 were included in this study. For men, no significantly longitudinal association of quadriceps strength with structural abnormalities was detected. In contrast, quadriceps strength was significantly and negatively associated with changes in cartilage damage and BMLs in lateral patellofemoral joint (PFJ) (cartilage damage: OR : 0.91, 95% CI 0.84 to 0.99, P = 0.023 BMLs: OR : 0.85, 95% CI 0.74 to 0.96, P = 0.011) and effusion-synovitis ( OR = 0.88, 95% CI 0.78 to 0.99, P = 0.045) among females longitudinally. Higher quadriceps strength was significantly associated with less progression of lateral PFJ cartilage damage, BMLs and effusion-synovitis in females. Higher quadriceps strength was associated with changes in cartilage damage and BMLs within the lateral PFJ and effusion-synovitis among females, suggesting the potential protective role of quadriceps strength on joint structures in women.
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.JOCA.2017.01.007
Abstract: To describe cross-sectional and longitudinal associations between magnetic resonance imaging (MRI)-detected osteophytes (OPs) and knee structural abnormalities and knee pain in older adults. A prospective population-based cohort study of 895 participants aged 50-80 years (mean age 62 years, 50% female) was performed. T1-or T2-weighted fat suppressed MRI was used to assess knee OPs, cartilage volume, cartilage defects and bone marrow lesions (BMLs) at baseline and after 2.6 years. Radiographically-detected OPs were scored according to the Osteoarthritis Research Society International (OARSI) atlas. Knee pain was assessed using a self-administered questionnaire at baseline, 2.6 and 5 years later. 85% of participants had MRI-detected OPs at baseline, while 10% of participants had radiographically-detected OPs. Cross-sectionally, higher gardes of MRI-detected OPs in all compartments were significantly, independently and site-specifically associated with higher prevalences of cartilage defects and BMLs, lower cartilage volume and higher prevalence of knee pain. Longitudinally, higher gardes of baseline MRI-detected OPs site-specifically predicted greater risks of any increase in cartilage defects or BMLs, and loss of cartilage volume in medial and lateral tibiofemoral (LTF) and total compartments over 2.6 years in multivariable analyses. These significant associations were similar in those without radiographically-detected OPs. MTF and total OP scores were significantly associated with change in total knee pain over 2.6 and 5 years but these became non-significant after adjustment for cartilage defects and BMLs. MRI-detected knee OPs are common and appear to be clinically relevant to knee structural changes in older adults.
Publisher: Wiley
Date: 02-11-2022
DOI: 10.1002/JOR.25204
Abstract: The study aimed to determine the associations between the morphological types of proximal tibiofibular joint (PTFJ) and the risk of total knee replacement (TKR) in a cohort of participants with progressive osteoarthritis. A nested case–control design was performed in Osteoarthritis Initiative study. The case knees were those with TKR at 24–60 months follow up (cases), and were 1:1 matched with control knees by age, sex, and Kellgren‐Lawrence grade at baseline. The morphological type of each PTFJ was identified according to the coronal and sagittal MR images. Conditional logistic regression models were used to examine the association of the PTFJ types with the risk of TKR at baseline and the time point before TKR ( T 0 ). A total of 193 case knees at baseline and 148 case knees at T 0 time point had matched controls between 12 and 60 M. Seven types of the PTFJ were identified and classified into three categories: plane, trochoid, and irregular types. The prevalence of the irregular type was higher in case knees than in controls both at baseline (cases vs. controls, 35.8% vs. 26.9%) and at T 0 time point (cases vs. controls, 33.1% vs. 27.0%). The irregular type of the PTFJ at baseline (odds ratio: 1.62, 95% confidence interval: 1.01–2.59) rather than at T 0 time point was significantly associated with increased odds of TKR. The irregular types of the PTFJ at baseline are associated with increased risk of TKR, suggesting PTFJ may play a role in knee osteoarthritis.
Publisher: American Medical Association (AMA)
Date: 18-04-2023
Publisher: BMJ
Date: 27-06-2018
Publisher: Elsevier BV
Date: 06-2023
Publisher: Cold Spring Harbor Laboratory
Date: 24-04-2023
DOI: 10.1101/2023.04.23.23288990
Abstract: To investigate the association of both in idual and combined healthy lifestyle factors with the risk of all-cause mortality among patients with osteoarthritis (OA). Prospective population-based cohort study. UK biobank and US National Health and Nutrition Examination Survey (US NHANES, 2007-2018) 104, 142 UK participants with OA aged 39-72 years and 3, 472 US participants with OA aged 20-80 years. In idual healthy lifestyle factors and a combined healthy lifestyle score were constructed from body mass index (BMI) and self-reported information on diet, sleep duration, physical activity, sedentary time, social connection, smoking and alcohol drinking. All-cause mortality was the primary outcome in both studies. Secondary outcomes included cause-specific mortalities (cardiovascular, cancer, digestive and respiratory). Hazard ratios were adjusted for age, sex, economic situation, race, education and employment (UK biobank only). UK Biobank documented 9,914 deaths during a median follow-up of 12.7 years, and US NHANES documented 463 deaths during a mean follow-up of 6.01 years. For all-cause mortality using restricted cubic spline graph (RCS) models, sleep duration had a U-shaped (with a nadir at 7 hours/day), moderate physical activity (MPA) had an L-shaped (with a turning point at 550 minutes/week), while BMI, vigorous physical activity (VPA) and sedentary time had J-shaped (with turning points at 28 kg/m 2 , 240 minutes/week and 5 hours/day, respectively) associations in the UK biobank. Similar results were observed in US NHANES. In multivariable Cox models, each healthy lifestyle factor was significantly associated with all-cause mortality (hazard ratio [HRs] range 0.49 to 0.84 for UK biobank, and 0.26 to 0.73 for US NHANES), and HRs (95% CI) for associations with combined healthy lifestyle score (scoring 6-8 vs. 0-2) were 0.38 (0.35, 0.41) in UK biobank and healthy lifestyle score (scoring 5-7 vs. 0-1) were 0.20 (0.13, 0.31) in US NHANES for all-cause mortality. The results for cause-specific mortality were largely similar and consistent across two cohorts. The nonlinear relationships suggested patients with OA had the lowest risk of all-cause mortality when BMI was 28 kg/m 2 , sleep was 7 hours/day, VPA was 240 minutes/week, sedentary time was less than 5 hours/day, MPA was more than 550 minutes/week. The newly constructed healthy lifestyle score for OA population was associated with a significantly lower risk of all-cause mortality. Healthy lifestyles are thought to reduce the risk of multiple causes of mortality in the general population. People with osteoarthritis (OA) are at higher risk of mortality than the general population. However, evidence of associations between combined healthy lifestyle and risks of all-cause and cause-specific mortality among OA patients are lacking. Whether and what kind of healthy lifestyles in patients with OA could offset the risk of mortality are unknown. By using two nationwide cohort studies in UK and US, a comprehensive healthy lifestyle pattern that integrates 8 or 7 lifestyle factors was established among OA in iduals for the first time. People who had the highest combined healthy lifestyle score were significantly associated with 62% to 80% lower risk of all-cause mortality compared with those who had the lowest score in both the UK and US OA populations.
Publisher: Springer Science and Business Media LLC
Date: 25-09-2021
DOI: 10.1007/S00011-021-01503-9
Abstract: This study aimed to investigate the biochemical effects of osteoarthritic infrapatellar fat pad (IPFP) on cartilage and the underlying mechanisms. Human IPFP and articular cartilage were collected from end-stage osteoarthritis (OA) patients during total knee arthroplasty. IPFP-derived fat-conditioned medium (FCM) was used to stimulate human primary chondrocytes and cartilage explants. Functional effect of osteoarthritic IPFP was explored in human primary chondrocytes and articular cartilage in vitro and ex vivo. Activation of relative pathways and its effects on chondrocytes were assessed through immunoblotting and inhibition experiments, respectively. Neutralization test was performed to identify the main factors and their associated pathways responsible for the effects of IPFP. Osteoarthritic IPFP-derived FCM significantly induced extracellular matrix (ECM) degradation in both human primary chondrocytes and cartilage explants. Several pathways, such as NF-κB, mTORC1, p38MAPK, JNK, and ERK1/2 signaling, were significantly activated in human chondrocytes with osteoarthritic IPFP-derived FCM stimulation. Interestingly, inhibition of p38MAPK and ERK1/2 signaling pathway could alleviate the detrimental effects of FCM on chondrocytes, while inhibition of other signaling pathways had no similar results. In addition, IL-1β and TNF-α instead of IL-6 in osteoarthritic IPFP-derived FCM played key roles in cartilage degradation via activating p38MAPK rather than ERK1/2 signaling pathway. Osteoarthritic IPFP induces the degradation and inflammation of cartilage via activation of p38MAPK and ERK1/2 pathways, in which IL-1β and TNF-α act as the key factors. Our study suggests that modulating the effects of IPFP on cartilage may be a promising strategy for knee OA intervention.
Publisher: Oxford University Press (OUP)
Date: 04-02-2014
DOI: 10.1093/RHEUMATOLOGY/KET418
Abstract: Vitamin D receptor (VDR) gene polymorphisms may be associated with the risk of OA, however, evidence for this is controversial. This meta-analysis aims to confirm whether VDR gene polymorphisms are associated with OA. Meta-analyses on the association between OA and VDR ApaI, BsmI, TaqI and FokI polymorphisms were conducted using allele and homozygote contrast and contrasts in the recessive and dominant models. Stratification analyses by different demographic regions (Europe vs Asian) were also performed and pooled odds ratios (ORs) were obtained using the random effects model if the results were heterogeneous. A total of 13 relevant studies involving OA patients (n = 2104) and controls (n = 2939) were included in the analysis. There were significant associations between VDR ApaI polymorphisms and OA in the Asian population (A vs a: OR= 1.16, 95% CI 1.02, 1.32, P = 0.025 AA vs Aa/aa: OR= 1.36, 95% CI 1.04, 1.77, P = 0.025 AA vs aa: OR= 1.35, 95% CI 1.00, 1.80, P = 0.047), but not in the whole population. There was also a statistically significant association between FokI polymorphism and OA (FF vs Ff/ff: OR= 0.65, 95% CI 0.44, 0.95, P = 0.024) however, this result was derived from only two studies. No significant associations were found between VDR TaqI and BsmI polymorphisms and OA. There are modest but statistically significant associations between VDR ApaI polymorphisms and the susceptibility of OA in the Asian population.
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.JOCA.2017.02.804
Abstract: To develop a measure of knee joint effusion-synovitis volume and to examine the effect of vitamin D supplementation on effusion-synovitis in people with knee osteoarthritis (OA) and low vitamin D levels over 24 months. Symptomatic knee OA patients with low 25-(OH)D levels (12.5-60 nmol/l) were recruited for a multi-centre, randomised, placebo-controlled and double-blind trial. Participants (age 63 ± 7 years, 208 females) were allocated to either 50,000 IU monthly vitamin D The reproducibilities of effusion-synovitis volume measurement were high with ICCs ranging from 0.93 to 0.99. Over 24 months, effusion-synovitis volume remained stable in the vitamin D group but increased in placebos with a significant between-group difference (-1.94 ml, 95% confidence interval (CI): -3.54, -0.33). This effect was evident in those with baseline effusion-synovitis and with suprapatellar effusion-synovitis. The proportion with an increase in effusion-synovitis volume was lower in the vitamin D group than placebo (risk ratio (RR): 0.87, 95% CI: 0.77, 0.97). This highly reproducible effusion-synovitis volume measurement could be a promising outcome measure in OA trials. Vitamin D supplementation could retard the progression of effusion-synovitis which can potentially benefit people with an inflammatory OA phenotype.
Publisher: Springer Science and Business Media LLC
Date: 29-07-2021
DOI: 10.1007/S00330-021-08193-1
Abstract: To determine whether pericruciate fat pad (PCFP) signal intensity alteration and maximal area are associated with incident radiographic osteoarthritis (ROA) over 4 years in the Osteoarthritis Initiative (OAI) study. Participants were from the Osteoarthritis Initiative (OAI) study. Case knees (n = 355) were defined by incident ROA between 12 and 48 months visits and were matched by sex, age, and radiographic status with control knees (n = 355). Magnetic resonance images (MRIs) were used to assess PCFP signal intensity alteration and PCFP maximal area at P0 (time of onset of ROA), P-1 (1 year prior to P0), and baseline. Conditional logistic regression analyses were applied to assess associations between PCFP measures and the risk of incident ROA. The mean age of participants was 60.1 years and 66.9% were women. In multivariable analyses, PCFP signal intensity alteration measured at three time points (OR [95%CI]: 1.28 [1.10-1.50], 1.52 [1.30-1.78], 1.50 [1.27-1.76], respectively) and PCFP maximal area (OR [95%CI]: 1.21 [1.03-1.42], 1.27 [1.07-1.52], 1.37 [1.15-1.62], respectively) were significantly associated with incident ROA. PCFP signal intensity alteration and maximal area were associated with incident ROA over 4 years, implying that they may have roles to play in ROA. • Pericruciate fat pad signal intensity alteration and maximal area were associated with incident ROA, implying that they may have roles to play in ROA.
Publisher: American Medical Association (AMA)
Date: 22-03-2022
Publisher: Informa UK Limited
Date: 24-10-2018
DOI: 10.1080/13543784.2018.1539075
Abstract: Osteoarthritis (OA) is the leading cause of pain, loss of function, and disability among elderly, with the knee the most affected joint. It is a heterogeneous condition characterized by complex and multifactorial etiologies which contribute to the broad variation in symptoms presentation and treatment responses that OA patients present. This poses a challenge for the development of effective treatment on OA. This review will discuss recent development of agents for the treatment of OA, updating our previous narrative review published in 2015. They include drugs for controlling local and systemic inflammation, regulating articular cartilage, targeting subchondral bone, and relieving pain. Although new OA drugs such as monoclonal antibodies have shown marked effects and favorable tolerance, current treatment options for OA remain limited. The authors believe there is no miracle drug that can be used for all OA patients' treatment and disease stage is crucial for the effectiveness of drugs. Therefore, early diagnosis, phenotyping OA patients and precise therapy would expedite the development of investigational drugs targeting at symptoms and disease progression of OA.
Publisher: Oxford University Press (OUP)
Date: 19-08-2022
DOI: 10.1093/RHEUMATOLOGY/KEAC467
Abstract: To investigate the therapeutic effect and mechanism of metformin on knee OA in normal diet (ND) mice or high-fat diet (HFD)-induced obese mice. Destabilization of the medial meniscus surgery was performed in ND mice or HFD mice, and metformin was administrated in drinking water or not. The changes of OA joint structure, infiltration and polarization of synovial macrophages and circulating and local levels of leptin and adiponectin were evaluated. In vitro, the effects of metformin on chondrocytes and macrophages, and of conditioned mediums derived from mouse abdominal fat on murine chondrogenic cell line ATDC5 and murine macrophage cell line RAW264.7, were detected. Metformin showed protective effects on OA, characterized by reductions on OARSI score [2.00, 95% CI (1.15, 2.86) for ND mice and 3.17, 95% CI (2.37, 3.96) for HFD mice] and synovitis score [1.17, 95% CI (0.27, 2.06) for ND mice and 2.50, 95% CI (1.49, 3.51) for HFD mice] after 10 weeks of treatment, and the effects were more significant in HFD mice than in ND mice. Mechanistically, in addition to decreasing apoptosis and matrix-degrading enzymes expression in chondrocytes as well as infiltration and pro-inflammatory differentiation of synovial macrophages, metformin reduced leptin secretion by adipose tissue in HFD mice. Metformin protects against knee OA which could be through reducing apoptosis and catabolism of chondrocytes, and suppressing infiltration and pro-inflammatory polarization of synovial macrophages. For obese mice, metformin has a greater protective effect in knee OA additionally through reducing leptin secretion from adipose tissue.
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.JOCA.2019.11.001
Abstract: To determine whether the morphology of proximal tibiofibular joint (PTFJ) is associated with increased risk of incident radiographic osteoarthritis (iROA) over 4 years in the OA Initiative (OAI) study. A nested matched case-control study design was used to select participants from OAI study. Case knees were defined as those with iROA. Control knees were matched one-to-one by sex, age and radiographic status with case knees. T2-weighted MR images were assessed at P0 (the visit when incident ROA was found on radiograph), P1 (1 year prior to P0) and at OAI baseline. The contacting area of PTFJ (S) and its projection areas onto the horizontal (load-bearing area, Sτ), sagittal (lateral stress-bolstering area, Sφ) and coronal plane (posterior stress-bolstering area, Sυ) were assessed, respectively. 354 case knees and 354 matched control knees were included, with a mean age of 60 and a mean body mass index (BMI) of 28 kg/m Greater contacting area, load-bearing area and posterior stress-bolstering area of PTFJ were associated with increased risks of iROA, largely in the medial tibiofemoral compartment.
Publisher: Cambridge University Press (CUP)
Date: 15-11-2018
Publisher: Wiley
Date: 28-09-2020
DOI: 10.1002/JOR.24862
Abstract: The association between proximal tibiofibular joint (PTFJ) and knee osteoarthritis (OA) has been understudied. The objective of this study was to determine whether the morphology of PTFJ has predictive value for the risk of total knee replacement (TKR). Case knees from Osteoarthritis Initiative participants with TKR at 24–60 months follow up (cases) were 1:1 matched with control knees (no TKR throughout 60 months) by baseline age, sex, and Kellgren–Lawrence grade. PTFJ morphological parameters, including coronal inclination angle (angle α ), sagittal inclination angle (angle β ), fibular contacting area ( S ), load‐bearing area ( Sτ ), lateral stress‐bolstering area ( Sφ ), and posterior stress‐bolstering area ( Sυ ) were assessed using coronal and sagittal magnetic resonance imaging (MRI), respectively. Associations of the morphological measures at baseline and the time point before TKR ( T 0 ) and their changes with TKR risks were examined using conditional logistic regression analyses. Two hundred and twenty‐three knees of 193 participants received TKR between 12 and 60 months and therefore were matched with 223 control knees. Of these, 173 paired knees had MRI readings available both at baseline and T 0 time point. While baseline angle α was positively associated with TKR risk, other measures at baseline and all measures at T 0 were not significantly associated with TKR risk. Changes in S , Sτ , and Sυ were significantly and negatively associated with the risk of TKR (Δ S , odds ratio [OR] = 0.38, 95% confidence interval [CI]: 0.19–0.76 Δ Sτ , OR = 0.37, 95% CI: 0.16–0.87 Δ Sυ , OR = 0.22, 95% CI: 0.08–0.62, respectively). This data shows that morphological changes of PTFJ predict the risk of TKR, suggesting PTFJ may play a role in knee OA.
Publisher: Wiley
Date: 27-04-2020
DOI: 10.1111/JDV.16331
Publisher: MDPI AG
Date: 30-08-2022
DOI: 10.3390/NU14173576
Abstract: Background: Osteoarthritis (OA), the most common joint disease in the elderly, has no cure. Macroelements are vital in human health and their relationships with OA are not clear. Clarifying the relationships between macroelements and OA may assist knee OA management. Methods: This study was a post-hoc analysis using data from a two-year randomized controlled trial among 392 participants with knee OA. Dietary macroelements, including calcium, magnesium, potassium, and phosphorus were computed-based on a semi-quantitative food frequency questionnaire at baseline. Knee joint structures (including cartilage volume, cartilage defect, bone marrow lesions, and effusion-synovitis volume), OA symptoms, quality of life, and OA comorbid conditions (including lower limb muscle strength and depressive symptoms) were assessed at baseline and month 24. Western Ontario and McMaster Universities (WOMAC) Index and depressive symptoms were assessed at baseline and months 3, 6, 12, and 24. Quality of life and lower limb muscle strength were assessed at baseline and months 6, 12, and 24. All analyses were conducted using mixed-effects models. Results: Higher dietary magnesium and potassium were associated with fewer OA symptoms, higher quality of life, greater lower limb muscle strength, and fewer depressive symptoms, but not with knee joint structures. Higher dietary calcium and phosphorus was not associated with any of the OA-related outcomes, except that dietary phosphorus was associated with greater lower limb muscle strength. Conclusions: In the longitudinal analyses, higher dietary magnesium and potassium intake are associated with fewer OA symptoms, higher quality of life, and milder comorbid conditions in patients with knee OA, suggesting dietary magnesium and potassium may have beneficial effects on OA and could be used for knee OA management.
Publisher: Elsevier BV
Date: 02-2023
DOI: 10.1016/J.JOCA.2022.10.014
Abstract: To develop and validate a nomogram to detect improved knee pain in osteoarthritis (OA) by integrating magnetic resonance imaging (MRI) radiomics signature of subchondral bone and clinical characteristics. Participants were selected from the Vitamin D Effects on Osteoarthritis (VIDEO) study. The primary outcome was 20% improvement of knee pain score over 2 years in participants administrated either vitamin D or placebo. Radiomics features of subchondral bone and clinical characteristics from 216 participants were extracted and analyzed. The participants were randomly split into the training and validation cohorts at a ratio of 8:2. Least absolute shrinkage and selection operator (LASSO) regression was used to select features and generate radiomics signatures. The optimal radiomics signature and clinical indicators were fitted into a nomogram using multivariable logistic regression model. The nomogram showed favorable discrimination performance [AUC The radiomics-based nomogram comprising the MR radiomics signature and clinical variables achieves a favorable predictive efficacy and accuracy in differentiating improvement in knee pain among OA patients. This proof-of-concept study provides a promising way to predict clinically meaningful outcomes.
Publisher: Informa UK Limited
Date: 20-04-2023
Publisher: Frontiers Media SA
Date: 16-03-2023
DOI: 10.3389/FGENE.2023.1122955
Abstract: Objective: To assess the causal effect of systemic iron status by using four biomarkers (serum iron transferrin saturation ferritin total iron-binding capacity) on knee osteoarthritis (OA), hip OA, total knee replacement, and total hip replacement using 2-s le Mendelian randomization (MR) design. Methods: Three instrument sets were used to construct the genetic instruments for the iron status: Liberal instruments (variants associated with one of the iron biomarkers), sensitivity instruments (liberal instruments exclude variants associated with potential confounders), and conservative instruments (variants associated with all four iron biomarkers). Summary-level data for four OA phenotypes, including knee OA, hip OA, total knee replacement, and total hip replacement were obtained from the largest genome-wide meta-analysis with 826,690 in iduals. Inverse-variance weighted based on the random-effect model as the main approach was conducted. Weighted median, MR-Egger, and Mendelian randomization pleiotropy residual sum and outlier methods were used as sensitivity MR approaches. Results: Based on liberal instruments, genetically predicted serum iron and transferrin saturation were significantly associated with hip OA and total hip replacement, but not with knee OA and total knee replacement. Statistical evidence of heterogeneity across the MR estimates indicated that mutation rs1800562 was the SNP significantly associated with hip OA in serum iron (odds ratio, OR = 1.48), transferrin saturation (OR = 1.57), ferritin (OR = 2.24), and total-iron binding capacity (OR = 0.79), and hip replacement in serum iron (OR = 1.45), transferrin saturation (OR = 1.25), ferritin (OR = 1.37), and total-iron binding capacity (OR = 0.80). Conclusion: Our study suggests that high iron status might be a causal factor of hip OA and total hip replacement where rs1800562 is the main contributor.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.JOCA.2017.05.013
Abstract: To describe the cross-sectional associations between proximal tibiofibular joint (PTFJ) type configurations and knee joint structural abnormalities in older adults. A total of 967 community-based participants were studied. T1-weighted fat-suppressed magnetic resonance image (MRI) with spoiled gradient recalled echo sequence was utilized to assess the PTFJ type configurations. Knee cartilage volume, cartilage defects, bone marrow lesions and osteophytes were measured. Linear regression and binary logistic regression analyses were used to examine the associations between PTFJ type configurations and knee joint cartilage volume as well as knee structural abnormalities, respectively, after adjustment for potential confounders. Seven PTFJ types including plane (49.4%), trochoid (31.9%), double trochoid (4.3%), saddle (5.4%), condylar (5.3%), trochlear (3.5%) and ball & socket (0.2%) were observed. Plane type was used as the comparator. In multivariable analyses, irregular joint types (comprising the five uncommon joint types) were associated negatively with cartilage volume, and positively with knee cartilage defects, bone marrow lesions and osteophytes in the lateral (but not medial) compartments. In contrast, trochoid type was only associated with reduced femoral cartilage volume, but not with knee cartilage defects, bone marrow lesions and osteophytes. Irregular PTFJ joint shapes are associated with osteoarthritic changes in the lateral, but not medial, tibiofemoral compartment in older adults. The causal relationship needs to be examined in future longitudinal studies.
Publisher: The Journal of Rheumatology
Date: 09-2017
Abstract: To describe the associations between effusion-synovitis and joint structural abnormalities in patients with knee osteoarthritis (OA) over 24 months. A posthoc analysis using data from a randomized controlled trial in 413 patients with symptomatic OA (aged 63 ± 7 yrs, 208 women). Knee effusion-synovitis volume and score, cartilage defects, cartilage volume, and bone marrow lesions (BML) were assessed using magnetic resonance imaging. Joint space narrowing (JSN) and osteophytes were assessed using radiograph. Least significant change criterion was used to define change in effusion-synovitis volume. Knee symptoms were assessed by Western Ontario and McMaster University OA Index. Multivariable linear/logistic regression and multilevel generalized mixed-effects models were used in longitudinal analyses. Total effusion-synovitis volume increased modestly from baseline (8.0 ± 8.5 ml) to followup (9.0 ± 10.5 ml). Baseline BML, cartilage defect, JSN, and osteophyte scores were positively associated with change in effusion-synovitis volume (p 0.05). Baseline cartilage defects and JSN were also associated with change in effusion-synovitis score (p 0.05). However, neither baseline effusion-synovitis score nor volume consistently predicted change in the above structures except cartilage volume. In the mixed-effects models, knee effusion-synovitis was positively associated with BML (volume: β = 1.19 ml/grade score: OR = 1.75/grade) and cartilage defects (volume: β = 1.87 ml/grade score: OR = 2.22/grade), while negatively associated with cartilage volume loss. Change in effusion-synovitis volume was positively correlated with changes in knee pain and stiffness scores (p 0.05). Knee cartilage and subchondral bone abnormalities predicted change in effusion-synovitis, but effusion-synovitis did not predict knee structural changes. These findings suggest that synovial inflammation is likely the result of joint structural abnormalities in established OA. ClinicalTrials.gov identifier: NCT01176344 . Australian New Zealand Clinical Trials Registry: ACTRN12610000495022.
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.JOCA.2018.08.020
Abstract: Animal studies suggest that S100A8/S100A9 may be involved in the pathogenesis of osteoarthritis (OA) however, there has been no clinical study examining the associations between serum S100A8/S100A9 and knee symptoms, joint structures and cartilage degradation enzymes in knee OA patients so far. Therefore, this study was designed to investigate the cross-sectional associations between serum levels of S100A8/S100A9 and the outcomes in patients with knee OA. A total of 141 subjects with clinical knee OA were included. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was used to assess joint symptoms. Magnetic resonance imaging (MRI) was used to measure knee structural abnormalities including cartilage defects. Knee radiography was used to assess joint space narrowing (JSN), osteophytes and the radiographic severity of OA. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of S100A8/S100A9, matrix metalloproteinase (MMP)-3, MMP10 and MMP13. In multivariable analyses, serum S100A8/S100A9 were positively associated with total WOMAC score (β: 0.111 per 10 ng/ml, P = 0.021), WOMAC weight-bearing pain (β: 0.015 per 10 ng/ml, P = 0.043) and WOMAC physical dysfunction (β: 0.091 per 10 ng/ml, P = 0.010), and had positive associations with total cartilage defects and cartilage defects at lateral femoral, lateral tibial and medial femoral sites (ORs: 1.006-1.008 per 10 ng/ml, all P < 0.05) and serum levels of MMP3 (β: 0.002 per 10 ng/ml, P = 0.032) in patients with clinical knee OA. Serum levels of S100A8/S100A9 were positively associated with increased knee symptoms, cartilage defects and serum cartilage degradation enzymes in patients with knee OA, suggesting that S100A8/S100A9 may have a role to play in knee OA. Future longitudinal studies are required to confirm these findings.
Publisher: Elsevier BV
Date: 03-2023
Publisher: BMJ
Date: 18-08-2023
Abstract: This study aims to identify circulating proteins that are causally associated with osteoarthritis (OA)-related traits through Mendelian randomisation (MR)-based analytical framework. Large-scale two-s le MR was employed to estimate the effects of thousands of plasma proteins on 12 OA-related traits. Additional analyses including Bayesian colocalisation, Steiger filtering analysis, assessment of protein-altering variants and mapping expression quantitative trait loci to protein quantitative trait loci were performed to investigate the reliability of the MR findings protein–protein interaction, pathway enrichment analysis and evaluation of drug targets were conducted to deepen the understanding and identify potential therapeutic targets of OA. Dozens of circulating proteins were identified to have putatively causal effects on OA-related traits, and a majority of these proteins were either drug targets or considered druggable. Through MR analysis, we have identified numerous plasma proteins associated with OA-related traits, shedding light on protein-mediated mechanisms and offering promising therapeutic targets for OA.
Publisher: Cambridge University Press (CUP)
Date: 25-06-2018
DOI: 10.1017/S0007114518001174
Abstract: The aim of this study was to determine whether vitamin D supplementation and maintaining vitamin D sufficiency are associated with changes in inflammatory and metabolic biomarkers in patients with knee osteoarthritis (OA) and vitamin D deficiency. A total of 413 participants with symptomatic knee OA and vitamin D deficiency were enrolled in a randomised, placebo-controlled trial and received 1·25 mg vitamin D 3 or placebo monthly for 24 months across two sites. In this post hoc analysis, 200 participants from one site (ninety-four from the placebo group and 106 from the vitamin D group mean age 63·1 ( sd 7·3) years, 53·3 % women) were randomly selected for measurement of serum levels of inflammatory and metabolic biomarkers at baseline and 24 months using immunoassays. In addition, participants were classified into two groups according to serum 25-hydroxyvitamin D (25(OH)D) levels at months 3 and 24: (1) not consistently sufficient (25(OH)D≤50 nmol/l at either month 3 or 24, n 61), and (2) consistently sufficient (25(OH)D nmol/l at both months 3 and 24, n 139). Compared with placebo, vitamin D supplementation had no significant effect on change in serum high-sensitive C-reactive protein, IL-6, IL-8, IL-10, leptin, adiponectin, resistin, adipsin and apelin. Being consistently vitamin D sufficient over 2 years was also not associated with changes in these biomarkers compared with not being consistently sufficient. Vitamin D supplementation and maintaining vitamin D sufficiency did not alter serum levels of inflammatory and metabolic biomarkers over 2 years in knee OA patients who were vitamin D insufficient, suggesting that they may not affect systemic inflammation in knee OA patients.
Publisher: Springer Science and Business Media LLC
Date: 16-09-2020
DOI: 10.1186/S13063-020-04687-3
Abstract: Osteoarthritis (OA) is a common chronic disease in older adults. Currently, there are no effective therapies to reduce disease severity and progression of knee OA (KOA), particularly in mid- to late-stages. This study aims to examine the effect of methotrexate (MTX) on knee effusion-synovitis and pain in symptomatic patients with mid- to late-stage KOA. This protocol describes a multicentre randomised placebo-controlled clinical trial aiming to recruit 200 participants with mid- to late-stage symptomatic KOA and with effusion-synovitis grade of ≥ 2. Participants will be randomly allocated to the MTX group (start from 5 mg per week for the first 2 weeks and increase to 10 mg per week for the second 2 weeks and 15 mg per week for the remaining period if tolerated) or the placebo group. Primary outcomes are effusion-synovitis size measured by magnetic resonance imaging (MRI) and knee pain assessed by visual analogue scale (VAS). Secondary outcomes are signal intensity alteration within infrapatellar fat pad (IPFP) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score and subscores, and the Outcome Measures in Rheumatology Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) responders. Both intention-to-treat and per-protocol analyses will be performed. If MTX intervention can relieve symptoms and reduce inflammation in patients with mid- to late-stage KOA, it has the potential for significant clinical and public health impact as this low-cost and commonly used intervention would delay the time to knee replacement, leading to substantial cost savings and improve quality of life. ClinicalTrials.gov NCT03815448 . Registered on 21 January 2019.
Publisher: Springer Science and Business Media LLC
Date: 04-2023
DOI: 10.1186/S13063-023-07122-5
Abstract: Repetitive transcranial magnetic stimulation (rTMS), as a non-invasive brain stimulation technique, has shown potentials for consciousness recovery of patients with disorders of consciousness (DoC), as, to a certain extent, it is effective in regulating the excitability of central nervous system. However, it is difficult to achieve satisfactory effect with “one size fits all” rTMS treatment due to different clinical conditions of patients. There is an urgent need to develop in idualized strategy to improve the effectiveness of rTMS on patients with DoC. Our protocol is a randomized double-blind sham-controlled crossover trial that includes 30 DoC patients. Each patient will received 20 sessions, in which 10 sessions will be rTMS-active stimulus, and the other 10 sessions will be sham stimulus, separated by no less than 10 days’ washout period. The rTMS-active will include 10 Hz rTMS over the in idualized-targeted selection area for each patient according to the different insult regions of the brain. Coma Recovery Scale-Revised (CRS-R) will be used as primary outcome at baseline, after the first stage of stimulation, at the end of the washout period, and after the second stage of stimulation. Secondary outcomes will be measured at the same time, including efficiency, relative spectral power, and functional connectivity of high-density electroencephalograph (EEG). Adverse events will be recorded during the study. rTMS has obtained grade A evidence in treating patients with several central nervous system diseases, and there has been some evidence showing partial improvement on level of consciousness in DoC patients. However, the effectiveness of rTMS in DoC is only 30~36%, mostly due to the non-specific target selection. In this protocol, we present a double-blind crossover randomized sham-controlled trial based on the in idualized-targeted selection strategy that aims to study the effectiveness of rTMS therapy for DoC, and the result may provide new insights to non-invasive brain stimulation. ClinicalTrials.gov : NCT05187000. Registered on January 10, 2022.
Publisher: Wiley
Date: 06-2021
DOI: 10.1002/ACR.24371
Abstract: The present study was undertaken to determine whether vitamin D supplementation or maintaining sufficient vitamin D level reduces foot pain over 2 years in patients with symptomatic knee osteoarthritis (OA). A post hoc study was conducted from a randomized, double‐blind, placebo‐controlled trial named the Vitamin D Effect on Osteoarthritis (VIDEO) study. Symptomatic knee OA patients with serum 25‐hydroxyvitamin D levels between 12.5 nmoles/liter and 60 nmoles/liter were included and randomly allocated to either monthly vitamin D 3 or placebo treatment (1:1) for 2 years. Manchester Foot Pain and Disability Index (MFPDI) was used to evaluate foot pain and disabling foot pain was defined as at least 1 of the 10 functional limitation items (items 1–9 and 11) being documented as on “most/every day(s)” in the last month. A repeated‐measures, mixed‐effects model was used to analyze the change of MFPDI scores between groups adjusting for potential confounders. A total of 413 patients with a mean age of 63.2 years (49.7% males) were enrolled and 340 completed the study. The mean MFPDI score was 22.8 ± 7.3, with 23.7% of participants having disabling foot pain at baseline. There were significant differences in MFPDI scores change between groups over 2 years, with more improvements in the vitamin D group than in the placebo group (–0.03 versus 1.30 P = 0.013) and more improvement in those maintaining sufficient vitamin D levels (n = 226) than those who did not (n = 114) (–0.09 versus 2.19 P = 0.001). Vitamin D supplementation and maintenance of sufficient vitamin D levels may improve foot pain in those with knee OA.
Publisher: American Medical Association (AMA)
Date: 10-10-2022
DOI: 10.1001/JAMANETWORKOPEN.2022.35060
Abstract: In osteoarthritis (OA) clinical trials, a placebo is often used as control. Therefore, a thorough understanding of the placebo response is important for guiding drug development in OA. To develop an oral placebo response model for OA. PubMed, EMBASE, and Cochrane Library databases were searched systematically from January 1, 1991, to July 2, 2022. Randomized double-blind placebo-controlled trials of patients with primary OA were included. The interventions and placebo were administered orally. A total of 3032 trials were identified of these, 130 (4.3%) met the inclusion criteria. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, dosage form of the placebo, s le size, proportion of patients who previously used nonsteroidal anti-inflammatory drugs, publication year, intervention categories, Kellgren-Lawrence grades, proportion of White patients, duration of pain, funding source, and risk of bias were extracted. A model-based meta-analysis was used to evaluate the time course of the placebo response in OA treatment and estimate the influencing factors. For subgroup analyses, a meta-analysis with a random-effects model was used to summarize the typical values of the model parameters and their SEs. The primary end point was the time course of the oral placebo response on the WOMAC pain, stiffness, and function subscale scores. The 130 trials selected for analysis included 12 673 participants (mean age, 59.9 years 68.9% women). The baseline scores of WOMAC pain, stiffness, and function subscales were found to be significantly associated with the placebo response. The placebo response reached 90% of its maximum response between 5 and 7 weeks. The placebo responses on the WOMAC subscales were also associated with the s le size, proportion of patients who had previously used nonsteroidal anti-inflammatory drugs, intervention drugs, and publication year. In this study, an oral placebo response model of OA was developed that may quantitatively describe the placebo response at different baseline levels of symptoms. The findings may provide valuable references for future clinical trial design and decision-making.
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.JOCA.2015.02.018
Abstract: To examine the cross-sectional and longitudinal associations of patellar bone marrow lesion (BMLs) with knee pain, cartilage defects and cartilage volume in older adults. A total of 904 randomly selected subjects (mean 62.4 years, 49.9% female) were studied. Fat suppressed T1-weighted spoiled gradient recall and T2-weighted fast spin echo magnetic resonance imaging (MRI) sequences were used to assess cartilage volume, cartilage defects and/or BMLs at baseline (n = 904) and 2.6 (range: 1.4-4.8) years' follow-up (n = 414). Knee pain was assessed by self-administered Western Ontario McMaster Osteoarthritis Index (WOMAC) questionnaire at baseline (n = 904) and follow-up (n = 790). The prevalence of any patellar BMLs was 19% and was higher in those with tibiofemoral BMLs. In multivariable analyses, patellar BMLs were positively associated with any knee pain at baseline and an increase in knee pain when going up/down stairs (odds ratio (OR): 1.67, 95% confidence interval (CI): 1.08, 2.59) but not with other knee pain subscales. Patella BMLs were also associated with patellar cartilage defects both at baseline and change over time (OR: 1.76, 95% CI: 1.00, 3.70) but not tibiofemoral defects. Patellar BMLs were negatively associated with baseline and change in patella cartilage volume (β: -2.10%, 95% CI: -3.39%, -0.80%). These associations remained significant after further adjustment for tibiofemoral BMLs. Patellar BMLs were consistently associated with increased knee pain especially going up/down stairs, increased patellar cartilage defects, and decreased patellar cartilage volume cross-sectionally and longitudinally, suggesting a predominantly compartment specific role for patellar BMLs.
Publisher: Informa UK Limited
Date: 20-11-2019
Publisher: Wiley
Date: 18-04-2023
DOI: 10.1002/JCSM.13200
Abstract: Vitamin D deficiency is a globally common situation and closely related with many chronic diseases. It is a hot topic to examine if vitamin D supplementation is effective for the treatment of diseases, and there have been dozens of clinical trials published in recent years. However, most studies have not proved the extra‐skeletal benefits of vitamin D supplementation on these diseases. Some inherent shortcomings of these trials, such as inclusion with vitamin D‐sufficient and obese participants, low response rate from participants and the insensitive changes in chosen outcomes over a shorter period, may be main reasons why most studies have yet to demonstrate effects of vitamin D supplementation. In this editorial, we aim to discuss the perspectives on how can we design a proper trial for vitamin D treatment of diseases based on the evidence‐based practice framework PICOS (participants, intervention, control, outcomes and study design) in the future. First, right participants should be chosen, which is crucial for the success of vitamin D clinical trials. Participants with vitamin D sufficiency (e.g., baseline 25(OH)D of nmol/L), obesity (e.g., body mass index 30 kg/m 2 ) and/or high vitamin D response index could be excluded from the trials. Second, intervention with vitamin D in right forms or dosages should be used. Vitamin D 3 supplementation with appropriate dosages that keep 25(OH)D levels between 75 and 100 nmol/L is recommended. Third, ‘contamination’ in the control groups needs to pay attention. To diminish this, it is ideal to include participants less interfered by sun exposure (such as living in places at a high latitude) or with greater compliance (less interference by supplemental vitamin D‐containing nutrients). Fourth, the outcome measures should be sensitive to change to avoid type II error. For outcomes such as bone density, radiographic osteoarthritis and cardiovascular diseases, follow‐up period of 3–5 years may be required to observe the changes. Last, precision clinical trials may be the only way to prove the benefits of vitamin D supplementation.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Wiley
Date: 30-11-2022
DOI: 10.1111/JDV.18767
Abstract: Capillary malformation (CM) is the most common vascular malformation. Large scale studies on its incidence and risk factors are limited in China. Our study aimed to investigate the incidence of CM in Chinese infants and to evaluate its potential risk factors. A cross‐sectional study, including 7299 infants (aged 1 year) were collected by a self‐administered questionnaire. Independent‐s les T tests or χ 2 tests and multivariable logistic models were used to examine the potential risk factors for CM. The incidences of salmon patches and port‐wine stains (PWSs) were 9.10% and 0.80%, respectively. In analyses, male sex (OR: 1.32, 95% CI: 1.12–1.55) and birth hypoxia (OR: 5.61, 95% CI: 4.39–7.16) were risk factors for salmon patches. Birth hypoxia (OR: 12.58, 95% CI: 7.26–21.79) and pregnancy‐induced hypertension syndrome (PIH OR: 3.66, 95% CI: 1.49–8.99) were associated with a higher risk of PWSs. This epidemiological study had the largest s le size of infants with CM in the world thus far, which updated its incidence in Chinese infants and found the potential risk factors for CM.
Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.JOCA.2022.06.004
Abstract: Although subchondral bone marrow lesions (BMLs) and synovitis have been well acknowledged as important sources of pain in knee osteoarthritis (KOA), it is unclear if synovitis plays the mediating role in the relationship between BMLs and knee pain. We analyzed 600 subjects with magnetic resonance imaging (MRI) in the Foundation for National Institutes of Health Osteoarthritis Biomarkers Consortium (FNIH) cohort at baseline and 24-month. BMLs and synovitis were measured according to the MRI Osteoarthritis Knee Score (MOAKS) scoring system. BMLs were scored in five subregions. A summary synovitis score of effusion and Hoffa-synovitis was calculated. Knee pain was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Linear regression models were applied to analyze the natural direct effect (NDE) of BMLs and synovitis with knee pain, respectively, and natural indirect effect (NIE) mediated by synovitis. 590 participants (58.8% females, with a mean age of 61.5) were included in the present analyses. For NDE, knee pain was cross-sectionally associated with medial femorotibial BMLs (β = 0.23, 95% CI: 0.09, 0.38) and synovitis (β = 0.40, 95% CI: 0.20, 0.60). Longitudinal associations retained significant [medial femorotibial BMLs (β = 0.37, 95% CI: 0.21, 0.53) synovitis (β = 0.72, 95% CI: 0.45, 0.99)]. In the NIE analyses, synovitis mediated the association between medial femorotibial BML and knee pain at baseline (β = 0.051, 95% CI: 0.01, 0.09) and over 24 months (β = 0.079, 95% CI: 0.023, 0.15), with the mediating proportion of 17.8% and 22.4%, respectively. Synovitis partially mediates the association between medial femorotibial BMLs and knee pain.
Publisher: BMJ
Date: 10-2020
DOI: 10.1136/BMJOPEN-2020-043088
Abstract: The infrapatellar fat pad (IPFP) is commonly resected during total knee arthroplasty (TKA) for better exposure. However, our previous studies have suggested that IPFP size was protective against, while IPFP signal intensity alteration was detrimental on knee symptoms and structural abnormalities. We hypothesise that an IPFP with normal qualities, rather than abnormal qualities, should be preserved during TKA. The aim of this study is to compare, over a 1-year period, the postoperative clinical outcomes of IPFP preservation versus resection after TKA in patients with normal or abnormal IPFP signal intensity alteration on MRI. Three hundred and sixty people with end-stage knee osteoarthritis and on the waiting list for TKA will be recruited and identified as normal IPFP quality (signal intensity alteration score ≤1) or abnormal IPFP quality (signal intensity alteration score ≥2). Patients in each hospital will then be randomly allocated to IPFP resection group or preservation group. The primary outcomes are the summed score of self-reported Knee Injury and Osteoarthritis Outcome Score (KOOS), KOOS subscales assessing function in daily activities and function in sport and recreation. Secondary endpoints will be included: KOOS subscales (pain, symptoms and quality of life), Knee Society Score, 100 mm Visual Analogue Scale (VAS) Pain, timed up-and-go test, patellar tendon shortening, 100 mm VAS self-reported efficacy of reduced pain and increased quality of life, and Insall-Salvati index assessed on plain X-ray. Adverse events will be recorded. Intention-to-treat analyses will be used. The study is approved by the local Medical Ethics Committee (Zhujiang Hospital Ethics Committee, reference number 2017-GJGBK-001) and will be conducted according to the principle of the Declaration of Helsinki (64th, 2013) and the Good Clinical Practice standard, and in compliance with the Medical Research Involving Human Subjects Act . Data will be published in peer-reviewed journals and presented at conferences, both nationally and internationally. This trial was registered at Clinicaltrial.gov website on 19 October 2018 with identify number NCT03763448 .
Publisher: BMJ
Date: 26-11-2015
DOI: 10.1136/ANNRHEUMDIS-2015-208360
Abstract: To describe the associations between infrapatellar fat pad (IPFP) signal intensity alteration at baseline and knee symptoms and structural changes in older adults. A total of 874 subjects (mean 62.1 years, 50.1% female) selected randomly from local community were studied at baseline and 770 were followed up (only 357 had MRI at follow-up) over 2.6 years. T1-weighted or T2-weighted fat suppressed MRI was used to assess IPFP signal intensity alteration (0-3), cartilage volume, cartilage defects and bone marrow lesions (BMLs) at baseline and 2.6 years later. Knee pain was assessed by self-administered Western Ontario and McMaster Osteoarthritis Index questionnaire. Radiographic osteoarthritis (OA) was assessed. In cross-sectional analyses, IPFP signal intensity alteration was significantly and positively associated with total knee pain as well as knee cartilage defects, BMLs and knee radiographic OA and negatively associated with patellar cartilage volume after adjustment for age, sex, body mass index and/or radiographic OA. Longitudinally, baseline signal intensity alteration within IPFP was significantly and positively associated with increases in knee pain when going upstairs/downstairs as well as increases in tibiofemoral cartilage defects and BMLs, and negatively associated with change in lateral tibial cartilage volume in multivariable analyses. IPFP signal intensity alteration at baseline was associated with knee structural abnormalities and clinical symptoms cross-sectionally and longitudinally in older adults, suggesting that it may serve as an important imaging biomarker in knee OA.
Publisher: American Medical Association (AMA)
Date: 08-03-2016
Abstract: Observational studies suggest that vitamin D supplementation is associated with benefits for knee osteoarthritis, but current trial evidence is contradictory. To compare the effects of vitamin D supplementation vs placebo on knee pain and knee cartilage volume in patients with symptomatic knee osteoarthritis and low vitamin D levels. A multicenter randomized, double-blind, placebo-controlled clinical trial in Tasmania and Victoria, Australia. Participants with symptomatic knee osteoarthritis and low 25-hydroxyvitamin D (12.5-60 nmol/L) were enrolled from June 2010 to December 2011. The trial was completed in December 2013. Participants were randomly assigned to receive monthly treatment with oral vitamin D3 (50,000 IU n = 209) or an identical placebo (n = 204) for 2 years. Primary outcomes were change in tibial cartilage volume (assessed using magnetic resonance imaging [MRI]) and change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score (0 [no pain] to 500 [worst pain]) from baseline to month 24. Secondary outcomes were cartilage defects and bone marrow lesions (assessed using MRI). Of 413 enrolled participants (mean age, 63.2 years 50% women), 340 (82.3%) completed the study. The level of 25-hydroxyvitamin D increased more in the vitamin D group (40.6 nmol/L) than in the placebo group (6.7 nmol/L) (P < .001) over 2 years. There were no significant differences in annual change of tibial cartilage volume or WOMAC pain score. There were no significant differences in change of tibiofemoral cartilage defects or change in tibiofemoral bone marrow lesions. Adverse events (≥ 1 per patient) occurred in 56 participants in the vitamin D group and in 37 participants in the placebo group (P = .04). [table: see text]. Among patients with symptomatic knee osteoarthritis and low serum 25-hydroxyvitamin D levels, vitamin D supplementation, compared with placebo, did not result in significant differences in change in MRI-measured tibial cartilage volume or WOMAC knee pain score over 2 years. These findings do not support the use of vitamin D supplementation for preventing tibial cartilage loss or improving WOMAC knee pain in patients with knee osteoarthritis. clinicaltrials.gov Identifier: NCT01176344 anzctr.org.au Identifier: ACTRN12610000495022.
Publisher: SAGE Publications
Date: 2023
DOI: 10.1177/1759720X231158198
Abstract: Osteoarthritis (OA) is the commonest musculoskeletal disease worldwide, with an increasing prevalence due to aging. It causes joint pain and disability, decreased quality of life, and a huge burden on healthcare services for society. However, the current main diagnostic methods are not suitable for early diagnosing patients of OA. The use of machine learning (ML) in OA diagnosis has increased dramatically in the past few years. Hence, in this review article, we describe the research progress in the application of ML in the early diagnosis of OA, discuss the current trends and limitations of ML approaches, and propose future research priorities to apply the tools in the field of OA. Accurate ML-based predictive models with imaging techniques that are sensitive to early changes in OA ahead of the emergence of clinical features are expected to address the current dilemma. The diagnostic ability of the fusion model that combines multidimensional information makes patient-specific early diagnosis and prognosis estimation of OA possible in the future.
Publisher: Elsevier BV
Date: 2023
DOI: 10.1016/J.CCA.2022.11.002
Abstract: The vital metabolic signatures for IA risk stratification and its potential biological underpinnings remain elusive. Our study aimed to develop an early diagnosis model and rupture classification model by analyzing plasma metabolic profiles of IA patients. Plasma s les from a cohort of 105 participants, including 75 IA patients in unruptured and ruptured status (UIA, RIA) and 30 control participants were collected for comprehensive metabolic evaluation using ultra-high-performance liquid chromatography-mass spectrometry-based pseudotargeted metabolomics method. Furthermore, an integrated machine learning strategy based on LASSO, random forest and logistic regression were used for feature selection and model construction. The metabolic profiling disturbed significantly in UIA and RIA patients. Notably, adenosine content was significantly downregulated in UIA, and various glycine-conjugated secondary bile acids were decreased in RIA patients. Enriched KEGG pathways included glutathione metabolism and bile acid metabolism. Two sets of biomarker panels were defined to discriminate IA and its rupture with the area under receiver operating characteristic curve of 0.843 and 0.929 on the validation sets, respectively. The present study could contribute to a better understanding of IA etiopathogenesis and facilitate discovery of new therapeutic targets. The metabolite panels may serve as potential non-invasive diagnostic and risk stratification tool for IA.
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.JOCA.2018.08.011
Abstract: To validate a method to measure the morphological parameters of the proximal tibiofibular joint (PTFJ) in patients with knee osteoarthritis (OA). 408 participants were examined in this cross-sectional subject-based study. We calculated the fibular contacting area of PTFJ (S) and its projection areas onto the horizontal plane (load-bearing area, Sτ), the sagittal plane (lateral stress-bolstering area, Sφ) and the coronal plane (posterior stress-bolstering area, Sυ). Joint space narrowing (JSN) and osteophyte was measured using radiographs. Cartilage defects, bone marrow lesions (BMLs) and cartilage volume were evaluated using magnetic resonance imaging (MRI). The average PTFJ fibular contacting area was 2.4 cm This novel method to assess the morphological parameters of PTFJ in MRI is reproducible. These parameters are associated with knee radiographic and MRI-based OA-related structural abnormalities, suggesting clinical construct validity. Its predictive validity needs to be examined in future longitudinal studies.
Publisher: Wiley
Date: 06-09-2016
DOI: 10.1002/ACR.22834
Abstract: To describe associations between serum high-sensitivity C-reactive protein (hsCRP), knee bone marrow lesions (BMLs), and knee pain, cross-sectionally and longitudinally, in patients with knee osteoarthritis (OA). Patients (n = 192) with symptomatic knee OA (mean age 63 years, range 50-79, women 53%) were assessed at baseline and after 24 months. Serum hsCRP was measured using enzyme-linked immunosorbent assay. Knee BMLs were scored using the modified Whole-Organ Magnetic Resonance Imaging (MRI) Score from T2-weighted fat-supressed fast spin-echo MRI. Knee pain was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index. Quartiles of baseline serum hsCRP were associated with the presence of knee BMLs (prevalence ratio 1.07 per quartile [95% confidence interval (95% CI) 1.00, 1.15]) and total knee pain scores (β 13.66 per quartile [95% CI 2.26, 25.07]) in multivariable analyses. Longitudinally, higher baseline hsCRP was associated with an increase in BML score (risk ratio 1.37 per quartile [95% CI 1.10, 1.70]), and change in hsCRP was positively associated with change in BML score (β 0.19 [95% CI 0.05, 0.34]) in adjusted analyses. Baseline hsCRP was not associated with change in total knee pain, but change in hsCRP was positively and significantly associated with change in total knee pain (β 4.71 [95% CI 0.48, 8.94]). This became nonsignificant after adjustment for changes in BML score. In patients with knee OA, serum hsCRP is associated with knee BML scores and, to a lesser extent, pain both cross-sectionally and longitudinally, suggesting that inflammation is linked with BMLs and their associated pain.
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.JAMDA.2019.07.001
Abstract: Resistin acts as an endogenous ligand of Toll-like receptor (TLR)-4 that triggers major inflammatory pathways and mediates inflammatory processes. The role of resistin in osteoarthritis (OA) pathogenesis is unclear. The aim of this study is to describe the longitudinal associations of serum levels of resistin with knee synovitis measures and structural abnormalities in patients with knee OA. A prospective cohort study. Patients (n = 200) with symptomatic knee OA (mean age 63.1 years, range 49-79 female 46.5%) participated. All measures were performed at baseline and 2 years later. Serum resistin was measured using enzyme-linked immunosorbent assay. Infrapatellar fat pad (IPFP) high signal intensity alteration and effusion synovitis were measured from magnetic resonance imaging (MRI). Knee structures including cartilage volume, cartilage defects, and bone marrow lesions (BMLs) were also assessed by MRI semiquantitatively or quantitatively. Linear or logistic mixed effects regression analyses were used in longitudinal analyses. Serum resistin was positively associated with high signal intensity alteration measures of IPFP as well as the presence [relative risk = 1.06, 95% confidence interval (CI) 1.02, 1.10] and volume (β = 0.77, 95% CI 0.01, 1.53) of effusion synovitis in multivariable analyses. Serum levels of resistin were also positively associated with higher tibiofemoral cartilage defect (β = 1.98, 95% CI 0.34, 3.57) and BML scores (β = 3.18, 95% CI 0.99, 5.37) after adjustment for covariates. Higher serum levels of resistin are associated with knee synovitis surrogate measures and structural abnormalities, suggesting that obesity may promote OA not only by increasing weight loading on joints but also by triggering 1 or more inflammatory pathways.
Publisher: Springer Science and Business Media LLC
Date: 08-09-2022
DOI: 10.1186/S13075-022-02905-8
Abstract: To investigate whether the associations between cartilage defects and cartilage volumes with changes in knee symptoms were mediated by osteophytes. Data from the Vitamin D Effects on Osteoarthritis (VIDEO) study were analyzed as a cohort. The Western Ontario and McMaster Universities Osteoarthritis Index was used to assess knee symptoms at baseline and follow-up. Osteophytes, cartilage defects, and cartilage volumes were measured using magnetic resonance imaging at baseline. Associations between cartilage morphology and changes in knee symptoms were assessed using linear regression models, and mediation analysis was used to test whether these associations were mediated by osteophytes. A total of 334 participants (aged 50 to 79 years) with symptomatic knee osteoarthritis were included in the analysis. Cartilage defects were significantly associated with change in total knee pain, change in weight-bearing pain, and change in non-weight-bearing pain after adjustment for age, sex, body mass index, and intervention. Cartilage volume was significantly associated with change in weight-bearing pain and change in physical dysfunction after adjustment. Lateral tibiofemoral and patellar osteophyte mediated the associations of cartilage defects with change in total knee pain (49–55%) and change in weight-bearing pain (61–62%) and the association of cartilage volume with change in weight-bearing pain (27–30%) and dysfunction (24–25%). Both cartilage defects and cartilage volume had no direct effects on change in knee symptoms. The significant associations between cartilage morphology and changes in knee symptoms were indirect and were partly mediated by osteophytes.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 24-05-2022
DOI: 10.1126/SCISIGNAL.ABM6265
Abstract: Inflammatory cytokine-induced activation of nuclear factor κB (NF-κB) signaling plays a critical role in the pathogenesis of osteoarthritis (OA). We identified PILA as a long noncoding RNA (lncRNA) that enhances NF-κB signaling and OA. The abundance of PILA was increased in damaged cartilage from patients with OA and in human articular chondrocytes stimulated with the proinflammatory cytokine tumor necrosis factor (TNF). Knockdown of PILA inhibited TNF-induced NF-κB signaling, extracellular matrix catabolism, and apoptosis in chondrocytes, whereas ectopic expression of PILA promoted NF-κB signaling and matrix degradation. PILA promoted PRMT1-mediated arginine methylation of DExH-box helicase 9 (DHX9), leading to an increase in the transcription of the gene encoding transforming growth factor β-activated kinase 1 (TAK1), an upstream activator of NF-κB signaling. Furthermore, intra-articular injection of an adenovirus vector encoding PILA triggered spontaneous cartilage loss and exacerbated posttraumatic OA in mice. This study provides insight into the regulation of NF-κB signaling in OA and identifies a potential therapeutic target for this disease.
Publisher: Radiological Society of North America (RSNA)
Date: 09-2022
Publisher: Wiley
Date: 10-2016
DOI: 10.1002/ACR.22871
Abstract: To describe the natural history of patellofemoral (PF) joint bone marrow lesions (BMLs) over 2.6 years and associations between changes in PF joint BMLs, knee pain, and knee cartilage morphology in older adults over 5 years. A prospective population-based cohort study of men and women ages 50-80 years (mean age 63 years, n = 406) was performed. PF joint BMLs, knee cartilage volume, and cartilage defect scores (range 0-4) were measured using the Whole-Organ Magnetic Resonance Imaging Score system at baseline and at 2.6 years. Knee pain was assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores at baseline and at 5 years. At baseline, 27% (n = 109) had PF joint BMLs 24% of these increased (WOMAC score change of ≥1) at followup, 44% persisted, 32% decreased, and 21% resolved completely. Of those without PF joint BMLs at baseline, 20% of participants developed PF joint BMLs over 2.6 years. In multivariable analyses, a change in PF joint BMLs was deleteriously associated with a change in total knee pain (β = 0.67, 95% confidence interval [95% CI] 0.03, 1.31) and knee pain when going up/down stairs (β = 0.24, 95% CI 0.04, 0.44) over 5 years. Baseline PF joint and tibiofemoral joint cartilage volume were protective for PF joint BMLs (relative risk [RR] 0.69, 95% CI 0.52, 0.90 for PF joint), while baseline PF joint cartilage defects were associated with an increase in PF joint BMLs (RR 1.73, 95% CI 1.38, 2.17) over 2.6 years. TF joint cartilage defects were not associated with increases in PF joint BMLs. PF joint BMLs are not static, and change is clinically relevant. PF joint cartilage morphology predicts increases in PF joint BMLs.
Publisher: CMA Impact Inc.
Date: 18-12-2022
DOI: 10.1503/CMAJ.220952
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.JOCA.2016.10.024
Abstract: To describe cross-sectional and longitudinal associations between serum levels of interleukin (IL) - 6, IL-17A, IL-17F, IL-23 and knee bone marrow lesions (BMLs) in patients with knee osteoarthritis (OA). Patients (n = 192) with symptomatic knee OA (mean 63 years, range 50-79, female 53%) were assessed at baseline and after 24 months. At each time point, serum IL-6, IL-17A, IL-17F and IL-23 were measured using Bio-Plex Baseline IL-6 (quarters) were significantly associated with total knee BMLs (P < 0.01 for the trend) as well as associated with an increase in BML score (P = 0.05 for the trend), after adjustment for confounders. Baseline IL-17F and IL-23 (highest quarters vs others) was associated with an increase in BML score in females (P = 0.04 for IL-17F P = 0.01 for IL-23), but not in males, in multivariable analyses. In contrast, IL-17A was not significantly associated with BMLs in either females or males. IL-6 is associated with increased knee BMLs in both females and males with OA. Serum IL-17F and IL-23 predicted increased knee BML scores in females only, suggesting that inflammation is involved in BML pathogenesis in knee OA, especially in women. ClinicalTrials.gov identifier: NCT01176344 Australian New Zealand Clinical Trials Registry: ACTRN12610000495022.
Publisher: Elsevier BV
Date: 05-2021
No related grants have been discovered for Zhaohua Zhu.