With a biomechanical treatment in knee osteoarthritis, less knee pain did not correlate with synovitis reduction.
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ABSTRACT:
SUBMITTER: Swaminathan V
PROVIDER: S-EPMC5553897 | biostudies-other | 2017 Aug
REPOSITORIES: biostudies-other
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Project description:ImportanceIndividually calibrated biomechanical footwear therapy may improve pain and physical function in people with symptomatic knee osteoarthritis, but the benefits of this therapy are unclear.ObjectiveTo assess the effect of a biomechanical footwear therapy vs control footwear over 24 weeks of follow-up.Design, setting, and participantsRandomized clinical trial conducted at a Swiss university hospital. Participants (N = 220) with symptomatic, radiologically confirmed knee osteoarthritis were recruited between April 20, 2015, and January 10, 2017. The last participant visit occurred on August 15, 2017.InterventionsParticipants were randomized to biomechanical footwear involving shoes with individually adjustable external convex pods attached to the outsole (n = 111) or to control footwear (n = 109) that had visible outsole pods that were not adjustable and did not create a convex walking surface.Main outcomes and measuresThe primary outcome was knee pain at 24 weeks of follow-up assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscore standardized to range from 0 (no symptoms) to 10 (extreme symptoms). The secondary outcomes included WOMAC physical function and stiffness subscores and the WOMAC global score, all ranging from 0 (no symptoms) to 10 (extreme symptoms) at 24 weeks of follow-up, and serious adverse events.ResultsAmong the 220 randomized participants (mean age, 65.2 years [SD, 9.3 years]; 104 women [47.3%]), 219 received the allocated treatment and 213 (96.8%) completed follow-up. At 24 weeks of follow-up, the mean standardized WOMAC pain subscore improved from 4.3 to 1.3 in the biomechanical footwear group and from 4.0 to 2.6 in the control footwear group (between-group difference in scores at 24 weeks of follow-up, -1.3 [95% CI, -1.8 to -0.9]; P < .001). The results were consistent for WOMAC physical function subscore (between-group difference, -1.1 [95% CI, -1.5 to -0.7]), WOMAC stiffness subscore (between-group difference, -1.4 [95% CI, -1.9 to -0.9]), and WOMAC global score (between-group difference, -1.2 [95% CI, -1.6 to -0.8]) at 24 weeks of follow-up. Three serious adverse events occurred in the biomechanical footwear group compared with 9 in the control footwear group (2.7% vs 8.3%, respectively); none were related to treatment.Conclusions and relevanceAmong participants with knee pain from osteoarthritis, use of biomechanical footwear compared with control footwear resulted in an improvement in pain at 24 weeks of follow-up that was statistically significant but of uncertain clinical importance. Further research would be needed to assess long-term efficacy and safety, as well as replication, before reaching conclusions about the clinical value of this device.Trial registrationClinicalTrials.gov Identifier: NCT02363712.
| S-EPMC7218497 | biostudies-literature
Project description:BackgroundOsteoarthritis (OA) and lower back pain (LBP) are most common health problems which lead to pain and disability. This study aimed to systematically review the evidence to find any relationship between knee osteoarthritis (KOA) and LBP or any potential causation.MethodsThe databases of Scopus, MEDLINE, and Embase were searched from inception to 01 October 2022. Any study published in English assessing live humans over 18 years with KOA and LBP was eligible to be included. Studies were independently screened by two researchers. Data of the included studies were extracted based on the participants, outcomes related to knee and lumbar spine, reported association or causation between LBP and KOA, and study design. Data were narratively analyzed and presented as graphs and table. Methodology quality was assessed.ResultsOf 9953 titles and abstracts, duplicates were removed, and 7552 were screened. Altogether, 88 full texts were screened, and 13 were eligible for the final inclusion. There were some biomechanical and clinical causations were observed for the concurrent presence of LBP and KOA. Biomechanically, high pelvic incidence is a risk factor for development of spondylolisthesis and KOA. Clinically, knee pain intensity was higher in KOA when presents with LBP. Less than 20% of studies have justified their sample size during the quality assessment.DiscussionDevelopment and progression of KOA in patients with degenerative spondylolisthesis may be induced by significantly greater mismatches of lumbo-pelvic sagittal alignment. Elderly patients with degenerative lumbar spondylolisthesis and severe KOA reported a different pelvic morphology, increased sagittal malalignment with a lack of lumbar lordosis due to double-level listhesis, and greater knee flexion contracture than in patients with no to mild and moderate KOA. People with concurrent LBP and KOA have reported poor function with more disability. Both LBP and lumbar kyphosis indicate functional disability and knee symptoms in patients with KOA.ConclusionsDifferent biomechanical and clinical causations were revealed for the concurrent existence of KOA and LBP. Therefore, careful assessment of both back and knee joints should be considered when treating KOA and vice versa.Systematic review registrationPROSPERO CRD42022238571.
| S-EPMC9979420 | biostudies-literature
Project description:BackgroundThis study aims to investigate the role of the mid-anterior cingulate cortex ?-aminobutyric acid levels in chronic nociceptive pain. The molecular mechanisms of pain chronification are not well understood. In fibromyalgia, low mid-anterior cingulate cortex ?-aminobutyric acid was associated with high pain suggesting a role of prefrontal disinhibition. We hypothesize that mid-anterior cingulate cortex GABAergic disinhibition may underpin chronic pain independent of the pain etiology and comorbid negative affect. Proton magnetic resonance spectra were acquired at 3T from the mid-anterior cingulate cortex in 20 patients with chronic painful knee osteoarthritis, and 19 healthy pain-free individuals using a point resolved spectroscopy sequence optimized for detection of ?-aminobutyric acid. Participants underwent questionnaires for negative affect (depression and anxiety) and psychophysical pain phenotyping.ResultsNo differences in mid-anterior cingulate cortex ?-aminobutyric acid or other metabolite levels were detected between groups. Ratings of perceived intensity of ongoing osteoarthritis pain were inversely correlated with ?-aminobutyric acid (r = -0.758, p < 0.001), but no correlations were seen for negative affect or pain thresholds. The pain ?-aminobutyric acid interrelation remained strong when controlling for depression (r = -0.820, p < 0.001). Combined levels of glutamine and glutamate were unrelated to psychometric or to pain thresholds.ConclusionOur study supports mid-anterior cingulate cortex ?-aminobutyric acid as a potential marker of pain severity in chronic nociceptive pain states independent of negative affect. The findings suggest that GABAergic disinhibition of the salience network may underlie sensitization to averse stimuli as a mechanism contributing to pain chronification.
| S-EPMC4956171 | biostudies-literature
Project description:To investigate the change in clinical outcomes and biomechanical properties of the knee in response to upper partial fibulectomy. Sixteen patients with medial compartment knee osteoarthritis (KOA) underwent upper partial fibulectomy. Visual analog scale (VAS) pain, the hospital for special surgery knee score (HSS), hip-knee-ankle (HKA) angle (measured in the frontal plane), and flexion/extension range of motion of the knee were assessed before and up to 6 months after surgery. Patients were evaluated for gait parameters and overall peak knee adduction moment (KAM). Patient-specific finite element knee models were developed to investigate changes in load in response to fibulectomy. Both VAS pain and HSS score were significantly improved (P < .001) one day after surgery and steadily improved during the subsequent 6 months. HKA angle improved (P = .006) immediately and remained stable by 3 months after surgery. A significant inverse relationship (R = -0.528, P = .012) between the overall peak KAM (decreased by 19.1%) and the HKA (increased by 1.24° from a more varus to more neutral alignment) angle was observed. The minor load supported by the fibula preoperatively was spread post-operatively over the cortical bone of the tibial shaft. The mean stress in the medial tibial plateau was significantly decreased (P < .001), with a portion of the stress transferred to the posterior-lateral region of the tibial plateau after upper partial fibulectomy. This pilot study provides objective 3D gait and plausible biomechanical evidence for the improvement in clinical symptoms from partial upper fibulectomy.
| S-EPMC7426888 | biostudies-literature
Project description:Synovitis contributes to the development of osteoarthritis (OA) of the knee. MicroRNAs regulate joint microenvironment homeostasis and deterioration. This study was undertaken to characterize the actions of microRNA-29a (miR-29a) to synovial remodeling in OA joints. Synovial specimens isolated from patients with end-stage OA knees showed abundant fibrotic matrix and vessel histopathology concomitant with weak miR-29a expression. In vitro, miR-29a knockdown caused synovial fibroblasts to exhibit high expressions of collagen III, TGF-?1, MMP9, MMP13, and ADAMTS5, whereas miR-29a overexpression diminished these joint-deleterious factors. In collagenase-mediated OA pathogenesis, miR-29a-overexpressing transgenic mice showed minor responses to hyperplasia, macrophage infiltration, fibrosis, hyperangiogenesis, and VEGF expression in synovial lesions. These effects mitigated articular cartilage loss and gait aberrance of injured joints. Intra-articular administration of miR-29a precursor lessened the collagenase aggravation of excessive synovial remodeling reactions and thereby sustained joint tissue integrity. miR-29a lowered VEGF production and angiogenic activities in synovial fibroblasts through targeting the 3'-UTR of VEGF. Taken together, miR-29a deficiency exacerbated synovitis pathogenesis in the end-stage OA knees. miR-29a signaling fends off excessive synovial angiogenesis and fibrosis, which delays joint destruction. This study sheds new light on the protective effects against synovial deterioration and the therapeutic advantage of miR-29a in OA knees.
| S-EPMC5472675 | biostudies-literature
Project description:Objectives : Joint pain causes a significant morbidity in osteoarthritis (OA). The synovium as an innervated joint structure might contribute to the peripheral pain in OA. Methods : We used a hypothesis-free next generation RNA sequencing to study protein coding and small non-coding transcriptomes in knee synovial tissues of OA patients (n=10) with high and low knee pain (evaluated by visual analogue scale) followed by Gene Ontology (GO) and pathway analyses and integration of mRNAs and small RNAs data sets. Results : We showed that 33 protein-coding genes and 35 small RNAs were differentially expressed in the knee synovium of patients with high compared to low intensity knee pain, with 30 mRNAs and 14 small RNAs being upregulated and 2 mRNAs and 21 small RNAs being downregulated. Top enriched genes, such as SDIM1 and CPE encode neuronal proteins that share molecular properties with neurotrophic factor BDNF and promote neuronal survival under cellular stress, and OTOF participates in calcium-dependent synaptic exocytosis and modulation of GABAergic activity. TrkB was enriched in several gene networks, suggesting its key role in pain-related transcriptional changes in OA joint. Downregulation of PTX3 in high pain group supports an argument that inflammation and pain are independent processes in symptomatic knee OA. MiR-146a-3p and miR150 appeared as the microRNA candidates in the pathogenesis of OA-related knee pain. Conclusions : Here we uncovered the molecular complexity of pain-related transcriptome changes in the synovium of knee joints in osteoarthritis. We identified new molecular candidates in OA pain setting a firm ground for future mechanistic studies and drug discovery in OA.
2018-11-05 | GSE99662 | GEO
Project description:BackgroundIncreased expression of nerve growth factor in injured or inflamed tissue is associated with increased pain. This proof-of-concept study was designed to investigate the safety and analgesic efficacy of tanezumab, a humanized monoclonal antibody that binds and inhibits nerve growth factor.MethodsWe randomly assigned 450 patients with osteoarthritis of the knee to receive tanezumab (administered at a dose of 10, 25, 50, 100, or 200 μg per kilogram of body weight) or placebo on days 1 and 56. The primary efficacy measures were knee pain while walking and the patient's global assessment of response to therapy. We also assessed pain, stiffness, and physical function using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); the rate of response using the criteria of the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI); and safety.ResultsWhen averaged over weeks 1 through 16, the mean reductions from baseline in knee pain while walking ranged from 45 to 62% with various doses of tanezumab, as compared with 22% with placebo (P<0.001). Tanezumab, as compared with placebo, was also associated with significantly greater improvements in the response to therapy as assessed with the use of the patients' global assessment measure (mean increases in score of 29 to 47% with various doses of tanezumab, as compared with 19% with placebo; P≤0.001). The rate of response according to the OMERACT-OARSI criteria ranged from 74 to 93% with tanezumab treatment, as compared with 44% with placebo (P<0.001). The rates of adverse events were 68% and 55% in the tanezumab and placebo groups, respectively. The most common adverse events among tanezumab-treated patients were headache (9% of the patients), upper respiratory tract infection (7%), and paresthesia (7%).ConclusionsIn this proof-of-concept study, treatment with tanezumab was associated with a reduction in joint pain and improvement in function, with mild and moderate adverse events, among patients with moderate-to-severe osteoarthritis of the knee. (Funded by Rinat Neuroscience; ClinicalTrials.gov number, NCT00394563.).
| S-EPMC6896791 | biostudies-literature
Project description:ObjectivesTo determine whether greater effusion-synovitis volume and infrapatellar fat pad (IFP) signal intensity alteration differentiate incident accelerated knee OA (KOA) from a gradual onset of KOA or no KOA.MethodsWe classified three sex-matched groups of participants in the Osteoarthritis Initiative who had a knee with no radiographic KOA at baseline (recruited 2004-06; Kellgren-Lawrence <2; n = 125/group): accelerated KOA: ⩾1 knee progressed to Kellgren-Lawrence grade ⩾3 within 48 months; common KOA: ⩾1 knee increased in radiographic scoring within 48 months; and no KOA: both knees had the same Kellgren-Lawrence grade at baseline and 48 months. The observation period included up to 2 years before and after when the group criteria were met. Two musculoskeletal radiologists reported presence of IFP signal intensity alteration and independent readers used a semi-automated method to segment effusion-synovitis volume. We used generalized linear mixed models with group and time as independent variables, as well as testing a group-by-time interaction.ResultsStarting at 2 years before disease onset, adults who developed accelerated KOA had greater effusion-synovitis volume than their peers (accelerated KOA: 11.94 ± 0.90 cm3, KOA: 8.29 ± 1.19 cm3, no KOA: 8.14 ± 0.90 cm3) and have greater odds of having IFP signal intensity alteration than those with no KOA (odds ratio = 2.07, 95% CI = 1.14-3.78). Starting at 1 year prior to disease onset, those with accelerated KOA have greater than twice the odds of having IFP signal intensity alteration than those with common KOA.ConclusionPeople with IFP signal intensity alteration and/or greater effusion-synovitis volume in the absence of radiographic KOA may be at high risk for accelerated KOA, which may be characterized by local inflammation.
| S-EPMC6381765 | biostudies-literature
Project description:The purpose of this study was to clarify the histological effect of reducing the loading to knee on cartilage degeneration, osteophyte formation, and synovitis in early-stage osteoarthritis (OA) using a post-traumatic rat model. Ten male rats were randomly allocated into two experimental groups: OA induction by surgical destabilization of medial meniscus (DMM, OA group) and hindlimb suspension after OA induction by DMM (OAHS group). The articular cartilage, osteophyte formation, and synovial membrane in the medial tibiofemoral joint were analyzed histologically and histomorphometrically at 2 and 4 weeks after surgery. The histological scores and changes in articular cartilage and osteophyte formation were significantly milder and slower in the OAHS group than in the OA group. At 2 and 4 weeks, there were no significant differences in cartilage thickness and matrix staining intensity between both the groups, but chondrocytes density was significantly lower in the OA group. Synovitis was milder in OAHS group than in OA group at 2 weeks. Reducing knee joint loading inhibited histological OA changes in articular cartilage, osteophyte formation, and synovial inflammation. This result supports the latest clinical guidelines for OA treatment. Further studies using biochemical and mechanical analyses are necessary to elucidate the mechanism underlying delayed OA progression caused by joint-load reduction.
| S-EPMC8284605 | biostudies-literature
Project description:BackgroundThis study examined the effect of treatment with a novel biomechanical device on the level of pain and function in patients with knee OA.MethodsPatients with bilateral knee OA were enrolled to active and control groups. Patients were evaluated at baseline, at 4 weeks and at the 8-week endpoint. A novel biomechanical device was individually calibrated to patients from the active group. Patients from the control group received an identical foot-worn platform without the biomechanical elements. Primary outcomes were the WOMAC Index and ALF assessments.ResultsThere were no baseline differences between the groups. At 8 weeks, the active group showed a mean improvement of 64.8% on the WOMAC pain scale, a mean improvement of 62.7% on the WOMAC function scale, and a mean improvement of 31.4% on the ALF scale. The control group demonstrated no improvement in the above parameters. Significant differences were found between the active and control groups in all the parameters of assessment.ConclusionsThe biomechanical device and treatment methodology is effective in significantly reducing pain and improving function in knee OA patients.The study is registered at clinicaltrials.gov, identifier NCT00457132, http://www.clinicaltrials.gov/ct/show/NCT00457132?order=1.
| S-EPMC2928172 | biostudies-literature