Evidence and mechanism by which upper partial fibulectomy improves knee biomechanics and decreases knee pain of osteoarthritis.
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ABSTRACT:
SUBMITTER: ZeYu Huang YN
PROVIDER: S-EPMC7480762 | biostudies-literature | 2018 Feb
REPOSITORIES: biostudies-literature
Publications
Evidence and mechanism by which upper partial fibulectomy improves knee biomechanics and decreases knee pain of osteoarthritis.
ZeYu Huang Yong Nie YN Xu Bin B Shen Bin B Kraus Virginia B VB Pei FuXing F
Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20180209
To investigate the change in short-term clinical outcomes and biomechanical properties of the knee in response to upper partial fibulectomy and to probe into the biomechanical mechanism underlying the clinical benefits of upper partial fibulectomy for medial compartment knee osteoarthritis (KOA). A total of 29 patients with medial compartment KOA underwent upper partial fibulectomy. Visual analog scale (VAS) pain, the hospital for special surgery knee score (HSS), hip-knee-ankle (HKA) angle (mea ...[more]
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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:BackgroundPain from osteoarthritis (OA) is one of the top causes of disability worldwide, but effective treatment is lacking. Nociceptive factors are released by activated synovial macrophages in OA, but depletion of synovial macrophages paradoxically worsens inflammation and tissue damage in previous studies. Rather than depleting macrophages, we hypothesized that inhibiting macrophage activation may improve pain without increasing tissue damage. We aimed to identify key mechanisms mediating synovial macrophage activation and test the role of STAT signaling in macrophages on pain outcomes in experimental knee OA.MethodsWe induced experimental knee OA in rats via knee destabilization surgery, and performed RNA sequencing analysis on sorted synovial tissue macrophages to identify macrophage activation mechanisms. Liposomes laden with STAT1 or STAT6 inhibitors, vehicle (control), or clodronate (depletion control) were delivered selectively to synovial macrophages via serial intra-articular injections up to 12 weeks after OA induction. Treatment effects on knee and hindpaw mechanical pain sensitivity were measured during OA development, along with synovitis, cartilage damage, and synovial macrophage infiltration using histopathology and immunofluorescence. Lastly, crosstalk between drug-treated synovial tissue and articular chondrocytes was assessed in co-culture.ResultsThe majority of pathways identified by transcriptomic analyses in OA synovial macrophages involve STAT signaling. As expected, macrophage depletion reduced pain, but increased synovial tissue fibrosis and vascularization. In contrast, STAT6 inhibition in macrophages led to marked, sustained improvements in mechanical pain sensitivity and synovial inflammation without worsening synovial or cartilage pathology. During co-culture, STAT6 inhibitor-treated synovial tissue had minimal effects on healthy chondrocyte gene expression, whereas STAT1 inhibitor-treated synovium induced changes in numerous cartilage turnover-related genes.ConclusionThese results suggest that STAT signaling is a major mediator of synovial macrophage activation in experimental knee OA. STAT6 may be a key mechanism mediating the release of nociceptive factors from macrophages and the development of mechanical pain sensitivity. Whereas therapeutic depletion of macrophages paradoxically increases inflammation and fibrosis, blocking STAT6-mediated synovial macrophage activation may be a novel strategy for OA-pain management without accelerating tissue damage.
| S-EPMC10953260 | biostudies-literature
Project description:Different profiles of pain progression have been reported in patients with knee osteoarthritis (OA), but the determinants of this heterogeneity are still to be sought. The aim of this systematic review was to analyze all studies providing information about knee OA pain trajectories to delineate, according to patients' characteristics, an evidence-based evolution pattern of this disabling disease, which is key for a more personalized and effective management of knee OA. A literature search was performed on PubMed, Web of Science, Cochrane Library, and grey literature databases. The Cochrane Collaboration's tool for assessing risk of bias was used, and a best-evidence synthesis was performed to define the predictors of pain evolution. Seven articles on 7747 patients affected by knee OA (mainly early/moderate) were included. Daily knee OA pain trajectories were unstable in almost half of the patients. In the mid-term, knee OA had a steady pain trajectory in 85% of the patients, 8% experienced pain reduction, while 7% experienced pain worsening. Low education, comorbidities, and depression were patient-related predictors of severe/worsening knee OA pain. Conversely, age, alcohol, smoking, pain coping strategies, and medications were unrelated to pain evolution. Conflicting/no evidence was found for all joint-related factors, such as baseline radiographic severity.
| S-EPMC7564930 | 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:IntroductionOsteoarthritis of the knee affects millions of people. Elastic knee sleeves aim at relieving symptoms. While symptomatic improvements have been demonstrated as a consequence of elastic knee sleeves, evidence for biomechanical alterations only exists for the sagittal plane. We therefore asked what effect an elastic knee sleeve would have on frontal plane gait biomechanics.Methods18 subjects (8 women, 10 men) with osteoarthritis of the medial tibiofemoral joint walked over ground with and without an elastic knee sleeve. Kinematics and forces were recorded and joint moments were calculated using an inverse dynamics approach. Conditions with sleeve and without sleeve were compared with paired t-Tests.ResultsWith the sleeve, knee adduction angle at ground contact was reduced by 1.9 ± 2.1° (P = 0.006). Peak knee adduction was reduced by 1.5 ± 1.6° (P = 0.004). The first peak knee adduction moment and positive knee adduction impulse were decreased by 10.1% (0.74 ± 0.9 Nm • kg-1; P = 0.002) and 12.9% (0.28 ± 0.3 Nm • s • kg-1; P < 0.004), respectively.ConclusionOur study provides evidence that wearing an elastic knee sleeve during walking can reduce knee adduction angles, moments and impulse in subjects with knee osteoarthritis. As a higher knee adduction moment has previously been identified as a risk factor for disease progression in patients with medial knee osteoarthritis, we speculate that wearing a knee sleeve may be beneficial for this specific subgroup.
| S-EPMC4306516 | biostudies-literature
Project description:CONTEXT: Knee injuries are prevalent, and the associated knee pain is linked to disability. The influence of knee pain on movement biomechanics, independent of other factors related to knee injuries, is difficult to study and unclear. OBJECTIVE: (1) To evaluate a novel experimental knee-pain model and (2) better understand the independent effects of knee pain on walking and running biomechanics. DESIGN: Crossover study. SETTING: Biomechanics laboratory. PATIENTS OR OTHER PARTICIPANTS: Twelve able-bodied volunteers (age = 23 ± 3 years, height = 1.73 ± 0.09 m, mass = 75 ± 14 kg). INTERVENTION(S): Participants walked and ran at 3 time intervals (preinfusion, infusion, and postinfusion) for 3 experimental conditions (control, sham, and pain). During the infusion time interval for the pain and sham conditions, hypertonic or isotonic saline, respectively, was continuously infused into the right infrapatellar fat pad for 22 minutes. MAIN OUTCOME MEASURE(S): We used repeated-measures analyses of variance to evaluate the effects of time and condition on (1) perceived knee pain and (2) key biomechanical characteristics (ground reaction forces, and joint kinematics and kinetics) of walking and running (P < .05). RESULTS: The hypertonic saline infusion (1) increased perceived knee pain throughout the infusion and (2) reduced discrete characteristics of each component of the walking ground reaction force, walking peak plantar-flexion angle (range = 62°-67°), walking peak plantar-flexion moment (range = 95-104 N·m), walking peak knee-extension moment (range = 36-49 N·m), walking peak hip-abduction moment (range = 62-73 N·m), walking peak support moment (range = 178-207 N·m), running peak plantar-flexion angle (range = 38°-77°), and running peak hip-adduction angle (range = 5-21°). CONCLUSIONS: This novel experimental knee pain model consistently increased perceived pain during various human movements and produced altered running and walking biomechanics that may cause abnormal knee joint-loading patterns.
| S-EPMC3655747 | biostudies-other
Project description:BackgroundRecent studies indicate that the administration of open-label placebos (OLP) can improve symptoms in various medical conditions. The primary aim of this 3-week randomized controlled trial was to examine the effects of OLP treatments on pain, functional disability, and mobility in patients with arthritic knee pain.MethodsSixty patients (55% females; mean age, 66.9 ± 9.7 SD years) were randomized to one of two OLP treatments (n = 41) or no treatment (NT; n = 19). OLP treatments were accompanied by the verbal suggestion "to decrease pain" (OLP-pain, n = 20) or "to improve mood" (OLP-mood, n = 21). Pain and mood levels were monitored on 11-point Numeric Rating Scales (NRSs) in a patient diary, and global clinical improvement (CGI-I) was assessed at the end of the study. At baseline and after 21 days, patients filled in validated questionnaires to assess symptoms and functional disability of the knee (WOMAC), mental and physical quality of life (SF-36), state anxiety (STAI-state), perceived stress (PSQ-20), and self-efficacy (GSE). In addition, knee mobility (neutral zero-method), heart rate variability (HRV), and diurnal cortisol levels were evaluated before and after treatment.ResultsEvaluation of daily pain ratings indicated significant pain decrease in the OLP groups compared to NT (p = 0.013, d = 0.64), with no difference between the OLP-pain and the OLP-mood groups (p = 0.856, d = 0.05). OLP treatment also improved WOMAC pain (p = 0.036, d = 0.55), again with no difference between the two OLP groups (p = 0.65, d = 0.17). WOMAC function and stiffness, knee mobility, stress, state anxiety, quality of life, and self-efficacy did not change differently between groups.ConclusionOLP treatment improved knee pain in elderly patients with symptomatic knee osteoarthritis (OA), while functional disability and mobility of the knee did not change. The content of the verbal suggestion was of minor importance. OLP administration may be considered as supportive analgesic treatment in elderly patients with symptomatic knee OA.Trial registrationGerman Clinical Trials Register (https://www.drks.de/), DRKS00015191 (retrospectively registered).
| S-EPMC9122028 | biostudies-literature
Project description:ObjectiveTo compare sagittal walking gait biomechanics between participants with knee osteoarthritis (KOA) who increased quadriceps strength following a lower-extremity strengthening intervention (responders) and those who did not increase strength following the same strengthening protocol (non-responders) both at baseline and following the lower extremity strengthening protocol.DesignFifty-three participants with radiographic KOA (47% female, 62.3 ± 7.1 years, BMI = 28.5 ± 3.9 kg/m2) were enrolled in 10 sessions of lower extremity strengthening over a 28-day period. Maximum isometric quadriceps strength and walking gait biomechanics were collected on the involved limb at baseline and 4-weeks following the strengthening intervention. Responders were classified as individuals who increased quadriceps strength greater than the upper limit of the 95% confidence interval (CI) for the minimal detectable change (MDC) in quadriceps strength (29 Nm) determined in a previous study. 2 × 2 functional analyses of variance were used to evaluate the effects of group (responders and non-responders) and time (baseline and 4-weeks) on time-normalized waveforms for knee flexion angle (KFA), vertical ground reaction force (vGRF), and internal knee extension moment (KEM).ResultsA significant group x time interaction for KFA demonstrated greater KFA in the first half of stance at baseline and greater knee extension in the second half of stance at 4-weeks in responders compared to non-responders. There was no significant group x time interaction for vGRF or internal KEM.ConclusionsQuadriceps strengthening may be used to stimulate small changes in KFA in individuals with KOA.
| S-EPMC6475608 | biostudies-literature
Project description:Osteoarthritis (OA), the most common form of arthritis, is a significant public health burden in U.S. adults. Among its many risk factors, obesity is a key player, causing inflammation, pain, impaired joint function, and reduced quality of life. Dietary polyphenols and other bioactive compounds in berries, curcumin, and tea have shown effects in ameliorating pain and inflammation in OA, but few clinical studies have been reported. The purpose of the present study was to examine the effects of dietary strawberries on pain, markers of inflammation, and quality of life indicators in obese adults with OA of the knee. In a randomized, double-blind cross-over trial, adults with radiographic evidence of knee OA (n = 17; body mass index (BMI): (mean ± SD) 39.1 ± 1.5; age (years): 57 ± 7) were randomized to a reconstituted freeze-dried strawberry beverage (50 g/day) or control beverage daily, each for 12 weeks, separated by a 2-week washout phase (total duration, 26 weeks). Blood draws and assessments of pain and quality of life indicators were conducted using the Visual Analog Scale for Pain (VAS Pain), Measures of Intermittent and Constant Osteoarthritis Pain (ICOAP), and Health Assessment Questionnaire-Disability Index (HAQ-DI) questionnaires, which were completed at baseline and at weeks 12, 14, and 26 of the study. Among the serum biomarkers of inflammation and cartilage degradation, interleukin (IL)-6, IL-1?, and matrix metalloproteinase (MMP)-3 were significantly decreased after strawberry vs. control treatment (all p < 0.05). Strawberry supplementation also significantly reduced constant, intermittent, and total pain as evaluated by the ICOAP questionnaire as well as the HAQ-DI scores (all p < 0.05). No effects of treatment were noted on serum C-reactive protein (CRP), nitrite, glucose, and lipid profiles. Dietary strawberries may have significant analgesic and anti-inflammatory effects in obese adults with established knee OA.
| S-EPMC5622709 | biostudies-literature
Project description:ObjectiveChronic pain due to osteoarthritis (OA) is a major clinical problem, and existing analgesics often have limited beneficial effects and/or adverse effects, necessitating the development of novel therapies. Epoxyeicosatrienoic acids (EETs) are endogenous antiinflammatory mediators, rapidly metabolized by soluble epoxide hydrolase (EH) to dihydroxyeicosatrienoic acids (DHETs). We undertook this study to assess whether soluble EH-driven metabolism of EETs to DHETs plays a critical role in chronic joint pain associated with OA and provides a new target for treatment.MethodsPotential associations of chronic knee pain with single-nucleotide polymorphisms (SNPs) in the gene-encoding soluble EH and with circulating levels of EETs and DHETs were investigated in human subjects. A surgically induced murine model of OA was used to determine the effects of both acute and chronic selective inhibition of soluble EH by N-[1-(1-oxopropy)-4-piperidinyl]-N'-(trifluoromethoxy)phenyl]-urea (TPPU) on weight-bearing asymmetry, hind paw withdrawal thresholds, joint histology, and circulating concentrations of EETs and DHETs.ResultsIn human subjects with chronic knee pain, 3 pain measures were associated with SNPs of the soluble EH gene EPHX2, and in 2 separate cohorts of subjects, circulating levels of EETs and DHETs were also associated with 3 pain measures. In the murine OA model, systemic administration of TPPU both acutely and chronically reversed established pain behaviors and decreased circulating levels of 8,9-DHET and 14,15-DHET. EET levels were unchanged by TPPU administration.ConclusionOur novel findings support a role of soluble EH in OA pain and suggest that inhibition of soluble EH and protection of endogenous EETs from catabolism represents a potential new therapeutic target for OA pain.
| S-EPMC8957539 | biostudies-literature