Osteoarthritis patients exhibit an autonomic dysfunction with indirect sympathetic dominance.

BACKGROUND: Osteoarthritis (OA) is a chronic degenerative joint disease causing limited mobility and pain, with no curative treatment available. Recent in vivo studies suggested autonomic alterations during OA progression in patients, yet clinical evidence is scarce. Therefore, autonomic tone was analyzed in OA patients via heart rate variability (HRV) measurements. METHODS: Time-domain (SDRR, RMSSD, pRR50) and frequency-domain (LF, HF, LF/HF) HRV indices were determined to quantify sympathetic and parasympathetic activities. In addition, perceived stress, WOMAC pain as well as serum catecholamines, cortisol and dehydroepiandrosterone-sulphate (DHEA-S) were analyzed. The impact of the grade of disease (GoD) was evaluated by linear regression analysis and correlations with clinical data were performed. RESULTS: GoD significantly impacted the autonomic tone in OA patients. All time-domain parameters reflected slightly decreased HRV in early OA patients and significantly reduced HRV in late OA patients. Moreover, frequency-domain analysis revealed decreased HF and LF power in all OA patients, reflecting diminished parasympathetic and sympathetic activities. However, LF/HF ratio was significantly higher in early OA patients compared to late OA patients and implied a clear sympathetic dominance. Furthermore, OA patients perceived significantly higher chronic stress and WOMAC pain levels compared to healthy controls. Serum cortisol and cortisol/DHEA-S ratio significantly increased with GoD and positively correlated with WOMAC pain. In contrast, serum catecholamines only trended to increase with GoD and pain level. CONCLUSIONS: This prospective study provides compelling evidence of an autonomic dysfunction with indirect sympathetic dominance in early and late knee OA patients for the first time based on HRV analyses and further confirmed by serum stress hormone measurements. Increased sympathetic activity and chronic low-grade inflammation in OA as well as in its major comorbidities reinforce each other and might therefore create a vicious cycle. The observed autonomic alterations coupled with increased stress and pain levels highlight the potential of HRV as a prognostic marker. In addition, modulation of autonomic activity represents an attractive future therapeutic option.

Three-dimensional motion analysis of pre- and postoperative thumb movement in trapeziometacarpal joint osteoarthritis-Comparison of arthrodesis and trapeziectomy with suspensionplasty.

Trapeziometacarpal osteoarthritis (TMC-OA) reduces the range of motion (ROM) of the thumb. However, the kinematic change achieved through surgical treatment remains unclear. Therefore, to quantify the kinematic change following TMC-OA surgery, we performed a three-dimensional motion analysis of the thumb using an optical motion capture system preoperatively and 1 year postoperatively in 23 patients with TMC-OA scheduled for arthrodesis (AD) or trapeziectomy with suspensionplasty (TS). Eighteen hands of nine healthy volunteers were also included as controls. Both procedures improved postoperative pain and Disability of the Arm, Shoulder and Hand scores, and AD increased pinch strength. The ROM of the base of the thumb was preserved in AD, which was thought to be due to the appearance of compensatory movements of adjacent joints even if the ROM of the TMC joint was lost. TS did not improve ROM. Quantifying thumb kinematic changes following TMC-OA surgery can improve our understanding of TMC-OA treatment and help select surgical procedures and postoperative assessment.

Three-Dimensional Printed Total Talus Replacement with a Concurrent Total Ankle Arthroplasty as a Personalized Approach for Advanced Ankle Osteoarthritis A Case Repor.

Ankle arthritis is becoming more common and can be pain-ful and debilitating. As the disease progresses, degenera-tive cystic changes may be found in the distal fibula, distal tibia, and talus. After failure of non-operative modalities, arthrodesis is often considered the surgical intervention of choice, but this leaves the patient with reduced range of motion, altered gait, and can negatively impact adjacent joints of the foot. Total ankle arthroplasty has been found to be an effective surgical option for ankle arthritis but is contraindicated in patients with talar collapse. When this is the case, a more personalized approach for preserving ankle motion is necessary. We present the case of a 65-year-old male with severe right ankle arthritis and talar collapse treated with a custom three-dimensionally printed talus and concurrent total ankle replacement with 2-year follow-up.

Reverse total shoulder arthroplasty for primary osteoarthritis with restricted preoperative forward elevation demonstrates similar outcomes but faster range of motion recovery compared to anatomic total shoulder arthroplasty.

BACKGROUND: Reverse total shoulder arthroplasty (RSA) has been increasingly utilized for a variety of shoulder pathologies that are difficult to treat with anatomical total shoulder arthroplasty (TSA). Few studies have compared the outcomes of TSA vs. RSA in patients with cuff intact glenohumeral osteoarthritis and poor preoperative forward elevation. This study aimed to determine whether there is a difference in functional outcomes and postoperative range of motion (ROM) between TSA and RSA in these patients. METHODS: This retrospective cohort study included 116 patients who underwent RSA or TSA between 2013 and 2022 for the treatment of rotator cuff intact primary osteoarthritis with restricted preoperative forward flexion (FF) and a minimum 1-year follow-up. Each arthroplasty group was divided into 2 subgroups: patients with preoperative FF between 91° and 120° or FF lower than or equal to 90°. Patients' clinical outcomes, including active ROM, American Shoulder and Elbow Surgeons score, visual analog scale for pain, and subjective shoulder value were collected. Clinical and radiographic complications were evaluated. RESULTS: There was no significant difference between RSA and TSA in terms of sex (58.3% male vs. 62.2% male, P = .692), or follow-up duration (20.1 months vs. 17.7 months, P = .230). However, the RSA cohort was significantly older (72.0 ± 8.2 vs. 65.4 ± 10.6, P = .012) and weaker in FF and (ER) before surgery (P < .001). There was no difference between RSA (57 patients) and TSA (59 patients) in visual analog scale pain score (1.2 ± 2.3 vs. 1.3 ± 2.3, P = .925), subjective shoulder value score (90 ± 15 vs. 90 ± 15, P = .859), or American Shoulder and Elbow Surgeons score (78.4 ± 20.5 vs. 82.1 ± 23.2, P = .476). Postoperative active ROM was statistically similar between RSA and TSA cohorts in FF (145 ± 26 vs. 146 ± 23, P = .728) and ER (39 ± 15 vs. 41 ± 15, P = .584). However, internal rotation was lower in the RSA cohort (P < .001). This was also true in each subgroup. RSA led to faster postoperative FF and ER achievement at 3 months (P < .001). There was no statistically significant difference in complication rates between cohorts. CONCLUSION: This study demonstrates that patients with glenohumeral osteoarthritis who have a structurally intact rotator cuff but limited preoperative forward elevation can achieve predictable clinical improvement in pain, ROM, and function after either TSA or RSA. Reverse arthroplasty may be a reliable treatment option in patients at risk for developing rotator cuff failure.

Erosive hand osteoarthritis and sarcopenia: data from Osteoarthritis Initiative cohort.

OBJECTIVES: There is no evidence linking specific osteoarthritis (OA) types, such as erosive hand OA (EHOA), with distant generalised changes in muscle composition (sarcopenia), which can potentially be modified. This study pioneers the exploration of the association between EHOA and sarcopenia, both of which are predominantly observed in the older adults. METHODS: Using the Osteoarthritis Initiative cohort, we selected hand OA (modified Kellgren and Lawrence (grade ≥2 in ≥1 hand joint) participants with radiographic central erosions in ≥1 joints (EHOA group) and propensity score-matched hand OA participants with no erosion (non-EHOA group). MRI biomarkers of thigh muscles were measured at baseline, year 2 and year 4 using a validated deep-learning algorithm. To adjust for 'local' effects of coexisting knee OA (KOA), participants were further stratified according to presence of radiographic KOA. The outcomes were the differences between EHOA and non-EHOA groups in the 4-year rate of change for both intramuscular adipose tissue (intra-MAT) deposition and contractile (non-fat) area of thigh muscles. RESULTS: After adjusting for potential confounders, 844 thighs were included (211 EHOA:633 non-EHOA; 67.1±7.5 years, female/male:2.9). Multilevel mixed-effect regression models showed that EHOA is associated a different 4-year rate of change in intra-MAT deposition (estimate, 95% CI: 71.5 mm2/4 years, 27.9 to 115.1) and contractile area (estimate, 95% CI: -1.8%/4 years, -2.6 to -1.0) of the Quadriceps. Stratified analyses showed that EHOA presence is associated with adverse changes in thigh muscle quality only in participants without KOA. CONCLUSIONS: EHOA is associated with longitudinal worsening of thigh muscle composition only in participants without concomitant KOA. Further research is needed to understand the systemic factors linking EHOA and sarcopenia, which unlike EHOA is modifiable through specific interventions.

LncNFYB promotes the proliferation of rheumatoid arthritis fibroblast-like synoviocytes via LncNFYB/ANXA2/ERK1/2 axis.

Long noncoding RNAs (lncRNAs) are specifically expressed in different diseases and regulate disease progression. To explore the functions of rheumatoid arthritis (RA)-specific lncRNA, we determined the lncRNA expression profile of fibroblast-like synoviocytes (FLS) obtained from patients with RA and osteoarthritis (OA) using a LncRNA microarray and identified up-regulated LncNFYB in RA as a potential therapeutic target. Using gain- and loss-of-function studies, LncNFYB was proven to promote FLS proliferation and cell cycle progress but not affect their invasion, migration, and apoptotic abilities. Further investigation discovered that LncRNA could combine with annexin A2 (ANXA2) and enhance the level of phospho-ANXA2 (Tyr24) in the plasma membrane area, which induced the activation of ERK1/2 to promote proliferation. These findings provide new insights into the biological functions of LncNFYB on modification of FLS, which may be exploited for the therapy of RA.

Toward Early and Objective Hand Osteoarthritis Detection by Using EMG during Grasps.

The early and objective detection of hand pathologies is a field that still requires more research. One of the main signs of hand osteoarthritis (HOA) is joint degeneration, which causes loss of strength, among other symptoms. HOA is usually diagnosed with imaging and radiography, but the disease is in an advanced stage when HOA is observable by these methods. Some authors suggest that muscle tissue changes seem to occur before joint degeneration. We propose recording muscular activity to look for indicators of these changes that might help in early diagnosis. Muscular activity is often measured using electromyography (EMG), which consists of recording electrical muscle activity. The aim of this study is to study whether different EMG characteristics (zero crossing, wavelength, mean absolute value, muscle activity) via collection of forearm and hand EMG signals are feasible alternatives to the existing methods of detecting HOA patients' hand function. We used surface EMG to measure the electrical activity of the dominant hand's forearm muscles with 22 healthy subjects and 20 HOA patients performing maximum force during six representative grasp types (the most commonly used in ADLs). The EMG characteristics were used to identify discriminant functions to detect HOA. The results show that forearm muscles are significantly affected by HOA in EMG terms, with very high success rates (between 93.3% and 100%) in the discriminant analyses, which suggest that EMG can be used as a preliminary step towards confirmation with current HOA diagnostic techniques. Digit flexors during cylindrical grasp, thumb muscles during oblique palmar grasp, and wrist extensors and radial deviators during the intermediate power-precision grasp are good candidates to help detect HOA.

Healthy working life expectancy at age 50 for people with and without osteoarthritis in local and national English populations.

Retirement ages are rising in many countries to offset the challenges of population ageing, but osteoarthritis is an age-associated disease that is becoming more prevalent and may limit capacity to work until older ages. We aimed to assess the impact of osteoarthritis on healthy working life expectancy (HWLE) by comparing HWLE for people with and without osteoarthritis from ages 50 and 65 nationally and in a local area in England. Mortality-linked data for adults aged ≥ 50 years were used from six waves (2002-13) of the English Longitudinal Study of Ageing and from three time points of the North Staffordshire Osteoarthritis Project. HWLE was defined as the average number of years expected to be spent healthy (no limiting long-standing illness) and in paid work (employment or self-employment), and was estimated for people with and without osteoarthritis and by sex and occupation type using interpolated Markov chain multi-state modelling. HWLE from age 50 years was a third lower for people with osteoarthritis compared to people without osteoarthritis both nationally (5.68 95% CI [5.29, 6.07] years compared to 10.00 [9.74, 10.26]) and in North Staffordshire (4.31 [3.68, 4.94] years compared to 6.90 [6.57, 7.24]). HWLE from age 65 years for self-employed people with osteoarthritis exceeded HWLE for people without osteoarthritis in manual or non-manual occupations. Osteoarthritis was associated with a significantly shorter HWLE. People with osteoarthritis are likely to have significantly impaired working ability and capacity to work until older ages, especially in regions with poorer health and work outcomes.

Gait analysis as a robust pain behavioural endpoint in the chronic phase of the monoiodoacetate-induced knee joint pain in the rat.

The monoiodoacetate-induced rat model of osteoarthritis knee pain is widely used. However, there are between-study differences in the pain behavioural endpoints assessed and in the dose of intraarticular monoiodoacetate administered. This study evaluated the robustness of gait analysis as a pain behavioural endpoint in the chronic phase of this model, in comparison with mechanical hyperalgesia in the injected (ipsilateral) joint and development of mechanical allodynia in the ipsilateral hind paws. Groups of Sprague-Dawley rats received a single intraarticular injection of monoiodoacetate at 0.5, 1, 2 or 3 mg or vehicle (saline) into the left (ipsilateral) knee joint. An additional group of rats were not injected (naïve group). The pain behavioural methods used were gait analysis, measurement of pressure algometry thresholds in the ipsilateral knee joints, and assessment of mechanical allodynia in the ipsilateral hind paws using von Frey filaments. These pain behavioural endpoints were assessed premonoiodoacetate injection and for up to 42-days postmonoiodoacetate injection in a blinded manner. Body weights were also assessed as a measure of general health. Good general health was maintained as all rats gained weight at a similar rate for the 42-day study period. In the chronic phase of the model (days 9-42), intraarticular monoiodoacetate at 3 mg evoked robust alterations in multiple gait parameters as well as persistent mechanical allodynia in the ipsilateral hind paws. For the chronic phase of the monoiodoacetate-induced rat model of osteoarthritis knee pain, gait analysis, such as mechanical allodynia in the ipsilateral hind paws, is a robust pain behavioural measure.

Light on osteoarthritic joint: from bench to bed.

Osteoarthritis (OA) is one of the rapidly growing disability-associated conditions with population aging worldwide. There is a pressing need for precise diagnosis and timely intervention for OA in the early stage. Current clinical imaging modalities, including pain radiography, magnetic resonance imaging, ultrasound, and optical coherent tomography, are limited to provide structural changes when the damage has been established or advanced. It prompts further endeavors in search of novel functional and molecular imaging, which potentially enables early diagnosis and intervention of OA. A hybrid imaging modality based on photothermal effects, photoacoustic imaging, has drawn wide attention in recent years and has seen a variety of biomedical applications, due to its great performance in yielding high-contrast and high-resolution images from structure to function, from tissue down to molecular levels, from animals to human subjects. Photoacoustic imaging has witnessed gratifying potentials and preliminary effects in OA diagnosis. Regarding the treatment of OA, photothermal-triggered therapy has exhibited its attractions for enhanced therapeutic outcomes. In this narrative review, we will discuss photoacoustic imaging for the diagnosis and monitoring of OA at different stages. Structural, functional, and molecular parameter changes associated with OA joints captured by photoacoustics will be summarized, forming the diagnosis perspective of the review. Photothermal therapy applications related to OA will also be discussed herein. Lastly, relevant clinical applications and its potential solutions to extend photoacoustic imaging to deeper OA situations have been proposed. Although some aspects may not be covered, this mini review provides a better understanding of the diagnosis and treatment of OA with exciting innovations based on tissue photothermal effects. It may also inspire more explorations in the field towards earlier and better theranostics of OA.

Emerging microfluidics-enabled platforms for osteoarthritis management: from benchtop to bedside.

Osteoarthritis (OA) is a prevalent debilitating age-related joint degenerative disease. It is a leading cause of pain and functional disability in older adults. Unfortunately, there is no cure for OA once the damage is established. Therefore, it promotes an urgent need for early detection and intervention of OA. Theranostics, combining therapy and diagnosis, emerges as a promising approach for OA management. However, OA theranostics is still in its infancy. Three fundamental needs have to be firstly fulfilled: i) a reliable OA model for disease pathogenesis investigation and drug screening, ii) an effective and precise diagnostic platform, and iii) an advanced fabrication approach for drug delivery and therapy. Meanwhile, microfluidics emerges as a versatile technology to address each of the needs and eventually boost the development of OA theranostics. Therefore, this review focuses on the applications of microfluidics, from benchtop to bedside, for OA modelling and drug screening, early diagnosis, and clinical therapy. We first introduce the basic pathophysiology of OA and point out the major unfilled research gaps in current OA management including lack of disease modelling and drug screening platforms, early diagnostic modalities and disease-modifying drugs and delivery approaches. Accordingly, we then summarize the state-of-the-art microfluidics technology for OA management from in vitro modelling and diagnosis to therapy. Given the existing promising results, we further discuss the future development of microfluidic platforms towards clinical translation at the crossroad of engineering and biomedicine.

Effects of Immobilization and Swimming on the Progression of Osteoarthritis in Mice.

Osteoarthritis (OA) is a chronic joint disease characterized by the degeneration of articular cartilage and thickening and sclerosis of the subchondral bone. Mechanical factors play significant roles in the development and progression of OA, but it is still controversial whether exercise or rest is a more effective treatment for OA patients. In this study, we compared the effects of swimming and immobilization at different stages of OA in mice. Four weeks (the middle stage of OA) or eight weeks (the late stage of OA) after DMM (destabilization of the medial meniscus) surgery, the mice were subjected to four-week immobilization or swimming. Ink blot analysis and a beam walking test were performed to measure the gait and balance ability. Histological analysis was performed to determine the trabecular bone area, the thickness of subchondral bone, the thickness of the cartilage, the OARSI score, and the expression of MMP13 (matrix metalloproteinases) and IL-6 (interleukin). The results showed that at the middle stage of OA, both immobilization and swimming slowed down the progression of OA. Immobilization relieved OA to a certain extent by decreasing the production of regulatory factors to attenuate the degeneration of cartilage, which partly relieved the effects of DMM on gait, mainly in the hindlimb. Swimming mainly attenuated the thickening and rescued the area of subchondral bone.

Imaging of Synovial Inflammation in Osteoarthritis, From the AJR Special Series on Inflammation.

Synovitis, inflammation of the synovial membrane, is a common manifestation of osteoarthritis (OA) and is recognized to play a role in the complex pathophysiology of OA. Increased recognition of the importance of synovitis in the OA disease process and its potential as a target for treatment has increased the need for noninvasive detection and characterization of synovitis using medical imaging. Numerous imaging methods can assess synovitis involvement in OA with varying sensitivity, specificity, and complexity. This article reviews the role of contrast-enhanced MRI, conventional MRI, novel unenhanced MRI, gray-scale ultrasound (US), and power Doppler US in the assessment of synovitis in patients with OA. The role of imaging in disease evaluation and the challenges of conventional imaging methods are discussed. We also provide an overview of the potential utility of emerging techniques for imaging of early inflammation and molecular inflammatory markers of synovitis, including quantitative MRI, superb microvascular imaging, and PET. The development of therapeutic treatments targeting inflammatory features, particularly in early OA, would greatly increase the importance of these imaging methods for clinical decision-making and evaluation of therapeutic efficacy.

Radiographic Severity May Not be Associated with Pain and Function in Glenohumeral Arthritis.

BACKGROUND: Despite the routine use of plain radiographs to stratify the severity of glenohumeral osteoarthritis, little is known about the relationship between radiographic measures and patient-perceived pain and function. QUESTIONS/PURPOSES: (1) What radiographic findings are associated with worse pain and function in patients with glenohumeral osteoarthritis? (2) What demographic factors are associated with worse pain and function in patients with glenohumeral osteoarthritis? METHODS: This retrospective study included patients presenting for an initial office visit for primary glenohumeral osteoarthritis. Patients with other concurrent shoulder pathologic findings, prior surgery, lack of pain and functional scores, recent injection, or inadequate radiographs were excluded. Between January 2017 and January 2019, 3133 patients were eligible based on these inclusion criteria; 59% (1860) had outcome assessments and 48% (893) of those had radiographs. An additional 42% (378) of those with radiographs were excluded because of other shoulder findings, recent injection, prior surgery, or inadequate radiographs, leaving 16% (515 of 3133) who were fully analyzed in this study. A radiographic review included the joint space width, posterior humeral head subluxation, inferior humeral head osteophyte size, cystic change, and head asphericity. Additionally, radiographic arthritis was classified according to the Walch, Samilson-Prieto, and Kellgren-Lawrence classifications by two separate reviewers. Radiographic and demographic criteria as well as the presence of psychologic or mental illness were correlated with VAS Pain (range 1-10; minimal clinically important difference [MCID] 1.6), American Shoulder and Elbow Surgeons (ASES; range 0-100; MCID 13.6), Single Assessment Numeric Evaluation (SANE; range 0-100; MCID 14), and Simple Shoulder Test (SST; range 0-12; MCID 1.5) scores using univariate and multivariable regression analyses. RESULTS: After accounting for age, gender, and psychologic illness in the multivariable analysis, we found that patients with Samilson-Prieto Grade 4 arthrosis had lower VAS Pain scores (ß = -1.9; p = 0.02) than those with Grade 0 or 1 did; however, no clinically important associations were found between Samilson-Prieto Grade 4 and ASES (ß = 7; p = 0.25), SANE (ß = 4; p = 0.63), or SST (ß = 0.5; p = 0.62) scores. No clinically important associations were found between Kellgren-Lawrence Grade 3 and VAS Pain (ß = 1.4; p = 0.10), ASES (ß = -8; p = 0.22), SANE (ß = -13; p = 0.11), or SST scores (ß = 0.4; p = 0.66). Radiographic joint space and posterior subluxation also did not have any clinically important associations with VAS Pain or functional scores. In assessing Walch glenoid type, there was no clinically important association between glenoid type and VAS Pain (F = 3.1; p < 0.01), ASES (F = 1.9; p = 0.15), SANE (F = 0.45; p = 0.66), or SST scores (F = 0.76; p = 0.71). Men had higher SST scores than women did (ß = 2.0; p < 0.01), but there were no clinically important differences in VAS Pain (ß = -0.4; p = 0.04), ASES (ß = 6; p < 0.01), or SANE (ß = 4; p = 0.07) scores. No clinically important association was found between age or the presence of any psychologic illness and VAS Pain or functional scores. CONCLUSION: In patients with glenohumeral arthritis, no consistent clinically important differences in pain or function were discovered with respect to radiographic or demographic factors. Surgeons should understand that the pain levels of patients with glenohumeral arthritis may not parallel radiographic severity. Future studies can build on these findings by examining other non-radiographic or demographic factors that affect pain in patients with shoulder arthritis, such as psychological factors. LEVEL OF EVIDENCE: Level III, prognostic study.

Regulation of osteoarthritis development by ADAM17/Tace in articular cartilage.

INTRODUCTION: A disintegrin and metalloproteinase 17 (Adam17), also known as TNFα-converting enzyme (Tace), is a membrane-anchored protein involved in shedding of TNF, IL-6 receptor, ligands of epidermal growth factor receptor (EGFR), and Notch receptor. This study aimed to examine the role of Adam17 in adult articular cartilage and osteoarthritis (OA) pathophysiology. MATERIALS AND METHODS: Adam17 expression was examined in mouse knee joints during OA development. We analyzed OA development in tamoxifen-inducible chondrocyte-specific Adam17 knockout mice of a resection of the medial meniscus and medial collateral ligament (medial) model, destabilization of the medial meniscus (DMM) model, and aging model. We analyzed downstream pathways by in vitro experiments, and further performed intra-articular administration of an Adam17 inhibitor TAPI-0 for surgically induced mouse OA. RESULTS: Adam17 expression in mouse articular cartilage was increased by OA progression. In all models, Adam17 knockout mice showed ameliorated progression of articular cartilage degradation. Adam17 knockout decreased matrix metallopeptidase 13 (Mmp13) expression in both in vivo and in vitro experiments, whereas Adam17 activation by phorbol-12-myristate-13-acetate (PMA) increased Mmp13 and decreased aggrecan in mouse primary chondrocytes. Adam17 activation enhanced release of soluble TNF and transforming growth factor alpha, a representative EGF ligand, from mouse primary chondrocytes, while it did not change release of soluble IL-6 receptor or nuclear translocation of Notch1 intercellular domain. Intra-articular administration of the Adam17 inhibitor ameliorated OA progression. CONCLUSIONS: This study demonstrates regulation of OA development by Adam17, involvement of EGFR and TNF pathways, and the possibility of Adam17 as a therapeutic target for OA.

Associations between radiographic features, clinical features and ultrasound of thumb-base osteoarthritis: A secondary analysis of the COMBO study.

AIM: To investigate the associations of ultrasound and radiographic features of thumb-base osteoarthritis (OA) with thumb-base pain and hand function at baseline and 12 weeks. METHOD: Data from a randomized controlled trial conducted in participants with symptomatic radiographic thumb-base OA were analyzed. Participants who finished follow up were included in this secondary analysis. Pain and hand function were assessed using self-reported measures. All participants underwent ultrasound examinations for synovitis, power Doppler signal (PDS), and osteophytes, and underwent radiography for osteophytes, joint space narrowing (JSN), and subchondral bone sclerosis at baseline. Hand pain and function were reassessed after the 12-week follow up. The associations of ultrasound and radiographic findings with clinical features were further evaluated, using linear regression analyses, after adjustment for relevant confounding factors. RESULTS: A total of 166 participants (average age 66.2 years; 76.5% female) were included. At baseline, radiographic JSN and subchondral bone sclerosis were associated with hand function. There was a significant association between ultrasound-detected PDS and patient's global assessment (PGA) at baseline. Baseline radiographic JSN was significantly associated with the changes in stiffness and PGA from baseline to 12 weeks. There was no association between ultrasound features and changes in the clinical outcomes over 12 weeks. CONCLUSION: This study indicates that radiographic features significantly correlate with hand function, and ultrasound PDS is closely related to the PGA at baseline in thumb-base OA. Radiographic JSN may be a predictor for stiffness and PGA in thumb-base OA.

Antinociceptive and chondroprotective effects of prolonged ß-caryophyllene treatment in the animal model of osteoarthritis: Focus on tolerance development.

Osteoarthritis (OA) is a chronic joint disease in which cartilage degeneration leads to chronic pain. The endocannabinoid system has attracted attention as an emerging drug target for OA. However, the therapeutic potential of cannabinoids is limited by psychoactive side-effects related to CB1 activation and tolerance development for analgesic effects. ß-Caryophyllene (BCP) is a low-efficacy natural agonist of CB2 and a common constituent of human diet with well-established anti-inflammatory properties. The results presented herein show the anti-nociceptive and chondroprotective potential of BCP in an animal model of OA induced by intra-articular injection of monoiodoacetate (MIA). Behavioural assessment included pressure application measurement and kinetic weight bearing tests. Histological assessment of cartilage degeneration was quantified using OARSI scoring. Experiments established the dose-response effects of BCP and pharmacological mechanisms of the antinociceptive action dependent on CB2 and opioid receptors. Chronic BCP treatment was able to hamper cartilage degeneration without producing tolerance for the analgesic effects. The data presented herein show that BCP is able to produce both acute and prolonged antinociceptive and chondroprotective effects. Together with the safety profile and legal status of BCP, these results indicate a novel and promising disease-modifying strategy for treating OA.

The relation between the gut microbiome and osteoarthritis: A systematic review of literature.

BACKGROUND: Along with mechanical and genetic factors, emerging evidence suggests that the presence of low-grade inflammation has a role in the pathogenesis of osteoarthritis (OA) and seems to be related to the microbiome composition of the gut. PURPOSE: To provide evidence whether there is clinical or preclinical evidence of gut-joint axis in the pathogenesis and symptoms of OA. METHODS: An extensive review of the current literature was performed using three different databases. Human, as well as animal studies, were included. The risk of bias was identified using ROBINS and SYRCLE tools, while the quality of evidence was assessed using GRADE and CAMADARES criteria. RESULTS: A total of nineteen articles were included. Multiple animal studies demonstrated that both obesity, and high-fat and high-sugar diets resulted in a gut dysbiosis status characterized by increased Firmicutes/Bacteroidetes (F/B) phyla ratio and increased permeability. These changes were associated with increased lipopolysaccharide serum levels, which consequently resulted in synovitis and OA severity. The administration of pre-and probiotics partially reversed this bacterial composition. In addition, in human studies, a decreased amount of gut Bacteroidetes, subsequent increased F/B ratio, have also been observed in OA patients. CONCLUSIONS: Our review confirms preliminary yet sound evidence supporting a gut-joint axis in OA in primarily preclinical models, by showing an association between diet, gut dysbiosis and OA radiological severity and self-reported symptoms. Clinical studies are needed to confirm these findings, and to investigate whether interventions targeting the composition of the microbiome will have a beneficial clinical effect.