Cetyl Myristoleate

The scientific and medical community remains skeptical regarding the efficacy of nutrition for osteoarthritis despite their broad acceptation by patients. In this context, this paper systematically reviews human clinical trials evaluating the effects of nutritional compounds on osteoarthritis. We searched the Medline, Embase, and Biosis databases from their inception to September 2005 using the terms random, double-blind method, trial, study, placebo, and osteoarthritis. We selected all peer-reviewed articles reporting the results of randomised human clinical trials (RCTs) in osteoarthritis that investigated the effects of oral interventions based on natural molecules. Studies on glucosamine and chondroitin sulfate were excluded. The quality of the RCTs was assessed with an osteoarthritic-specific standardised set of 12 criteria and a validated instrument. A best-evidence synthesis was used to categorise the scientific evidence behind each nutritional compound as good, moderate, or limited. A summary of the most relevant in vitro and animal studies is used to shed light on the potential mechanisms of action. Inclusion criteria were met by 53 RCTs out of the 2,026 identified studies. Good evidence was found for avocado soybean unsaponifiables. Moderate evidence was found for methylsulfonylmethane and SKI306X, a cocktail of plant extracts. Limited evidence was found for the Chinese plant extract duhuo jisheng Wan, cetyl myristoleate, lipids from green-lipped mussels, and plant extracts from Harpagophytum procumbens. Overall, scientific evidence exists for some specific nutritional interventions to provide symptom relief to osteoarthritic patients. It remains to be investigated whether nutritional compounds can have structure-modifying effects.

BACKGROUND: Nutraceuticals containing cis-9-cetylmyristoleate (CMO) are used to improve knee pain despite the lack of placebo-controlled studies in humans. The aim of the study was to explore the minimal effective dose of CMO for relieving knee joint pain. METHODS: Twenty-eight subjects with mild degree arthritic knee joint pain were randomized into 4 groups; groups A, B, and C that contained 100%, 80%, and 62.4% of fatty acid component with 12.5% of CMO, and control group D (starch 100%). The pain intensity, functional disability, and the Patient Global Impression of Change (PGIC) were assessed for a 12-week ingestion period. RESULTS: Compared to group D (n = 6), there were significant differences in pain score in group A (n = 7, P = 0.005) and group C (n = 7, P = 0.012), but not significant in group B (n = 6, P = 0.180). Western Ontario and McMaster Universities Arthritis (WOMAC) score decreased significantly in groups A and C. The PGIC was positive in the majority (>50%) in groups A, B, and C, whereas negative in 83.3% in group D (control). CONCLUSION: CMO is effective in alleviating knee pain in persons with mild degree arthritis of the knee joint, at an effective dose of 62.4%.

OBJECTIVE: To examine the effect of a topical cream consisting of cetylated fatty acids on functional performance in patients diagnosed with osteoarthritis (OA) of one or both knees. METHODS: Forty patients diagnosed with knee OA were randomly assigned to one of 2 topical treatment groups: (1) cetylated fatty acid (CFA) (n = 20; age 62.7 +/- 11.7 yrs); or (2) placebo group (n = 20; age 64.6 +/- 10.5 yrs). Patients were tested on 3 occasions: (1) baseline (T1), (2) 30 min after initial treatment (T2), and (3) after 30-day treatment of cream application twice per day (T3). Assessments included knee range of motion (ROM), timed "up-and-go" from a chair and stair climbing, medial step-down test, and the unilateral anterior reach. RESULTS: For stair climbing ability and the up-and-go test, significant decreases in time were observed at T2 and T3 compared to T1 in the CFA group only. These differences were significant between groups. Supine ROM of the knees increased at T2 and T3 in CFA group, whereas no difference was observed in the placebo group. For the medial step-down test, significant improvement was observed at T2 and T3 compared to T1 in CFA group. For the unilateral anterior reach, significant improvement was observed for both legs in CFA group and in only the left leg in the placebo group. However, the improvements observed in CFA group were significantly greater than placebo group for both legs. CONCLUSION: Use of a CFA topical cream is an effective treatment for improving knee ROM, ability to ascend/descend stairs, ability to rise from sitting, walk and sit down, and unilateral balance.

OBJECTIVE: To determine the benefit of cetylated fatty acids (CFA) on knee range of motion and function in patients with osteoarthritis (OA). METHODS: Sixty-four patients with chronic knee OA were evaluated at baseline and at 30 and 68 days after consuming either placebo (vegetable oil; n = 31) or CFA (Celadrin; n = 33). Evaluations included physician assessment, knee range of motion with goniometry, and the Lequesne Algofunctional Index (LAI). RESULTS: After 68 days, patients treated with CFA exhibited significant (p < 0.001) increase in knee flexion (10.1 degrees) compared to patients given placebo (1.1 degrees). Neither group reported improvement in knee extension. Patient responses to the LAI indicated a significant (p < 0.001) shift towards functional improvement for the CFA group (-5.4 points) after 68 days compared to a modest improvement in the placebo group (-2.1 points). CONCLUSION: Compared to placebo, CFA provides an improvement in knee range of motion and overall function in patients with OA of the knee. CFA may be an alternative to the use of nonsteroidal antiinflammatory drugs for the treatment of OA.

OBJECTIVE: Cetylated fatty acids are a group of naturally occurring fats of plant and/or animal origin. Cetyl myristoleate, in particular, was initially involved in osteoarthritis related research as its therapeutic administration prevented experimentally induced arthritis in Swiss Albino mice. In this context, the aim of our study was to investigate the possible mechanisms of Celadrin cetylated fatty acids action at the cellular level inflammation related pain relief and chondrogenesis. DESIGN: For this, we tested the effects of the cetylated fatty acids mixture from Celadrin on an in vitro scaffold-free 3-dimensional mesenchymal stem cells culture model of chondrogenesis. Furthermore, we treated stimulated mouse macrophage cells with the cetylated fatty acids mixture to investigate the expression profile of secreted inflammatory cytokines. RESULTS: The cetylated fatty acids mixture from Celadrin significantly decreased the production of IL-6, MCP-1, and TNF, key regulators of the inflammatory process, in stimulated RAW264.7 mouse macrophage cells. The treatment with cetylated fatty acids mixture initiated and propagated the process of chondrogenesis as demonstrated by the increased expression and deposition of chondrogenic markers by the differentiating mesenchymal cells. CONCLUSION: The cetylated fatty acids mixture from Celadrin reduces inflammation in vitro by significantly decreasing the expression of IL-6, MCP-1, and TNF in stimulated RAW264.7 mouse macrophage cells. These compounds facilitate the chondrogenic differentiation process of human adipose-derived stem cells by stimulating the expression of chondrogenic markers under chondrogenic induction conditions.

Comment in Am Fam Physician. 2003 Nov 1;68(9):1713; author reply 1713. Americans spend more on natural remedies for osteoarthritis than for any other medical condition. In treating osteoarthritis, glucosamine and chondroitin sulfate, two of the molecular building blocks found in articular cartilage, are the most commonly used alternative supplements. In randomized trials of variable quality, these compounds show efficacy in reducing symptoms, but neither has been shown to arrest progression of the disease or regenerate damaged cartilage. Although few clinical trials on S-adenosylmethionine exist, preliminary evidence indicates that it relieves pain to a degree similar to that of nonsteroidal anti-inflammatory drugs but with fewer side effects. Clinical trials of dimethyl sulfoxide offer conflicting results. Neither ginger nor cetyl myristoleate has proven clinical usefulness.

Cetyl myristoleate (CM) was reported by Diehl and May [J Pharm Sci 83 (1994) 296] to block inflammation and prevent adjuvant-induced arthritis in rats. To verify this earlier work, we have synthesized pure CM and tested its anti-arthritic properties in a collagen-induced arthritis model in DBA/1LacJ mice. Multiple intraperitoneal injections of CM in 450 and 900 mg kg(-1) doses resulted in a significantly lower incidence of disease and caused a modest but significant diminution in clinical signs in those mice that developed arthritis. CM administered in daily oral doses of 20 mg kg(-1) also reduced the incidence of arthritis and caused a small reduction in the clinical signs in mice that developed arthritis. Although the protective effect of CM in collagen-induced arthritis observed in the present study was less dramatic than that reported earlier, our results confirm the anti-arthritic properties of pure CM.

OBJECTIVE: In the past few years access to the Internet has become readily available. Patients are increasingly seeking and obtaining health information through the Internet, most often the World Wide Web (WWW). We assessed the content, authorship, and scope of the information available on WWW in relation to rheumatoid arthritis. METHODS: In an attempt to replicate use by the average person, a broad search of the Internet was conducted for the phrase "rheumatoid arthritis" using WebCrawler, a commonly used search engine. All the "hits" were critically assessed after visiting and collecting information from the respective Web sites in relation to relevance, scope, authorship, type of publication, and financial objectives. RESULTS: The search returned 537 hits. We evaluated 531-2 did not exist, 2 could not be contacted, one was not in English, and one required a membership to access. The 531 hits originated from 388 Web sites. Only 198 (51%) were considered to be relevant and 7 (2%) were of doubtful relevance. Thirty-four (17%) were posted by an individual, 57 (28%) by a nonprofit organization, 104 (51%) by a profit industry, and 10 (5%) by universities. Ninety-one (44%) promoted alternative therapies, the most common including cetyl-myristoleate, colloidal minerals, Pycnogenol, shark cartilage, and Tahitian Noni. Of the 107 sites with financial interests, 76 (71%) promoted alternative medicine. The first 100 hits only identified about a third of the nonprofit organizations or university owned Web pages. CONCLUSION: Many sites easily accessed by consumers appear to be profit based companies advertising an alternative product claimed to be effective for many conditions. These findings emphasize the need for critical evaluation of Web site contents.

Cetyl myristoleate was isolated from National Institutes of Health, general purpose, Swiss albino mice that were immune to the polyarthritis induced in rats with Freund's adjuvant. This substance, or material synthesized from cetyl alcohol and myristoleic acid, afforded good protection against adjuvant-induced arthritic states in rats. In limited comparisons, cetyl oleate, also found in Swiss albino mice, gave lesser protection, whereas cetyl myristate and cetyl elaidate, the trans-isomer of cetyl oleate, appeared to be virtually ineffective. Dosage of the protective compound as well as the site of injection of Freund's adjuvant was important.

OBJECTIVE: To explore associations between patient-reported pain outcomes and knee osteoarthritis (OA) subtypes based on systemic biochemical markers and joint structural pathology as defined by MRI. METHODS: Data were obtained from 297 knee OA patients from the IMI-APPROACH study. Pain outcomes were assessed using the KOOS, WOMAC, ICOAP, NRS, PainDETECT, and a pain diary. Biochemical markers in serum and urine were used to classify patients into systemic biomarker subtypes (low tissue turnover, structural damage, and systemic inflammation) via k-means clustering. Structural pathology subtypes were determined using MRI into an inflammatory, meniscus/cartilage damage, and subchondral bone pathology subtype. Associations between pain measures and subtypes were analyzed using multivariable regression models adjusted for age, sex, and BMI. RESULTS: The systemic inflammation biomarker subtype was significantly associated with higher KOOS pain, WOMAC weight-bearing pain, NRS knee pain, and PainDETECT scores (all p ​≤ ​0.042 and β ​≥ ​0.12). The low tissue turnover subtype negatively associated with lower KOOS, WOMAC, and ICOAP constant pain (all p ​≤ ​0.22 and β ​≤ ​-0.13), and the structural damage subtype with lower PainDETECT scores (more nociceptive-like pain; p ​= ​0.046 and β ​= ​-0.12). Among MRI subtypes, meniscus/cartilage damage was significantly associated with lower PainDETECT scores (p ​= ​0.005 and β ​= ​-0.16). No significant associations were found for the subchondral bone subtype or pain diary outcomes. CONCLUSION: For commonly used pain questionnaires, pain severity seems linked with inflammatory activity more than structural damage. Structural damage is primarily associated with nociceptive-like pain according to PainDETECT, which might be valuable for patient selection to clinical trials and observational studies. © 2025 The Author(s).

This cross-sectional study compares TMD signs and symptoms in patients aged ≥ 65 (elderly) and ≥ 85 (super-elderly) with younger age groups. Additionally, this study sought to identify the key factors contributing to increased pain intensity in elderly and super-elderly patients with TMD. A total of 4,661 patients with TMD (mean age = 42.22 ± 20.08 years, 3069 women and 1592 men) were analyzed, categorized into six age groups, including those aged 65–74, 75–84, and 85 + years. The clinical characteristics, pain intensity (VAS), and TMD subgroup distribution were examined. Generalized linear models and 2D/3D visualizations were used to explore the correlations and multivariable relationships. Of the 4,661 patients aged 7–113 years, 16.8% were elderly and 1.1% were super-elderly. The female-to-male ratios in the elderly group were 1.93:1 and 1.78:1, with females being predominant across all age groups. Elderly groups, including those aged 65–74 (3.92 ± 2.49), 75–84 (3.94 ± 2.73), and 85 + years (3.92 ± 2.49), had significantly higher VAS scores compared to younger age groups (p < 0.001), indicating moderate pain levels. Maximum mouth opening values were significantly smaller in the 75–84 (38.81 ± 10.79 mm) and 85 + groups (38.08 ± 12.79 mm) compared to younger groups (p < 0.001). Arthralgia was one of the most prevalent TMD subgroups in both elderly (58.2%) and super-elderly (50.0%) patients. Degenerative joint disease was more prevalent in the super-elderly group (48.0%) than in the elderly group (37.9%) (P < 0.05). Chronic TMD was most prevalent in the 0–19 years group (50.3%), followed by the super-elderly group (44.0%) (p < 0.001). GLM analysis showed that TMJ pain (B = 1.324, p < 0.001), TMJ noise (B = 0.757, p < 0.001), and age (B = 0.014, p < 0.001) were significantly associated with higher VAS scores, whereas increases in CMO (B = -0.011, p < 0.001) were associated with lower VAS scores. In the super-elderly group, the VAS score was also significantly associated with degenerative joint disease. The 2D and 3D visualizations revealed a tangled web of relationships among these clinical and diagnostic variables, showing how intricately they are intertwined and

Osteoarthritis (OA) is a chronic degenerative joint disorder and a leading cause of pain and disability among the elderly. Traditional nonsteroidal anti-inflammatory drugs (NSAIDs), though effective in symptom relief, pose significant risks of gastrointestinal, cardiovascular, and renal complications, especially in long-term use. Polmacoxib (CG100649) is a newer NSAID with its dual inhibitory role on cyclooxygenase-2 (COX-2) and carbonic anhydrase (CA), planned to offer higher therapeutic efficacy and safety. This review critically examines the pharmacodynamic and pharmacokinetic properties of polmacoxib, along with its clinical efficacy and safety in OA and acute pain conditions. Clinical trials across phases I-III consistently show polmacoxib to be well tolerated and effective in pain relief and efficient improvement of the joint, with a safety profile comparable to or better than traditional COX-2 inhibitors like celecoxib. Recent trials also explore its role in combination therapies for acute pain management, including dental and postoperative settings, showing noninferiority to standard regimens and fewer adverse events. Its innovative mechanism and pharmacological profile support its potential as a next-generation NSAID for OA and pain management, particularly in populations at high risk for NSAID-induced adverse effects. Further larger long-term studies are warranted to confirm its medical benefits and broader therapeutic applications. © Journal of The Association of Physicians of India 2025.

OBJECTIVE: We examined whether the trajectory of femorotibial cartilage loss differs between knees meeting a clinically defined virtual knee replacement (vKR) status based on patient-reported outcomes vs. those with low probability. DESIGN: vKR cases (highest 10 ​% of probabilities for having surgical KR) were selected using knee pain and quality of life criteria, developed from knees with actual KR. Knees reaching such symptom state at 48 months (M) follow-up (vKR case 60 ​M) were matched 1:1 with vKR controls (lowest 20 ​% probability) by sex, age, and baseline radiographic status. Of 65 knees displaying vKR case status at 60 ​M; 33 maintained or increased pain and QOL levels at 72 ​M (vKR+/+); 32 did not (vKR+/-). The thickness of medial and lateral tibial and femoral cartilages was determined from MRI, at up to five annual visits prior to 60 ​M. RESULTS: vKR case knees displayed substantially greater central medial femorotibial compartment cartilage thickness loss 2 years prior to reaching case status (-151 ​± ​337 [mean ​± ​SD] vs. -38 ​± ​249 ​μm; odds ratio [OR] 1.95 (95 ​% confidence interval: 1.23-3.08). Cartilage loss did not apparently differ between vKR+/+ and vKR +/- knees (p ​= ​0.73). CONCLUSIONS: Substantially greater cartilage thickness loss was detected in knees reaching vKR case status defined by patient-reported clinical criteria vs. vKR controls. This was found independently of whether this status was maintained at a later annual visit. The observed association suggests greater knee cartilage loss to be prospectively related to worse clinical outcome. It indicates further that the vKR criterion used here may be useful to explore relationships with other structural (imaging) assessments. © 2025 The Author(s).

OBJECTIVE: To investigate the clinical effects of Leukocyte-poor-Platelet-Rich-Plasma (LpPRP) injections to treat chronic facet joint syndrome. METHODS: 78 patients suffering from chronic facet joint syndrome at the Center for Molecular Orthopedics (CMO) agreed to participate to this prospective controlled study to receiving a series of CT-guided PAT-injections (periarticular therapy) to lumbar facet joints. The patients were free to decide to receive either injections based on Platelet-Rich-Plasma (PRP) or local anesthetics (LA/bupivacaine). In this study leucocyte-poor PRP (LpPRP) was used for all patients of the verum group, namely autologous conditioned plasma (Arthrex ACP® / Arthrex Inc., Naples, FL, USA) as the verum group. 59 patients were treated 3-5 times in at least two levels of facet joints in the PRP group, 19 patients decided to join the LA group receiving local anesthetics (LA group) each in a weekly interval. All patients agreed to answer an automated email questionnaire for up to one year starting at baseline before receiving the first injections. The follow up protocol was based on a pain scale, and the Oswestry disability score. Data analysis was evaluated using the Excel analysis tools. RESULTS: Data analysis revealed that both, PRP and local anesthetics had a pain reducing effect initially at week 2 after receiving the first PAT, but from week six on up to one year post injection, PRP infiltrations were superior with a significantly reduced pain score compared to baseline up to one year (p<0.001). Oswestry score showed similar results with a significant improvement to about one half compared to baseline (p<0.001) up to six months, still being significantly better at one year (p<0.01). The comparison of the PRP group to the LA group showed a better pain relief and better values at the Oswestry disability score between three and six months and one year. CONCLUSIONS: We show that a CT-guided injection therapy (PAT) based on LpPRP addressing the facet joint mediated low back pain syndrome leads to a significant long term pain reduction, and to a significant improvement in the Oswestry disability score for at least one year.

OBJECTIVE: To use patient-reported outcomes (PROs) and performance measures to develop a multi-component outcome (virtual knee replacement [vKR]) that predicts knee replacement (KR). METHODS: Osteoarthritis Initiative (OAI) participants with baseline radiographs, clinical assessments and health insurance were followed for 60 months. Of 8205 knees (4143 participants), 206 knees (187 participants) had KR. Eighteen clinical measures available at annual visits were considered, (e.g., Knee injury and Osteoarthritis Outcome Score knee pain (KOOS KP), frequency, severity, and Quality of Life (QoL), frequent knee pain, knee pain severity, SF12 Mental Health and Physical Health subscales, physical activity, depression, 20-meter walk and chair stands). Combinations of these were evaluated utilizing logistic regression to predict KRs in the next year. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were assessed. RESULTS: The most accurate models for predicting KR incorporated KOOS KP and KOOS QoL at a specific annual visit, and KOOS KP worsening over the previous year combined as weighted sums. Per 10 points of these assessments the odds of vKR increased by 30 % to 65 %. AUCs ranged from 0.87 to 0.92 (vKR1). Constraining KOOS KP and KOOS QoL to be worse at follow-up than at baseline, AUCs exceeded 0.85 (vKR2). When KOOS KP and KOOS QoL remained unchanged or worsened over one year, AUCs were >0.80 (vKR3). CONCLUSION: The three vKR criteria represent potential clinical multi-component outcomes for clinical trials of knee OA. After further validation, any of them may serve as a standalone clinical outcome or in combination with actual knee replacement.

Plasmodium knowlesi (Pk) causes zoonotic malaria and is known as the "fifth human malaria parasite". Pk malaria is an emerging threat because infections are increasing and can be fatal. While most infections are in Southeast Asia (SEA), especially Malaysia, travelers frequently visit this region and can present with Pk malaria around the world. So, clinicians need to know (1) patients who present with fever after recent travel to SEA might be infected with Pk and (2) Pk is often misdiagnosed as P. malariae (which typically causes less severe malaria). Here we review the history, pathophysiology, clinical features, diagnosis, and treatment of Pk malaria. Severe disease is most common in adults. Signs and symptoms can include fever, abdominal pain, jaundice, acute kidney injury, acute respiratory distress syndrome, hyponatremia, hyperparasitemia, and thrombocytopenia. Dengue is one of the diseases to be considered in the differential. Regarding pathophysiologic mechanisms, when Pk parasites invade mature red blood cells (RBCs, i.e., normocytes) and reticulocytes, changes in the red blood cell (RBC) surface can result in life-threatening cytoadherence, sequestration, and reduced RBC deformability. Since molecular mechanisms involving the erythrocytic stage are responsible for onset of severe disease and lethal outcomes, it is biologically plausible that manual exchange transfusion (ET) or automated RBC exchange (RBCX) could be highly beneficial by replacing "sticky" parasitized RBCs with uninfected, deformable, healthy donor RBCs. Here we suggest use of special Pk-resistant donor RBCs to optimize adjunctive manual ET/RBCX for malaria. "Therapeutically-rational exchange transfusion" (T-REX) is proposed in which Pk-resistant RBCs are transfused (instead of disease-promoting RBCs). Because expression of the Duffy antigen on the surface of human RBCs is essential for parasite invasion, T-REX of Duffy-negative RBCs-also known as Fy(a-b-) RBCs-could replace the majority of the patient's circulating normocytes with Pk invasion-resistant RBCs (in a single procedure lasting about 2 h). When sequestered or non-sequestered iRBCs rupture-in a 24 h Pk asexual life cycle-the rel

The purpose of this paper is to summarise the consensus methodology that was used to inform the International Consensus Statement on Concussion in Sport (Amsterdam 2022). Building on a Delphi process to inform the questions and outcomes from the 5th International Conference on Concussion in Sport, the Scientific Committee identified key questions, the answers to which would help encapsulate the current science in sport-related concussion and help guide clinical practice. Over 3½ years, delayed by 2 years due to the pandemic, author groups conducted systematic reviews on each selected topic. The 6th International Conference on Concussion in Sport was held in Amsterdam (27-30 October 2022) and consisted of 2 days of systematic review presentations, panel discussions, question and answer engagement with the 600 attendees, and abstract presentations. This was followed by a closed third day of consensus deliberations by an expert panel of 29 with observers in attendance. The fourth day, also closed, was dedicated to a workshop to discuss and refine the sports concussion tools (Concussion Recognition Tool 6 (CRT6), Sport Concussion Assessment Tool 6 (SCAT6), Child SCAT6, Sport Concussion Office Assessment Tool 6 (SCOAT6) and Child SCOAT6). We include a summary of recommendations for methodological improvements for future research that grew out of the systematic reviews. © Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

OBJECTIVE: Therapy for osteoarthritis ideally aims at preserving structure before radiographic change occurs. This study tests: a) whether longitudinal deterioration in cartilage thickness and composition (transverse relaxation-time T2) are greater in radiographically normal knees "at risk" of incident osteoarthritis than in those without risk factors; and b) which risk factors may be associated with these deteriorations. DESIGN: 755 knees from the Osteoarthritis Initiative were studied; all were bilaterally Kellgren Lawrence grade [KLG] 0 initially, and had magnetic resonance images available at 12- and 48-month follow-up. 678 knees were "at risk", whereas 77 were not (i.e., non-exposed reference). Cartilage thickness and composition change was determined in 16 femorotibial subregions, with deep and superficial T2 being analyzed in a subset (n ​= ​59/52). Subregion values were used to compute location-independent change scores. RESULTS: In KLG0 knees "at risk", the femorotibial cartilage thinning score (-634 ​± ​516 ​μm) over 3 years exceeded the thickening score by approximately 20%, and was 27% greater (p ​< ​0.01; Cohen D -0.27) than the thinning score in "non-exposed" knees (-501 ​± ​319 ​μm). Superficial and deep cartilage T2 change, however, did not differ significantly between both groups (p ​≥ ​0.38). Age, sex, body mass index, knee trauma/surgery history, family history of joint replacement, presence of Heberden's nodes, repetitive knee bending were not significantly associated with cartilage thinning (r2<1%), with only knee pain reaching statistical significance. CONCLUSIONS: Knees "at risk" of incident knee OA displayed greater cartilage thinning scores than those "non-exposed". Except for knee pain, the greater cartilage loss was not significantly associated with demographic or clinical risk factors. © 2023 The Author(s).

AIM: The purpose of this study is to comparatively evaluate the Vitamin D supplementation and stabilization splint therapy in patients exhibiting temporomandibular disorders (TMD). SETTINGS AND DESIGN: The study design was double-blinded, parallel-group, randomized and placebo-controlled trial conducted in patients with low Vitamin D and TMDs, which were allocated to two groups, Study group S + D (Stabilization splint with Vitamin D supplementation) and Control Group S (Stabilization Splint with placebo drug). SUBJECTS AND METHODS: Thirty-six participants of 18-45 years of age gap with Vitamin D deficiency and TMD were included in the study. Preoperative values of Vitamin D levels in ng/ml, comfort mouth opening (CMO) in mm, maximum mouth opening (MMO) in mm, temporomandibular joint (TMJ) tenderness (grading 0-3), Visual analog scale score (VAS Score 0-10 cm), and total energy (TE) integral values of both left and right TMJ's in Hertz (Hz) were recorded using joint vibration analysis All the values of CMO, MMO, TMJ Tenderness and VAS were recorded at each follow-up at 1st week, 1st month, 2nd month, and 3rd month, respectively. Postoperative Vitamin D levels and TE of both TMJs were recorded at end of 3 months. STATISTICAL ANALYSIS USED: For intergroup comparison, Mann-Whitney U-test and Pearson Chi-square tests were done. For Intragroup comparison, Wilcoxon signed rank test was used for comparison. RESULTS: In Intergroup comparison, a significant difference was seen in CMO, VAS score and MMO (P < 0.05) but not among mean values of TE of right and left TMJ, and Vitamin D levels (P < 0.05). In both groups, there were significant statistical variations in CMO, VAS score, MMO, and TE integral before and after treatment in the right and left TMJs (P < 0.05). CONCLUSIONS: The study concludes centric stabilization splint helps in improving symptoms of TMD patients and Vitamin D supplementation provided faster relief in those cases.

INTRODUCTION: Knee osteoarthritis (KOA) is a highly prevalent disabling joint disease. Intra-articular stem cell therapy is increasingly being used for treating KOA with little high-quality evidence to support its use. The aim of this study is to investigate the efficacy, safety and cost-effectiveness of allogeneic mesenchymal stem cells (Cymerus MSCs) for treating symptomatic tibiofemoral KOA and improving knee structure over 24 months. METHODS AND ANALYSIS: The Stem Cell injections for symptomatic relief and strUctural improvement in people with Tibiofemoral knee OsteoaRthritis study is a phase III, multi-centre, parallel, superiority, randomised, double-blind, placebo-controlled trial, which will be conducted in Sydney and Hobart, Australia. 440 participants (220 per arm) aged over 40 years with painful KOA and mild to moderate structural change on X-ray (Kellgren and Lawrence grade 2 or 3) with medial minimum joint space width between 1 and 4 mm in the study knee will be recruited from the community and randomly allocated to receive either intra-articular MSCs or saline at baseline, week 3 and week 52. The coprimary outcomes will be the proportion of participants achieving patient-acceptable symptom state for knee pain at 24 months and quantitative central medial femorotibial compartment cartilage thickness change from baseline to 24 months. Main secondary outcomes include change in knee pain, Patient Global Assessment, physical function, quality of life and other structural changes. Additional data for cost-effectiveness analysis will also be recorded. Adverse events will be monitored throughout the study. The primary analysis will be conducted using modified intention-to-treat. ETHICS AND DISSEMINATION: This protocol has been approved by The University of Sydney (USYD) Human Research Ethics Committee (HREC) #: 2020/119 and The University of Tasmania (UTAS) HREC #: H0021868. All participants will be required to provide informed consent. Dissemination will occur through conferences, social media, and scientific publications. TRIAL REGISTRATION NUMBERS: Australian New Zealand Clinical Trials Registry (ACTRN12620000870954); U1111-1234-4897. © Author(s) (or th

Treatment of osteoarthritis (OA) is mainly symptomatic by alleviating pain to postpone total joint replacement. Bone morphogenetic protein 7 (BMP7) is a candidate morphogen for experimental OA treatment that favorably alters the chondrocyte and cartilage phenotype. Intra-articular delivery and sustained release of a recombinant growth factor for treating OA are challenging, whereas the use of peptide technology potentially circumvents many of these challenges. In this study, we screened a high-resolution BMP7 peptide library and discovered several overlapping peptide sequences from two regions in BMP7 with nanomolar bioactivity that attenuated the pathological OA chondrocyte phenotype. A single exposure of OA chondrocytes to peptides p[63-82] and p[113-132] ameliorated the OA chondrocyte phenotype for up to 8 days, and peptides were bioactive on chondrocytes in OA synovial fluid. Peptides p[63-82] and p[113-132] required NKX3-2 for their bioactivity on chondrocytes and provoke changes in SMAD signaling activity. The bioactivity of p[63-82] depended on specific evolutionary conserved sequence elements common to BMP family members. Intra-articular injection of a rat medial meniscal tear (MMT) model with peptide p[63-82] attenuated cartilage degeneration. Together, this study identified two regions in BMP7 from which bioactive peptides are able to attenuate the OA chondrocyte phenotype. These BMP7-derived peptides provide potential novel disease-modifying treatment options for OA. © 2021 The Authors.

Rheumatology teams care for patients with diverse, systemic autoimmune diseases who are often immunosuppressed and at high risk of infections. The current COVID-19 pandemic has presented particular challenges in caring for and managing this patient group. The office of the chief medical officer (CMO) for England contacted the rheumatology community to provide expert advice on the identification of extremely vulnerable patients at very high risk during the COVID-19 pandemic who should be 'shielded'. This involves the patients being asked to strictly self-isolate for at least 12 weeks with additional funded support provided for them to remain at home. A group of rheumatologists (the authors) have devised a pragmatic guide to identifying the very highest risk group using a rapidly developed scoring system which went live simultaneous with the Government announcement on shielding and was cascaded to all rheumatologists working in England. © Royal College of Physicians 2020. All rights reserved.

BACKGROUND: Osteoarthritis (OA) is highly prevalent in older adults and a growing cause of disability. Easily accessible first-line treatment of OA is increasingly important. Digital self-management programs have in recent years become available. Evidence of short-term effects of such programs are abundant, yet reports on long-term benefits and adherence to treatment are scarce. The current study's objective was to investigate the long-term pain and function outcomes of people with hip or knee OA participating in a digital self-management programme. METHODS AND FINDINGS: In this longitudinal cohort study, individuals with hip and knee OA, from the register of a digital self-management program and with 0-24-week (n = 499) or 0-48-week adherence (n = 138), were included. The treatment effect in terms of monthly pain (NRS, 0-10 worst to best) and physical function (30-second chair stand test (30CST), number of repetitions) change were investigated using a mixed model, controlling for the effect of age, body mass index (BMI), gender and index joint. For the 24-week sub-sample, pain NRS decreased monthly by -0.43 units (95% CI -0.51, -0.35, mean knee pain from 5.6 to 3.1, and hip pain from 5.9 to 3.8) and 30CST repetitions increased monthly by 0.76 repetitions (95% CI 0.64, 0.89 mean for knee from 10.0 to 14.3, and for hip from 10.9 to 14.8). For the 48-week sub-sample, pain decreased monthly by -0.39 units (95% CI -0.43, -0.36, mean knee pain from 5.7 to 3.2, and hip pain from 5.8 to 3.8), and repetitions increased by 0.72 repetitions (95% CI 0.65, 0.79, mean repetitions for knee from 10.3 to 14.4, and for hip from 11.1 to 14.9). There were no clinically relevant effects on the improvement of pain or function by any covariate (age, sex, index joint). The lack of a control group and randomization limit our ability to explain the mechanisms of the observed results. CONCLUSIONS: Continuously participating in a digital OA treatment program for 6 or 12 months was associated with a clinically important decrease in joint pain and increased physical function, in hip and knee OA. Future research should follow OA-related outcomes in participants that end their treatment to ex

OBJECTIVE: Determine the relation of symptomatic and structural features of patellofemoral osteoarthritis (PFOA) to psychological characteristics and measures of pain sensitization, in older adults with or at risk of knee osteoarthritis (OA). METHODS: This study included 1112 participants from the Multicenter Osteoarthritis Study (713 females, mean age 66.8 ± SD 7.6 yrs, body mass index 29.5 ± 4.8 kg/m2). Participants were grouped based on the presence of PFOA symptoms (anterior knee pain and pain on stairs) and magnetic resonance imaging (MRI) PFOA (full-thickness cartilage lesion with bone marrow lesion): (1) patellofemoral (PF) symptoms with MRI PFOA; (2) PF symptoms without MRI PFOA; (3) MRI PFOA without PF symptoms; and (4) no PF symptoms or MRI PFOA (no PFOA). Relation of PFOA classification to depressive symptoms, catastrophizing, temporal summation (TS) and pressure pain thresholds (PPT) was evaluated using logistic (categorical variables) and linear regression (continuous variables). RESULTS: Compared with no PFOA, those with PF symptoms with or without MRI PFOA had significantly greater odds of depressive symptoms, catastrophizing, and patellar TS (OR range 1.5-2.01), and those with PF symptoms without MRI PFOA had significantly greater odds of wrist TS (OR 1.66). Males with PF symptoms without MRI PFOA had significantly lower pressure PPT at the patella compared with no PFOA and those with MRI PFOA only (no symptoms). There were no significant differences at the wrist for males, or the patella or wrist for females. CONCLUSION: Persons with PFOA symptoms, regardless of MRI PFOA status, are more likely to demonstrate depressive symptoms, catastrophizing, and TS. Males with PFOA symptoms without MRI PFOA demonstrate local hyperalgesia.

OBJECTIVE: To determine the sex-specific relation of frontal plane alignment (FPA) to magnetic resonance imaging (MRI)-defined features of patellofemoral osteoarthritis, and also to tibiofemoral osteoarthritis and knee pain. METHOD: The Multicenter Osteoarthritis Study is cohort study comprised of individuals with or at risk of knee osteoarthritis. We determined the sex-specific dose-response relation of baseline FPA to MRI-defined patellofemoral and tibiofemoral structural worsening, and incident knee pain, over 7 years. RESULTS: In women only, greater varus alignment was associated with medial patellofemoral osteophytes (risk ratio [RR] 1.7 [95% CI 1.2, 2.6]) and valgus with lateral patellofemoral osteophytes (RR 1.9 [1.0, 3.6]). In men, greater varus increased risk for medial tibiofemoral cartilage worsening (RR 1.7 [1.1, 2.6]), and valgus for lateral tibiofemoral cartilage worsening (RR 1.8 [1.6, 2.2]). In women, findings were similar for tibiofemoral cartilage, but varus also increased risk for medial bone marrow lesions [BMLs] (RR 2.2 [1.6, 3.1]) and medial osteophytes (RR 1.8 [1.3, 2.5]), and valgus for lateral BMLs (RR 3.3 [2.2, 4.5]) and osteophytes (RR 2.0 [1.2, 3.2]). Varus increased risk of incident pain in men (RR 1.7 [1.4, 2.2]) and women (RR 1.3 [1.0, 1.6]), valgus did so in men only (RR 1.5 [1.1, 1.9]). CONCLUSION: FPA was associated with patellofemoral osteophyte worsening in women, though overall was more strongly associated with tibiofemoral than patellofemoral osteoarthritis feature worsening. FPA in women was more consistently associated with structural worsening, yet men had higher associations with incident pain.

BACKGROUND: To investigate the differences in clinical characteristics and long-term treatment outcomes according to antinuclear antibody(ANA) and rheumatoid factor(RF) positivity and the correlation between pain-related and hematological indices in temporomandibular disorders(TMD) patients. METHODS: Clinical examinations were done following the Research Diagnostic Criteria for TMD in 257 patients. Comprehensive screening along with psychological and hematological evaluations (ANA, RF, complete blood cell count, C-reactive protein[CRP] and erythrocyte sedimentation rate[ESR]) were conducted. Clinical characteristics and treatment outcomes were statistically compared between ANA/RF positive and negative groups. RESULTS: Thirty-nine patients showed ANA/RF positivity. Male patients had smaller comfortable mouth opening(CMO)(p = 0.033) and maximum mouth opening(MMO)(p = 0.016) ranges with more painful neck muscles on palpation when RF/ANA positive. Pain duration, intensity, disability days and psychological distress levels were also higher in RF/ANA positive male patients. Significant correlation was shown in ESR with pain duration(p < 0.05) and numeric rating scale(NRS) before treatment(p < 0.05), CRP with NRS before treatment(p < 0.01), and red blood cell (RBC) with pain intensity(p < 0.05), NRS before treatment(p < 0.01), CMO(p < 0.01), pain on palpation of cervical muscles(p < 0.01), CMO(p < 0.05), and MMO(p < 0.05) 6 months after treatment. CONCLUSIONS: These results may point towards a nonspecific autoimmune disposition in a subgroup of TMD patients. RF and ANA could be considered as a screening test for the detection of autoimmune phenomena in TMD.

INTRODUCTION: Despite favourable results from structured face-to-face treatment of osteoarthritis (OA) in Sweden through the Better management of patients with OsteoArthritis (BOA) initiative, only around 20% of people with knee or hip OA receive the primary treatment recommended by international guidelines (ie, information, exercise, weight management). In 2014, a digital treatment programme named Joint Academy was introduced in Sweden, based on the same concept as the face-to-face BOA programme. In line with BOA, Joint Academy follows national and international guidelines and best practice for OA treatment. Results from observational studies suggest that this digital treatment is a valuable alternative to the traditional treatment approach and can positively impact patients' function and pain. However, conclusions from such studies commonly suggest that more rigorous testing is necessary to ascertain the benefits of digital treatment delivery for people with OA. METHODS AND ANALYSIS: A randomised clinical trial will be performed, comparing regular face-to-face care according to BOA with the digital version, Joint Academy. A total of 270 participants with clinically diagnosed knee OA will be recruited at primary care centres and randomised to either standard treatment (BOA) for 3 months, or the experimental group (digital intervention programme). Both groups will receive educational sessions and exercises yet with a difference in programme deliverance. The objective of the trial is to evaluate the effectiveness of the online treatment programme, in comparison with BOA. The two treatment groups will be compared with respect to the number of repetitions of the 30 s chair stand test at 3, 6 and 12 months, using a mixed model repeated measures analysis of variance. ETHICS AND DISSEMINATION: Ethical approval has been attained from the Regional Board of Ethics in Lund, Sweden (Dnr 2017/719). Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03328741. © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

OBJECTIVE: To assess structural progression in knees with no/mild radiographic osteoarthritis (OA) (i.e., Kellgren/Lawrence [K/L] grades 0-2) that will undergo knee replacement during a 5-year period; to assess differences in structural damage on magnetic resonance imaging (MRI) in knees with no/mild radiographic OA versus those with severe radiographic OA (i.e., K/L grades 3 and 4) at baseline; and to assess differences in pain levels between those groups. METHODS: All participants who underwent knee replacement from baseline to 60 months were drawn from the Osteoarthritis Initiative. MRIs were assessed for bone marrow lesions (BMLs), Hoffa synovitis, and effusion synovitis (i.e., hyperintensity signal changes in the fat pad and abnormal amount of capsular distension due to intraarticular joint fluid and/or synovial thickening) at baseline and at the time point before knee replacement (T0). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score (KOOS) pain were used for pain characterization. WOMAC activities of daily living and KOOS quality of life were applied to characterize functional status of the included participants. Logistic regression was used to assess the association of no/mild radiographic OA with these MRI features and pain. RESULTS: Based on inclusion criteria, 181 knees were selected. Participants were predominantly female (57.8%) with a mean age of 64.4 years. A total of 51 knees (28.2%) had no/mild radiographic OA at baseline. Of these, 51.0% progressed to severe radiographic OA. No/mild radiographic OA knees showed higher odds of BMLs in the patellofemoral joint at baseline (odds ratio [OR] 7.92 [95% confidence interval (95% CI) 3.45-18.16]) and T0 (OR 9.44 [95% CI 4.00-22.28]) compared to severe radiographic OA knees. In addition, no/mild radiographic OA knees were associated with change from no pain to pain from baseline to T0 (adjusted OR 5.48 [95% CI 1.25-24.00]). CONCLUSION: More than half of the knees with no/mild radiographic OA before knee replacement progressed to severe radiographic OA during 4 years of follow-up. BMLs in the patellofemoral joint were more often se

OBJECTIVE: To investigate the predictive and concurrent validity of magnetic resonance imaging (MRI)-based cartilage thickness change between baseline (BL) and year-two (Y2) follow-up (predictive validity) and between Y2 and Y4 follow-up (concurrent validity) for symptomatic and radiographic knee osteoarthritis (OA) progression during Y2→Y4. METHODS: 777 knees from 777 Osteoarthritis Initiative (OAI) participants (age: 61.3 ± 9.0 years, BMI: 30.1 ± 4.8 kg/m2) with Kellgren Lawrence (KL) grade 1-3 at Y2 (visit before progression interval) had cartilage thickness measurements from 3T MRI at BL, Y2 (n = 777), and Y4 (n = 708). Analysis of covariance and logistic regression were used to assess the association of pain progression (≥9 WOMAC units [scale 0-100], n = 205/572 with/without progression) and radiographic progression (≥0.7 mm minimum joint space width (mJSW) loss, n = 166/611 with/without progression) between Y2 and Y4 with preceding (BL→Y2) and concurrent (Y2→Y4) change in central medial femorotibial (cMFTC) compartment cartilage thickness. RESULTS: Symptomatic progression was associated with concurrent (Y2→Y4: -305 ± 470 μm vs -155 ± 346 μm, Odds ratios (OR) = 1.5 [1.2, 1.7]) but not with preceding cartilage thickness loss in cMFTC (-150 ± 276 μm vs -151 ± 299 μm, OR = 0.9 95% CI: [0.8, 1.1]). Radiographic progression, in contrast, was significantly associated with both concurrent (-542 ± 550 μm vs -98 ± 255 μm, OR = 3.4 [2.6, 4.3]) and preceding cMFTC thickness loss (-229 ± 355 μm vs -130 ± 270 μm, OR = 1.3 [1.1, 1.5]). CONCLUSIONS: These results extend previous reports that did not discern predictive vs concurrent associations of cartilage thickness loss with OA progression. The observed predictive and concurrent validity of cartilage thickness loss for radiographic progression and observed concurrent validity for symptomatic progression provide an important step in qualifying cartilage thickness loss as a biomarker of knee OA progression. CLINICALTRIALS. GOV IDENTIFICATION: NCT00080171.