Exploring different models of pain phenotypes and their association with pain worsening in people with early knee osteoarthritis: The MOST cohort study.

OBJECTIVE: To determine i) pain phenotypes (PP) in people with early-stage knee osteoarthritis (EKOA); ii) the longitudinal association between the phenotypes and pain worsening at two years. DESIGN: We studied participants with EKOA from the Multicenter Osteoarthritis Study defined as pain intensity ≤3/10, Kellgren and Lawrence grade ≤2, intermittent pain none to sometimes, and no constant pain. Two models of PP were explored. Model A included pressure pain thresholds, temporal summation, conditioned pain modulation, pain catastrophizing, sleep quality, depression, and widespread pain (WSP). In Model B, gait characteristics, quadriceps strength, comorbidities, and magnetic resonance imaging features were added to Model A. Latent Class Analysis was used to create phenotypes, and logistic regression was used to determine their association with pain worsening. RESULTS: 750 individuals (60% females), mean age [standard deviation (SD)]: 60.3 (9.4) were included in Model A and 333 individuals (60% females), mean age (SD): 59.4 (8.1) in Model B. 3-class and 4-class solutions were chosen for Model A and Model B. In Model A, the most "severe" phenotype was dominated by psychosocial factors, WSP, and measures of nervous system sensitization. Similarly in Model B, the Model A phenotype plus gait variables, quadriceps strength, and comorbidities were dominant. Surprisingly, none of the phenotypes in either model had a significant relationship with pain worsening. CONCLUSION: Phenotypes based upon various factors thought to be important for the pain experience were identified in those with EKOA but were not significantly related to pain worsening. These phenotypes require validation with clinically relevant endpoints.

Constructing a clinical radiographic knee osteoarthritis database using artificial intelligence tools with limited human labor: A proof of principle.

OBJECTIVE: To create a scalable and feasible retrospective consecutive knee osteoarthritis (OA) radiographic database with limited human labor using commercial and custom-built artificial intelligence (AI) tools. METHODS: We applied four AI tools, two commercially available and two custom-built tools, to analyze 6 years of clinical consecutive knee radiographs from patients aged 35-79 at the University of Copenhagen Hospital, Bispebjerg-Frederiksberg Hospital, Denmark. The tools provided Kellgren-Lawrence (KL) grades, joint space widths, patella osteophyte detection, radiographic view detection, knee joint implant detection, and radiographic marker detection. RESULTS: In total, 25,778 knee radiographs from 8575 patients were included in the database after excluding inapplicable radiographs, and 92.5% of the knees had a complete OA dataset. Using the four AI tools, we saved about 800 hours of radiologist reading time and only manually reviewed 16.0% of the images in the database. CONCLUSIONS: This study shows that clinical knee OA databases can be built using AI with limited human reading time for uniform grading and measurements. The concept is scalable temporally and across geographic regions and could help diversify further OA research by efficiently including radiographic knee OA data from different populations globally. We can prevent data dredging and overfitting OA theories on existing trite cohorts by including various gene pools and continuous expansion of new clinical cohorts. Furthermore, the suggested tools and applied approaches provide an ability to retest previous hypotheses and test new hypotheses on real-life clinical data with current disease prevalence and trends.

Effects of a Combination of Polynucleotide and Hyaluronic Acid for Treating Osteoarthritis.

Knee osteoarthritis (OA), an age-related degenerative disease characterized by severe pain and disability, is treated using polynucleotides (PNs) and hyaluronic acid (HA). The intra-articular (IA) injection of HA has been studied extensively in both animal models and in humans; however, the efficacy and mechanisms of action remain unclear. In addition, there has been a paucity of research regarding the use of PN alone or in combination with HA in OA. To investigate the effect of the combined injection of PN and HA in vivo, pathological and behavioral changes were assessed in an OA model. Anterior cruciate ligament transection and medial meniscectomy were performed in Sprague-Dawley rats to create the OA animal model. The locomotor activity improved following PNHA injection, while the OARSI grade improved in the medial tibia and femur. In mild OA, TNFα levels decreased histologically in the PN, HA, and PNHA groups but only the PNHA group showed behavioral improvement in terms of distance. In conclusion, PNHA exhibited anti-inflammatory effects during OA progression and improved locomotor activity regardless of the OARSI grade.

Potential surrogate outcomes in individuals at high risk for incident knee osteoarthritis.

OBJECTIVE: To study potential surrogate outcomes for osteoarthritis (OA) incidence by evaluating the association of short-term changes in clinical and imaging biomarkers with long-term clinical knee OA incidence. DESIGN: Middle-aged women with overweight/obesity, but free of knee symptoms were recruited through their general practitioners. At baseline, after 2.5 years, and after 6.5 years, questionnaires, physical examination, radiographs, and Magnetic resonance imaging (MRI) scans were obtained. The percentage of knees with a minimal clinically important difference for knee pain severity, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain/stiffness/function, and joint space narrowing, and of those with progression/regression of medial knee alignment, chronic knee pain, radiographic osteophytes, and cartilage defects, bone marrow lesions, osteophytes, and effusion/synovitis on MRI were determined. For each of these potential surrogate outcomes with ≥10% improvement or progression in the population over 2.5 years, the association with incident clinical knee OA, defined using the combined ACR-criteria, after 6.5 years was determined. RESULTS: Most pre-defined potential surrogate outcomes showed ≥10% change in the population over 2.5 years, but only worsening of TF cartilage defects, worsening of TF osteophytes on MRI, and an increase in pain severity were significantly associated with greater clinical knee OA incidence after 6.5 years. These potential surrogate outcomes had high specificity and negative predictive value (89-91%) and low sensitivity and positive predictive value (20-28%) CONCLUSIONS: Worsening of TF cartilage defects and TF osteophytes on MRI, and increased pain severity could be seen as surrogate outcomes for long-term OA incidence. However, higher positive predictive values seem warranted for the applicability of these factors in future preventive trials.

A machine learning approach reveals features related to clinicians' diagnosis of clinically relevant knee osteoarthritis.

OBJECTIVES: To identify highly ranked features related to clinicians' diagnosis of clinically relevant knee OA. METHODS: General practitioners (GPs) and secondary care physicians (SPs) were recruited to evaluate 5-10 years follow-up clinical and radiographic data of knees from the CHECK cohort for the presence of clinically relevant OA. GPs and SPs were gathered in pairs; each pair consisted of one GP and one SP, and the paired clinicians independently evaluated the same subset of knees. A diagnosis was made for each knee by the GP and SP before and after viewing radiographic data. Nested 5-fold cross-validation enhanced random forest models were built to identify the top 10 features related to the diagnosis. RESULTS: Seventeen clinician pairs evaluated 1106 knees with 139 clinical and 36 radiographic features. GPs diagnosed clinically relevant OA in 42% and 43% knees, before and after viewing radiographic data, respectively. SPs diagnosed in 43% and 51% knees, respectively. Models containing top 10 features had good performance for explaining clinicians' diagnosis with area under the curve ranging from 0.76-0.83. Before viewing radiographic data, quantitative symptomatic features (i.e. WOMAC scores) were the most important ones related to the diagnosis of both GPs and SPs; after viewing radiographic data, radiographic features appeared in the top lists for both, but seemed to be more important for SPs than GPs. CONCLUSIONS: Random forest models presented good performance in explaining clinicians' diagnosis, which helped to reveal typical features of patients recognized as clinically relevant knee OA by clinicians from two different care settings.

Whole grain consumption and risk of radiographic knee osteoarthritis: a prospective study from the Osteoarthritis Initiative.

OBJECTIVES: To assess the association of whole grain consumption with the risk of incident knee OA. MATERIAL AND METHODS: We followed 2846 participants in the Osteoarthritis Initiative ages 45-79 years. Participants were free from radiographic knee OA (Kellgren-Lawrence grade <2) in at least one knee at baseline. Dietary data from baseline were obtained using the Block Brief Food Frequency Questionnaire. We defined radiographic knee OA incidence as a Kellgren-Lawrence grade ≥2 during the subsequent 96 months. Cox proportional hazards models were used to assess the association between whole grain food intake and the risk of incident knee OA. RESULTS: During the 96 month follow-up, 518 participants (691 knees) developed incident radiographic knee OA. Higher total whole grain consumption was significantly associated with a lower knee OA risk [hazard ratio (HR)quartile 4vs1 = 0.66 (95% CI 0.52, 0.84), P for trend < 0.01] after adjusting for demographic and socio-economic factors, clinical factors and other dietary factors related to OA. Consistently, a significant inverse association of dark bread consumption with knee OA risk was observed [HRquartile 4vs1 = 0.68 (95% CI 0.53, 0.87), P for trend < 0.01). In addition, we observed a significant inverse association between higher cereal fibre intake and reduced knee OA risk [HRquartile 4vs1 = 0.61 (95% CI 0.46, 0.81), P for trend < 0.01). CONCLUSIONS: Our findings revealed a significant inverse association of whole grain consumption with knee OA risk. These findings provide evidence that eating a diet rich in whole grains may be a potential nutritional strategy to prevent knee OA.

A systematic review of the sex differences in risk factors for knee osteoarthritis.

OBJECTIVES: Previous systematic reviews focused on the evidence of common risk factors for knee OA (KOA); however, the effect and strength of association between risk factors and KOA might be different between the two sexes. The aim of the present systematic review was to determine the current evidence on sex differences in the association between risk factors and KOA and their prevalence. METHODS: We searched the following electronic bibliographic databases: MEDLINE (PubMed), EMBASE and Web of Science. A methodological quality assessment was conducted independently by two researchers according to an adapted version of the standardized set of criteria known as the Newcastle-Ottawa Quality Assessment Scale (NOS). The NOS, a star system, was converted to three categories of quality. RESULTS: In total, 27 studies reported sex-specific risk estimates on several risk factors for KOA. Out of the 22 longitudinal cohort studies (except one nested case-control), 12 were of good quality and 10 were of fair quality. The five cross-sectional studies consisted of one of good, three of fair and one of poor quality. There was an indication of sex differences in risk factors leading to higher risk of KOA: high BMI, alcohol consumption, atherosclerosis and high vitamin E levels in women, and high physical activity, soft drink consumption and abdominal obesity in men. Knee injury, high blood pressure and low step rate seem to affect both women and men. CONCLUSION: More good quality studies are needed to assess sex differences in risk factors for KOA, especially for symptomatic/clinical OA.

Mesenchymal stem cell implantation provides short-term clinical improvement and satisfactory cartilage restoration in patients with knee osteoarthritis but the evidence is limited: a systematic review performed by the early-osteoarthritis group of ESSKA-European knee associates section.

PURPOSE: Implantation of mesenchymal stem cells (MSCs) is a potential cell-based modality for cartilage repair. Currently, its clinical use largely surrounds focal cartilage defect repair and intra-articular injections in knee osteoarthritis. The MSCs' implantation efficacy as a treatment option for osteoarthritis remains contentious. This systematic review aims to evaluate studies that focused on MSCs implantation in patients with knee OA to provide a summary of this treatment option outcomes. METHODS: A systematic search was performed in PubMed (Medline), Scopus, Cinahl, and the Cochrane Library. Original studies investigating outcomes of MSCs implantations in patients with knee OA were included. Data on clinical outcomes using subjective scores, radiological outcomes, and second-look arthroscopy gradings were extracted. RESULTS: Nine studies were included in this review. In all included studies, clinical outcome scores revealed significantly improved functionality and better postoperative pain scores at 2-3 years follow-up. Improved cartilage volume and quality at the lesion site was observed in five studies that included a postoperative magnetic resonance imaging assessment and studies that performed second-look arthroscopy. No major complications or tumorigenesis occurred. Outcomes were consistent in both single MSCs implantation and concurrent HTO with MSCs implantation in cases with excessive varus deformity. CONCLUSION: According to the available literature, MSCs implantation in patients with mild to moderate knee osteoarthritis is safe and provides short-term clinical improvement and satisfactory cartilage restoration, either as a standalone procedure or combined with HTO in cases with axial deformity. However, the evidence is limited due to the high heterogeneity among studies and the insufficient number of studies including a control group and mid-term outcomes. LEVEL OF EVIDENCE: IV.

The impact of post-traumatic stress on the clinical outcome in a cohort of patients with knee osteoarthritis and knee arthroplasty: A prospective study.

BACKGROUND: Knee osteoarthritis (KOA) is one of the most common musculoskeletal disorders and commonly occurs in older adults, predominantly female populations. Both populations have intimate links with trauma-related stress. Therefore, we intended to evaluate the prevalence of post-traumatic stress disorder (PTSD), which arises from KOA and determine its effects on the postoperative results in patients undergoing total knee arthroplasty (TKA). METHODS: The patients who fulfilled the diagnosis of KOA from February 2018 to October 2020 were interviewed. Patients were interviewed by a senior psychiatrist about evaluating their overall experience during their most difficult or stressful situations. KOA patients who underwent TKA were further analyzed to investigate whether PTSD influences the postoperative results. The PTSD Checklist-Civilian Version (PCL-C) and Western Ontario McMaster Universities (WOMAC) Osteoarthritis Index were used to assess PTS symptoms and clinical outcomes after TKA, respectively. RESULTS: 212 KOA patients completed this study with a mean follow-up of 16.7 months (7-36 months). The mean age was 62.5 ± 12.3 years, and 53.3% (113/212) were women. 64.6% of the sample (137/212) underwent TKA to relieve the symptoms of KOA. Patients with either PTS or PTSD tended to be younger (P < 0.05), female (P < 0.05) and undergo TKA (P < 0.05) than their counterparts. WOMAC-pain (P < 0.05), WOMAC-stiffness (P < 0.05), and WOMAC-physical function (P < 0.05) both before TKA and 6 months after TKA in the PTSD group is significantly higher compared to their counterparts. Logistic regression analysis showed that a history of OA-inducing trauma (adjusted OR = 2.0, 95% CI = 1.7-2.3, P = 0.003), posttraumatic KOA (adjusted OR = 1.7, 95% CI = 1.4-2.0, P < 0.001), and invasive treatment (adjusted OR = 2.0, 95% CI = 1.7-2.3, P = 0.032), were significantly associated with PTSD in KOA patients. CONCLUSIONS: Patients with KOA, especially those undergoing TKA, are associated with PTS symptoms and PTSD, indicating the need to evaluate it and offer care for them.

Patients with stage II of the knee osteoarthritis most likely benefit from the intra-articular injections of autologous adipose tissue-from 2 years of follow-up studies.

BACKGROUND: Knee osteoarthritis (OA) is a common, chronic, progressive and degenerative disease which affects patients' quality of life and may cause disability and social isolation. OA is a huge economic burden for the patient and a large strain for the whole healthcare system. Articular cartilage has a small potential to repair, with progressively more clinicians emphasizing cellular therapy. Subcutaneous fat tissue in human body is a large reservoir of mesenchymal stem cells (MSCs) and is been harvested in minimally invasive, simple procedure. The purpose of this study was to define a specific group of patients with knee osteoarthritis, who are the most likely to benefit from the treatment with intra-articular injection of an autologous adipose tissue (AAT). METHODS: From 2016 to 2018, 59 symptomatic bilateral and unilateral knee OA patients were treated with a single intra-articular (IA) injection of an autologous adipose tissue (AAT). Before the treatment and at the follow-up, the participant was asked to fulfill the Knee Injury and Osteoarthritis Outcome Score (KOOS), the International Knee Documentation Committee 2000 (IKDC 2000), The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Health Questionnaire EQ-5D-5L and to quantify the pain in the affected joint with a Numeric Rating Scale (NRS). Moreover, the patients were asked to: (i) assess their satisfaction with the effects of the conducted treatment: from 0 (unsatisfied) to 10 (very satisfied), (ii) describe the rehabilitation, if it was performed (supervised or individual and duration in weeks) and (iii) indicate any additional treatment applied, like IA injections of hyaluronic acid (HA) or platelet-rich plasma (PRP), knee arthroscopy, partial or total knee arthroplasty (TKA) at the follow-up. RESULTS: The mean age of 37 participants (16 males and 21 females) included into statistical analysis was 57.78 ± 7.39 years, the mean BMI was 31.30 ± 7.51. The questionnaires were fulfilled after the average follow-up time of 27 ± 6.5 months. A significant difference (p < 0.05) compared with the baseline, was observed in pain [NRS], WOMAC, KOOS index, pain, symptoms, ADL, Sport and Rec, QoL, EQ-5D-5L index. The satisfaction in the whole group was 6.16 ± 3.07. There was no significant difference between satisfied and unsatisfied patients in BMI and pain [NRS] at the baseline. 6 out of 7 patients with stage IV in K-L were unsatisfied with the effects of the treatment with AAT. DISCUSSION: The main conclusion of this study is that the patients with stage II of the knee OA with normal BMI are were most likely to benefit from IA injection of AAT, in contrast to the patients with stage IV, who will not beware not satisfied with the effectiveness of this kind of treatment. There were no adverse events reported at the donor site as well as in the treated knee joints.

Health-Related Quality of Life in Patients with Osteoarthritis of the Knee attending two Outpatient Clinics in Jos, Nigeria: A Cross-Sectional Descriptive Study.

BACKGROUND: It appears particularly suitable to measure healthrelated quality of life (HRQoL) in patients with knee osteoarthritis (OA) because the chronic debilitating nature of this disease likely takes a considerable toll on HRQoL. The study aims to assess the health-related quality of life in patients with symptomatic knee osteoarthritis attending the two outpatient clinics. The study also aimed to determine factors affecting the HRQoL in patients with knee OA. METHODS: A facility based, cross sectional descriptive study using the abbreviated World Health Organisation Quality of Life (WHOQOL-BREF) (26-item) questionnaire was carried out in two out-patient (general and orthopaedic) clinics of the University Teaching Hospital, Jos, Nigeria over a period of two months. The medical assistants, record staffs and nurses were involved in recruiting the patients while the Family Physicians performed the interview. RESULTS: A total of 120 participants were recruited. The mean age was 58.41±13.03 years and the majority of the respondents were female, constituting 102 (85%) of the participants. The mean body mass index (BMI) was 30.83±7.12 kg/m2 and more than half of the participants were obese. The most common associated chronic disease was hypertension, reported by 93(77.5%). A majority, 86(72%) of the respondents reported their overall QoL and General Health (GH) as poor or fair and all the domains (physical, psychological, social relationships, and environmental) of the QoL were low. QoL scores were relatively low for domain due to psychological health and environment with that of psychological health being more severely affected. Epilepsy was found to affect QoL in patients with knee OA (p= 0.022). There was no significant effect of age, sex, educational status, employment status, marital status, and family income on QoL. CONCLUSION: This study has shown that patients with knee OA attending the outpatient clinics in JUTH, Jos have relatively poor HRQoL with the domain due to psychological health being more severely affected.

CONTEXTE: Il semble particulièrement approprié de mesurer la qualité de vie liée à la santé (QVLS) chez les patients souffrant d'arthrose du genou, car la nature chronique et débilitante de cette maladie a probablement un impact considérable sur la QVLS. L'étude vise à évaluer la qualité de vie liée à la santé des patients souffrant d'arthrose symptomatique du genou qui fréquentent les deux centres de soins ambulatoires. L'étude vise également à déterminer les facteurs affectant la QVLS chez les patients souffrant d'arthrose du genou. MÉTHODES: Une étude descriptive transversale basée sur l'établissement et utilisant le questionnaire abrégé de l'Organisation mondiale de la santé sur la qualité de vie (WHOQOL-BREF) (26 éléments) a été réalisée dans deux cliniques ambulatoires (générale et orthopédique) de l'hôpital universitaire de Jos, au Nigeria, sur une période de deux mois. Les assistants médicaux, le personnel chargé des dossiers et les infirmières ont participé au recrutement des patients, tandis que les médecins de famille ont mené les entretiens. RÉSULTATS: Au total, 120 participants ont été recrutés. L'âge moyen était de 58,41±13,03 ans et la majorité des répondants étaient des femmes, constituant 102 (85%) des participants. L'indice de masse corporelle (IMC) moyen était de 30,83±7,12 kg/m2 et plus de la moitié des participants étaient obèses. La maladie chronique associée la plus fréquente était l'hypertension, signalée par 93 (77,5 %). Une majorité, 86 (72%) des personnes interrogées ont déclaré que leur qualité de vie globale et leur état de santé général étaient mauvais ou moyens et que tous les domaines (physique, psychologique, relations sociales et environnement) de la qualité de vie étaient faibles. Les scores de qualité de vie étaient relativement bas dans les domaines de la santé psychologique et de l'environnement, la santé psychologique étant plus gravement affectée. On a constaté que l'épilepsie affectait la qualité de vie des patients souffrant d'arthrose du genou (p = 0,022). L'âge, le sexe, le niveau d'éducation, la situation professionnelle, la situation matrimoniale et le revenu familial n'avaient pas d'effet significatif sur la qualité de vie. CONCLUSION: Cette étude a montré que les patients atteints d'arthrose du genou qui fréquentent les services de consultation externe de l'hôpital JUTH de Jos ont une qualité de vie relativement médiocre, le domaine de la santé psychologique étant le plus gravement touché. Mots-clés: Qualité de vie liée à la santé, Arthrose du genou, Questionnaire WHOQOL-BREF, Consultations externes.

Osteoarthritis knee and modifiable cardiovascular risk factors: play in tandem.

Objective: To know the frequency of modifiable cardiovascular risk factors in knee osteoarthritis patients. Method: Cross sectional study was done at Department of Rheumatology Indus Medical College, Tando Mohammad Khan from March 25, 2022 to November 24, 2022. Total 246 Osteoarthritis of knee cases with (Kellgren-Lawrence grad-II and above) on x-ray, were selected after demographic details, blood pressure, body mass index and physical examination was done, 5ml of venous blood was drawn by phlebotomist, sent for fasting blood sugar, serum lipids analysis and Framingham 10years risk score was calculated afterward for each participant. Results: In this study males (126) and females (120). Overall (78%) had risk factors, Patients having one CVD risk factor were (22.8%), two risk factors in (21.1%), three in (21.5%), four (9.8%) and five factors in (1.6%) while frequency of modifiable cardiovascular risk shows obesity (45.5%) hypertension (40.2%) intermediate to high risk of framingham score (40%) diabetes mellitus (25%), smoking (17%), high low density lipoproteins (8.1%). In males obesity(54.2%), hypertension (47.5% ) and (45.8%) were on medication, diabetes mellitus(31.7%), smoker(31%), high risk FRS(39.2%), K-L grade-IV(58.4%) and in females: obesity (42%), hypertension (43.7%) and (40.5%) were on medication, diabetes mellitus in (19%), smoking (4%), high risk FRS (13.5%), K-L Grade-4 (42%), significant association of diabetes mellitus, smoking, FRS and K-L grades with gender (p<0.05). Conclusion: In OA knee there is high prevalence of modifiable cardiovascular risk factors and together these imposes a major health risk for future cardiac events and disability.

Italian Orthopaedic and Traumatology Society (SIOT) position statement on the non-surgical management of knee osteoarthritis.

BACKGROUND: Knee osteoarthritis (OA) is a chronic disease associated with a severe impact on quality of life. However, unfortunately, there are no evidence-based guidelines for the non-surgical management of this disease. While recognising the gap between scientific evidence and clinical practice, this position statement aims to present recommendations for the non-surgical management of knee OA, considering the available evidence and the clinical knowledge of experienced surgeons. The overall goal is to offer an evidenced-based expert opinion, aiding clinicians in the management of knee OA while considering the condition, values, needs and preferences of individual patients. METHODS: The study design for this position statement involved a preliminary search of PubMed, Google Scholar, Medline and Cochrane databases for literature spanning the period between January 2021 and April 2023, followed by screening of relevant articles (systematic reviews and meta-analyses). A Società Italiana Ortopedia e Traumatologia (SIOT) multidisciplinary task force (composed of four orthopaedic surgeons and a rheumatologist) subsequently formulated the recommendations. RESULTS: Evidence-based recommendations for the non-surgical management of knee OA were developed, covering assessment, general approach, patient information and education, lifestyle changes and physical therapy, walking aids, balneotherapy, transcutaneous electrical nerve stimulation, pulsed electromagnetic field therapy, pharmacological interventions and injections. CONCLUSIONS: For non-surgical management of knee OA, the recommended first step is to bring about lifestyle changes, particularly management of body weight combined with physical exercise and/or hydrotherapy. For acute symptoms, non-steroidal anti-inflammatory drugs (NSAIDs), topic or oral, can be used. Opioids can only be used as third-line pharmacological treatment. Glucosamine and chondroitin are also suggested as chronic pharmacological treatment. Regarding intra-articular infiltrative therapy, the use of hyaluronic acid is recommended in cases of chronic knee OA [platelet-rich plasma (PRP) as second line), in the absence of active acute disease, while the use of intra-articular injections of cortisone is effective and preferred for severe acute symptoms.

Effusion-synovitis worsening mediates the association between body mass index and Kellgren-Lawrence progression in obese individuals: data from the Osteoarthritis Initiative.

OBJECTIVE: Both obesity and synovitis are independently associated with knee osteoarthritis (KOA) progression. We examined whether synovitis mediates the relationship between body mass index (BMI) and KOA radiographic progression in the Osteoarthritis Initiative (OAI) cohort. DESIGN: We conducted a case-control study within the OAI. Cases (n = 315) were right knees with an increase of ≥1 Kellgren-Lawrence from baseline to 48 months of follow-up. Controls (n = 315) were right knees with no KL change. Cases and controls were matched by age, sex, race, and baseline KL. MRI Osteoarthritis Knee Score (MOAKS) at baseline and at 2 years was used for a semi-quantitative scoring (0-3) of effusion-synovitis and Hoffa-synovitis. Conditional logistic regression estimated associations between BMI and synovitis with KOA progression. Mediation analysis was used to assess the mediating effects of synovitis. RESULTS: The mean age of participants was 61 years, 70.8% were women, and 87% were White. KOA progression was associated with higher BMI (adjusted OR 1.05; 95%CI 1.01-1.09) and effusion-synovitis relative to no effusion-synovitis (adjusted OR 2.2; 95%CI 1.6-3.1). Associations between effusion-synovitis worsening and KOA progression were more pronounced among obese individuals (OR 34.1; 95%CI 4.2-274.8; P = 0.001) compared to normal weight (OR 3.2; 95%CI 0.8-12.8, P=0.096) individuals. Effusion-synovitis at 2 years, but not at baseline, mediated the relationship between BMI and KOA progression over a 4-year period. CONCLUSIONS: We found that effusion-synovitis worsening mediated the association between BMI and KOA progression and was associated with increased risk of KOA progression, particularly among obese individuals.

Does weight-bearing versus non-weight-bearing pain reflect different pain mechanisms in knee osteoarthritis?: the Multicenter Osteoarthritis Study (MOST).

OBJECTIVE: Knee osteoarthritis (OA) is predominantly characterized by pain with weight-bearing activities. Pain at rest also occurs but the mechanisms for this are not clear. We evaluated the relations of nociceptive signal alterations to weight-bearing and non-weight-bearing pain in knee OA. DESIGN: We used data from a NIH-funded longitudinal cohort of older adults with or at risk of knee OA. We evaluated quantitative sensory testing (QST) measures (pressure pain threshold (PPT) at patellae and the wrist; mechanical temporal summation (TS); conditioned pain modulation (CPM)). Each WOMAC pain question was dichotomized as having at least moderate pain, and we further categorized them as weight-bearing pain and non-weight-bearing pain. We evaluated the relation of QST measures to each pain outcome using logistic regression, adjusting for potential confounders. RESULTS: 2,749 participants (5,479 knees) were included (mean age 64 ± 11, 57% female). Each SD unit decrease in patellar PPT was associated with greater odds of both weight-bearing pain (OR 1.51 (95% CI 1.27, 1.79)) and non-weight-bearing pain (OR 1.46 (1.20-1.77)), while wrist PPT was associated with greater odds of weight-bearing pain (OR 1.27 (1.15, 1.39)) but only with pain during sitting/lying (OR 1.20 (1.01, 1.43)). TS was significantly associated with greater odds of pain with walking and stairs (OR 1.11 (1.01, 1.23), 1.11 (1.03, 1.20), respectively). CPM was not associated with any pain outcomes. CONCLUSIONS: Our findings challenge the hypothesis that non-weight-bearing pain may reflect greater pain sensitization and/or inefficient CPM than weight-bearing pain in knee OA, suggesting other mechanisms are likely responsible.

The Efficacy of Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis Symptoms and Structural Changes: A Systematic Review and Meta-Analysis.

BACKGROUND: Platelet-rich plasma (PRP) usage in orthopedics continues to rise, despite guidelines suggesting non-superiority to comparative cohorts. Therefore, we performed a systematic review and meta-analysis on PRP efficacy using two clinical assessments: (1) Visual Analog Scale and (2) Western Ontario and McMaster Universities Osteoarthritis Index. We assessed consistency and clinical relevancy by determining study heterogeneity (eg, sample sizes, ages, body mass index, arthritic severities, etc.). Comparative cohorts were: (A) hyaluronic acid (HA); (B) corticosteroid (CS); (C) normal saline (NS); and (D) exercise therapy. We performed sub-analyses of structural changes assessed on ultrasound, radiograph, or magnetic resonance imaging . METHODS: We utilized PubMed, Cochrane Library, and Embase databases up to December 1, 2021, according to Preferred Reporting Items for Systematic-Reviews and Meta-Analyses guidelines. Twenty-four studies met criteria, with comparisons to: HA (n = 11); CS (n = 6); NS (n = 5); and exercise therapy (n = 3). Seven studies assessed structural changes. Evaluations utilized a methodological scoring system. I2 statistics and forest plots pooled analyses and delineated study results. RESULTS: PRP led to Visual Analog Scale and Western Ontario and McMaster Universities Osteoarthritis Index improvements in most studies when compared to HA, CS, and NS (P ≤ .05). Comparison to exercise therapy resulted in inconclusive findings (P ≥ .05). However, substantial heterogeneity (I2 ≥ 76%) was reported due to study variability. No differences were found when assessing structural changes or cartilage thickness by magnetic resonance imaging (standardized mean difference -0.01 [-0.19, 0.18], P = .91). CONCLUSIONS: PRP may be associated with pain and functional improvements but was not clinically relevant (inconsistent study- and patient-metrics). In addition, PRP did not confer superiority when assessing knee-related structural changes.

Causal association of adipokines with osteoarthritis: a Mendelian randomization study.

OBJECTIVE: This two-sample Mendelian randomization study aimed to delve into the effects of genetically predicted adipokine levels on OA. METHODS: Summary statistic data for OA originated from a meta-analysis of a genome-wide association study with an overall 50 508 subjects of European ancestry. Publicly available summary data from four genome-wide association studies were exploited to respectively identify instrumental variables of adiponectin, leptin, resistin, chemerin and retinol-blinding protein 4. Subsequently, Mendelian randomization analyses were conducted with inverse variance weighted (IVW), weighted median and Mendelian randomization-Egger regression. Furthermore, sensitivity analyses were then conducted to assess the robustness of our results. RESULTS: The positive causality between genetically predicted leptin level and risk of total OA was indicated by IVW [odds ratio (OR): 2.40, 95% CI: 1.13-5.09] and weighted median (OR: 2.94, 95% CI: 1.23-6.99). In subgroup analyses, evidence of potential harmful effects of higher level of adiponectin (OR: 1.28, 95% CI: 1.01-1.61 using IVW), leptin (OR: 3.44, 95% CI: 1.18-10.03 using IVW) and resistin (OR: 1.18, 95% CI: 1.03-1.36 using IVW) on risk of knee OA were acquired. However, the mentioned effects on risk of hip OA were not statistically significant. Slight evidence was identified supporting causality of chemerin and retinol-blinding protein 4 for OA. The findings of this study were verified by the results from sensitivity analysis. CONCLUSIONS: An association between genetically predicted leptin level and risk of total OA was identified. Furthermore, association of genetically predicted levels of adiponectin, leptin and resistin with risk of knee OA were reported.

Maturation process of regenerated tissues after single-stage simultaneous autologous particulated cartilage implantation and open wedge high tibial osteotomy for articular cartilage defects with medial osteoarthritis of bilateral knees: a case report.

BACKGROUND: Open wedge high tibial osteotomy (OWHTO) is an effective treatment option for young and middle-aged active patients with medial unicompartmental knee osteoarthritis (OA). In addition, particulated cartilage implantation has been developed as a simple procedure for cartilage regeneration. Thus, to improve the OWHTO outcomes, a single-stage, simultaneous bilateral knee arthroscopic particulated cartilage implantation with OWHTO was performed. CASE PRESENTATION: A 60-year-old male patient presented with severe bilateral knee pain, with grade 2 varus knee OA of the Kellgren-Lawrence classification. Primary arthroscopic evaluations based on the International Cartilage Repair Society grading system showed grade 3c articular cartilage defects of 1.5 cm in diameter at the center of the bilateral medial femoral condyles. Following bilateral OWHTO, the healthy cartilage tissue was harvested from the lateral wall of the unilateral femoral intercondylar notch and minced with the cartilage processor. Then, subchondral drillings and cartilage fragment implantations into the bilateral defects were performed arthroscopically. One year postsurgery, second-look arthroscopy findings revealed that the defects were filled with cartilage-like tissues. The maturation process of the regenerated tissues was confirmed with T2 mapping magnetic resonance imaging during the 3-year follow-up period. The patient could walk without a cane, and all Knee Injury and Osteoarthritis Outcome Score parameters were improved without any correction loss in 3 years. CONCLUSIONS: This is the first report to evaluate the maturation process of the implanted particulated cartilage tissue with T2 mapping magnetic resonance imaging for 3 years. The effect of chondral resurfacing procedure with OWHTO remains unclear; however, the implantation of arthroscopic particulated cartilage fragments is a single-stage and less-invasive procedure. This treatment could regenerate cartilage-like tissue in the present case. Therefore, this additional procedure could potentially improve the long-term outcomes of OWHTO.

To what extent is severe osteoarthritis preventable? Occupational and non-occupational risk factors for knee and hip osteoarthritis.

OBJECTIVES: To explore the relative contribution of cumulative physical workload, sociodemographic and lifestyle factors, as well as prior injury to hospitalization due to knee and hip OA. METHODS: We examined a nationally representative sample of persons aged 30-59 years, who participated in a comprehensive health examination (the Health 2000 Study). A total of 4642 participants were followed from mid-2000 to end-2015 for the first hospitalization due to knee or hip OA using the National Hospital Discharge Register. We examined the association of possible risk factors with the outcome using a competing risk regression model (death was treated as competing risk) and calculated population attributable fractions for statistically significant risk factors. RESULTS: Baseline age and BMI as well as injury were associated with the risk of first hospitalization due to knee and hip OA. Composite cumulative workload was associated with a dose-response pattern with hospitalizations due to knee OA and with hospitalizations due to hip OA at a younger age only. Altogether, prior injury, high BMI and intermediate to high composite cumulative workload accounted for 70% of hospitalizations due to knee OA. High BMI alone accounted for 61% and prior injury only for 6% of hospitalizations due to hip OA. CONCLUSION: Our results suggest that overweight/obesity, prior injury and cumulative physical workload are the most important modifiable risk factors that need to be targeted in the prevention of knee OA leading to hospitalization. A substantial proportion of hospitalizations due to hip OA can be reduced by controlling excess body weight.

Incidence and risk factors of symptomatic knee osteoarthritis among the Chinese population: analysis from a nationwide longitudinal study.

BACKGROUND: Knee osteoarthritis (OA) is a common disease condition associated with aging and a frequent cause of primary care consultations. Few longitudinal studies have been conducted to investigate the incidence of symptomatic knee osteoarthritis (OA) and to identify its risk factors among the Chinese population. METHODS: The China Health and Retirement Longitudinal Study (CHARLS) is a nationwide longitudinal survey of persons aged ≥45 years. Symptomatic knee OA was diagnosed when both self-reported knee pain and self-reported physician-diagnosis arthritis existed. Using the national survey data collected from the CHARLS, we estimated the incidence of symptomatic knee OA, taking into account the complex survey design and response rate. We applied weighted logistic regression analysis to identify its risk factors. RESULTS: In the 4-year follow-up, the cumulative incidence of symptomatic knee OA among middle-aged and older Chinese adults was 8.5%; the incidence was higher among females (11.2%) than males (5.6%). Female (odds ratio (OR) 1.98 [95% confidence interval (CI) 1.65-2.37]), rural area (OR 1.32 [95% CI 1.08-1.60]), and West region (OR 2.33 [95% CI 1.89-2.87]) were associated with a higher risk of incident symptomatic knee OA. Physical activities (OR 0.47 [95% CI 0.29-0.76]) and high education level (OR 0.60 [95% CI 0.41-0.88]) was associated with a lower risk of incident symptomatic knee OA, while histories of heart disease (OR 1.40 [95% CI 1.07-1.82]), kidney disease (OR 1.80 [95% CI 1.35-2.39]), and digestive disease (OR 1.54 [95% CI 1.30-1.82]) were associated with a higher risk of incident symptomatic knee OA. CONCLUSION: The cumulative incidence of symptomatic knee OA over 4 years was relatively high, and varied by province and region. Lack of physical activities was confirmed to be risk factors of incident symptomatic knee OA. The presence of heart disease, kidney disease, and digestive disease may be associated with a higher risk of incident symptomatic knee OA, further research need to confirm these findings.