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Objective: To investigate to what extent the higher risk of tibiofemoral radiographic osteoarthritis (TFROA) in females vs. males can be explained by knee malalignment., Design: Using data from Multicenter Osteoarthritis Study (MOST) and Osteoarthritis Initiative (OAI), we examined the relation of sex to the incident medial and lateral TFROA and performed mediation analyses to assess to what extent varus and valgus malalignments account for sex differences in the incident medial or lateral TFROA., Results: Of the 3462 knees without medial and lateral TFROA in MOST, the 7-year risks of medial and lateral TFROA were 16.9% and 10.0% in females, and 15.8% and 4.2% in males, respectively. Females had 2.31-fold (95% confidence interval [95% CI]: 1.73 to 3.08) higher incident lateral TFROA than males, and the relative risk (RR) of the indirect effect of sex on lateral TFROA through valgus malalignment was 1.15 (95% CI: 1.09 to 1.20), accounting for 23% of its total effect on lateral TFROA. In OAI (n = 3095 knees), females had 1.54-fold (95% CI: 1.15 to 2.04) higher incident lateral TFROA than males, and RR of the indirect effect of sex on lateral TFROA through valgus malalignment was 1.10 (95% CI: 1.04 to 1.21), accounting for 26% of its total effect on lateral TFROA. No apparent sex difference in the incident medial TFROA was found in MOST (RR = 1.05, 95% CI: 0.89 to 1.25) or OAI (RR = 1.02, 95% CI: 0.84 to 1.19)., Conclusion: Females had a higher risk of developing lateral TFROA than males; however, valgus malalignment only modestly explained such a difference., Competing Interests: Declaration of Competing Interest The authors declare no competing interest., (Copyright © 2024 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: The current guidelines recommend weight loss for patients with overweight or obesity and knee or hip osteoarthritis (OA); however, there is a paucity of data on the relation of weight loss to death among patients with OA. We aimed to examine the relation of the rate of weight loss induced by antiobesity medications over one year to all-cause mortality among patients with overweight or obesity and knee or hip OA., Methods: Using the IQVIA Medical Research Database, we identified people with overweight or obesity and knee or hip OA. We emulated analyses of a hypothetical target trial to assess the effect of slow-to-moderate (2%-10%) or fast (≥10%) weight loss induced by the initiation of antiobesity medications within one year on all-cause mortality and secondary outcomes over five years' follow-up., Results: Among 6,524 participants, the five-year all-cause mortality rates were 5.3%, 4.0%, and 5.4% for weight gain or stable, slow-to-moderate weight loss, and fast weight loss arms, respectively. Compared with the weight gain or stable arm, hazard ratios of all-cause mortality were 0.72 (95% confidence interval [CI] 0.56-0.92) for the slow-to-moderate weight loss arm and 0.99 (95% CI 0.67-1.44) for the fast weight loss arm. We found dose-response protective effects of weight loss on incident hypertension, type 2 diabetes, and venous thromboembolism but a slightly higher risk of cardiovascular disease, albeit not statistically significant, in the fast rate of weight loss arm than in the weight gain or stable arm and no significant relations of weight loss to the risk of cancer., Conclusion: In this population-based study, a slow-to-moderate, but not fast, rate of weight loss induced by antiobesity medications is associated with a lower risk of all-cause mortality in people with overweight or obesity and knee or hip OA., (© 2023 American College of Rheumatology.)

Melatonin exhibits potential for pain relief and long-term safety profile. We examined the analgesic effects of oral melatonin on osteoarthritis (OA) and investigated the underlying mechanism. Using data from a UK primary care database, we conducted a cohort study in individuals with OA to compare the number of oral analgesic prescriptions and the risk of knee/hip replacement between melatonin initiators and hypnotic benzodiazepines (i.e., active comparator) initiators using quantile regression models and Cox-proportional hazard models, respectively. To elucidate causation, we examined the effects of melatonin on pain behaviors and explored several metabolites that may serve as potential regulatory agents of melatonin in the monoiodoacetate rat model of OA. Using data from another community-based cohort study, that is, the Xiangya OA Study, we verified the association between the key serum metabolite and incident symptomatic knee OA. Compared with the hypnotic benzodiazepines cohort (n = 8135), the melatonin cohort (n = 813) had significantly fewer subsequent prescriptions of oral analgesics (50th percentile: 5 vs. 7, 75th percentile: 19 vs. 29, and 99th percentile: 140 vs. 162) and experienced a lower risk of knee/hip replacement (hazard ratio = 0.47, 95% Cl: 0.30-0.73) during the follow-up period. In rats, oral melatonin alleviated pain behaviors and increased serum levels of glycine. There was an inverse association between baseline serum glycine levels and the risk of incident symptomatic knee OA in humans (n = 760). In conclusion, our findings indicate that oral melatonin shows significant potential to be a novel treatment for OA pain. The potential role of glycine in its analgesic mechanism warrants further investigation., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Identification of knee osteoarthritis (OA) pain phenotypes, their transition patterns, and risk factors for worse phenotypes, may guide prognosis and targeted treatment; however, few studies have described them. We aimed to investigate different pain phenotypes, their transition patterns, and potential risk factors for worse pain phenotypes., Methods: Utilizing data from the Osteoarthritis Initiative (OAI), pain severity was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. We identified the activity-related pain phenotypes and estimated the transition probabilities of pain phenotypes from baseline to the 24-month using latent transition analysis. We examined the risk factors at baseline with the 24-month pain phenotypes and the transition of pain phenotypes., Results: In 4796 participants, we identified four distinct knee pain phenotypes at both baseline and 24-month follow-up: no pain, mild pain during activity (Mild P-A), mild pain during both rest and activity (Mild P-R-A), and moderate pain during both rest and activity (Mod P-R-A). 82.9% knees with no pain at baseline stayed the same at 24-month follow-up, 17.1% progressed to worse pain phenotypes. Among "Mild P-A" at baseline, 32.0% converted to no-pain, 12.8% progressed to "Mild P-R-A", and 53.2% remained. Approximately 46.1% of "Mild P-R-A" and 54.5% of "Mod P-R-A" at baseline experienced remission by 24-month. Female, non-whites, participants with higher depression score, higher body mass index (BMI), higher Kellgren and Lawrence (KL) grade, and knee injury history were more likely to be in the worse pain phenotypes, while participants aged 65 years or older and with higher education were less likely to be in worse pain phenotypes at 24-month follow-up visit. Risk factors for greater transition probability to worse pain phenotypes at 24-month included being female, non-whites, participants with higher depression score, higher BMI, and higher KL grade., Conclusions: We identified four distinct knee pain phenotypes. While the pain phenotypes remained stable in the majority of knees over 24 months period, substantial proportion of knees switched to different pain phenotypes. Several socio-demographics as well as radiographic lesions at baseline are associated with worse pain phenotypes at 24-month follow-up visit and transition of pain phenotypes., (© 2024. The Author(s).)

Objective: Clinical guidelines recommend exercise as a core treatment for knee or hip osteoarthritis (OA). However, how its analgesic effect compares to analgesics, for example, oral non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol-the most commonly used analgesics for OA, remains unknown., Design: Network meta-analysis., Data Sources: PubMed, Embase, Scopus, Cochrane Library and Web of Science from database inception to January 2022., Eligibility Criteria for Selecting Studies: Randomised controlled trials (RCTs) comparing exercise therapy with oral NSAIDs and paracetamol directly or indirectly in knee or hip OA., Results: A total of n=152 RCTs (17 431 participants) were included. For pain relief, there was no difference between exercise and oral NSAIDs and paracetamol at or nearest to 4 (standardised mean difference (SMD)=-0.12, 95% credibility interval (CrI) -1.74 to 1.50; n=47 RCTs), 8 (SMD=0.22, 95% CrI -0.05 to 0.49; n=2 RCTs) and 24 weeks (SMD=0.17, 95% CrI -0.77 to 1.12; n=9 RCTs). Similarly, there was no difference between exercise and oral NSAIDs and paracetamol in functional improvement at or nearest to 4 (SMD=0.09, 95% CrI -1.69 to 1.85; n=40 RCTs), 8 (SMD=0.06, 95% CrI -0.20 to 0.33; n=2 RCTs) and 24 weeks (SMD=0.05, 95% CrI -1.15 to 1.24; n=9 RCTs)., Conclusions: Exercise has similar effects on pain and function to that of oral NSAIDs and paracetamol. Given its excellent safety profile, exercise should be given more prominence in clinical care, especially in older people with comorbidity or at higher risk of adverse events related to NSAIDs and paracetamol.CRD42019135166., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To examine efficacy and safety of tramadol for knee or hip osteoarthritis (OA)., Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched up to May 2020 for randomized controlled trials (RCTs) comparing any of the following interventions: tramadol 100 mg/day, 200 mg/day, and 300 mg/day, and placebo for knee or hip OA. Pain and function were measured at or near 12 weeks for efficacy. Gastrointestinal, cardiovascular, and central nervous system (CNS) adverse events (AEs), and withdrawals were measured for safety. Bayesian network meta-analysis was conducted., Results: Six RCTs (3,611 participants) were included. Tramadol 100 mg/day (standardized mean difference [SMD] -0.16 [95% confidence interval (95% CI) -0.34, 0.00]), 200 mg/day (SMD -0.21 [95% CI -0.37, -0.06]), and 300 mg/day (SMD -0.30 [95% CI -0.48, -0.14]) were statistically more effective than placebo in pain relief, but only tramadol 300 mg/day was better than placebo in functional improvement (SMD -0.24 [95% CI -0.47, -0.03]). Tramadol 100 mg/day (relative risk [RR] 2.29 [95% credible interval (CrI) 1.22, 4.25]), 200 mg/day (RR 4.35 [95% CrI 2.31, 8.01]), and 300 mg/day (RR 6.02 [95% CrI 3.22, 11.1]) involved a higher risk of gastrointestinal AEs. Similarly, tramadol 100-300 mg/day showed a higher risk of CNS AEs and withdrawals. However, the risk of cardiovascular AEs remained unclear., Conclusion: Only tramadol 300 mg/day showed minimal improvement in pain and function but with increasing AEs compared with placebo. Tramadol may not be sufficiently recommended for knee or hip OA based on the presented evidence, especially in patients with the risk of gastrointestinal and CNS AEs., (© 2021 American College of Rheumatology.)

Background: Baker's cyst is the most common cystic disease of the knee, and a fast and accurate diagnosis of Baker's cyst is essential for a better management. Ultrasound is a rapid, portable, widely available, inexpensive and noninvasive imaging modality. However, the diagnostic accuracy of ultrasound on Baker's cyst still remains undetermined. We conducted the first meta-analysis to comprehensively assess the accuracy of ultrasound for the detection of Baker's cyst., Methods: PubMed, Embase and Web of Science were searched from inception to July 14, 2022, without language restrictions. Studies providing cross-tabulations of ultrasound versus pathology (gold standard) or MRI (standard imaging technique) for diagnosis of Baker's cyst were included. Indicators for the diagnostic accuracy of ultrasound, including sensitivity, specificity and area under the curve, were calculated using a bivariate model. Sensitivity analysis was conducted to evaluate the heterogeneity and robustness of the results., Results: A total of 13 studies with 1,011 subjects (mean age 32.2 years; men 53.5%) met the inclusion criteria. The pooled sensitivity, specificity and area under the curve of ultrasound for diagnosis of Baker's cyst, compared with pathology, were 0.97 (95% confidence intervals: 0.73-1.00), 1.00 (0.98-1.00) and 1.00 (0.99-1.00), respectively. The pooled estimates of ultrasound versus MRI were 0.94 (0.87-0.98) for sensitivity, 1.00 (0.83-1.00) for specificity and 0.97 (0.95-0.98) for area under the curve. Sensitivity analysis did not change the results materially., Conclusion: Ultrasound shows excellent diagnostic accuracy for the assessment of Baker's cyst and provides similar diagnostic information (absent or present) compared to MRI. Because of its advantages of low cost, portability and accessibility, ultrasound is likely to be a choice of imaging technique for screening Baker's cyst in clinical and population settings as well as in follow-ups., (© 2022. The Author(s).)

Background: There is paucity of data on the prevalence of ultrasound-detected synovial abnormalities in the general population, and the relationship between synovial changes and knee pain remains unclear. We examined the prevalence of synovial abnormalities on ultrasound and the relationship of these features with knee pain and radiographic osteoarthritis (ROA) in a community sample., Methods: Participants aged 50 years or over were from the Xiangya Osteoarthritis Study, a community-based cohort study. Participants were questioned about chronic knee pain and underwent (1) ultrasonography of both knees to determine presence of synovial hypertrophy (≥ 4 mm), effusion (≥ 4 mm), and Power Doppler signal [PDS; yes/no]; and (2) standard radiographs of both knees (tibiofemoral and patellofemoral views) to determine ROA., Results: There were 3755 participants (mean age 64.4 years; women 57.4%). The prevalence of synovial hypertrophy, effusion, and PDS were 18.1% (men 20.2%; women 16.5%), 46.6% (men 49.9%; women 44.2%), and 4.9% (men 4.9%; women 5.0%), respectively, and increased with age (P for trend < 0.05). Synovial abnormalities were associated with knee pain, with adjusted odds ratios (aORs) of 2.39 (95% confidence interval [CI] 2.00-2.86) for synovial hypertrophy, 1.58 (95%CI 1.39-1.80) for effusion, and 4.36 (95%CI 3.09-6.17) for PDS. Similar associations with ROA were observed, the corresponding aORs being 4.03 (95%CI 3.38-4.82), 2.01 (95%CI 1.76-2.29), and 6.49 (95%CI 4.51-9.35), respectively. The associations between synovial hypertrophy and effusion with knee pain were more pronounced among knees with ROA than those without ROA, and the corresponding P for interaction were 0.004 and 0.067, respectively., Conclusions: Knee synovial hypertrophy and effusion are more common and increase with age, affecting men more than women. All three ultrasound-detected synovial abnormalities associate both with knee pain and ROA, and knee synovial hypertrophy or effusion and ROA may interact to increase the risk of knee pain.

Objective: To assess the relation of symptomatic knee osteoarthritis (OA), knee pain, and radiographic knee OA to All-cause mortality and to identify mediators in the causal pathway., Methods: Participants from the Osteoarthritis Initiative were divided into 4 groups: 1) symptomatic knee OA (i.e., both radiographic knee OA [Kellgren/Lawrence grade ≥2] and knee pain); 2) knee pain only; 3) radiographic knee OA only; and 4) neither radiographic knee OA nor knee pain. We examined the relation of knee OA status to All-cause mortality using a multivariable Cox proportional hazards model and assessed the extent to which the association was mediated by disability, physical component summary (PCS) and mental component summary (MCS) scores for quality of life (QoL), and use of oral pain-relief medications (i.e., nonsteroidal antiinflammatory drugs and opioids)., Results: Among 4,796 participants, 282 died over the 96-month follow-up period. Compared with those with neither radiographic knee OA nor knee pain, multivariable-adjusted hazard ratios (HRs) of mortality were 2.2 (95% confidence interval [95% CI] 1.6-3.1) for symptomatic knee OA, 0.9 (95% CI 0.6-1.4) for knee pain only, and 2.0 (95% CI 1.4-2.9) for radiographic knee OA only, respectively. Indirect effects (HRs) of symptomatic knee OA on mortality via disability and PCS of QoL were 1.1 (95% CI 1.0-1.4) and 1.2 (95% CI 1.0-1.4), respectively. No apparent mediation effect was observed through either MCS of QoL or oral pain-relief medications use., Conclusion: Participants with either symptomatic or radiographic knee OA were at an increased risk of All-cause mortality. Increased risk of mortality from symptomatic knee OA was partially mediated through its effect on disability and PCS of QoL., (© 2020, American College of Rheumatology.)

Introduction: The infrapatellar fat pad (IPFP) is commonly resected during total knee arthroplasty (TKA) for better exposure. However, our previous studies have suggested that IPFP size was protective against, while IPFP signal intensity alteration was detrimental on knee symptoms and structural abnormalities. We hypothesise that an IPFP with normal qualities, rather than abnormal qualities, should be preserved during TKA. The aim of this study is to compare, over a 1-year period, the postoperative clinical outcomes of IPFP preservation versus resection after TKA in patients with normal or abnormal IPFP signal intensity alteration on MRI., Methods and Analysis: Three hundred and sixty people with end-stage knee osteoarthritis and on the waiting list for TKA will be recruited and identified as normal IPFP quality (signal intensity alteration score ≤1) or abnormal IPFP quality (signal intensity alteration score ≥2). Patients in each hospital will then be randomly allocated to IPFP resection group or preservation group. The primary outcomes are the summed score of self-reported Knee Injury and Osteoarthritis Outcome Score (KOOS), KOOS subscales assessing function in daily activities and function in sport and recreation. Secondary endpoints will be included: KOOS subscales (pain, symptoms and quality of life), Knee Society Score, 100 mm Visual Analogue Scale (VAS) Pain, timed up-and-go test, patellar tendon shortening, 100 mm VAS self-reported efficacy of reduced pain and increased quality of life, and Insall-Salvati index assessed on plain X-ray. Adverse events will be recorded. Intention-to-treat analyses will be used., Ethics and Dissemination: The study is approved by the local Medical Ethics Committee (Zhujiang Hospital Ethics Committee, reference number 2017-GJGBK-001) and will be conducted according to the principle of the Declaration of Helsinki (64th, 2013) and the Good Clinical Practice standard, and in compliance with the Medical Research Involving Human Subjects Act . Data will be published in peer-reviewed journals and presented at conferences, both nationally and internationally., Trial Registration Number: This trial was registered at Clinicaltrial.gov website on 19 October 2018 with identify number NCT03763448., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Statins are reported to have a potential benefit on progression of OA and on disease activity in RA, but existing evidence is conflicting. Our objective was to examine whether statins associate with reduction in the risk for joint replacement due to OA and RA., Methods: This was a propensity score-matched cohort study. Electronic health records from the UK Clinical Practice Research Datalink were used. We selected people prescribed statins and people never prescribed statins. Each statin user was matched to a non-user by age, gender, practice and propensity score for statin prescription. The main outcome measures were knee or hip joint replacement overall, and specifically because of OA or RA. The association between statins and risk of joint replacement was assessed using Cox proportional hazard regression. Statin exposure was categorized according to the potency of reducing low-density lipoprotein as low (21-28%), medium (32-38%) or high (42-55%) intensity., Results: A total of 178 467 statin users were matched with 178 467 non-users by age, gender, practice and propensity score. Overall, statin was not associated with reduced risk of knee or hip replacement (hazard ratio 0.99, 95% CI: 0.97, 1.03), unless prescribed at high strength (0.86, 0.75-0.98). The reduced risk was only observed for joint replacement due to RA (0.77, 0.63-0.94) but not OA (0.97, 0.94-1.01)., Conclusion: Statins at high intensity may reduce the risk of hip or knee replacement. This effect may be RA specific. Further studies to investigate mechanisms of risk reduction and the impact in people with RA are warranted., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: To examine the relation between inflammatory potential of diet and incident knee osteoarthritis (OA) and the role of BMI in the association of interest., Methods: In the Osteoarthritis Initiative, the energy-adjusted dietary inflammatory index (E-DII™) scores were calculated based on the Block Brief 2000 Food Frequency Questionnaire and categorized into sex-specific quartiles. Outcomes were incident (1) radiographic knee OA (ROA) (i.e., a KL grade ≥ 2) and (2) symptomatic knee OA (SxOA) (i.e., a combination of frequent knee pain and ROA). We fitted generalized estimating equation models to examine the association between E-DII scores and incident knee OA. We performed mediation analyses to assess the potential mediation by BMI in the DII-OA relation., Results: Over a 48-month follow-up period, 232 and 978 knees developed ROA and SxOA, respectively. Compared with the lowest (most anti-inflammatory) E-DII quartile, the odds ratio (OR) of incident ROA for the highest (most pro-inflammatory) E-DII quartile was 1.73 (95% confidence interval (CI) 1.15 to 2.62, P trend  = 0.007). The corresponding OR for SxOA was 1.43 (95% CI 1.16 to 1.76, P trend  = 0.001). The DII-OA association was significantly mediated via BMI with an indirect effect of 1.08 (95% CI 1.04, 1.13) for ROA and 1.13 (95% CI 1.09, 1.16) for SxOA, accounting for 20.4% and 44.5% of the total effect, respectively., Conclusions: A higher inflammatory potential of diet increased the risk of knee OA. The association was significantly mediated via BMI. Targeting the inflammatory potential of diet may be beneficial to reduce the risk of knee OA.

Background: Metformin could activate adenosine monophosphate-activated protein kinase (AMPK) which was postulated as a potential therapeutic target for osteoarthritis. This study aimed to examine the effects of metformin on cartilage and pain in osteoarthritis mouse model., Methods: Eighty 10-week-old male C57BL/6 mice were randomized to 6 groups: non-operation, sham-operation, destabilization of the medial meniscus (DMM)-operation with intragastric saline/metformin, and DMM-operation with intraarticular saline/metformin. Articular cartilage degeneration was examined by scanning electron microscopy (SEM) and graded using the scoring system recommended by Osteoarthritis Research Society International (OARSI). Mechanical withdrawal threshold and hind paw weight distribution were measured to assess the pain-related behavior. Cell Counting Kit-8 assay, quantificational real-time polymerase chain reaction, and western blot analysis were conducted to examine the anabolic and anti-catabolic effect of metformin and the role of AMPK in mediating its effects on interleukin-1β stimulated primary mice chondrocytes., Results: Compared with mice receiving intragastric and intraarticular saline, mice in both intragastric and intraarticular metformin displayed attenuated articular cartilage degeneration, indicated by less cartilage damage under SEM and significantly lower OARSI scores. A higher paw withdrawal threshold and a decreased weight-bearing asymmetry were observed in the intragastric and intraarticular metformin mice compared with their corresponding saline groups in DMM model of osteoarthritis. In vitro experiments showed that metformin not only decreased the level of matrix metalloproteinase 13, but also elevated type II collagen production through activating AMPK pathway., Conclusions: Metformin attenuates osteoarthritis structural worsening and modulates pain, suggesting its potential for osteoarthritis prevention or treatment.

Objectives: To examine the association between body composition and osteoarthritis (OA)., Methods: An extensive literature review was performed to identify studies that examined the association between body composition and OA. The mean difference (MD), odds ratio (OR), relative risk (RR) and corresponding 95% confidence intervals (CIs) were determined using RevMan statistical software., Results: A total of 19 studies were included. The combined MD showed the fat mass of the subjects with knee OA was higher than that of the control group (MD 4.38, 95% CI: 2.84-5.92). Both fat mass and fat mass percentage were positively associated with knee OA (ORs ranged from 1.49, 95% CI: 1.15-1.92, to 2.37, 95% CI: 1.18-4.74). Similar findings were observed in hip and hand joints as well (ORs ranged from 1.20, 95% CI: 1.08-1.32, to 1.87, 95% CI: 1.11-3.15), and such results were also confirmed by most cohort studies of knee and hip OA (RRs ranged from 0.98, 95% CI: 0.95-1.01, to 3.60, 95% CI: 2.60-5.00). Lean mass was also positively associated with knee OA (OR 1.48, 95% CI: 1.13-1.94). However, lean mass percentage was negatively associated with knee OA (OR 0.65, 95% CI: 0.46-0.92)., Conclusions: Both fat mass and fat mass percentage were likely to be risk factors for knee, hip and hand OA. Similarly, lean mass also seemed to be a risk factor for knee OA, while lean mass percentage seemed to be a protective factor., (© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objective: This study aimed at examining the association between symptomatic knee osteoarthritis and all-cause mortality based on four population-based longitudinal surveys., Method: Data were retrieved from the English Longitudinal Study of Aging (ELSA), the Survey of Health, Aging and Retirement in Europe (SHARE), the Korean Longitudinal Study of Aging (KLoSA), and the Indonesian Family Life Survey (IFLS). The association between symptomatic knee osteoarthritis and all-cause mortality over the 8- to 12-year follow-up period was assessed using Cox-proportional hazard models., Results: In the entire sample of 59,522 participants (4823 with symptomatic knee osteoarthritis; 54,699 without symptomatic knee osteoarthritis [control group]; mean age: 61.8 years; female percentage: 55.3%), 8375 died (937 in the symptomatic knee osteoarthritis group, 7438 in the control group) during the follow-up period. Patients with symptomatic knee osteoarthritis had a higher risk of all-cause mortality than control group without adjusting for potential confounders in each survey, and the unadjusted hazard ratios (HRs) of all-cause mortality were 1.32 (95% confidence interval [CI] 1.18 to 1.47) in ELSA, 1.40 (95%CI 1.24 to 1.56) in SHARE, 1.25 (95%CI 1.06 to 1.47) in KLoSA, and 1.65 (95%CI 1.31 to 2.07) in IFLS. However, with adjustment of potential confounders, the corresponding HRs dropped to 1.07 (95%CI 0.94 to 1.20) in ELSA, 1.08 (95%CI 0.97 to 1.22) in SHARE, 0.91 (95%CI 0.77 to 1.08) in KLoSA, and 0.89 (95%CI 0.66 to 1.21) in IFLS, respectively., Conclusions: In these four population-based longitudinal studies, no association between symptomatic knee osteoarthritis and increased risk of all-cause mortality was observed after adjusting for potential confounders. Key Points • This study evaluated the association between symptomatic knee OA and the risk of all-cause mortality among the participants retrieved from four large population-based longitudinal studies across the world. • No association between symptomatic knee osteoarthritis and increased risk of all-cause mortality was observed after considering potential confounders, and our findings were consistent with the results derived from four independent longitudinal studies. • The present study included four international population-based longitudinal studies, comprising both developed and developing areas, which allowed the findings to be interpreted under larger circumstance.

Aim: To systematically examine the existing literature on the associations between chondrocalcinosis (CC) and osteoarthritis (OA) at different joints, and to quantify such associations through meta-analysis., Methods: PubMed, Embase and Scopus databases were searched through from inception to June 2017. Cohort, case-control or cross-sectional studies were included if they examined the association between CC and OA. Data on the odds ratios (OR) and their 95% confidence intervals (CI) of the prevalence or progression of OA between the CC group and non-CC group with respect to the same joint were extracted., Results: A total of 14 studies were identified. Twelve studies were eligible for assessing the association between knee CC and knee OA. The combined data showed a positive association between them (OR = 2.84; 95% CI, 2.12-3.81; P < 0.001). Three studies were eligible for assessing the association between hip CC and hip OA. The data on the OR could only be extracted from one study (OR = 0.92; 95% CI, 0.68-1.24; P = 0.59). Two studies were eligible for assessing the association between hand CC and hand OA, and the data on the OR could only be extracted from one study which reported significant associations between CC and OA at the metacarpophalangeal joint (OR = 4.75; 95% CI, 2.12-10.64; P < 0.001) and the wrist joint (OR = 4.44; 95% CI, 3.56-5.54; P < 0.001)., Conclusion: This study established a strong association between knee CC and knee OA. However, the associations between CC and OA at the hip or hand still remain controversial and warrant further study., (© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objectives: To examine the associations between serum magnesium (Mg) concentration with the prevalence of metabolic syndrome (MetS), diabetes mellitus (DM), hypertension (HP) and hyperuricaemia (HU) in patients with radiographic knee osteoarthritis (OA)., Methods: The present study was conducted at the Health Management Center of Xiangya Hospital. Radiographic OA was evaluated for patients aged over 40 years with basic characteristics and blood biochemical assessment. Serum Mg concentration was measured using the chemiluminescence method. MetS, DM, HP and HU were diagnosed based on standard protocols. The associations between serum Mg concentration with MetS, DM, HP and HU were evaluated by conducting multivariable adjusted logistic regression., Results: A total of 962 patients with radiographic knee OA were included. Compared with the lowest quintile, the multivariable adjusted ORs and related 95% CIs of DM were 0.40 (95% CI 0.23 to 0.70, p=0.001), 0.33 (95% CI 0.18 to 0.60, p<0.001), 0.27 (95% CI 0.14 to 0.52, p<0.001) and 0.22 (95% CI 0.11 to 0.44, p<0.001) in the second, third, fourth and highest quintiles of serum Mg, respectively (p for trend <0.001); the multivariable adjusted ORs of HU were 0.33 (95% CI 0.19 to 0.59, p<0.001), 0.52 (95% CI 0.30 to 0.91, p=0.022) and 0.39 (95% CI 0.22 to 0.70, p=0.001) in the third, fourth and highest quintiles of serum Mg, respectively (p for trend <0.001); and the multivariable adjusted ORs of MetS were 0.59 (95% CI 0.36 to 0.94, p=0.027) in the second and 0.56 (95% CI 0.34 to 0.93, p=0.024) in the highest quintiles of serum Mg. However, the inverse association between serum Mg and the prevalence of MetS was non-linear (p for trend=0.067). There was no significant association between serum Mg and HP in patients with OA., Conclusions: The serum Mg concentration was inversely associated with the prevalence of MetS, DM and HU in patients with radiographic knee OA., Level of Evidence: Level III, cross-sectional study., Competing Interests: Competing interests: None declared., (© 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.)

Background: The study aims to investigate the expression of SIRT1 in articular cartilage of patients with primary knee osteoarthritis (OA) and its relationship with disease severity., Methods: Cartilage tissue samples were collected from 38 knee OA patients and 9 normal healthy controls and then ascribed to normal, mild, moderate, and severe groups on the basis of the improved Mankin grading system. The expression of SIRT1 in articular cartilage was detected by immunohistochemistry and western blots. The expression of p53 and acetylated p53 (Ac-p53) was also measured by western blots., Results: The mutual comparisons of the SIRT1 expression levels in all groups have statistical significance except the one between the mild and moderate groups. Moreover, western blot results showed that the SIRT1 was decreased and p53/Ac-p53 were increased in the OA group. The average gray level of SIRT1 increases with the improving grade of the improved Mankin grading system scorers., Conclusions: The expression of SIRT1 in articular cartilage is negatively associated with severity of knee OA, indicating that SIRT1 may act as a monitoring indicator for determining development and progression of knee OA.

Objectives: High-sensitivity C-reactive protein (hsCRP) is possibly related to osteoarthritis (OA) progression and a variety of OA-related symptoms. This study aimed to examine associations between cigarette smoking, betel quid chewing and alcohol consumption and hsCRP in early radiographic knee OA., Design: Cross-sectional health examination survey., Setting: This primary study was conducted in a health examination centre in China., Participants: 936 (656 men and 280 women) patients with early radiographic knee OA were included in this cross-sectional study., Primary and Secondary Outcome Measures: Smoking status was classified into four levels based on daily smoking habit: 0/day, 1-10/day, 11-20/day and >20/day. Betel quid chewing and alcohol consumption status was divided into 'Yes' or 'No'. Early radiographic knee OA was defined as Kellgren Lawrence (K-L) grade 1 or 2 in at least one leg, and elevated hsCRP was assessed as ≥ 3.0 mg/L., Results: After adjustment for a number of potential confounding factors, a significant positive association between cigarette smoking and hsCRP was observed in the multivariable model. The multivariable-adjusted ORs (95% CI) of elevated hsCRP (≥ 3.0 mg/L) in the second (1-10/day, n=133), third (11-20/day, n=59) and highest (>20/day, n=104) cigarette smoking categories were 1.54 (95% CI 0.91 to 2.61), 1.27 (95% CI 0.57 to 2.79) and 2.09 (95% CI 1.20 to 3.64), respectively, compared with the non-smoker category (n=640). In addition, there was a positive dose-response relationship between cigarette smoking and elevated hsCRP (p for trend=0.01). No significant associations between betel quid chewing and alcohol consumption and hsCRP were observed in the multivariable model., Conclusions: This study indicated that cigarette smoking was positively associated with serum hsCRP level in patients with early radiographic knee OA. However, in view of the nature of cross-sectional designs, the results need to be confirmed by further prospective studies., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objectives. This study is undertaken to investigate the relation between osteopontin (OPN) and Wnt5a expression in the progression and pathogenesis of osteoarthritis (OA). Methods. 50 cartilage tissues from knee OA patients and normal controls were divided into four groups of severe, moderate, minor, and normal lesions based on the modified grading system of Mankin. Immunohistochemistry and real-time PCR were utilized to analyze the OPN and Wnt5a expression in articular cartilage. Besides, the relations between OPN and Wnt5a expression and the severity of OA were explored. Results. OPN and Wnt5a could be identified in four groups' tissues. Amongst the groups, the intercomparisons of OPN expression levels showed statistical differences (P < 0.01). Besides, the intercomparisons of Wnt5a expression degrees showed statistical differences (P < 0.05), except that between the minor and normal groups (P > 0.05). The scores of Mankin were demonstrated to relate to OPN expression (r = -0.847, P < 0.01) and Wnt5a expression in every group (r = -0.843, P < 0.01). Also, a positive correlation can be observed between the OPN and Wnt5a expression (r = 0.769, P < 0.01). Conclusion. In articular cartilage, the expressions of OPN and Wnt5a are positively related to progressive damage of knee OA joint. The correlation between Wnt5a and OPN might be important to the progression and pathogenesis of knee OA.

Objective: To investigate the role of osteopontin (OPN) on the expressions of matrix metalloproteinase 13 (MMP-13) mRNA and protein in human knee osteoarthritic chondrocytes and to find the optimal time and concentration for OPN treatment., Methods: Chondrocytes were isolated from articular cartilage tissues of patients with primary osteoarthritis (OA) and cultured using one step digestive treatment with collagenase type II. The chondrocytes were then identified using immunohistochemistry of collagen type II. The first generation of chondrocytes were stimulated with OPN at a concentration of 1 μg/mL for 0, 24, 48, and 72 hours, and with OPN at the concentrations of 0, 0.5, 1, 2, and 4 μg/mL for 48 hours. The levels of MMP-13 mRNA and protein expressions were measured with real-time fluorescent quantitative PCR and Western blot., Results: The immunohistochemical staining showed that first generation of chondrocytes expressed collagen type II. Both MMP-13 mRNA and protein expression levels in OA chondrocytes increased significantly in the presence of OPN (1 μg/mL) and peaked at 48 hours after incubation, showing significant difference between different time points (P < 0.05). The MMP-13 mRNA expression level in OA chondrocytes at the OPN concentration of 1 μg/mL was significantly higher than those at the other concentrations (P < 0.05), and the MMP-13 protein expression level at the OPN concentration of 1 μg/mL was significantly higher than that at 0 μg/mL (P < 0.05). MMP-13 protein expression level at the OPN concentrations of 0.5, 2, and 4 μg/mL were significantly higher than that at 0 μg/mL (P < 0.05)., Conclusion: OPN induces up-regulation of MMP-13 mRNA and protein expressions in human knee osteoarthritic chondrocytes in time- and dose-dependent manners. The optimal time and concentration for OPN treatment are 48 hours and 1 μg/mL, respectively.

The purpose of this study is to observe the differences of osteopontin (OPN) phosphorylation in osteoarthritis (OA) cartilage and normal cartilage, and evaluate the possible correlations between the OPN phosphorylation and MMP-13 expression. Degenerative cartilage (n = 29) and normal cartilage (n = 10) were identified by hematoxylin-eosin, safranin-O staining and modified Mankin score. The phosphorylation level of OPN in OA cartilage and normal cartilage was detected by immunoprecipitation. Chondrocytes were treated with phospho-OPN, OPN or buffer. Quantitative reverse transcription polymerase chain reaction (qPCR) and ELISA were used to assess the expression of MMP-13 in different treatments. The OD values of phosphorylation of OPN in normal cartilage and OA cartilage were 137.89 ± 10.59 and 153.52 ± 8.80, respectively, (P = 0.000). Chondrocytes treated with OPN showed a higher MMP-13 expression at gene and protein level compared with control group. Chondrocytes treated with phospho-OPN showed the highest MMP-13 expression in gene and protein. In conclusion, our results revealed a higher phosphorylation level of OPN in OA cartilage than in normal cartilage. We found OPN leads to elevated expression of MMP-13 (both at gene level and protein level), and phospho-OPN had a more obvious upregulation effect on MMP-13 expression than nonphospho-OPN. Further studies are needed to reveal the mechanism of OPN phosphorylation on cartilage degeneration.

Objective: To discuss short-term effect of rotating hinge knee prosthesis., Methods: From July 2002 to April 2005, 17 cases of severe knee joint deformity and instability received rotating hinge knee prosthesis for total knee arthroplasty. There were 8 males and 9 females, aging from 4l to 79 years. The left joints were involved in 10 cases and right joint in 7 cases. All patients were admitted because of pain. The course of disease was from 1 to 7 years. There were 10 cases of osteoarthritis, 5 cases of rheumatoid arthritis, 1 case of traumatic arthritis after operation of left femur fracture,and 1 case of traumatic arthritis with injury of anterior cruciate ligament, meniscus medialis and medial collateral ligament after operation of left fracture of tibial plateau. According to HSS (hospital for special surgery) scoring system, the preoperative score was 36 to 58 with an average of 48.6. The preoperative flexed motion range of articulation was 21 degrees to 80 degrees with an average of 57.4 degrees., Results: All patients were followed up from 7 months to 3 years with an average of 23. 6 months. There were no complications of thrombogenesis of veins of lower extremity, pulmonary embolism, palsy of peroneal nerve, fracture, and breakage of extended knee structure. Infection occurred in 1 case at 3 months postoperatively, the prosthesis was dislodged, antibiotic-impregnated cement was filled with knee joint, two-stage arthroplasty was expected. At the last follow-up, the HSS score was 78 to 98 with an average of 91.1 in 16 patients. The flexed motion range of articulation was 75 degrees to 100 degrees with an average of 85.2 degrees at 2 weeks postoperatively. The flexed motion range of articular was 85 degrees to 123 degrees with an average of 108.3 degrees at the last follow-up. There were significant differences in HSS score and motion range of articular between preoperation and the last follow-up (P < 0.05)., Conclusion: The short-term outcome of rotating hinge knee prosthesis is good and a long term follow-up is necessary.