Chronic pain in multiple sites is associated with cardiovascular dysfunction: an observational UK Biobank cohort study.

BACKGROUND: Chronic pain is associated with development of cardiovascular disease. We investigated the association between how widespread chronic pain is and the development of cardiovascular dysfunction. METHODS: We analysed data from participants enrolled in the UK Biobank study who underwent examinations at baseline, plus first follow-up and two imaging visits. Pain sites (including hip, knee, back, neck/shoulder, or 'all over the body') and pain duration were recorded at each visit. Chronic pain was defined as pain lasting for ≥3 months. Participants were categorised into six groups: no chronic pain, chronic pain in one, two, three, or four sites, or 'all over the body'. Arterial stiffness index was measured at each time point. Carotid intima-media thickness, cardiac index, and left ventricular ejection fraction (LVEF) were measured using ultrasound and heart MRI at two additional imaging visits in a subset of participants. Mixed-effect linear regression models were used for the analyses. RESULTS: The number of chronic pain sites was directly related to increased arterial stiffness index (n=159,360; ß=0.06 per one site increase, 95% confidence interval 0.04 to 0.08). In 23,899 participants, lower LVEF was associated with widespread chronic pain (ß=-0.17 per one site increase, 95% confidence interval -0.27 to -0.07). The number of chronic pain sites was not associated with carotid intima-media thickness (n=30,628) or cardiac index (n=23,899). CONCLUSION: A greater number of chronic pain sites is associated with increased arterial stiffness and poorer cardiac function, suggesting that widespread chronic pain is an important contributor to cardiovascular dysfunction.

Bone mineral density is not associated with incident high-intensity back pain: a 10-year cohort study in men.

Although patients believe that osteoporosis is a painful condition, health professionals assume it is painless unless a fracture occurs. The association between BMD and back pain has not been examined longitudinally in community-based adults in an unbiased population using gold-standard measures. This study aimed to examine the association between BMD and incident high-intensity back pain and/or high disability over 10 years in Australian men without high-intensity symptoms at baseline. Men with no high-intensity back pain and/or high disability attending the Geelong Osteoporosis Study at the 5-year visit (occurring between 2006-2010) (considered the baseline for the current study) were followed for 10 years (reassessed between 2016-2021). Back pain and disability were assessed using the Graded Chronic Pain Scale at both time points. At baseline, DXA was used to measure lumbar spine and total hip BMD and spinal artefacts. The relationships between BMD and incident high-intensity pain and/or high disability at follow-up were examined using binary logistic regression, adjusted for age, body mass index, depression, education, smoking, mobility, and spinal artefacts. A total of 679 participants had no to low-intensity pain and/or no to low disability at baseline. A total of 441 attended follow-up, providing back pain and disability data. Thirty-seven men developed high-intensity pain and/or high disability. No association of BMD at any site was seen with incident high-intensity pain and/or high disability. BMD was not associated with incident high-intensity pain or disability in community-based men. These data provide evidence to dispel the erroneous community-held belief that low BMD is related to back pain and disability.

Association between medial meniscal extrusion and knee structural progression in adults with symptomatic knee osteoarthritis - a prospective cohort study.

OBJECTIVE: To examine the association between medial meniscal extrusion and structural progression in adults with symptomatic knee osteoarthritis (OA). METHODS: This prospective cohort study examined 176 participants with symptomatic knee OA recruited into a randomised controlled trial. The participants underwent magnetic resonance imaging (MRI) of the study knee at baseline and approximately 2 years later. Meniscal extrusion, tibial cartilage volume, and tibiofemoral bone marrow lesions (BMLs) were measured from MRI using validated methods. RESULTS: Participants with medial meniscal extrusion ≥ 3 mm had a higher prevalence of lateral tibiofemoral BMLs at baseline (OR = 2.21, 95% CI 1.06-4.61, p = 0.035), and those with medial meniscal extrusion 2-3 mm had a higher likelihood of lateral BML worsening over 2 years (OR = 3.76, 95% CI 1.35-10.52, p = 0.011), compared with those with medial meniscal extrusion < 2 mm. Participants with stable medial meniscal extrusion had a lower likelihood of lateral BML worsening compared with those with regression of medial meniscal extrusion over 2 years (OR = 0.20, 95% CI 0.07-0.56, p = 0.002). There were no associations between medial meniscal extrusion and tibial cartilage volume or medial tibiofemoral BMLs. CONCLUSIONS: Our study showed associations between medial meniscal extrusion and baseline prevalence and worsening over 2 years of lateral tibiofemoral BMLs in people with symptomatic knee OA. Although the reasons for the lack of associations in the medial compartment are not clear, our results suggest a role of medial meniscal extrusion in predicting structural progression in lateral knee OA and that meniscal extrusion might be a potential target in the management of knee OA.

Prior nonmelanoma skin cancer is associated with fewer fractures, more vitamin D sufficiency, greater bone mineral density and improved bone microarchitecture in older adults.

INTRODUCTION: Prior nonmelanoma skin cancer (NMSC), a biomarker of cumulative lifetime sun exposure, is associated with reduced fracture risk later in life. The mechanism is unknown. METHODS: Prospective cohort analysis of 1,099 community-dwelling adults aged 50-80 years with baseline and 10 year follow up assessments. Histopathologically-confirmed NMSC diagnosis was established by linkage with the Tasmanian Cancer Registry. Bone mineral density (BMD) and vertebral deformity were quantified by DXA, 25(OH)D by radioimmunoassay, bone microarchitecture by high resolution peripheral quantitative CT, melanin density by spectrophotometry and skin photosensitivity and clinical fracture by questionnaire. 25(OH)D <50 nmol/L was considered deficient. RESULTS: Participants with a NMSC reported prior to baseline were less likely to sustain an incident vertebral deformity over 10 years (RR=0.74, p=0.036). There were similar reductions for other fracture types but these did not reach significance. Prior NMSC was associated with baseline (RR=1.23, p=0.005) and 10 year longitudinal (RR=5.9, p=0.014) vitamin D sufficiency and greater total body BMD (ß=0.021g/cm2, p=0.034), but not falls risk or muscle strength. The relationship between prior NMSC and bone microarchitecture was age dependent (pinteraction<0.05). In the oldest age tertile, prior NMSC was associated with greater volumetric BMD (ß=57.8-62.6, p=0.002-0.01) and less porosity (ß= -4.6 - -5.2, p=0.002-0.009) at cortical, compact cortical and outer transitional zones. CONCLUSION: Prior NMSC was associated with fewer incident fractures in community-dwelling older adults. This protective association is most likely mediated by modifiable fracture risk factors associated with an outdoor lifestyle, including 25(OH)D, BMD and bone microarchitecture.

Krill Oil for Knee Osteoarthritis: A Randomized Clinical Trial.

Importance: Knee osteoarthritis is disabling, with few effective treatments. Preliminary evidence suggested that krill oil supplementation improved knee pain, but effects on knee osteoarthritis remain unclear. Objective: To evaluate efficacy of krill oil supplementation, compared with placebo, on knee pain in people with knee osteoarthritis who have significant knee pain and effusion-synovitis. Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled clinical trial in 5 Australian cities. Participants with clinical knee osteoarthritis, significant knee pain, and effusion-synovitis on magnetic resonance imaging were enrolled from December 2016 to June 2019; final follow-up occurred on February 7, 2020. Interventions: Participants were randomized to 2 g/d of krill oil (n = 130) or matching placebo (n = 132) for 24 weeks. Main Outcomes and Measures: The primary outcome was change in knee pain as assessed by visual analog scale (range, 0-100; 0 indicating least pain; minimum clinically important improvement = 15) over 24 weeks. Results: Of 262 participants randomized (mean age, 61.6 [SD, 9.6] years; 53% women), 222 (85%) completed the trial. Krill oil did not improve knee pain compared with placebo (mean change in VAS score, -19.9 [krill oil] vs -20.2 [placebo]; between-group mean difference, -0.3; 95% CI, -6.9 to 6.4) over 24 weeks. One or more adverse events was reported by 51% in the krill oil group (67/130) and by 54% in the placebo group (71/132). The most common adverse events were musculoskeletal and connective tissue disorders, which occurred 32 times in the krill oil group and 42 times in the placebo group, including knee pain (n = 10 with krill oil; n = 9 with placebo), lower extremity pain (n = 1 with krill oil; n = 5 with placebo), and hip pain (n = 3 with krill oil; n = 2 with placebo). Conclusions and Relevance: Among people with knee osteoarthritis who have significant knee pain and effusion-synovitis on magnetic resonance imaging, 2 g/d of daily krill oil supplementation did not improve knee pain over 24 weeks compared with placebo. These findings do not support krill oil for treating knee pain in this population. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12616000726459; Universal Trial Number: U1111-1181-7087.

Cohort profile: Worldwide Collaboration on OsteoArthritis prediCtion for the Hip (World COACH) - an international consortium of prospective cohort studies with individual participant data on hip osteoarthritis.

PURPOSE: Hip osteoarthritis (OA) is a major cause of pain and disability worldwide. Lack of effective therapies may reflect poor knowledge on its aetiology and risk factors, and result in the management of end-stage hip OA with costly joint replacement. The Worldwide Collaboration on OsteoArthritis prediCtion for the Hip (World COACH) consortium was established to pool and harmonise individual participant data from prospective cohort studies. The consortium aims to better understand determinants and risk factors for the development and progression of hip OA, to optimise and automate methods for (imaging) analysis, and to develop a personalised prediction model for hip OA. PARTICIPANTS: World COACH aimed to include participants of prospective cohort studies with ≥200 participants, that have hip imaging data available from at least 2 time points at least 4 years apart. All individual participant data, including clinical data, imaging (data), biochemical markers, questionnaires and genetic data, were collected and pooled into a single, individual-level database. FINDINGS TO DATE: World COACH currently consists of 9 cohorts, with 38 021 participants aged 18-80 years at baseline. Overall, 71% of the participants were women and mean baseline age was 65.3±8.6 years. Over 34 000 participants had baseline pelvic radiographs available, and over 22 000 had an additional pelvic radiograph after 8-12 years of follow-up. Even longer radiographic follow-up (15-25 years) is available for over 6000 of these participants. FUTURE PLANS: The World COACH consortium offers unique opportunities for studies on the relationship between determinants/risk factors and the development or progression of hip OA, by using harmonised data on clinical findings, imaging, biomarkers, genetics and lifestyle. This provides a unique opportunity to develop a personalised hip OA risk prediction model and to optimise methods for imaging analysis of the hip.

Effect of Intravenous Zoledronic Acid on Total Knee Replacement in Patients With Symptomatic Knee Osteoarthritis and Without Severe Joint Space Narrowing: A Prespecified Secondary Analysis of a Two-Year, Multicenter, Double-Blind, Placebo-Controlled Clinical Trial.

OBJECTIVE: To determine the effect of zoledronic acid (ZA) on the risk of total knee replacement (TKR) in patients with symptomatic knee osteoarthritis and without severe joint space narrowing (JSN). METHODS: We included 222 participants (mean age 62 years, 52% female) from the two-year Zoledronic Acid for Osteoarthritis Knee Pain trial (113 received 5 mg of ZA annually and 109 received placebo) conducted between November 2013 and October 2017. Primary TKR were identified until February 22, 2022. The effect of ZA on TKR risk was evaluated using Cox proportional hazard regression models. Because the treatment effect failed the proportional hazards assumption, a time-varying coefficients analysis for treatment was conducted by splitting the study into two periods (ie, within and after two years of randomization). RESULTS: Over a mean follow-up of seven years, 39% and 30% of participants had any TKR in the ZA and placebo groups, and 28% and 18% had TKR in the study knee, respectively. Use of ZA was associated with a higher risk of TKR in any knee (hazard ratio [HR] 4.2, 95% confidence interval [CI] 1.2-14.7) and showed a trend in the study knee (HR 6.8, 95%CI 0.9-53.9) during the trial. In the posttrial period, the risk of TKR was similar in the ZA and the placebo groups for any knee (HR 1.2, 95%CI 0.5-1.8) and the study knee (HR 1.4, 95%CI 0.5-2.2). CONCLUSION: These results suggest that ZA is not protective against TKR in patients with symptomatic knee osteoarthritis and without severe JSN.

Associations of Osteoarthritis with Prevalence and Incidence of Cardiovascular Disease over 10 Years in Community-Dwelling Older Adults: The Sydney Memory and Ageing Study.

INTRODUCTION: The data are limited for the association between osteoarthritis (OA) and cardiovascular disease (CVD) in community-based older populations and whether there is sex difference. This study aimed to examine the relationship between OA and prevalence and incidence of CVD over 10 years in community-dwelling older adults. METHODS: Data on self-reported OA, high cholesterol, hypertension, and type 2 diabetes were collected from 1,025 community-dwelling participants aged 70-90 years in the Sydney Memory and Ageing Study. The presence of CVD at baseline was defined as self-reported presence of stroke, heart attack, transient ischaemic attack, angina, aortic aneurysm, or claudication. The incidence of CVD was defined by a combination of incident self-reported CVD or CVD mortality at different follow-up timepoints over 10 years. RESULTS: At baseline, 395 (38.5%) participants self-reported OA (252 [44.6%] women, 143 [31.1%] men). Self-reported OA was associated with increased prevalence of CVD in women (OR 1.67, 95% CI 1.12-2.47) but not men (1.26, 0.80-1.98). In the total population, self-reported OA at baseline was associated with increased incidence of CVD at 4 years (OR 1.77, 95% CI 1.10-2.83), 6 years (1.59, 1.03-2.46), 8 years (1.56, 1.02-2.38), and 10 years (1.66, 1.10-2.50), but not at 2 years (1.43, 0.79-2.57). Significant associations were observed in female participants at 4, 8, and 10 years, with no significant associations seen in male participants. CONCLUSION: OA was associated with increased prevalence at baseline and incidence of CVD over 10 years in community-based older adults, especially women. Identifying those with OA to target their cardiovascular risk factors while managing their OA has the potential to reduce the burden of CVD in older people, particularly women.

30 Years of MRI-based cartilage & bone morphometry in knee osteoarthritis: From correlation to clinical trials.

OBJECTIVE: The first publication on morphometric analysis of articular cartilage using magnetic resonance imaging (MRI) in 1994 set the scene for a game change in osteoarthritis (OA) research. The current review highlights milestones in cartilage and bone morphometry, summarizing the rapid progress made in imaging, its application to understanding joint (patho-)physiology, and its use in interventional clinical trials. METHODS: Based on a Pubmed search of articles from 1994 to 2023, the authors subjectively selected representative work illustrating important steps in the development or application of magnetic resonance-based cartilage and bone morphometry, with a focus on studies in humans, and on the knee. Research on OA-pathophysiology is addressed only briefly, given length constraints. Compositional and semi-quantitative assessment are not covered here. RESULTS: The selected articles are presented in historical order as well as by content. We review progress in the technical aspects of image acquisition, segmentation and analysis, advances in understanding tissue growth, physiology, function, and adaptation, and a selection of clinical trials examining the efficacy of interventions on knee cartilage and bone. A perspective is provided of how lessons learned may be applied to future research and clinical management. CONCLUSIONS: Over the past 30 years, MRI-based morphometry of cartilage and bone has contributed to a paradigm shift in understanding articular tissue physiology and OA pathophysiology, and to the development of new treatment strategies. It is likely that these technologies will continue to play a key role in the development and (accelerated) approval of therapy, potentially targeted to different OA phenotypes.

Dietary Inflammatory Index and Magnetic Resonance Imaging-Detected Knee Structural Change and Pain: A 10.7-Year Follow-up Study.

OBJECTIVE: To determine whether the dietary inflammatory index (DII) scores were associated with knee structural changes and pain over a 10.7-year follow-up. METHODS: This study used data from a prospective population-based cohort study (mean age 63 years, 51% female) in which 1,099, 875, 768, and 566 participants completed assessments at baseline, 2.6, 5.1, and 10.7 years, respectively. T1-weighted and T2-weighted magnetic resonance imaging was performed to measure cartilage volume (CV) and bone marrow lesions (BMLs) at baseline and 10.7 years. The Western Ontario and McMaster Universities Osteoarthritis Index pain questionnaire was used to measure knee pain at each visit. Pain trajectories ("minimal pain," "mild pain," and "moderate pain") were previously identified. Baseline energy-adjusted DII (E-DII) scores were calculated. Linear, log-binomial regression, linear mixed-effects modeling, and multi-nominal logistic regression were used for analyses. RESULTS: The mean ± SD E-DII score at baseline was -0.48 ± 1.39. In multivariable analyses, higher E-DII scores were not associated with tibial CV loss or BML size increase except for medial tibial BML size increase. Higher E-DII scores were associated with a higher pain score (ß = 0.21; 95% confidence interval [CI] 0.004-0.43) and an increased risk of belonging to the "moderate pain" compared to the "minimal pain" trajectory group (relative risk ratio 1.19; 95% CI 1.02-1.39). CONCLUSION: A proinflammatory diet, as indicated by a higher DII score, may be associated with a greater pain score and higher risk of more severe pain trajectory over 10 years. However, inconsistent findings related to structural changes suggest a discordance between the potential impact of diet on structural damage and pain in knee OA.

Association between knee magnetic resonance imaging markers and knee symptoms over 6-9 years in young adults.

OBJECTIVES: To describe associations between MRI markers with knee symptoms in young adults. METHODS: Knee symptoms were assessed using the WOMAC scale during the Childhood Determinants of Adult Health Knee Cartilage study (CDAH-knee; 2008-2010) and at the 6- to 9-year follow-up (CDAH-3; 2014-2019). Knee MRI scans obtained at baseline were assessed for morphological markers (cartilage volume, cartilage thickness, subchondral bone area) and structural abnormalities [cartilage defects and bone marrow lesions (BMLs)]. Univariable and multivariable (age, sex, BMI adjusted) zero-inflated Poisson (ZIP) regression models were used for analysis. RESULTS: The participants' mean age in CDAH-knee and CDAH-3 were 34.95 (s.d. 2.72) and 43.27 (s.d. 3.28) years, with 49% and 48% females, respectively. Cross-sectionally, there was a weak but significant negative association between medial femorotibial compartment (MFTC) [ratio of the mean (RoM) 0.99971084 (95% CI 0.9995525, 0.99986921), P < 0.001], lateral femorotibial compartment (LFTC) [RoM 0.99982602 (95% CI 0.99969915, 0.9999529), P = 0.007] and patellar cartilage volume [RoM 0.99981722 (95% CI 0.99965326, 0.9999811), P = 0.029] with knee symptoms. Similarly, there was a negative association between patellar cartilage volume [RoM 0.99975523 (95% CI 0.99961427, 0.99989621), P = 0.014], MFTC cartilage thickness [RoM 0.72090775 (95% CI 0.59481806, 0.87372596), P = 0.001] and knee symptoms assessed after 6-9 years. The total bone area was negatively associated with knee symptoms at baseline [RoM 0.9210485 (95% CI 0.8939677, 0.9489496), P < 0.001] and 6-9 years [RoM 0.9588811 (95% CI 0.9313379, 0.9872388), P = 0.005]. The cartilage defects and BMLs were associated with greater knee symptoms at baseline and 6-9 years. CONCLUSION: BMLs and cartilage defects were positively associated with knee symptoms, whereas cartilage volume and thickness at MFTC and total bone area were weakly and negatively associated with knee symptoms. These results suggest that the quantitative and semiquantitative MRI markers can be explored as a marker of clinical progression of OA in young adults.

Metformin for knee osteoarthritis with obesity: study protocol for a randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Over half of the populations with knee osteoarthritis (OA) have obesity. These individuals have many other shared metabolic risk factors. Metformin is a safe, inexpensive, well-tolerated drug that has pleiotropic effects, including structural protection, anti-inflammatory and analgesic effects in OA, specifically the knee. The aim of this randomised, double-blind, placebo-controlled trial is to determine whether metformin reduces knee pain over 6 months in individuals with symptomatic knee OA who are overweight or obese. METHODS AND ANALYSIS: One hundred and two participants with symptomatic knee OA and overweight or obesity will be recruited from the community in Melbourne, Australia, and randomly allocated in a 1:1 ratio to receive either metformin 2 g or identical placebo daily for 6 months. The primary outcome is reduction of knee pain [assessed by 100 mm Visual Analogue Scale (VAS)] at 6 months. The secondary outcomes are OMERACT-OARSI (Outcome Measures in Rheumatology-Osteoarthritis Research Society International) responder criteria [Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, function and participant's global assessment (VAS)] at 6 months; change in knee pain, stiffness, function using WOMAC at 6 months and quality of life at 6 months. Adverse events will be recorded. The primary analysis will be by intention to treat, including all participants in their randomised groups. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Alfred Hospital Ethics Committee (708/20) and Monash University Human Research Ethics Committee (28498). Written informed consent will be obtained from all the participants. The findings will be disseminated through peer-review publications and conference presentations. TRIAL REGISTRATION NUMBER: ACTRN12621000710820 .

Patterns and natural history of hand pain in individuals with symptomatic hand osteoarthritis in a prospective cohort study: A post-hoc analysis of a randomised controlled trial.

Objective: To investigate the variation in the distribution and the natural history of hand pain over 6 weeks in individuals with symptomatic hand osteoarthritis. Design: Patient-reported outcome data were collected at baseline and weekly for 6 weeks from community-based participants enrolled in a randomised controlled trial. Participants were grouped based on location of significant pain (Visual Analogue Scale, VAS≥40/100 â€‹mm) (both carpometacarpal (CMC) and interphalangeal (IP), CMC only, and IP only). Results: At baseline, of the 106 participants, 55(51.9 %) had pain in both CMC and IP joints, 28(26.4 %) in IP joints only, and 16(15.1 %) in CMC joint only. Those with CMC and IP pain had significantly higher VAS pain [68.1 (2.6) vs 59.3 (3.5) vs 51.2 (4.7)]; Australian Canadian Osteoarthritis Hand Index, (AUSCAN) pain [290.1 (15.7) vs 225.3 (21.2) vs 237.9 (28.4)], stiffness [57.1 (3.7) vs 44.6 (5.0) vs 32.2 (6.7)] and functional limitation [527.5 (30.9) vs 356.0 (41.7) vs 433.3 (55.7)]; and pain sensitization [PainDETECT score 11.1 (1.1) vs 8.1 (1.8) vs 5.8 (1.9)] compared to those with IP or CMC only pain, respectively. All groups showed improvement in outcomes over 6 weeks without significant inter-group differences. Conclusion: In a population with significant hand pain, pain in both CMC and IP joints was most common and identified a more severe phenotype than pain in IP or CMC only with higher pain, more functional limitation and pain sensitization. These data have the potential to inform clinical management of patients with hand pain and patient selection in clinical trials.

Negative back beliefs are associated with increased odds of low back pain and disability: a 10-year cohort study in men.

OBJECTIVE: Although negative back beliefs are associated with high-intensity low back pain (LBP)/disability, whether they influence incident high-intensity LBP/high-disability over the long-term is unknown. This study aimed to investigate whether negative back beliefs were associated with developing high-intensity LBP and/or high-disability over 10 years in men. METHODS: Men with no or low-intensity LBP and/or disability attending the Geelong Osteoporosis Study between 2006-2010 were included. Data on age, body mass index, mobility, education, back beliefs (Back Beliefs Questionnaire), LBP and disability (Graded Chronic Pain Scale) were collected between 2006-2010. Beliefs, LBP and disability were re-assessed in 2016-2021. Binary logistic regression was used to examine the association between negative back beliefs and incident high-intensity pain and/or high-disability, adjusting for age, body mass index, mobility, and education. RESULTS: At baseline, 705 participants (mean age 53.8 years) had no or low LBP and no or low-disability; 441 (62.6%) participants completed a 10-year follow-up. Of these, 37 (8.4%) developed high-intensity pain and/or high-disability. In multivariate analyses, participants with more negative back beliefs at baseline were more likely to develop high-intensity pain and/or high-disability (Odds ratio 1.05, 95% CI 1.00-1.11). Developing more negative back beliefs was also associated with incident high-intensity pain and/or high-disability (Odds Ratio 1.20, 95% CI 1.12-1.30). CONCLUSION: In a male community-based population, negative beliefs regarding the consequences of LBP were associated with an increased likelihood of developing high-intensity pain and/or high-disability. Addressing negative back beliefs in the community may reduce the incidence of high-intensity pain and/or high-disability over 10 years in men.

Methotrexate to treat hand osteoarthritis with synovitis (METHODS): an Australian, multisite, parallel-group, double-blind, randomised, placebo-controlled trial.

BACKGROUND: Hand osteoarthritis is a disabling condition with few effective therapies. Hand osteoarthritis with synovitis is a common inflammatory phenotype associated with pain. We aimed to examine the efficacy and safety of methotrexate at 6 months in participants with hand osteoarthritis and synovitis. METHODS: In this multisite, parallel-group, double-blind, randomised, placebo-controlled trial, participants (aged 40-75 years) with hand osteoarthritis (Kellgren and Lawrence grade ≥2 in at least one joint) and MRI-detected synovitis of grade 1 or more were recruited from the community in Melbourne, Hobart, Adelaide, and Perth, Australia. Participants were randomly assigned (1:1) using block randomisation, stratified by study site and self-reported sex, to receive methotrexate 20 mg or identical placebo orally once weekly for 6 months. The primary outcome was pain reduction (measured with a 100 mm visual analogue scale; VAS) in the study hand at 6 months assessed in the intention-to-treat population. Safety outcomes were assessed in all randomly assigned participants. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000877381). FINDINGS: Between Nov 22, 2017, and Nov 8, 2021, of 202 participants who were assessed for eligibility, 97 (48%) were randomly assigned to receive methotrexate (n=50) or placebo (n=47). 68 (70%) of 97 participants were female and 29 (30%) were male. 42 (84%) of 50 participants in the methotrexate group and 40 (85%) of 47 in the placebo group provided primary outcome data. The mean change in VAS pain at 6 months was -15·2 mm (SD 24·0) in the methotrexate group and -7·7 mm (25·3) in the placebo group, with a mean between-group difference of -9·9 (95% CI -19·3 to -0·6; p=0·037) and an effect size (standardised mean difference) of 0·45 (0·03 to 0·87). Adverse events occurred in 31 (62%) of 50 participants in the methotrexate group and 28 (60%) of 47 participants in the placebo group. INTERPRETATION: Treatment of hand osteoarthritis and synovitis with 20 mg methotrexate for 6 months had a moderate but potentially clinically meaningful effect on reducing pain, providing proof of concept that methotrexate might have a role in the management of hand osteoarthritis with an inflammatory phenotype. FUNDING: National Health and Medical Research Council of Australia.

Our biology working against us in obesity: A narrative review on implications for management of osteoarthritis.

Obesity is the major modifiable risk factor for osteoarthritis (OA). A major focus of management in OA is weight loss. Although we live in an obesogenic environment, obesity has a predominantly genetic and epigenetic basis. This explains a person's weight set point which is defended by biological mechanisms making weight loss difficult to achieve and maintain long term, regardless of the methods used. Significant weight regain occurs after weight loss, with weight tending to return to pre-treatment levels after cessation of interventions including the glucagon-like peptide-1 (GLP-1) agonists. An area that has received little attention is the slow, insidious weight creep of 0.5-1 kg/year over adulthood that sees individuals relentlessly increase weight. There is evidence that low intensity, personalised lifestyle interventions can prevent this weight creep, providing patients with achievable goals. In this narrative review, we examine the evidence for weight loss in OA, the biological mechanisms that make weight loss difficult to achieve and maintain and the potential negative impacts on patients. We review the evidence for preventing weight gain, the improvement in patient outcomes and the potential for significant healthcare savings through reduced knee replacements. We propose a combined approach of weight loss when indicated, together with targeting weight creep across adult years and the potential role of metformin. Implementing these combined approaches is likely to be more effective in improving patient related outcomes, reducing joint damage and healthcare costs, than our current focus on achieving weight loss in OA.

Efficacy of tumor necrosis factor inhibitors in hand osteoarthritis: A systematic review and meta-analysis of randomized controlled trials.

Objectives: This study aimed at systematically review the evidence for the efficacy of Tumor Necrosis Factor (TNF) inhibitors on symptoms and structural outcomes in hand osteoarthritis. Methods: Three databases were searched for randomized controlled trials examining the efficacy of TNF inhibitors in hand osteoarthritis. Two authors extracted data and assessed the risk of bias. The mean difference (MD) was calculated, and a random-effects meta-analysis was performed. Results: Four studies were identified involving 276 participants. Meta-analysis showed that TNF inhibitors had no effect on pain at 4-6 weeks (MD -0.93, 95%CI -7.41 to 5.55; 2 studies) and 24-26 weeks (MD -3.82, 95%CI -11.46 to 3.83; 2 studies) and no effect on grip strength at 12 months (MD -0.35, 95%CI -1.08 to 0.37; 2 studies). There was limited evidence for the effect of TNF inhibitors on structural outcomes at 12 months. Subgroup analysis from 2 studies showed beneficial effect of TNF inhibitors on reducing the progression of structural outcomes in hand OA patients with signs of inflammation but not in those without inflammation. The certainty of the evidence was low for the effect of TNF inhibitor on pain and moderate for the effect on grip strength. Conclusion: This study found no effect of TNF inhibitors on clinical outcomes in hand osteoarthritis over the short term (<6 weeks) and within one year, with some evidence for beneficial effect on structural outcomes.

Effect of 6-week treatment with topical betamethasone dipropionate in patients with symptomatic hand osteoarthritis: A randomized double-blind, placebo-controlled trial.

Objective: To examine the efficacy and safety of topical corticosteroid over 6 weeks in patients with symptomatic hand osteoarthritis. Design: In a randomized, double-blind, placebo-controlled trial, community-based participants with hand osteoarthritis were randomly assigned (1:1) to topical Diprosone OV (betamethasone dipropionate 0.5 â€‹mg/g in optimised vehicle, n=54) or placebo (plain paraffin, n=52) ointment to painful joints 3 times daily for 6 weeks. Primary outcome was pain reduction [assessed by 100 â€‹mm visual analogue scale (VAS)] at 6 weeks. Secondary outcomes included changes in pain and function using the Australian Canadian Osteoarthritis Hand Index (AUSCAN), Functional Index for Hand Osteoarthritis (FIHOA), and Michigan Hand Outcomes Questionnaire (MHQ) at 6 weeks. Adverse events were recorded. Results: Of 106 participants (mean age 64.2 years, 85.9% female), 103 (97.2%) completed the study. Change in VAS at 6 weeks was similar in the Diprosone OV and placebo groups (-19.9 vs. -20.9, adjusted difference 0.6, 95% CI -8.9 to 10.2). There were no significant between-group differences in change in AUSCAN pain [adjusted difference 25.8 (-16.0 to 67.5)], AUSCAN function [21.2 (-55.0 to 97.4)], FIHOA [-0.1 (-1.7 to 1.5)], or MHQ [-1.2 (-6.0 to 3.6)]. Incidence of adverse events was 16.7% in Diprosone OV and 19.2% in placebo group. Conclusions: Topical Diprosone OV ointment, although well-tolerated, was no better than placebo in improving pain or function over 6 weeks in patient with symptomatic hand osteoarthritis. Future studies should consider examining joints with synovitis and whether delivery approaches enhancing transdermal penetration of corticosteroids into joints are effective in hand osteoarthritis. Trial registration: ACTRN 12620000599976. Registered May 22, 2020.

Prevalence and correlates of the use of complementary and alternative medicines among older adults with joint pain.

BACKGROUND: There is increasing use of complementary and alternative medicines (CAMs) alone or as an adjuvant therapy to conventional medicines in osteoarthritis (OA) patients. OBJECTIVES: This study aimed to describe the prevalence and correlates of the use of CAMs among community-dwelling older adults. METHODS: Data from the Tasmania Older Adult Cohort Study (TASOAC, n = 1099) were used to describe the prevalence of CAM use. Correlates of CAM use were assessed by comparing CAM users and non-users. To further assess correlates of CAM use, participants with at least one joint with pain were classified into four categories: CAM-only, analgesics-only, co-therapy, and "neither CAMs nor analgesics" (NCNA). RESULTS: In all, 385 (35.0%) of our participants reported use of CAMs, among which vitamins/minerals were used most (22.6%, n = 232). Compared with CAM non-users, CAM users were more likely to be female, were less likely to be overweight, were better educated, had more joints with OA, had fewer WOMAC scores, and did more steps per day. Among participants with any joint pain, the CAM-only group were less likely to be overweight, consumed more alcohol, had higher quality of life, had more steps per day, and had fewer pain-related symptoms compared with the analgesic-only group. CONCLUSION: Complementary and alternative medicines were commonly used among Tasmanian older adults, with 35% of the population using CAMs either alone or in combination with conventional analgesics. CAM users were more likely to be female, be better educated, have more joints with OA, and had healthier lifestyles, including lower body mass index and higher number of steps per day.

High levels of back disability, not back pain, are associated with reduced physical activity across key activity domains.

BACKGROUND: Although remaining physically active is the cornerstone of management for low back pain, our understanding of the physical activity performed by those with back pain is limited. OBJECTIVES: To examine the physical activity reported by individuals with different levels of low back pain and disability across key activity domains. DESIGN: Community-based, cross-sectional study. METHODS: 542 women were recruited from a research database formed from an electoral roll and completed validated, self-report questionnaires. The amount and intensity of physical activity was reported using the International Physical Activity Questionnaire. Low back pain and disability were examined using the Graded Chronic Pain Scale. Participants were categorised into no, low or high pain and disability groups. RESULTS: Individuals who reported high disability performed 55% of the physical activity of those without disability (MET(hours/week):median(95%CI) = 27.1(13.2-41.0); 48.8(37.8-59.9),p = 0.01), including less moderate (18.0(10.4-25.6); 31.0(24.0-38.1),p = 0.007), and domestic and gardening activity (14.7(7.2-22.3); 25.7(19.8-31.7),p = 0.001). Fewer women with high disability performed vigorous (OR(95%CI) = 0.29(0.13-0.65),p = 0.002) and leisure activities (0.17(0.04-0.75),p = 0.02) compared to those with no disability. Those with low disability reported less leisure activity ((0.55(0.35-0.88),p = 0.01), but more work-related activities and active transport than individuals without disability (1.65(1.01-2.7),p = 0.04; 1.6(1.04-2.6),p = 0.03). There were no differences in activity between pain groups, with the exception of those with low intensity pain performing less leisure activity (0.51(0.30-0.88),p = 0.01). CONCLUSIONS: Individuals who reported high back disability, not back pain, were found to perform reduced physical activity, including less total, moderate, vigorous, and discretionary activity. These findings highlight the altered activity levels of people with back disability and the need to examine its impact on their health and wellbeing.