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Objective There is increasing evidence for the involvement of vascular disease in the pathogenesis of knee OA. Popliteal artery wall thickness can be used as a surrogate marker of atherosclerosis. We examined the association between popliteal artery wall thickness and knee cartilage volume in individuals with symptomatic knee OA. Methods This prospective cohort study analysed 176 participants from a randomized placebo-controlled trial examining the effect of atorvastatin on structural progression in knee OA. The participants underwent MRI of the study knee at baseline and 2-year follow-up. Popliteal artery wall thickness and tibial cartilage volume were measured from MRI using validated methods. The top quartile of the rate of tibial cartilage volume loss was defined as rapid progression. Results At baseline, every 10% increase in popliteal artery wall thickness was associated with 120.8 mm3 (95% CI 5.4, 236.2, P  = 0.04) lower of medial tibial cartilage volume and 151.9 mm3 (95% CI 12.1, 291.7, P  = 0.03) lower of lateral tibial cartilage volume. Longitudinally, for every 10% increase in popliteal artery wall thickness, the annual rate of medial tibial cartilage volume loss was increased by 1.14% (95% CI 0.09%, 2.20%, P  = 0.03), and there was a 2.28-fold (95% CI 1.07, 4.83, P  = 0.03) risk of rapid progression of medial tibial cartilage loss, adjusted for age, sex, BMI, tibial bone area, smoking, vigorous physical activity, and intervention group allocation. Conclusion The findings support a role for vascular pathology in the progression of knee OA. Targeting atherosclerosis has the potential to improve outcomes in knee OA. [ABSTRACT FROM AUTHOR]

We examined the effect of person‐related factors on capacity to obtain needed healthcare for non‐COVID‐19 health conditions/disabilities under COVID‐19 restrictions. This was an anonymous online survey of Australian residents ≥18 years (3rd April to 2nd May 2020). We determined the ability to obtain care needed for non‐COVID‐19 health conditions/disabilities, experience of COVID‐19, COVID‐19 restrictions and sociodemographic characteristics using study‐specific questions; and clinically significant depressive and anxiety symptoms using Patient Health Questionnaire 9 and Generalised Anxiety Disorder Scale 7 respectively. We calculated the population attributable fraction (PAF) to determine the proportion of worse access to non‐COVID‐19 health/disability care attributable to independent risk factors. 13,829 (91.5%) participants had complete data. 6,712 (46.4%) identified a need for healthcare/disability services (<45 years 42.1%, ≥45 years 50.3%). 31.6% aged <45 years and 24.3% aged ≥45 years reported worse access to health/disability care than experienced prior to the pandemic. In those aged <45 years the PAF was highest for depressive symptoms (21.4%; 95% CI 12.6%–29.3%) and anxiety (PAF 19.9%, 12.3%–26.9%). with a PAF of 49.6% (40.1%–57.6%) if any one of the following was being experienced: doing unpaid work; being a student; depressive symptoms; symptoms of anxiety; experiencing high adverse impact of COVID‐19 restrictions. In those ≥45 years, PAF was highest for having depressive symptoms (PAF 20.9%, 16.6–24.8) with a PAF of 44.1% (36.0%–51.2%) if any one of the following was being experienced: depressive symptoms; symptoms of anxiety; doing unpaid work; living alone; being in lowest socioeconomic quintile; main source of income from government benefits; any personal experience of COVID‐19. The identified risk factors, which include many that characterise those with worse health outcomes generally, explained 44%–50% of worse access to necessary health/disability care. These data have the potential to inform targeted strategies aimed at reducing a post‐pandemic escalation of poor health outcomes, especially in vulnerable populations. [ABSTRACT FROM AUTHOR]

Objective: To determine whether atorvastatin slows tibial cartilage volume loss in patients with symptomatic knee osteoarthritis (OA) in a multicenter, randomized, double‐blind, placebo‐controlled trial. Methods: Participants ages 40–70 years were randomized to receive oral atorvastatin (40 mg once daily) (n = 151) or matching placebo (n = 153). The primary end point was annual percentage change in tibial cartilage volume over 2 years, assessed using magnetic resonance imaging (MRI). The prespecified secondary end points were progression of cartilage defects and bone marrow lesions over 2 years, which were assessed using MRI and change in Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index pain, stiffness, and function scores. Results: A total of 248 of 304 participants (81.6%) completed the trial (mean age 55.7 years; 55.6% women). The annual change in tibial cartilage volume differed minimally between the atorvastatin and placebo groups (mean change –1.66% versus –2.17%, between‐group difference 0.50% [95% confidence interval (95% CI) –0.17%, 1.17%]). There were no significant differences in the progression of cartilage defects (odds ratio [OR] 0.86 [95% CI 0.52, 1.41]) or progression of bone marrow lesions (OR 1.00 [95% CI 0.62, 1.63]). Moreover, there were no significant differences in change in WOMAC pain, stiffness, or function scores over 2 years between the atorvastatin and placebo groups (mean change in pain score –36.0 versus –29.5, adjusted difference –2.7 [95% CI –27.1, 21.7]; mean change in stiffness score –14.2 versus –11.8, adjusted difference –0.2 [95% CI –12.2, 11.8]; mean change in function score –89.4 versus –87.5, adjusted difference 0.3 [95% CI –83.1, 83.6]). The incidence of adverse events (AEs) was similar between the atorvastatin and placebo groups (57 [37.7%] versus 52 [34.0%] experiencing AEs). Conclusion: Treatment with oral atorvastatin (40 mg once daily), compared to placebo, did not significantly reduce cartilage volume loss over 2 years in patients with symptomatic knee OA. These findings do not support the use of atorvastatin for the treatment of knee OA. [ABSTRACT FROM AUTHOR]

Background: To examine the association between circulating 25(OH)D concentrations and incidence of total hip replacement for osteoarthritis in a prospective cohort study.Methods: This study examined a random sample of 2651 participants in the Melbourne Collaborative Cohort Study who had 25(OH)D concentrations measured from dried blood spots collected in 1990-1994. Participants who underwent total hip replacement for osteoarthritis between January 2001 and December 2018 were identified by linking the cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of total hip replacement for osteoarthritis in relation to 25(OH)D concentrations, adjusted for confounders.Results: Eighty-six men and eighty-seven women had a total hip replacement for osteoarthritis. Compared with men in the lowest (1st) quartile of 25(OH)D concentration, the HR for total hip replacement was 2.32 (95% CI 1.05, 5.13) for those in the 2nd quartile, 2.77 (95% CI 1.28, 6.00) for those in the 3rd quartile, and 1.73 (95% CI 0.75, 4.02) for those in the highest quartile of 25(OH)D concentrations (p for trend 0.02). There was little evidence of an association in women.Conclusions: Higher circulating 25(OH)D concentrations were associated with an increased risk of total hip replacement for osteoarthritis in men but not in women. Although the underlying mechanism warrants further investigation, our findings highlight the need to determine the optimal levels of circulating 25(OH)D to reduce the risk of hip osteoarthritis. [ABSTRACT FROM AUTHOR]

Objective To examine whether the presence of bulge sign or patellar tap was associated with frequent knee pain, progression of radiographic OA (ROA) and total knee replacement (TKR). Methods This study included 4344 Osteoarthritis Initiative participants examined at baseline for bulge sign and/or patellar tap. The clinical signs were categorized as no (none at baseline and 2 years), resolved (present at baseline only), developed (present at 2 years only) and persistent (present at both time points). Frequent knee pain and progression of ROA over 4 years and TKR over 6 years were assessed. Binary logistic regression was used to examine the associations. Results A total of 12.7% of participants had bulge sign only, 2.0% had patellar tap only and 3.3% had both. A positive baseline bulge sign was associated with an increased risk of frequent knee pain [OR 1.31 (95% CI 1.04, 1.64), P = 0.02] and TKR [OR 1.47 (95% CI 1.06, 2.05), P = 0.02]. Developed bulge sign was associated with an increased risk of frequent knee pain [OR 1.75 (95% CI 1.34, 2.29), P < 0.001] and progressive ROA [OR 1.67 (95% CI 1.11, 2.51), P = 0.01]. Persistent bulge sign was associated with an increased risk of frequent knee pain [OR 1.60 (95% CI 1.09, 2.35), P = 0.02], progressive ROA [OR 1.84 (95% CI 1.01, 3.33), P = 0.045] and TKR [OR 2.13 (95% CI 1.23, 3.68), P = 0.007]. Patellar tap was not examined for its association with joint outcomes due to its low prevalence. Conclusion The presence of bulge sign identifies individuals at increased risk of frequent knee pain, progression of ROA and TKR. This provides clinicians with a quick, simple, inexpensive method for identifying those at higher risk of progressive knee OA who should be targeted for therapy. [ABSTRACT FROM AUTHOR]

Objective To examine whether baseline knee joint effusion volume and the change in effusion volume over 1 year are associated with cartilage volume loss, progression of radiographic OA (ROA) over 4 years and risk of total knee replacement over 6 years. Methods This study included 4115 Osteoarthritis Initiative participants with knee joint effusion volume quantified by MRI at baseline. The change in effusion volume over 1 year was assessed. Cartilage volume loss and progression of ROA over 4 years were assessed using MRI and X-ray and total knee replacement over 6 years was assessed. Multiple linear regression and binary logistic regression were used for data analyses. Results Baseline knee effusion volume (per 5 ml) was positively associated with a loss of medial and lateral cartilage volume [regression coefficient 0.13%/year (95% CI 0.10, 0.17) and 0.13%/year (95% CI 0.10, 0.16), respectively, both P < 0.001], progression of ROA [odds ratio (OR) 1.28 (95% CI 1.20, 1.37), P < 0.001], and risk of knee replacement [OR 1.12 (95% CI 1.05, 1.20), P = 0.001]. A 5 ml increase in knee effusion volume over 1 year was positively associated with medial cartilage volume loss [regression coefficient 0.09%/year (95% CI 0.04, 0.15), P = 0.001], progression of ROA [OR 1.21 (95% CI 1.11, 1.33), P < 0.001] and risk of knee replacement [OR 1.24 (95% CI 1.12, 1.37), P < 0.001]. Conclusions Knee joint effusion volume assessed from MRI provides a continuous and sensitive measure that was associated with cartilage volume loss, progression of ROA and risk of total knee replacement. It may provide a method to identify individuals with an inflammatory OA phenotype who are at higher risk of disease progression. [ABSTRACT FROM AUTHOR]

Objective: To examine the associations of female reproductive and hormonal factors with incidence of total knee arthroplasty (TKA) for osteoarthritis (OA), and to determine whether the associations differ according to overweight/obesity status. Methods: This study included 22,289 women in the Melbourne Collaborative Cohort Study. Data on age at menarche, pregnancy, parity, years of menstruation, oral contraceptive (OC) use, menopausal status, and hormone replacement therapy (HRT) were collected in 1990–1994. Incidence of TKA during 2001–2013 was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. All analyses were adjusted for age, body mass index (BMI) at midlife, change in BMI (from early reproductive age to midlife), country of birth, physical activity, smoking, and education level. Results: Over the course of 12.7 years, 1,208 TKAs for OA were identified. Ever being pregnant was associated with increased risk of TKA (hazard ratio [HR] 1.32 [95% confidence interval (95% CI) 1.06–1.63]). Parity was positively associated with risk of TKA (P for trend = 0.003). OC users had increased risk of TKA compared with non‐users (for OC use of <5 years, HR 1.25 [95% CI 1.08–1.45]; for OC use of ≥5 years, HR 1.17 [95% CI 1.00–1.37]). A 1‐year increase in menstruation was associated with a 1% decrease in risk of TKA (HR 0.99 [95% CI 0.97–0.99]). These associations remained significant only in women of normal weight at early reproductive age. Current HRT users had increased risk of TKA compared with non‐users (HR 1.37 [95% CI 1.14–1.64]); the association was significant only in non‐obese women at midlife. Conclusion: Reproductive and hormonal factors were associated with risk of knee OA. These associations remained significant in women of normal weight at early reproductive age and in non‐obese women at midlife. Further work is needed to understand the complex effect of these factors on knee OA. [ABSTRACT FROM AUTHOR]

Objective The increased prevalence of osteoarthritis (OA) in postmenopausal women suggests that changes in either circulating sex steroid concentrations or the tissue response to sex steroids may have a role in the pathogenesis of OA. The aim of this study was to examine whether circulating sex steroid concentrations are associated with the incidence of total knee and total hip replacement for OA. Methods Study subjects (n = 2,621; all women) were recruited in 1990-1994 from the Melbourne Collaborative Cohort Study (MCCS). Circulating sex steroid concentrations were measured in blood samples obtained from the women at the time of recruitment. The incidence of total knee and total hip replacement for OA during 2001-2011 was determined by linking the MCCS records to the Australian Orthopaedic Association National Joint Replacement Registry. Results During the followup period, 115 women had undergone total knee replacement and 99 had undergone total hip replacement for OA. Greater log-transformed concentrations of estradiol were associated with a lower incidence of knee replacement (hazard ratio [HR] 0.70, 95% confidence interval [95% CI] 0.50-0.96), and greater log-transformed concentrations of androstenedione were associated with a lower incidence of hip replacement (HR 0.70, 95% CI 0.52-0.93). In contrast, greater log-transformed concentrations of sex hormone binding globulin (SHBG) were associated with a higher incidence of hip replacement (HR 1.70, 95% CI 1.05-2.77). Conclusion A lower estradiol concentration is a risk factor for knee OA, while a lower androstenedione concentration and higher SHBG concentration are risk factors for hip OA in women. These findings suggest that circulating sex steroids have a role in the pathogenesis of OA, and that modifying these steroid concentrations may provide a potential strategy for the prevention and treatment of knee and hip OA. [ABSTRACT FROM AUTHOR]

Objective. The data are conflicting for the association between the index-to-ring finger length ratio (2D:4D) and the risk of OA. The aim of this cohort study was to examine the relationship between 2D:4D and the risk of severe knee and hip OA requiring total joint replacement.Methods. A total of 14 511 participants in the Melbourne Collaborative Cohort Study had 2D:4D assessed from hand photocopies. The incidence of total knee replacement and total hip replacement between 2001 and 2011 was determined by linking the cohort records to the Australian Orthopaedic Association National Joint Replacement Registry.Results. Over an average 10.5 years of follow-up, 580 participants had total knee replacement and 499 had total hip replacement. Greater right 2D:4D [hazard ratio (HR) 0.91 for a s.d. increase in 2D:4D, 95% CI 0.84, 0.99, P = 0.03] and average right and left 2D:4D (HR 0.91 for a s.d. increase in 2D:4D, 95% CI 0.84, 0.99, P = 0.02) were associated with a reduced incidence of total knee replacement. These associations persisted when participants whose fingers had any features that might have affected the validity of 2D:4D measurements were excluded. No significant associations were observed between 2D:4D and the incidence of total hip replacement.Conclusion. A lower 2D:4D is associated with an increased risk of severe knee OA requiring total knee replacement, but not the risk of severe hip OA. The underlying mechanisms for the association warrant further investigation. [ABSTRACT FROM PUBLISHER]