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Few studies have explored the impact of low back or lower limb pain severity on recurrent (≥2) falls in older adults.Investigate the association between the severity of low back or lower limb pain, and ≥2 falls or falls-related injuries.Community-dwelling Australian males and females in the ASPREE Longitudinal Study of Older Persons (ALSOP), aged ≥70 years. Self-reported, cross-sectional questionnaire data regarding number of falls and falls-related injuries in the last 12 months; and sites and severity of pain experienced on most days. Adjusted relative risks (RR) were estimated from multivariable Poisson regression models, for males and females separately.Of 14,892 ALSOP participants, 13% (n = 1983) reported ≥2 falls ('recurrent fallers') in the last 12 months. Males and females who reported severe low back, or severe lower limb pain on most days were more likely to report ≥2 falls in the last 12 months compared to those with mild pain (lower back: males RR = 1.70 and females RR = 1.5, p = 0.001; lower limb: males RR = 2.0, p 0.001 and females RR = 1.4, p = 0.003). Female recurrent fallers who reported severe low back (RR = 1.3, p = 0.029) or lower limb (RR = 1.2, p = 0.024) pain on most days were more likely to report a falls-related injury in the last 12 months compared to females with mild pain.Severe low back or lower limb pain was associated with an increased likelihood of recurrent falls (males/females) or falls-related injuries (females only). Assessment of severe low back and lower limb pain should be considered as a priority when undertaking falls-risk evaluation.Severe low back pain, or severe lower limb pain is associated with an increased likelihood of recurrent falls in older males and females, and an increased likelihood of falls-related injuries in older female recurrent fallers. Assessment and management of severe low back and lower limb pain should be prioritized when undertaking falls-risk assessment. Future longitudinal research is required to further interrogate this relationship and its underlying mechanisms.

Background: Impaired cerebral blood flow has been associated with an increased risk of falls. Mean arterial pressure (MAP) and variability in MAP have been reported to affect cerebral blood flow but their relationships to the risk of falls have not previously been reported. Methods: Utilising data from the Aspirin in Reducing Events in the Elderly trial participants, we estimated MAP and variability in MAP, defined as within-individual SD of MAP from baseline and first 2 annual visits. The relationship with MAP was studied in 16 703 participants amongst whom 1539 falls were recorded over 7.3 years. Variability in MAP was studied in 14 818 of these participants who experienced 974 falls over 4.1 years. Falls were confined to those involving hospital presentation. Cox regression was used to calculate hazard ratio and 95% CI for associations with falls. Results: Long-term variability in MAP was not associated with falls except amongst frail or prefrail participants using antihypertensive medications. Within this group each 5 mm Hg increase in long-term variability in MAP increased the risk of falls by 16% (hazard ratio, 1.16 [95% CI, 1.02–1.33]). Amongst the antihypertensive drugs studied, beta-blocker monotherapy (hazard ratio, 1.93 [95% CI, 1.17–3.18]) was associated with an increased risk of falls compared with calcium channel blockers. Conclusions: Higher levels of long-term variability in MAP increase the risk of serious falls in older frail and prefrail individuals taking antihypertensive medications. The observation that the relationship was limited to frail and prefrail individuals might explain some of the variability of previous studies linking blood pressure indices and falls.

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.

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.

Background Knee osteoarthritis is a major cause of pain and disability. Pain control is poor, with most patients remaining in moderate to severe pain. This may be because central causes of pain, a common contributor to knee pain, are not affected by current treatment strategies. Antidepressants, such as amitriptyline, have been used to treat chronic pain in other conditions. The aim of this randomised, double blind, controlled trial, is to determine whether low dose amitriptyline reduces pain in people with painful knee osteoarthritis over 3 months compared to benztropine, an active placebo. Methods/design One hundred and sixty people with painful radiographic knee osteoarthritis will be recruited via clinicians, local and social media advertising. Participants will be randomly allocated in a 1:1 ratio to receive either low dose amitriptyline (25 mg) or active placebo (benztropine mesylate, 1 mg) for 3 months. The primary outcome is change from baseline in knee pain (WOMAC pain subscale) at 12 weeks. Secondary outcomes include change in function (total WOMAC) and the proportion of individuals achieving a substantial response (≥ 50% reduction in pain intensity, measured by Visual Analog Scale, VAS, from no pain to worst pain imaginable, 0-100 mm) and moderate response (≥ 30% reduction in pain intensity, measured by VAS) at 12 weeks. Intention to treat analyses will be performed. Subgroup analyses will be done. Discussion This study will provide high level evidence regarding the effectiveness of low dose amitriptyline compared to benztropine in reducing pain and improving function in knee OA. This trial has the potential to provide an effective new therapeutic approach for pain management in knee osteoarthritis, with the potential of ready translation into clinical practice, as it is repurposing an old drug, which is familiar to clinicians and with a well described safety record. Trial registration Australian New Zealand Clinical Trials Registry prior to recruitment commencing (ACTRN12615000301561, March 31, 2015, amended 14 December 2018, February 2021). Additional amendment requested 18 July 2021.

Summary Objective To determine the prevalence of neuropathic-like pain (NP) and pain sensitization (PS) defined by self-report questionnaires in knee and hip osteoarthritis, and whether prevalence is potentially explained by disease-severity or affected joint. Design MEDLINE, EMBASE, CINAHL were systematically searched (1990–April 2020) for studies describing the prevalence of NP and PS in knee and hip osteoarthritis using self-report questionnaires. Random-effects meta-analysis was performed. Statistical heterogeneity between studies and sub-groups (affected joint and population source as a proxy for disease severity) was assessed (I2 statistic and the Chi-squared test). Results From 2,706 non-duplicated references, 39 studies were included (2011–2020). Thirty-six studies reported on knee pain and six on hip pain. For knee osteoarthritis, the pooled prevalence of NP was: using PainDETECT, possible NP(score ≥13) 40% (95%CI 32–48%); probable NP(score >18) 20% (95%CI 15–24%); using Self-Report Leeds Assessment of Neuropathic Symptoms and Signs, 32% (95%CI 26–38%); using Douleur Neuropathique (DN4) 41% (95% CI 24–59%). The prevalence of PS using Central Sensitization Inventory (CSI) was 36% (95% CI 12–59%). For hip osteoarthritis, the pooled prevalence of NP was: using PainDETECT, possible NP 29% (95%CI 22–37%%); probable NP 9% (95%CI 6–13%); using DN4 22% (95%CI 12–31%) in one study. The prevalence of possible NP pain was higher at the knee (40%) than the hip (29%) (difference 11% (95% CI 0–22%), P = 0.05). Conclusions Using self-report questionnaire tools, NP was more prevalent in knee than hip osteoarthritis. The prevalence of NP in knee and hip osteoarthritis were similar for each joint regardless of study population source or tool used. Whether defining NP using self-report questionnaires enables more effective targeted therapy in osteoarthritis requires investigation.

ImportanceThe association between weight change and subsequent cause-specific mortality among older adults is not well described. The significance of changes in waist circumference (WC) has also not been compared with weight change for this purpose.ObjectiveTo examine the associations of changes in body weight and WC with all-cause and cause-specific mortality.Design, Setting, and ParticipantsThis cohort study is a post hoc analysis of data from the Aspirin in Reducing Events in the Elderly (ASPREE) randomized clinical trial, which recruited participants between March 1, 2010, and December 31, 2014. The study included community-based older adults (16 703 Australian participants aged ≥70 years and 2411 US participants aged ≥65 years) without evident cardiovascular disease (CVD), dementia, physical disability, or life-limiting chronic illness. Data analysis was performed from April to September 2022.ExposuresBody weight and WC were measured at baseline and at annual visit 2. Analysis models were adjusted for baseline body mass index because height and weight were measured at baseline, allowing for calculation of body mass index and other variables. Both body weight and WC changes were categorized as change within 5% (stable), decrease by 5% to 10%, decrease by more than 10%, increase by 5% to 10%, and increase by more than 10%.Main Outcomes and MeasuresAll-cause, cancer-specific, CVD-specific, and noncancer non-CVD–specific mortality. Mortality events were adjudicated by an expert review panel. Cox proportional hazards regression and competing risk analyses were used to calculate hazard ratios (HRs) and 95% CIs.ResultsAmong 16 523 participants (mean [SD] age, 75.0 [4.3] years; 9193 women [55.6%]), 1256 deaths were observed over a mean (SD) of 4.4 (1.7) years. Compared with men with stable weight, those with a 5% to 10% weight loss had a 33% higher (HR, 1.33; 95% CI, 1.07-1.66) risk of all-cause mortality, and those with more than a 10% decrease in body weight had a 289% higher (HR, 3.89; 95% CI, 2.93-5.18) risk. Compared with women with stable weight, those with a 5% to 10% weight loss had a 26% higher (HR, 1.26; 95% CI, 1.00-1.60) risk of all-cause mortality, and those with more than a 10% decrease in body weight had a 114% higher (HR, 2.14; 95% CI, 1.58-2.91) risk. Weight loss was associated with a higher cancer-specific mortality (>10% decrease among men: HR, 3.49; 95% CI, 2.26-5.40; 5%-10% decrease among women: HR, 1.44; 95% CI, 1.46-2.04; >10% decrease among women: HR, 2.78; 95% CI, 1.82-4.26), CVD-specific mortality (>10% decrease among men: HR, 3.14; 95% CI, 1.63-6.04; >10% decrease among women: HR, 1.92; 95% CI, 1.05-3.51), and noncancer non-CVD–specific mortality (>10% decrease among men: HR, 4.98; 95% CI, 3.14-7.91). A decrease in WC was also associated with mortality.Conclusions and RelevanceThis cohort study of healthy older adults suggests that weight loss was associated with an increase in all-cause and cause-specific mortality, including an increased risk of cancer, CVD, and other life-limiting conditions. Physicians should be aware of the significance of weight loss, especially among older men.

ImportanceIncreased levels of high-density lipoprotein cholesterol (HDL-C) have been associated with osteoporosis. Preclinical studies have reported that HDL-C reduces bone mineral density by reducing osteoblast number and function. However, the clinical significance of these findings is unclear.ObjectiveTo determine whether higher HDL-C levels are predictive of an increased fracture risk in healthy older adults.Design, Setting, and ParticipantsThis cohort study is a post hoc analysis of data from the Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial and the ASPREE-Fracture substudy. ASPREE was a double-blind, randomized, placebo-controlled primary prevention trial of aspirin that recruited participants between 2010 and 2014. These comprised community-based older adults (16 703 Australians aged ≥70 years, 2411 US participants ≥65 years) without evident cardiovascular disease, dementia, physical disability, and life-limiting chronic illness. The ASPREE-Fracture substudy collected data on fractures reported postrandomization from Australian participants. Cox regression was used to calculate hazard ratio (HR) and 95% CI. Data analysis for this study was performed from April to August 2022.ExposurePlasma HDL-C.Main Outcomes and MeasuresFractures included were confirmed by medical imaging and included both traumatic and minimal trauma fractures. Fractures were adjudicated by an expert review panel.ResultsOf the 16 262 participants who had a plasma HDL-C measurement at baseline (8945 female participants [55%] and 7319 male [45%]), 1659 experienced at least 1 fracture over a median (IQR) of 4.0 years (0.02-7.0 years). In a fully adjusted model, each 1-SD increment in HDL-C level was associated with a 14% higher risk of fractures (HR, 1.14; 95% CI, 1.08-1.20). The results remained similar when these analyses were stratified by sex. Sensitivity and stratified analyses demonstrated that these associations persisted when the analyses were repeated to include only (1) minimal trauma fractures, (2) participants not taking osteoporosis medications, (3) participants who were never smokers and reported that they did not drink alcohol, and (4) participants who walked outside for less than 30 minutes per day and reported no participation in moderate/vigorous physical activity and to examine only (5) statin use. No association was observed between non–HDL-C levels and fractures.Conclusions and RelevanceThis study suggests that higher levels of HDL-C are associated with an increased fracture risk. This association was independent of common risk factors for fractures.

The ASPirin in Reducing Events in the Elderly trial participants (ASPREE, aged >70-years Australians), for whom high-density lipoprotein cholesterol (HDL-C) levels were measured were included. Fractures included were confirmed by medical imaging and included both traumatic and pathological fractures. Fractures were confirmed by an expert review panel. Cox proportional hazards regression was used to calculate hazard ratio (HR) and 95% confidence interval (CI) for associations with fractures. Of the 16262 participants who had a plasma HDL-C measurement at baseline 1,659 experienced at least one episode of fracture over a median of 3.98 years (interquartile range, 0.02, 7.0 years). In the fully adjusted model, each mmol/L increment in HDL-C was associated with a 34% (HR 1.34, 95% CI 1.20–1.50) higher risk of fractures. The results remained similar when these analyses were stratified by sex. Sensitivity analyses demonstrated that these associations persisted when the analyses were repeated including only: 1) nontraumatic fractures, 2) participants not on osteoporotic medications, 3) participants who were never-smokers and reported that they did not drink alcohol, and 4) participants who walked outside less than 30 minutes and reported no participation in moderate/vigorous physical activity. No association was observed between non-HDL-C and fractures. This prospective observational study suggests that higher levels of HDL-C are associated with higher fracture risk. This association was independent of the common risk factors of fractures.

ObjectiveTo systematically review the evidence for the efficacy of mesenchymal stem cell (MSC) injections in improving osteoarthritis (OA)-related structural outcomes.MethodsOvid Medline and EMBASE were searched from their inceptions to April 2020 using MeSH terms and key words. Independent reviewers extracted data and assessed methodological quality. Qualitative evidence synthesis was performed due to the heterogeneity of interventions and outcome measures.ResultsThirteen randomized controlled trials (phase I or II) were identified: 10 in OA populations and 3 in populations at risk of OA, with low (n = 9), moderate (n = 3), or high (n = 1) risk of bias. Seven studies used allogeneic MSCs (4 bone marrow, 1 umbilical cord, 1 placenta, 1 adipose tissue), 6 studies used autologous MSCs (3 adipose tissue, 2 bone marrow, 1 peripheral blood). Among the 11 studies examining cartilage outcomes, 10 found a benefit of MSCs on cartilage volume, morphology, quality, regeneration, and repair, assessed by magnetic resonance imaging, arthroscopy, or histology. The evidence for subchondral bone was consistent in all 3 studies in populations at risk of OA, showing beneficial effects. Sixteen unpublished, eligible trials were identified by searching trial registries, including 8 with actual or estimated completion dates before 2016.ConclusionOur systematic review of early-phase clinical trials demonstrated consistent evidence of a beneficial effect of intraarticular MSC injections on articular cartilage and subchondral bone. Due to the heterogeneity of MSCs, modest sample sizes, methodological limitations, and potential for publication bias, further work is needed before this therapy is recommended in the management of OA.

Objectives Chronic inflammation increases the production of cytokines and activates proinflammatory pathways which may lead to nonspecific low back pain (LBP). We systematically reviewed the literature to investigate whether inflammatory biomarkers are associated with nonspecific LBP. Materials and methods CINAHL, Medline, and Embase were searched between January 1946 and May 2018. MeSH terms and key words were used to identify studies examining the association between inflammatory biomarkers and LBP. Two reviewers performed the risk of bias assessment and 3 reviewers extracted data independently. Qualitative evidence synthesis was performed. Results Thirteen studies, ranging from fair to low quality, were included. Five studies examined the association between C-reactive protein (CRP)/high-sensitivity CRP and LBP; 6 studies assessed tumor necrosis factors (TNFs); 8 studies assessed interleukins (ILs); and 2 studies assessed fibrinogen. There was evidence for an association of elevated levels of CRP, TNFs, and IL-6 with LBP. There was conflicting evidence for an association between IL-1β, fibrinogen, and LBP. Discussion Our findings support the notion of a positive association between inflammatory biomarkers and nonspecific LBP, specifically for CRP, TNFs, and IL-6. Although further high quality longitudinal studies are needed to confirm these findings and evaluate the magnitude of these associations, our findings suggest a role of inflammation in the pathogenesis of nonspecific LBP.

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% aged45 years and 24.3% aged ≥45 years reported worse access to health/disability care than experienced prior to the pandemic. In those aged45 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.

ImportanceFalls and fractures are frequent and deleterious to the health of older people. Aspirin has been reported to reduce bone fragility and slow bone loss.ObjectiveTo determine if daily low-dose aspirin (100 mg) reduces the risk of fractures or serious falls (fall-related hospital presentations) in healthy older men and women.Design, Setting, and ParticipantsThis substudy of a double-blind, randomized, placebo-controlled trial studied older adult men and women in 16 major sites across southeastern Australia. The ASPREE-FRACTURE substudy was conducted as part of the Australian component of the ASPREE trial. Between 2010 and 2014 healthy (free of cardiovascular disease, dementia or physical disability), community-dwelling volunteers aged 70 years or older were recruited to participate in the ASPREE trial. Potentially eligible participants were identified by medical practitioners and trial personnel and were then sent a letter of invitation to participate. Interested participants were screened for suitability. Eligible participants with medical practitioner authorization and adherent to a 4-week run-in medication trial were randomized. Data were analyzed from October 17, 2019, to August 31, 2022.InterventionsParticipants in the intervention group received a daily dose of oral 100 mg enteric-coated (low-dose) aspirin. The control group received a daily identical enteric-coated placebo tablet.Main Outcomes and MeasuresThe primary outcome of ASPREE-FRACTURE was the occurrence of any fracture. The secondary outcome was serious fall resulting in hospital presentation.ResultsIn total, 16 703 people with a median (IQR) age of 74 (72-78) years were recruited, and 9179 (55.0%) were women. There were 8322 intervention participants and 8381 control participants included in the primary and secondary outcome analysis of 2865 fractures and 1688 serious falls over the median follow-up of 4.6 years. While there was no difference in the risk of first fracture between the intervention and control participants (hazard ratio, 0.97; 95% CI, 0.87-1.06; P = .50), aspirin was associated with a higher risk of serious falls (total falls 884 vs 804; incidence rate ratio, 1.17; 95% CI, 1.03-1.33; P = .01). Results remained unchanged in analyses that adjusted for covariates known to influence fracture and fall risk.Conclusions and RelevanceIn this substudy of a randomized clinical trial, the failure of low-dose aspirin to reduce the risk of fractures while increasing the risk of serious falls adds to evidence that this agent provides little favorable benefit in a healthy, White older adult population.Trial RegistrationThis substudy is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000347561).

BackgroundTo examine the association between circulating 25(OH)D concentrations and incidence of total hip replacement for osteoarthritis in a prospective cohort study.MethodsThis 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.ResultsEighty-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 (pfor trend 0.02). There was little evidence of an association in women.ConclusionsHigher 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.

Background Back and lower limb pain have a major impact on physical function and quality of life. While obesity is a modifiable risk factor for musculoskeletal pain, the role of adiposity is less clear. This systematic review aimed to examine the relationship between both adiposity and its distribution and back and lower limb pain. Methods A systematic search of electronic databases was conducted to identify studies that examined the association between anthropometric and/or direct measures of adiposity and site specific musculoskeletal pain. Risk of bias was assessed and a best evidence synthesis was performed. Results A total of 56 studies were identified which examined 4 pain regions, including the lower back (36 studies), hip (two studies), knee (13 studies) and foot (eight studies). 31(55%) studies were assessed as having low to moderate risk of bias. 17(30%) studies were cohort in design. The best evidence synthesis provided evidence of a relationship between central adiposity and low back and knee pain, but not hip or foot pain. There was also evidence of a longitudinal relationship between adiposity and the presence of back, knee and foot pain, as well as incident and increasing foot pain. Conclusions This systematic review provides evidence of an association between both body fat and its central distribution and low back and knee pain, and a longitudinal relationship between adiposity and back, knee and foot pain. These results highlight the potential for targeting adiposity in the development of novel treatments at these sites.

Utilising data from the ASPirin in Reducing Events in the Elderly trial participants [aged >70-years (Australians), >65-years (US)], we estimated percent change in body size (BMI: body mass index, WC: waist circumference) from baseline and the second annual visits. Both BMI and WC changes were categorised as 1) change within 5% (stable), 2) decrease by 5–10%, 3) decrease by >10%, 4) increase by 5–10%, and 5) increase by >10%. Mortality events were classified according to the underlying cause by adjudicators. Hazard ratios were calculated to compare mortality between body size change categories. Amongst 16,773 participants, 1,269 mortality were observed over an average 4.4±1.7 years. In men compared to stable BMI, a 5–10% decrease in BMI had a 35% higher (HR 1.35, 95% CI 1.08–1.67), and a >10% decrease in BMI had a 3.84-fold higher (HR 2.99, 95% CI 2.44–3.68) risk in all-cause mortality. A decrease in BMI was associated with a higher cause-specific (cancer, cardiovascular disease [CVD], and non-cancer non-CVD) mortality. A decrease in BMI was associated with higher mortality risk in women, however, the magnitude of association was weaker than men. A decrease in WC was predictive of mortality but with a much weaker relationship than a decrease in BMI. Weight gain was not predictive of mortality except for non-cancer non-CVD mortality in women. Physicians should be aware of the ominous consequence of weight loss, especially amongst older men. The risk extends beyond an increased risk of cancer, extending to CVD and a range of other life-limiting conditions.

Objective.Vascular pathology (changes in blood vessels) and osteoarthritis (OA) are both common chronic conditions associated with aging and obesity, but whether vascular pathology is a risk factor for OA is unclear. The aim of this study was to systematically review the evidence for an association between vascular pathology and risk of joint-specific OA.Methods.Scopus, Ovid Medline, and EMBASE were searched from inception to February 2019. MeSH terms and keywords were used to identify studies examining the association between vascular pathology and OA. Two reviewers independently extracted the data and assessed the methodological quality. Qualitative evidence synthesis was performed.Results.Fifteen studies with high (n = 3), fair (n = 3), or low (n = 9) quality were included. Features of vascular pathology included atherosclerosis, vascular stiffness, and endothelial dysfunction in different vascular beds. There was evidence for an association between vascular pathology and risk of hand OA in women but not men, and between vascular pathology and risk of knee OA in both men and women. Only 2 studies examined hip OA showing no association between vascular pathology and risk of hip OA.Conclusion.There is evidence suggesting an association between vascular pathology and risk of hand and knee OA, with a potential causal relationship for knee OA. Based on the limited evidence, it is hard to conclude an association for hip OA. Further stronger evidence is needed to determine whether there is a causal relationship.

ObjectiveTo examine the risk of total knee arthroplasty (TKA) due to osteoarthritis associated with obesity defined by body mass index (BMI) or waist circumference (WC) and whether there is discordance between these measures in assessing this risk.Methods36,784 participants from the Melbourne Collaborative Cohort Study with BMI and WC measured at 1990–1994 were included. Obesity was defined by BMI (≥30 kg/m2) or WC (men ≥102cm, women ≥88cm). The incidence of TKA between January 2001 and December 2018 was determined by linking participant records to the National Joint Replacement Registry.ResultsOver 15.4±4.8 years, 2,683 participants underwent TKA. There were 20.4% participants with BMI-defined obesity, 20.8% with WC-defined obesity, and 73.6% without obesity defined by either BMI or WC. Obesity was classified as non-obese (misclassified obesity) in 11.7% of participants if BMI or WC alone was used to define obesity. BMI-defined obesity (HR 2.69, 95%CI 2.48–2.92), WC-defined obesity (HR 2.28, 95%CI 2.10–2.48), and obesity defined by either BMI or WC (HR 2.53, 95%CI 2.33–2.74) were associated with an increased risk of TKA. Compared with those without obesity, participants with misclassified obesity had an increased risk of TKA (HR 2.06, 95%CI 1.85–2.30). 22.7% of TKA in the community can be attributable to BMI-defined obesity, and a further 3.3% of TKA can be identified if WC was also used to define obesity.ConclusionsBoth BMI and WC should be used to identify obese individuals who are at risk of TKA for osteoarthritis and should be targeted for prevention and treatment.

Background To determine the relationship between clusters of back pain and joint pain and prescription opioid dispensing. Methods Of 11,221 middle-aged participants from the Australian Longitudinal Study of Women’s Health, clusters of back pain and joint pain from 2001 to 2013 were identified using group-based trajectory modelling. Prescription opioid dispensing from 2003 to 2015 was identified by linking the cohort to Pharmaceutical Benefit Scheme dispensing data. Multinomial logistic regression was used to examine the association between back pain and joint pain clusters and dispensing of prescription opioids. The proportion of opioids dispensed in the population attributable to back and join pain was calculated. Results Over 12 years, 68.5 and 72.0% women reported frequent or persistent back pain and joint pain, respectively. There were three clusters (‘none or infrequent’, ‘frequent’ and ‘persistent’) for both back pain and joint pain. Those in the persistent back pain cluster had a 6.33 (95%CI 4.38-9.16) times increased risk of having > 50 opioid prescriptions and those in persistent joint pain cluster had a 6.19 (95%CI 4.18-9.16) times increased risk of having > 50 opioid prescriptions. Frequent and persistent back and joint pain clusters together explained 41.7% (95%CI 34.9-47.8%) of prescription opioid dispensing. Women in the frequent and persistent back pain and joint pain clusters were less educated and reported more depression and physical inactivity. Conclusion Back pain and joint pain are major contributors to opioid prescription dispensing in community-based middle-aged women. Additional approaches to reduce opioid use, targeted at those with frequent and persistent back pain and joint pain, will be important in order to reduce the use of opioids and their consequent harm in this population.

Background To examine the associations between hip muscle cross-sectional area and hip pain and function in community-based individuals with mild-to-moderate hip osteoarthritis. Methods This study included 27 participants with mild-to-moderate hip osteoarthritis. Cross-sectional area of hip muscles, including psoas major, rectus femoris, gluteus maximus, gluteus medius and minimus, adductor longus and magnus, obturator internus, and obturator externus, were measured from magnetic resonance images. Hip pain and function were evaluated using the Hip Disability and Osteoarthritis Outcome Score (HOOS) categorised into 5 subscales: pain, symptoms, activity of daily living, sport and recreation function, and hip-related quality of life (for each subscale 0 representing extreme problems and 100 representing no problems). Results Mean age of the 27 participants was 63.2 (SD 7.6) years and 66.7% (n = 18) were female. After adjusting for age and gender, greater cross-sectional area of adductor longus and magnus was associated with a higher HOOS score in quality of life (regression coefficient 1.4, 95% confidence interval (CI) 0.2–2.7, p = 0.02), activity of daily living (regression coefficient 1.3, 95% CI 0.1–2.6, p = 0.04) and sport and recreation function (regression coefficient 1.6, 95% CI 0.1–3.0, p = 0.04). There was a trend towards an association between greater cross-sectional area of psoas major and a higher quality of life score (regression coefficient 3.6, 95% CI − 0.5 to 7.7, p = 0.08). The cross-sectional area of hip muscles was not significantly associated with HOOS pain or symptom score. Conclusion Greater cross-sectional area of hip adductors was associated with better function and quality of life in individuals with mild-to-moderate hip osteoarthritis. Greater cross-sectional area of hip flexors might be associated with better quality of life. These findings, while need to be confirmed in longitudinal studies, suggest that targeting the hip adductor and flexor muscles may improve function and quality of life in those with mild-to-moderate hip osteoarthritis.

Background: There is a discordance in classification of obesity when defined by body mass index (BMI) or waist circumference (WC). We aimed to examine whether categories of BMI- and WC-defined obesity are differentially associated with the risk of total knee arthroplasty for osteoarthritis.Methods: 38,924 participants from the Melbourne Collaborative Cohort Study with BMI and WC measured at baseline (1990-1994) were included. Obesity status was defined as: not obese (non-obese BMI and non-obese WC); WC-defined obesity only (non-obese BMI and obese WC); BMI-defined obesity only (non-obese WC and obese BMI); and BMI- and WC-defined obesity. The incidence of total knee arthroplasty for osteoarthritis between January 2001 and December 2013 was determined by linking participant records to the National Joint Replacement Registry. Results: Over 11.5±3.1 years follow-up, 1,875 participants underwent total knee arthroplasty for osteoarthritis. Participants with WC-defined obesity only (HR=1.79, 95%CI 1.51-2.53), BMI-defined obesity only (HR=2.39, 95%CI 2.02-2.84), and BMI- and WC-defined obesity (HR=3.14, 95%CI 2.82-3.49) had an increased risk of total knee arthroplasty compared with those who were not obese. Conclusions: Individuals with either BMI- or WC-defined obesity should be targeted for prevention of knee osteoarthritis as both are significant predictors for severe osteoarthritis requiring a total knee arthroplasty.

Background Histological and epidemiological data suggest that increased signal intensity at the proximal patellar tendon on magnetic resonance imaging is a response to tendon loading. As patellofemoral geometry is a mediator of loading, we examined the association between patellofemoral geometry and the prevalence of increased signal intensity at the patellar tendon in community-based middle-aged adults. Methods Two hundred-one adults aged 25–60 years in a study of obesity and musculoskeletal health had the patellar tendon assessed from magnetic resonance imaging. Increased signal intensity at the proximal patellar tendon was defined as hyper-intense regions of characteristic pattern, size and distribution on both T1- and T2-weighted sequences. Indices of patellofemoral geometry, including Insall-Salvati ratio, patellofemoral congruence angle, sulcus angle, and lateral condyle-patella angle, were measured from magnetic resonance imaging using validated methods. Binary logistic regression was used to examine the association between patellofemoral geometrical indices and the prevalence of increased signal intensity at the patellar tendon. Results The prevalence of increased signal intensity at the patellar tendon was 37.3%. A greater Insall-Salvati ratio (odds ratio 0.80, 95% confidence interval 0.66–0.97 per 0.1 change in the ratio, p = 0.02), indicative of a higher-riding patella, and a larger patellofemoral congruence angle (odds ratio 0.91, 95% confidence interval 0.85–0.98 per 5 degree change in the angle, p = 0.01), indicating a more laterally placed patella, were associated with reduced odds of increased signal intensity at the patellar tendon. Sulcus angle and lateral condyle-patella angle were not significantly associated with the odds of increased signal intensity at the patellar tendon. Conclusions In community-based asymptomatic middle-aged adults, increased signal intensity at the patellar tendon was common and associated with Insall-Salvati ratio and patellofemoral congruence angle, suggesting a biomechanical mechanism. Such work is likely to inform tissue engineering and cell regeneration approaches to improving outcomes in those with tendon pathology.

Objective There are concerns that lumbar spine imaging represents low value care. Our aim was to examine the use of lumbar spine imaging [radiography, computed tomography (CT), magnetic resonance imaging (MRI)] over 20 years, and costs and person-level characteristics of imaging in a large cohort of Australian women. Methods The Australian Longitudinal Study on Women’s Health (ALSWH) is a longitudinal population-based survey of women randomly selected from national health insurance scheme (Medicare) database. This study examined 13458 women born in 1973–1978 who consented to link their ALSWH and Medical Benefits Scheme records. Self-reported data on demographics, body mass index, depression, physical and mental health, and back pain were collected in each survey performed in 1996, 2000, 2003, 2006, 2009, 2012, and 2015. Data on lumbar spine imaging from 1996 to 2015 were obtained from the Medical Benefits Scheme database. Results 38.9% of women underwent some form of lumbar spine imaging over 20 years. While radiography increased from 1996 to 2011 and decreased thereafter, CT and MRI continued to increase from 1996 to 2015. In women with self-reported back pain, depression and poorer physical health were associated with imaging, with no significant differences in types of imaging. Based on imaging rates in ALSWH, the estimated costs for Australian women aged 30–39 years were AU$51,735,649 over 2011–2015. Conclusions Lumbar spine imaging was common in population-based Australian women, with rates increasing over 20 years. Depression and poor physical health were associated with lumbar spine imaging. Raising awareness of this in clinicians is likely to result in significant cost savings if clinical guidelines are followed, with the potential of freeing resources for high value care and health outcomes.

Summary Background Almost a third of those undergoing knee replacement for osteoarthritis have poor outcomes despite technically successful surgery. Preoperative neuropathic-like pain and/or pain sensitisation may increase the risk of pain following joint replacement. Objective To examine whether preoperative neuropathic-like pain and pain sensitisation predicts pain, function and satisfaction following joint replacement for knee osteoarthritis. Design Systematic review with meta-analysis. Methods Medline, EMBASE and CINAHL were systematically searched until March 2020. Studies detecting neuropathic-like pain and/or sensitisation using self-report questionnaires prior to knee replacement for osteoarthritis, and relating this to post-operative outcomes were identified. Data extraction, risk of bias assessment and meta-analysis were performed, where appropriate. Results Five manuscripts, including one preprint, examining six cohorts were included: four used painDETECT or modified painDETECT, one the Self-Report Leeds Assessment of Neuropathic Symptoms and Signs, and another the Central Sensitisation Inventory to identify preoperative characteristics. Three studies showed preoperative neuropathic-like pain or sensitisation was associated with more intense post-operative pain. All four studies examining the risk of significant pain after knee replacement suggested it was increased after > 3 months. The only study examining patient satisfaction and function found reduced satisfaction, but no difference in function in those with preoperative sensitisation. Meta-analysis found the relative risk of increased pain following knee replacement in those with neuropathic-like pain(painDETECT > 13) to be 2.05(95% confidence intervals 1.51, 2.79). Conclusion These results provide consistent but limited evidence that self-report tools detecting neuropathic-like pain and/or pain sensitisation, predict patients at higher risk of pain following knee replacement.

Chronic low back pain (CLBP) is a major health issue, yet its underlying mechanisms remain unknown. Studies have demonstrated the importance of emotion and cognition in chronic pain; however, the relevant brain physiology in magnetic resonance imaging (MRI) studies are unclear in CLBP populations. Therefore, this review aimed to identify MRI brain changes and examine their potential relationship with emotional and cognitive processes in CLBP.A systematic search was conducted in 5 databases. Studies that recruited adult, CLBP populations, and used brain MRI protocols were included.In total, 55 studies met the inclusion criteria. Of the structural MRI studies, 10 of 15 studies found decreased gray matter and 7 of 8 studies found white matter changes in CLBP groups compared with controls. Fourteen resting-state functional MRI studies all reported differences between CLBP and control groups in the default mode network. Interestingly, only 3 of 10 functional MRI studies observed significant differences during noxious stimulation between CLBP and control groups, whereas 13 of 16 studies observed significant brain activation differences in CLBP groups during various external tasks. Finally, there were 3 studies that observed a degree of recovery in functional connectivity following intervention.The brain changes in CLBP groups were mainly observed in areas and networks important in emotion and cognition, rather than those typically associated with nociception. This supports the understanding that emotional and cognitive processes may be the core contributor to the CLBP experience; however, future studies need to explore these processes further.

Osteoarthritis is a leading cause of disability with no cure. The incidence of osteoarthritis is sexually dimorphic: women have a higher rate of osteoarthritis than men after the age of 50. Research has investigated the contribution of sex hormones, reproductive factors and hormone supplementation to osteoarthritis. It has been recognized that different joints are susceptible to different risk factors for osteoarthritis. We reviewed the evidence for the effect of endogenous sex hormones, reproductive factors and hormone supplementation on joint-specific osteoarthritis of the knee, hip and hand. Although the role of these hormonal factors in the pathogenesis of osteoarthritis is complex, data suggest that endogenous hormones and reproductive factors have a role in the pathogenesis of osteoarthritis, especially knee osteoarthritis, with uncertainty for the effect of exogenous hormones. From the available data, it is hard to conclude whether this is a direct effect of hormonal factors, or whether other factors related to these hormonal factors, i.e. obesity and inflammation, have a role in this association. Further studies should consider the mediation effect of body weight and inflammation, change in body weight throughout life, circulatory levels of all endogenous hormones and circulatory levels of hormones after hormone supplementation in this complex relationship.

Utilising data from the ASPirin in Reducing Events in the Elderly trial participants aged 70-years, we estimated MAP and variation in MAP defined as within-individual SD of MAP from baseline and first 2 annual visits. Falls were confined to those involving presentation to a hospital. Cox proportional hazards regression was used to calculate hazard ratio (HR) and 95% confidence interval (CI) for associations with falls. Amongst 16,703 participants (1,540 falls), MAP was not associated with falls irrespective of antihypertensive medication status (all: HR 1.00, 95% CI 0.99-1.01, not on antihypertensive: HR 1.01, 95% CI 0.99, 1.02, on antihypertensive: HR 1.01, 95% CI 0.99-1.02). Amongst 14,818 participants who remained in the study up to year 2 without falls, 1 unit escalation in MAP variability increased the risk (HR 1.01, 95% CI 1.00-1.03). Compared with those in the lowest tercile of variability, those in the middle or highest tercile of variability experienced an increased risk of falling (middle: HR 1.32, 95% CI 1.06-1.65; highest: HR 1.25, 95% CI 1.01-1.55). When stratified for antihypertensive medication status, those receiving diuretics (HR 1.18, 95% CI 1.00-1.39) or beta-blockers (HR 1.37, 95% CI 1.08-1.73) were at increased risk compared to those receiving renin-angiotensin-system acting agents. All results persisted after adjustment for multiple covariates. The association of diuretics and beta-blockers with falls remained significant even after excluding those with history of heart failure. Older community-dwelling adults with high variability in MAP are at increases risk of falls, particularly amongst those receiving beta-blockers or diuretics.