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Background: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are commonly ordered tests in general medical practice. However, their distribution and significance in older adults are understudied. As such, we aimed to evaluate sex-stratified distribution of both ALT and AST in older adults (≥70 years) and assess for associations with mortality., Methods: Post-hoc analysis of the ASPirin in Reducing Events in the Elderly (ASPREE) randomized, placebo-controlled trial of daily low-dose aspirin for initially relatively healthy older persons. Univariate analysis and multiple logistic regression were used to explore baseline characteristics. Cox regression and restricted cubic splines were used to examine links between transaminase levels and mortality., Results: Of the 11 853 participants with ALT and AST levels, 1 054 (8.9%) deaths were recorded over a median of 6.4 (interquartile range [IQR] 5.4-7.6) years. For ALT, the lowest quintiles for males and females were 6-15 and 5-13 U/L, respectively; for AST, the lowest quintiles were 8-18 and 7-17 U/L, respectively. On both univariate and models adjusted for covariates including age, body mass index, frailty, diabetes, and kidney disease, males and females in the lowest quintile of ALT had an increased hazard of mortality (aHR 1.51 [95% confidence interval {CI} 1.14-1.99] and aHR 1.39 [95% CI 1.03-1.88], respectively). For the lowest quintile of AST, only males were at increased risk (aHR 1.33 [95% CI 1.04-1.70]). Associations remained significant when removing outliers., Conclusions: Low ALT levels independently confer an increased hazard of mortality for older males and females; low AST only affected older male survival. Further evaluation of mechanisms would be worthwhile, and re-evaluating the lower limit of normal for ALT in older adults should be considered., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Objectives: As thyroid disorders are common amongst the elderly, this study aims to evaluate the reference interval (RI) for thyroid stimulating hormone (TSH) in healthy adults aged 70 years and over., Methods: A proposed RI was determined from the Australian participants of the ASPirin in Reducing Events in the Elderly (ASPREE) randomised trial. Participants had no history of cardiovascular disease, thyroid cancer, dementia, or life-threatening illnesses. Participants prescribed with any thyroid-related medication at baseline were excluded. TSH levels were measured using a commercial chemiluminescence microparticle immunoassay. The RI was determined using the middle 95th percentile of the logarithmic transformed data of baseline TSH. Cox proportional hazard regression models were used to validate the RI by assessing disease incidence over time., Results: A total of 10,995 participants had baseline TSH measures. Median (IQR) age was 73.9 (71.8-77.3) years. We propose a RI of 0.34-3.75 mU/L. TSH levels did not differ by age or sex. At baseline, there was no association between symptoms associated with thyroid disease and levels of TSH. Over the follow-up period of up to 11 years, no association was seen between baseline TSH levels and relevant disease outcomes for participants within the RI., Conclusions: From a group of initially healthy, community-dwelling adults aged >=70 years, we propose a RI of TSH to best represent euthyroidism. This concentration was not associated with an increased risk of thyroid related symptoms or outcomes, confirming its appropriateness for clinical use., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: A cardiovascular safety trial of testosterone in men with cardiovascular risk factors or disease found no difference in rates of major adverse cardiovascular events (MACE) or death but noted more atrial fibrillation (AF) events in testosterone-treated men. We investigated the relationship between endogenous testosterone concentrations with risk of developing AF in healthy older men., Methods: Post-hoc analysis of 4570 male participants in the ASPirin in Reducing Events in the Elderly (ASPREE) study. Men were aged ≥ 70 years, had no history of cardiovascular disease (including AF), thyroid disease, prostate cancer, dementia, or life-threatening illnesses. Risk of AF was modelled using Cox proportional hazards regression., Findings: Median (IQR) age was 73.7 (71.6-77.1) years and median (IQR) follow-up 4.4 (3.3-5.5) years, during which 286 men developed AF (15.3 per 1000 participant-years). Baseline testosterone was higher in men who developed incident AF compared men who did not [17.0 (12.4-21.2) vs 15.7 (12.2-20.0) nmol/L]. There was a non-linear association of baseline testosterone with incident AF. The risk for AF was higher in men with testosterone in quintiles (Q) 4&5 (Q4:Q3, HR = 1.91; 95%CI = 1.29-2.83 and Q5:Q3HR = 1.98; 95%CI = 1.33-2.94). Results were similar after excluding men who experienced MACE or heart failure during follow-up., Interpretation: Circulating testosterone concentrations within the high-normal range are independently associated with an increased risk of incident AF amongst healthy older men. This suggests that AF may be an adverse consequence of high-normal total testosterone concentrations., Funding: National Institute on Aging and National Cancer Institute at the National Institutes of Health; Australian Government (NHMRC, CSIRO); Monash University; and AlfredHealth., Competing Interests: Professor Yeap reported receiving research support funding from University of Western Australian, and an honoraria for presentations and participation in advisory committee, both of which are outside of the submitted work. Professor Schneider reported receiving a grant from Abbott Diagnostics for consumables and is an unpaid board member of Public Pathology Australia. Dr Woods reported receiving National Institute of Health (NIH) and National Health and Medical Research Council (NHMRC) funding, which is paid to Monash University., (© 2024 The Author(s).)

Background: Blood concentrations of testosterone and estrone tend to increase in women aged ≥70 years, whereas concentrations of their precursor hormone dehydroepiandrosterone decline. It is unknown whether these changes influence physical function. We investigated whether concentrations of these hormones were associated with grip strength and self-reported physical function in community-dwelling older women., Methods: A total of 9 179 Australian women, aged ≥70 years, were recruited to the ASPirin in Reducing Events in the Elderly (ASPREE) trial. Sex hormones were measured in Sex Hormones in Older Women, an ASPREE substudy, by liquid chromatography-tandem mass spectrometry in 6 358 women. The associations between hormone concentrations and physical function (handgrip strength and self-reported physical function assessed by SF-12v2 physical component summary [PCS]) were examined using multiple linear regression., Results: The median age of the 5,447 participants was 74.0 (interquartile range 71.7-77.6) years. Testosterone concentrations above the lowest quartile were associated with less decline in grip strength (mean -1.39 [95% CI -1.54 to -1.24] vs -1.75 [-2.00 to -1.50] kg, p = .02), and dehydroepiandrosterone concentrations above the lowest quartile were associated with less decline in grip strength (-1.39 [-1.54 to -1.25] vs -1.82 [-2.11 to -1.55] kg, p = .007) and PCS scores (-1.49 [-1.80 to -1.17] vs -2.33 [-2.93 to -1.72], p = .02) over 4 years, compared with those in the respective lowest quartile., Conclusions: Low endogenous concentrations of testosterone and dehydroepiandrosterone were associated the greatest likelihood of physical function decline in community-based women aged ≥70 years. Further studies are warranted to determine whether testosterone and dehydroepiandrosterone therapy prevent functional decline in this at-risk group using sensitive measures of muscle strength and performance., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

The relationship between high plasma high-density lipoprotein cholesterol (HDL-C) and cause and mortality are not well established in healthy older people. This study examined the associations between HDL-C levels and mortality in initially healthy older men and women. This analysis included participants from the Aspirin in Reducing Events in the Elderly (ASPREE; n=18,668) trial and a matched cohort from the UK Biobank (UKB; n=62,849 ≥65 years). Cox regression was used to examine hazard ratios between HDL-C categories <1.03 mmol/L, 1.03-1.55 mmol/L (referent category), 1.55-2.07 mmol/L, and >2.07 mmol/L and all-cause, cancer, cardiovascular disease (CVD), and "non-cancer non-CVD" mortality. Genetic contributions were assessed using a polygenic score for HDL-C. Among ASPREE participants (aged 75±5 years), 1836 deaths occurred over a mean follow-up of 6.3±1.8 years. In men, the highest category of HDL-C levels was associated with increased risk of all-cause (HR 1.60, 95% CI 1.26-2.03), cancer (HR 1.37, 95% CI 0.96-2.00), and "non-cancer non-CVD" mortality (HR 2.35, 95% CI 1.41-3.42) but not CVD mortality (HR 1.08, 95% CI 0.60-1.94). The associations were replicated among UKB participants (aged 66.9±1.5 years), including 8739 deaths over a mean follow-up of 12.7±0.8 years. There was a non-linear association between HDL-C levels and all-cause and cause-specific mortality. The association between HDL-C levels and mortality was unrelated to variations in the HDL-C polygenic score. No significant association was found between HDL-C levels and mortality in women. Higher HDL-C levels are associated with increased risk from cancer and "non-cancer non-CVD" mortality in healthy older men but no such relationship was observed in women., (© 2023. The Author(s).)

Background: Aging increases fracture risk through bone loss and microarchitecture deterioration due to an age-related imbalance in bone resorption and formation during bone remodelling. We examined the associations between levels of phosphate, calcium, and alkaline phosphatase, and fracture risk in initially-healthy older individuals., Methods: A post-hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial recruited 16,703 Australian participants aged ≥70 years and 2,411 US participants aged ≥65 years. Analyses were conducted on ASPREE-Fracture substudy participants from Australia with serum calcium, phosphate, and alkaline phosphatase measurement. Fracture data were collected post-randomization. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CIs). Phosphate, calcium, and alkaline phosphatase were analysed in deciles (D1-D10), with deciles 4-7 (31-70%) as the reference category. Restricted cubic spline curves were used to identify nonlinear associations., Results: Of the 9915 participants, 907 (9·2%) persons had incident fractures recorded over 3·9 (SD 1·4) years. In the fully adjusted model, males in the top decile (D10) of phosphate had 78% higher risk of incident fracture (HR 1·78, 95% CI 1·25-2·54). No such association was observed for females (HR 1·09, 95% CI 0·83-1·44). The population attributable fraction in men within the D10 phosphate category is 6·9%., Conclusion: This result confirms that, high-normal serum phosphate levels are associated with increased fracture risk in older men., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Recent studies have reported associations between high plasma high-density lipoprotein cholesterol (HDL-C) levels and risk of all-cause mortality, age-related macular degeneration, sepsis and fractures, but associations with dementia risk remain unclear. To determine whether high plasma HDL-C levels are associated with increased incident dementia risk in initially-healthy older people., Methods: We conducted a post-hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial; a double-blind, randomized, placebo-controlled trial of daily low-dose aspirin in healthy older people. ASPREE recruited 16,703 participants aged ≥70 years (from Australia) and 2411 participants aged ≥65 years (from the US) between 2010 and 2014. Participants had no diagnosed cardiovascular disease, dementia, physical disability, or life-threatening illness at enrolment and were cognitively healthy (3MS score ≥78). All-cause dementia was a primary trial endpoint, and determined by DSM-IV criteria. Cox regression was used to examine hazard ratios between HDL-C categories <40 mg/dL, 40-60 mg/dL (reference category), 60-80 mg/dL, and >80 mg/dL and dementia. Restricted cubic spline curves were used to determine nonlinear associations. Data analysis was performed from October 2022 to January 2023., Findings: Of the 18,668 participants, 850 (4.6%) cases of incident dementia were recorded over 6.3 (SD 1.8) years. Participants with high HDL-C (>80 mg/dL) had a 27% higher risk of dementia (HR 1.27, 95% CI 1.03, 1.58). Age stratified analyses demonstrated that the risk of incident dementia was higher in participants ≥75 years compared to participants <75 years (HR 1.42, 95% CI 1.10, 1.83 vs HR 1.02, 95% CI 0.68, 1.51). Associations remained significant after adjusting for covariates including age, sex, country of enrolment, daily exercise, education, alcohol consumption, weight change over time, non-HDL-C, HDL-C-PRS, and APOE genotype., Interpretation: In a population of initially-healthy older adults aged ≥75 years, high HDL-C levels were associated with increased risk of all-cause dementia., Funding: National Institutes of Health, USA; National Health and Medical Research Council Australia; Monash University (Melbourne, VIC, Australia); and the Victorian Cancer Agency (Australia)., Competing Interests: SMH is the recipient of National Health and Medical Research Council (NHMRC) Early Career Fellowship (APP1142198), JMCN is supported through an NHMRC Leadership Fellowship (IG 1173690). PL is supported by a National Heart Foundation Future Leader Fellowship (102604). JR is supported by an NHMRC Leadership Investigator Grant (2016438). TC is supported by an Australian Research Council Future Fellowship (FT220100294), and has received honoraria from Roche for lectures. GFW received grants from Arrowhead Pharma, Amgen, Novartis, Silence Therapeutics; consulting fee from Amgen, Novartis, Sanofi, Esperion; honoraria from Amgen, Novartis, Sanofi; support for attending meetings from Novartis, Silence Therapeutics. No other disclosures are reported by the other authors., (© 2023 The Author(s).)

Background and Objectives: It has been suggested that higher triglyceride levels were associated with a lower risk of Alzheimer disease. This study aimed to examine the association of triglycerides with dementia and cognition change in community-dwelling older adults., Methods: This prospective longitudinal study used data from the Aspirin in Reducing Events in the Elderly (ASPREE) randomized trial of adults aged 65 years or older without dementia or previous cardiovascular events at enrollment. The main outcome was incident dementia. Other outcomes included changes in composite cognition and domain-specific cognition (global cognition, memory, language and executive function, and psychomotor speed). The association between baseline triglycerides and dementia risk was estimated using Cox proportional hazard models adjusting for relevant risk factors. Linear mixed models were used to investigate cognitive change. The analysis was repeated in a subcohort of participants with available APOE -ε4 genetic data with additional adjustment for APOE -ε4 carrier status and an external cohort (UK Biobank) with similar selection criteria applied., Results: This study included 18,294 ASPREE participants and 68,200 UK Biobank participants (mean age: 75.1 and 66.9 years; female: 56.3% and 52.7%; median [interquartile range] triglyceride: 106 [80-142] mg/dL and 139 [101-193] mg/dL), with dementia recorded in 823 and 2,778 individuals over a median follow-up of 6.4 and 12.5 years, respectively. Higher triglyceride levels were associated with lower dementia risk in the entire ASPREE cohort (hazard ratio [HR] with doubling of triglyceride: 0.82, 95% CI 0.72-0.94). Findings were similar in the subcohort of participants with APOE-ε4 genetic data (n = 13,976) and in the UK Biobank cohort (HR was 0.82 and 0.83, respectively, all p ≤ 0.01). Higher triglycerides were also associated with slower decline in composite cognition and memory over time ( p ≤ 0.05)., Discussion: Older adults with higher triglyceride levels within the normal to high-normal range had a lower dementia risk and slower cognitive decline over time compared with individuals with lower triglyceride levels. Higher triglyceride levels may be reflective of better overall health and/or lifestyle behaviors that would protect against dementia development. Future studies are warranted to investigate whether specific components within the total circulating pool of plasma triglycerides may promote better cognitive function, with the hope of informing the development of new preventive strategies., (© 2023 American Academy of Neurology.)

Objective: Both grip strength and gait speed can be used as markers of muscle function, however, no previous study has examined them in the same population with respect to risk of falls., Methods: In this prospective cohort study, utilising data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial and ASPREE-Fracture substudy, we analysed the association of grip strength and gait speed and serious falls in healthy older adults. Grip strength was measured using a handheld dynamometer and gait speed from 3-metre timed walks. Serious falls were confined to those involving hospital presentation. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for associations with falls., Results: Over an average of 4.0±1.3 years, amongst 16,445 participants, 1,533 had at least one serious fall. After adjustment for age, sex, physical activity, body mass index, Short Form 12 (state of health), chronic kidney disease, polypharmacy and aspirin, each standard deviation (SD) lower grip strength was associated with 27% (HR 1.27, 95% CI 1.17-1.38) higher risk of falls. The results remained the same for males and females. There was a dose-response relationship in the association between grip strength and falls risk. The higher risk of falls was observed in males in all body mass index (BMI) categories, but only in obese females. The association between gait speed and falls risk was weaker than the association between grip strength and falls risk., Conclusions: All males and only obese females with low grip strength appear to be at the greatest risk of serious falls. These findings may assist in early identification of falls., Competing Interests: Dr Hussain is the recipient of National Health and Medical Research Council (NHMRC) Early Career Fellowship (APP1142198), Professor McNeil is supported through an NHMRC Leadership Fellowship (IG 1173690). No other disclosures are reported by the other authors., (Copyright: © 2023 Pham et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Importance: The 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., Objective: To examine the associations of changes in body weight and WC with all-cause and cause-specific mortality., Design, Setting, and Participants: This 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., Exposures: Body 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 Measures: All-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., Results: Among 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 Relevance: This 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.

Importance: Increased 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., Objective: To determine whether higher HDL-C levels are predictive of an increased fracture risk in healthy older adults., Design, Setting, and Participants: This 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., Exposure: Plasma HDL-C., Main Outcomes and Measures: Fractures included were confirmed by medical imaging and included both traumatic and minimal trauma fractures. Fractures were adjudicated by an expert review panel., Results: Of 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 Relevance: This 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.

Importance: Falls and fractures are frequent and deleterious to the health of older people. Aspirin has been reported to reduce bone fragility and slow bone loss., Objective: To 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 Participants: This 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., Interventions: Participants 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 Measures: The primary outcome of ASPREE-FRACTURE was the occurrence of any fracture. The secondary outcome was serious fall resulting in hospital presentation., Results: In 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 Relevance: In 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 Registration: This substudy is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000347561).

Background: Few studies have explored the impact of low back or lower limb pain severity on recurrent (≥2) falls in older adults., Objectives: Investigate the association between the severity of low back or lower limb pain, and ≥2 falls or falls-related injuries., Methods: 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., Results: 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., Conclusion: 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., Significance: 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., (© 2022 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®.)

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., (© 2022 John Wiley & Sons Ltd.)

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: While targeting obesity is central to osteoarthritis management, recent meta-analyses demonstrate only modest effects of weight loss on symptoms, and little on structure. The World Health Organisation recommends that effective management of obesity include prevention of weight gain, weight maintenance and weight loss. Therefore, we systematically reviewed the recommendations and approaches for management of obesity in clinical practice guidelines (CPGs) for osteoarthritis., Design: Nine databases were searched (01.01.2010-15.03.2022) to identify guidelines informing the non-pharmacological management of osteoarthritis. Three reviewers appraised guidelines according to the AGREE II instrument, and independently extracted data on their characteristics. One author extracted and summarised guideline recommendations on weight management. This systematic review is registered on PROSPERO (CRD42021274195)., Results: Of the included fifteen CPGs (median AGREE II domain score 78.7%), weight loss was recommended for knee (12 of 13) and hip (10 of 11) but not hand (0 of 4) osteoarthritis. Combination approaches of diet and/or exercise were recommended for overweight or obese individuals in knee (8 of 12) and hip (4 of 10) osteoarthritis. Two guidelines specified ≥5% weight loss. One guideline specified strategies for maintenance of lost weight; none specifically recommended preventing weight gain. There was discordance between strength of recommendation for weight loss and level of evidence (3 of 15)., Conclusion: Most CPGs for knee and hip osteoarthritis recommend weight loss to manage obesity in osteoarthritis. As steady weight accumulation is common in adults, preventing weight gain should also be considered as it is a missed opportunity to improve outcomes in osteoarthritis., Competing Interests: All authors declare that they have no conflict of interest., (© 2022 The Authors.)

Background: There is some evidence that corticosteroids may have a beneficial effect in hand osteoarthritis. We examined the efficacy of corticosteroids on symptoms and structural outcomes in hand osteoarthritis., Methods: Ovid MEDLINE, Embase and Cochrane Central Register of Controlled Trials were searched from inception to October 2021 for randomized controlled trials investigating the efficacy of corticosteroids in hand osteoarthritis. Two authors independently screened records, extracted data, and assessed risk of bias using the RoB 2 tool. Standardized mean difference (SMD) or mean difference (MD) was calculated, and random-effects meta-analyses were performed., Results: Of 13 included trials, 3 examined oral corticosteroids and clinical outcomes in any hand joints, 9 examined intra-articular injection of corticosteroids and clinical outcomes at the first carpometacarpal joint and one in the interphalangeal joints. In meta-analysis, oral corticosteroids reduced pain (SMD -0.53, 95% CI -0.79 to -0.28) and improved stiffness (MD -5.03, 95% CI -9.91 to -0.15; Australian Canadian Osteoarthritis Hand Index stiffness subscale) and function (SMD -0.37, 95% CI -0.63 to -0.12) at 4-6 weeks. However, there was no significant persistent effect on pain and function at 3 months which was 6-8 weeks after study medication was stopped. There was no significant effect of intra-articular corticosteroids on pain or function at 4-6 weeks or over 3-12 months in first carpometacarpal osteoarthritis. Two trials evaluated joint structure at 4-6 weeks: one study showed oral corticosteroids reduced synovial thickening, neither showed an effect on synovitis., Conclusions: There was low-certainty evidence for a medium effect of oral corticosteroids on pain relief and stiffness improvement and small-to-medium effect on functional improvement at 4-6 weeks, with no significant effect for intra-articular corticosteroids. Corticosteroids had no significant effect on any outcomes over longer term (3-12 months) off treatment. No trials examined the effect of corticosteroids on disease progression. The role of corticosteroids in hand osteoarthritis is limited., (© 2022. The Author(s).)

Background: Undertreated risk factors are major contributors to the burden of cardiovascular disease (CVD). Those with arthritis have an increased prevalence of CVD risk factors. CVD risk factors are often asymptomatic, which may be a barrier their treatment. Arthritis causes pain and immobility, and is a common reason for individuals to seek healthcare. Our aims were to (1) examine the relationship between arthritis and CVD risk factors in Australian adults, and (2) calculate the proportion of CVD risk factors that could be reduced if individuals with arthritis were targeted., Methods: This cross-sectional study uses data from the 2017-18 Australian National Health Survey which included 13,776 participants, categorised into young (18-39 years), middle aged (40-64 years) and older (≥ 65 years) adults. Hypertension, height and weight were measured. Arthritis, dyslipidemia and diabetes were self-reported. The associations between arthritis and CVD risk factors were examined using logistic regression, and the population attributable fraction (PAF) of arthritis for each CVD risk factor was calculated., Results: Arthritis was reported by 4.0% of young adults, 28.8% of middle-aged adults and 54.5% of older adults. Those with arthritis were at increased odds of obesity (2.07 fold in young, 1.75 fold in middle-aged and 1.89 fold in older adults), increased odds of diabetes (5.70 fold in young, 1.64 fold in middle-aged and 1.37 fold in older adults), increased odds of hypertension (2.72 fold in young, 1.78 fold in middle-aged and 1.48 fold in older adults) and an increased odds of dyslipidaemia (4.64 fold in young, 2.14 fold in middle-aged and 1.22 fold in older adults) compared to those without arthritis. This elevated chance remained significant even after adjusting for obesity, with the exception of diabetes in the older population. This elevated chance remained significant even after adjusting for obesity, with the exception of diabetes in the older population. The PAF of the presence of arthritis for having at least one CVD risk factor was 30.7% in middle-aged adults and 70.4% in older adults., Conclusion: Australian adults of all ages with arthritis are at increased odds of having CVD risk factors. For young and middle-aged adults, this increased odds remains significant even when adjusted for obesity. Presentation to healthcare practitioners with arthritis is an opportunity to screen for asymptomatic CVD risk factors with the potential of improving outcomes for both diseases. By adopting an approach of managing arthritis and CVD risk factors in parallel, rather than in silos, we could reduce the burden of CVD risk factors by 20-30%., (© 2022. The Author(s).)

Background: Pain sensitisation plays a major role in musculoskeletal pain. However, effective treatments are limited, and although there is growing evidence that exercise may improve pain sensitisation, the amount and type of exercise remains unclear. This systematic review examines the evidence for an effect of aerobic exercise on pain sensitisation in musculoskeletal conditions., Methods: Systematic searches of six electronic databases were conducted. Studies were included if they examined the relationship between aerobic physical activity and pain sensitisation in individuals with chronic musculoskeletal pain, but excluding specific patient subgroups such as fibromyalgia. Risk of bias was assessed using Cochrane methods and a qualitative analysis was conducted., Results: Eleven studies (seven repeated measures studies and four clinical trials) of 590 participants were included. Eight studies had low to moderate risk of bias. All 11 studies found that aerobic exercise increased pressure pain thresholds or decreased pain ratings in those with musculoskeletal pain [median (minimum, maximum) improvement in pain sensitisation: 10.6% (2.2%, 24.1%)]. In these studies, the aerobic exercise involved walking or cycling, performed at a submaximal intensity but with incremental increases, for a 4-60 min duration. Improvement in pain sensitisation occurred after one session in the observational studies and after 2-12 weeks in the clinical trials., Conclusions: These findings provide evidence that aerobic exercise reduces pain sensitisation in individuals with musculoskeletal pain. Further work is needed to determine whether this translates to improved patient outcomes, including reduced disability and greater quality of life., (© 2022. The Author(s).)

Background: Hand osteoarthritis is a common and disabling chronic joint disease with a lack of effective therapies. Emerging evidence suggests the role of local inflammation in causing pain in hand osteoarthritis. Corticosteroids are potent anti-inflammatory drugs used in many rheumatic diseases. The aim of this randomised, double-blind, placebo-controlled trial is to determine whether topical corticosteroid reduces pain over 6 weeks in patients with hand osteoarthritis., Methods: One hundred participants with hand osteoarthritis will be recruited from the community in Melbourne, Australia, and randomly allocated in a 1:1 ratio to receive either topical Diprosone OV or placebo ointment administered 3 times daily on the painful hand joints for 6 weeks. The primary outcome is pain reduction (assessed by 100 mm visual analogue scale) at 6 weeks. The secondary outcomes include changes in pain and function assessed using Functional Index for Hand Osteoarthritis, Australian Canadian Osteoarthritis Hand Index, Michigan Hand Outcomes Questionnaire, and tender and swollen joint count at 6 weeks. Adverse events will be recorded. The primary analysis will be by intention to treat, including all participants in their randomised groups., Discussion: This study will provide high-quality evidence to determine whether topical corticosteroid reduces pain over 6 weeks in patients with hand osteoarthritis, with major clinical and public health importance by informing clinical practice guidelines for the management of hand osteoarthritis and reducing the burden of the disabling disease., Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12620000599976 . Registered 22 May 2020., (© 2021. The Author(s).)

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., (© 2021, American College of Rheumatology.)

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., (© 2021. The Author(s).)

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., (© 2021. The Author(s).)

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., (© 2021. The Author(s).)

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., Competing Interests: The authors have declared that no competing interests exist.

Objective: To systematically review the evidence for the efficacy of mesenchymal stem cell (MSC) injections in improving osteoarthritis (OA)-related structural outcomes., Methods: Ovid 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., Results: Thirteen 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., Conclusion: Our 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., (Copyright © 2021 by the Journal of Rheumatology.)

Objective: To 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., Methods: 36,784 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., Results: Over 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., Conclusions: Both 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., Competing Interests: The authors have declared that no competing interests exist.

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., Competing Interests: The authors have declared that no competing interests exist.

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: 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., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: To examine the 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.

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.

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.

Objectives: Low back pain is the largest contributor to disability worldwide. The role of body composition as a risk factor for back pain remains unclear. Our aim was to examine the relationship between fat mass and fat distribution on back pain intensity and disability using validated tools over 3 years., Methods: Participants (aged 25-60 years) were assessed at baseline using dual-energy X-ray absorptiometry (DXA) to measure body composition. All participants completed the Chronic Pain Grade Scale at baseline and 3-year follow-up. Of the 150 participants, 123 (82%) completed the follow-up., Results: Higher baseline body mass index (BMI) and fat mass (total, trunk, upper limb, lower limb, android, and gynoid) were all associated with high intensity back pain at either baseline and/or follow-up (total fat mass: multivariable OR 1.05, 95% CI 1.01-1.09, p < 0.001). There were similar findings for all fat mass measures and high levels of back disability. A higher android to gynoid ratio was associated with high intensity back pain (multivariable OR 1.04, 95% CI 1.01-1.08, p = 0.009). There were no associations between lean mass and back pain., Conclusions: This cohort study provides evidence for the important role of fat mass, specifically android fat relative to gynoid fat, on back pain and disability.

Objective: To examine whether metformin use was associated with knee cartilage volume loss over 4 years and risk of total knee replacement over 6 years in obese individuals with knee osteoarthritis., Methods: This study analysed the Osteoarthritis Initiative participants with radiographic knee osteoarthritis (Kellgren-Lawrence grade ≥ 2) who were obese (body mass index [BMI] ≥ 30 kg/m 2 ). Participants were classified as metformin users if they self-reported regular metformin use at baseline, 1-year and 2-year follow-up (n = 56). Non-users of metformin were defined as participants who did not report the use of metformin at any visit from baseline to 4-year follow-up (n = 762). Medial and lateral cartilage volume (femoral condyle and tibial plateau) were assessed using magnetic resonance imaging at baseline and 4 years. Total knee replacement over 6 years was assessed. General linear model and binary logistic regression were used for statistical analyses., Results: The rate of medial cartilage volume loss was lower in metformin users compared with non-users (0.71% vs. 1.57% per annum), with a difference of - 0.86% per annum (95% CI - 1.58% to - 0.15%, p = 0.02), after adjustment for age, gender, BMI, pain score, Kellgren-Lawrence grade, self-reported diabetes, and weight change over 4 years. Metformin use was associated with a trend towards a significant reduction in risk of total knee replacement over 6 years (odds ratio 0.30, 95% CI 0.07-1.30, p = 0.11), after adjustment for age, gender, BMI, Kellgren-Lawrence grade, pain score, and self-reported diabetes., Conclusions: These data suggest that metformin use may have a beneficial effect on long-term knee joint outcomes in those with knee osteoarthritis and obesity. Randomised controlled trials are needed to confirm these findings and determine whether metformin would be a potential disease-modifying drug for knee osteoarthritis with the obese phenotype.

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.

Study Design: Community-based, cohort study., Objective: Our aim was to determine the course of back pain in middle-aged women over a 9-year period, and assess whether obesity and physical inactivity are associated with more frequent back pain., Summary of Background Data: Back pain is the leading cause of disability worldwide. With minimal effective therapies and rising financial burden, identifying modifiable risk factors remains a key priority., Methods: The Australian Longitudinal Study on Women's Health is a cohort study of community-based, middle-aged women who completed questionnaires every 3 years between 2004 and 2013. Approximately, 10,530 women completed the survey in 2004 (mean age 55.5 yrs), and 9020 completed follow-up 9 years later. Self-reported data on back pain in the last 12 months and other sociodemographic factors were collected at all four surveys. 'Frequent back pain' was defined as back pain reported at ≥ three surveys., Results: Back pain was common and persistent, with 48% having back pain in ≥ three out of four surveys. Baseline obesity (relative risk [RR] 1.18, 95% confidence interval [CI] 1.12-1.25), lack of vigorous physical activity (RR 1.17, 95% CI 1.10-1.25), depressive symptoms (RR 1.40, 95% CI 1.33-1.47), and low-education status (RR 1.17, 95% CI 1.12-1.24), were independently associated with an increased risk of frequent back pain (all P < 0.001). Overall, 28% of the risk of frequent back pain could be attributed to these factors, equating to one extra case of frequent back pain for every five women with depressive symptoms, for every 11 obese women, for every 12 women with low-education status, and for every 13 women who do not do vigorous physical activity, at baseline., Conclusion: Obesity, depressive symptoms, low-education status, and lack of vigorous physical activity are associated with higher risk of frequent back pain over the following 9 years among women in their mid-50 s. Targeting these risk factors may lessen the burden of back pain., Level of Evidence: 2.

Background: There is evidence that knee pain not only is a consequence of structural deterioration in osteoarthritis (OA) but also contributes to structural progression. Clarifying this is important because targeting the factors related to knee pain may offer a clinical approach for slowing the progression of knee OA. The aim of this study was to examine whether knee pain over 1 year predicted cartilage volume loss, incidence and progression of radiographic osteoarthritis (ROA) over 4 years., Methods: Osteoarthritis Initiative participants with no ROA (Kellgren-Lawrence grade ≤ 1) (n = 2120) and with ROA (Kellgren-Lawrence grade > 2) (n = 2249) were examined. Knee pain was assessed at baseline and 1 year using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Knee pain patterns were categorised as no pain (WOMAC pain < 5 at baseline and 1 year), fluctuating pain (WOMAC pain > 5 at either time point) and persistent pain (WOMAC pain > 5 at both time points). Cartilage volume, incidence and progression of ROA were assessed using magnetic resonance imaging and x-rays at baseline and 4-years., Results: In both non-ROA and ROA, greater baseline WOMAC knee pain score was associated with increased medial and lateral cartilage volume loss (p ≤ 0.001), incidence (OR 1.07, 95% CI 1.01-1.13) and progression (OR 1.07, 95% CI 1.03-1.10) of ROA. Non-ROA and ROA participants with fluctuating and persistent knee pain had increased cartilage volume loss compared with those with no pain (p for trend ≤ 0.01). Non-ROA participants with fluctuating knee pain had increased risk of incident ROA (OR 1.62, 95% CI 1.04-2.54), corresponding to a number needed to harm of 19.5. In ROA the risk of progressive ROA increased in participants with persistent knee pain (OR 1.82, 95% CI 1.28-2.60), corresponding to a number needed to harm of 9.6., Conclusions: Knee pain over 1 year predicted accelerated cartilage volume loss and increased risk of incident and progressive ROA. Early management of knee pain and controlling knee pain over time by targeting the underlying mechanisms may be important for preserving knee structure and reducing the burden of knee OA.

Objective: Diabetes (DM) and osteoarthritis (OA) are two common co-existing chronic conditions. However, whether this is due to shared risk factors or may differ between joints is unclear. We performed a systematic review to determine whether abnormal glucose metabolism is a risk factor for knee, hip and hand OA, separately, independent of age and obesity., Methods: A systematic search of Ovid Medline and EMBASE was performed from inception until October 2016 to identify studies relating glucose metabolism to osteoarthritis-related outcomes. Studies were included if they related DM and OA and the knee, hip, or hand were examined separately. In the structured synthesis, objective measures of DM and adjustment for age and obesity were also required., Results: Of the 40 included studies, 28 examined the knee, nine the hip and 14 the hand. Five studies with a longitudinal component used objective measures of DM (blood glucose) and knee OA (radiography or joint replacement) and adjusted for age and obesity (21,299 participants). Of these, three found no association, one found a reduction in risk and one, which adjusted for the presence but not magnitude of obesity, found an increase in risk. Of the longitudinal studies examining the relationship between DM and OA that accounted for obesity, none provided evidence of an independent relationship between DM and hip (2 studies) or hand OA (1 study)., Conclusion: There is little evidence to suggest that impaired glucose metabolism is a risk factor, independent of obesity, for knee OA and no evidence that impaired glucose metabolism is an independent risk factor for hip or hand OA., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (© 2018, American College of Rheumatology.)

Background: Approaches for the prevention and treatment of hip osteoarthritis (OA) remain limited. There are recent data suggesting that low birth weight (LBW) and preterm birth may be risk factors for hip osteoarthritis. This has the potential to change the current paradigm of hip osteoarthritis prevention by targeting early life factors. The aim of this review was to examine the available evidence for an association of LBW and preterm birth with hip OA. The potential cost implications associated with total hip arthroplasty were also evaluated., Methods: Ovid Medline, EMBASE, and Cinahl were searched up until August 2017 using MeSH terms and key words. Methodological quality was evaluated using the National Heart Lung and Blood Institute (NHLBI) quality assessment tool. Qualitative evidence synthesis was performed to summarise the results. Bradford Hill's criteria for causation including the temporal relationship, consistency, strength of the association, specificity, dose-response relationship, and analogy were used to assess the evidence for causation. Economic modelling was used to calculate the potential economic burden associated with LBW or preterm birth related total hip arthroplasty using Australian data from 2012 to 2015., Results: Five studies, ranging from high to low quality, were included. Hip bone shape abnormalities examined included developmental hip dysplasia and immature hip, and hip osteoarthritis included osteophytes and total hip arthroplasty. A causal link between low birth weight or preterm birth and hip osteoarthritis was found. Of the 30,477 total hip arthroplasties performed for hip osteoarthritis in Australia in 2015, 5791 were estimated to be born preterm and 5273 with low birth weight. This equated to a potential total hip arthroplasty cost of AU$145,136,082 and AU$132,150,222 for these subgroups, respectively., Conclusion: Available data suggest that low birth weight and preterm birth are associated with hip bone shape abnormalities and hip osteoarthritis requiring total hip arthroplasty, with a substantial associated financial burden. Given the current lack of effective treatment and prevention strategies for hip osteoarthritis, this offers a new avenue for reducing the future burden of hip osteoarthritis.

Background: Knee pain is common with obesity and weight gain being important risk factors. Previous clinical trials have focused on overweight or obese adults with knee pain and osteoarthritis and demonstrated modest effects of intense weight loss programs on reducing knee pain despite very significant weight loss. There has been no lifestyle intervention that targets community-based adults to test its effect on prevention of knee pain. We aimed to determine the effect of a simple low-intensity self-management lifestyle intervention (HeLP-her), proven in randomised controlled trials to improve lifestyle and prevent weight gain, on knee pain in community-based young to middle-aged rural women., Methods: A 1-year pragmatic, cluster randomised controlled trial was conducted in 649 community-based women (aged 18-50 years) to receive either the HeLP-her program (consisting of one group session, monthly SMS text messages, one phone coaching session, and a program manual) or one general women's health education session. Secondary analyses were performed in 390 women who had knee pain measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline and 12-month follow-up. "Any knee pain" was defined as a WOMAC pain score ≥ 1. Knee pain worsening was defined as an increase in WOMAC pain score over 12 months., Results: Thirty-five percent of women had "any knee pain" at baseline. The risk of knee pain worsening did not differ between the intervention and control groups over 12 months. For women with any knee pain at baseline, those in the intervention arm had a lower risk of knee pain worsening compared with those in the control arm (OR 0.37, 95% CI 0.14-1.01, p = 0.05), with a stronger effect observed in women with body mass index ≥ 25 kg/m 2 (OR 0.28, 95% CI 0.09-0.87, p = 0.03)., Conclusions: In community-based young to middle-aged women, a simple low-intensity lifestyle program reduced the risk of knee pain worsening in those with any knee pain at baseline, particularly in those overweight or obese. Pragmatic lifestyle programs such as HeLP-her may represent a feasible lifestyle intervention to reduce the burden of knee pain in the community., Trial Registration: ACTRN12612000115831 , registered 24 January 2012.

The aim of this systematic review is to assess patient-related factors affecting glycaemic control among people with type 2 diabetes in the Arabian Gulf Council countries. MEDLINE, Embase, PsycINFO, CINAHL, and Cochrane CENTRAL databases were searched from their date of inception to May 2016. Two researchers independently identified eligible studies and assessed the risk of bias. A total of 13 studies met the inclusion criteria. One study was population based, six recruited participants from multiple centres, and the remaining were single centred. The majority of the studies were of low to moderate quality. Factors associated with poor glycaemic control include longer duration of diabetes, low level of education, poor compliance to diet and medication, poor attitude towards the disease, poor self-management behaviour, anxiety, depression, renal impairment, hypertension, and dyslipidaemia. Healthcare providers should be aware of these factors and provide appropriate education and care especially for those who have poor glycaemic control. Innovative educational programs should be implemented in the healthcare systems to improve patient compliance and practices. A variation in the results of the included studies was observed, and some potentially important risk factors such as dietary habits, physical activity, family support, and cognitive function were not adequately addressed. Further research is needed in this area.

Background Context: Although previous studies have investigated the association between paraspinal muscle morphology and low back pain (LBP), the results are conflicting., Purpose: This systematic review examined the relationship between size and composition of the paraspinal muscles and LBP., Study Design/setting: A systematic review was carried out., Patient Sample: No patient sample was required., Outcome Measures: This review had no outcome measures., Methods: A systematic search of electronic databases was conducted to identify studies investigating the association between the cross-sectional area or fatty infiltration of the paraspinal muscles (erector spinae, multifidus, psoas, and quadratus lumborum) and LBP. Descriptive data regarding study design and methodology were tabulated and a risk of bias assessment was performed., Results: Of the 119 studies identified, 25 met the inclusion criteria. Eight studies were reported as having low to moderate risk of bias. There was evidence for a negative association between cross-sectional area (CSA) of multifidus and LBP, but conflicting evidence for a relationship between erector spinae, psoas, and quadratus lumborum CSA and LBP. Moreover, there was evidence to indicate multifidus CSA was predictive of LBP for up to 12 months in men, but insufficient evidence to indicate a relationship for longer time periods. Although there was conflicting evidence for a relationship between multifidus fat infiltration and LBP, there was no or limited evidence for an association for the other paraspinal musculature., Conclusions: This review found evidence that multifidus CSA was negatively associated with and predictive of LBP up to 12 months but conflicting evidence for an association between erector spinae, psoas, and quadratus lumborum CSA and LBP. To further understand the role of the paraspinal musculature in LBP, there is a need for high-quality cohort studies which extend over both the short and longer term., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The aim of this review was to systematically examine the evidence for an association between measures of obesity [weight and body mass index (BMI)] and body composition (fat mass and fat-free mass) and patellar cartilage, assessed using magnetic resonance imaging., Methods: Three electronic databases (MEDLINE, EMBASE, and CINAHL) were searched up to April 2016 using full text and MeSH terms to identify studies examining the associations between obesity and body composition, and patellar cartilage. Two independent reviewers extracted the data and assessed the methodological quality of included studies., Results: Seventeen studies were included: 5 cross-sectional, 10 cohort studies measuring outcomes at 2 timepoints, and 2 longitudinal studies assessing outcome only at the timepoint. Eleven studies were of high or moderate quality. In asymptomatic middle-aged adults, elevated body weight and BMI were systematically associated with worse patellofemoral cartilage scores. There was more consistent evidence for patellar cartilage defects than patellar cartilage volume, particularly in women. Increased BMI was also consistently associated with increased cartilage loss in longitudinal studies, although not all attained statistical significance., Conclusion: There is a need for more high-quality research to confirm these findings and to better explain the relative contributions of metabolic and biomechanical factors to the initiation of patellofemoral osteoarthritis, to devise effective strategies to manage this common and disabling condition.

Objective: The aim of this prospective cohort study was to determine whether dairy product consumption was associated with the incidence of total hip arthroplasty for osteoarthritis (OA)., Methods: There were 38,924 participants from the Melbourne Collaborative Cohort Study who had dairy product consumption recorded in 1990-1994. The incidence of total hip arthroplasty for OA during 2001-2013 was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry., Results: Over an average of 11.8 years of followup, 1505 total hip arthroplasties for OA were identified (524 in men, 981 in women). In men, a 1 SD increase in dairy product consumption was associated with a 21% increased incidence of total hip arthroplasty for OA (HR 1.21, 95% CI 1.10-1.33), with a dose-response relationship observed for quartiles of dairy product consumption (p for trend = 0.001). These results were independent of age, body mass index, country of birth, education, smoking status, vigorous physical activity, calcium supplementation, energy consumption, circulating 25-hydroxy vitamin D, hypertension, and diabetes. No significant association was observed for women (HR 1.02, 95% CI 0.95-1.09)., Conclusion: Increasing dairy product consumption was associated with an increased risk of total hip arthroplasty for men with OA, with no significant association observed for women. Understanding the mechanisms may help identify strategies to prevent hip OA, particularly for men.

Background: Determining the association between body composition and low back pain (LBP) will improve our understanding of the mechanisms by which obesity affects LBP, and inform novel approaches to managing LBP. The aim of this study was to examine the relationship between body composition and LBP intensity and disability., Methods: A total of 5058 participants (44% men) of the Australian Diabetes, Obesity and Lifestyle Study were assessed for LBP intensity and disability using the Chronic Pain Grade Questionnaire (2013-2014). Body mass index (BMI) and waist circumference were directly obtained. Fat mass and percentage fat were estimated from bioelectrical impedance analysis at study inception (1999-2000)., Results: Eighty-two percent of participants reported LBP, of whom 27% also reported LBP disability. BMI, waist circumference, percent fat, and fat mass were each positively associated with LBP intensity and disability at 12 years after adjustment for potential confounders. LBP intensity and disability showed significant dose-responses to sex-specific quartiles of BMI, waist circumference, percent fat and fat mass. For example, the adjusted OR for LBP intensity in women increased with increasing fat mass quartiles [Q1: 1, Q2: 1.05 (95%CI 0.84-1.32); Q3: 1.25 (1.00-1.57); and Q4: 1.78 (1.42-2.24); p < 0.001]., Conclusions: Fat mass and distribution are associated with LBP intensity and disability, suggesting systemic metabolic factors associated with adiposity play a major role in the pathogenesis of LBP. Clarifying the mechanisms will facilitate developing novel preventive and therapeutic approaches for LBP.

Objective: To systematically review the evidence for duloxetine in the management of painful diabetic neuropathy (PDN)., Methods: Electronic searches of Medline and PubMed were performed from 2005 till October 2015 using medical subject headings and free-text words. Two independent reviewers extracted the data and assessed the methodological quality of the selected studies., Results: Twenty-three studies met our inclusion criteria and 8 were considered of high quality and were included to this review. Because of heterogeneity of the studies included in this review, statistical pooling of the data was not possible. We found good evidence for use of duloxetine in PDN over placebo and pregabalin but there was no benefit of duloxetine over amitriptyline., Conclusions: Duloxetine has a beneficial effect over placebo. Nevertheless, the evidence of superiority of duloxetine over pregabalin and amitriptyline should be explored further as there was only 1 trial for each category. Provided majority of the PDN patients share cardiovascular complications, use of duloxetine will be a good option for treating pain associated with PDN over amitriptyline. Future randomized controlled trials should be designed keeping this in mind.