Yuanyuan Wang

This study aimed to examine the association between concentrations of sex hormone binding globulin (SHBG) and fracture risk in community-dwelling older women and explore whether this was explained by the genetic regulation of SHBG. This prospective cohort study examined 4871 women aged ≥70 years who were not taking medications influencing SHBG concentrations. A genome-wide association study was undertaken to identify single nucleotide polymorphisms (SNPs) associated with SHBG concentrations. Incident fracture was confirmed by medical imaging and adjudicated by expert review committee. The median age of participants was 74.0 years. Over 3.9 (standard deviation 1.4) years of follow-up, 484 participants had an incident fracture. There was a linear trend for a positive association between SHBG concentrations and fracture risk (p = 0.001), with the highest SHBG quartile associated with a significantly greater fracture risk compared with the lowest quartile (hazard ratio 1.54, 95% confidence interval 1.16-2.04, p = 0.003), adjusting for age, body mass index, alcohol consumption, smoking, diabetes, impaired renal function, treatment allocation, medications affecting bone and high-density lipoprotein cholesterol. Two independent SNPs were associated with SHBG concentrations, rs10822163 and rs727428, but neither was associated with fracture risk. SHBG concentrations were positively associated with a greater fracture risk in community-dwelling women aged ≥70 years, which was not explained by genetic variants associated with SHBG regulation.

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

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

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. 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. 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. 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.

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