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Background A socioeconomic gradient exists in the utilisation of total hip replacements (THR) and total knee replacements (TKR) for osteoarthritis. However, the relations between socioeconomic status (SES) and time to THR or TKR is unknown. Aim To describe the association between SES and time to THR and TKR. Methods 1072 older-adults residing in Tasmania, Australia were studied. Incident primary THR and TKR were determined by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry. At baseline, each participant's area-level SES was determined by the Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD), from the Australian Bureau of Statistics' 2001 census data. IRSAD was analysed in two ways; 1) categorised into quartiles, whereby quartile 1 represented the most socioeconomically disadvantaged group, 2) the cohort dichotomised at the quartile 1 cut-point. Results The mean age was 63.0 (±7.5) years, and 51% were women. Over the median follow-up of 12.9 (Interquartile range: 12.2-13.9) years, 56 (5%) participants had a THR, and 79 (7%) had a TKR. Compared to the most disadvantaged quartile, less disadvantaged participants were less likely to have a THR (i.e. less disadvantaged participants had a longer time to THR) (HR: 0.56, 95% CI 0.32, 1.00) but not TKR (HR: 0.90, 95% CI 0.53, 1.54). However, the former became non-significant after adjustment for pain and radiographic osteoarthritis, suggesting that the associations may be mediated by these factors. Conclusions This study suggests that time to joint replacement was determined according to the symptoms/need of the participants rather than their SES. This article is protected by copyright. All rights reserved.

Health state utility values (HSUVs) are a key input in health economic modeling, but HSUVs of people with osteoarthritis (OA)-related conditions have not been systematically reviewed and meta-analyzed. Our objective was to systematically review and meta-analyze the HSUVs for people with OA.Searches within health economic/biomedical databases were performed to identify eligible studies reporting OA-related HSUVs. Data on study design, participant characteristics, affected OA joint sites, treatment type, HSUV elicitation method, considered health states, and the reported HSUVs were extracted. HSUVs for people with knee, hip, and mixed OA in pre- and posttreatment populations were meta-analyzed using random effects models.A total of 151 studies were included in the systematic review, and 88 in meta-analyses. Of 151 studies, 56% were conducted in Europe, 75% were in people with knee and/or hip OA, and 79% were based on the EuroQoL 5-dimension instrument. The pooled mean baseline HSUVs for knee OA core interventions, medication, injection, and primary surgery treatments were 0.64 (95% confidence interval [95% CI] 0.61-0.66), 0.56 (95% CI 0.45-0.68), 0.58 (95% CI 0.50-0.66), and 0.52 (95% CI 0.49-0.55), respectively. These were 0.71 (95% CI 0.59-0.84) for hip OA core interventions and 0.52 (95% CI 0.49-0.56) for hip OA primary surgery. For all knee OA treatments and hip OA primary surgery, pooled HSUVs were significantly higher in the post- than the pretreatment populations.This study provides a comprehensive summary of OA-related HSUVs and generates an HSUV database for people with different affected OA joint sites undergoing different treatments to guide HSUV choices in future health economic modeling of OA interventions.

Background: Curcuma longa (CL) extract is modestly effective for relieving knee symptoms in knee osteoarthritis (OA) patients; however, its mechanism of action is unclear. Purpose: We aimed to determine the effects of CL treatment on serum inflammatory markers over 12 weeks and to explore its potential effects on synovitis assessed by contrast-enhanced magnetic resonance imaging (CE-MRI) of the knee. Methods: Secondary analyses were conducted on the CL for knee OA (CurKOA) trial, which compared CL (n = 36) and placebo (n = 34) over 12 weeks for the treatment of knee OA. Systemic inflammatory markers (TNFα, IL6, and hsCRP) and a cartilage extracellular matrix degradative enzyme (MMP-3) were measured. A subgroup of participants (CL, n = 7; placebo, n = 5) underwent CE-MRI at baseline and a 12-week follow-up. Results: Over 12 weeks, there were no between-group differences in change in hsCRP, IL-6, and TNFα levels. MMP-3 levels decreased in both CL (-1.31 ng/ml [95%CI: -1.89 to -0.73]) and placebo (-2.34 ng/ml [95%CI: -2.95 to -1.73]) groups, with the placebo group having a slightly greater decrease (1.03 ng/ml [95%CI: 0.19 to 1.88]). Most (10 of 12) sub-study participants had normal synovial thickness scores at baseline. One participant had mild synovitis in each of the placebo and CL groups. Synovitis status was stable for all except two participants, one each in the CL and placebo group, whose synovitis score increased. Conclusion: This is the first study that explored the effect of CL treatment on local and systemic inflammation using biochemical markers and CE-MRI outcomes on knee OA patients. Secondary analyses from this pilot study suggest that CL is unlikely to have clinically significant effects on systemic (inflammatory and cartilage) or local synovitis (CE-MRI) biomarkers compared to placebo. The mechanism of action for CL effect on pain remains unclear.

Objective: To comprehensively synthesise the evolution of health-economic evaluation models (HEEMs) of all OA interventions including preventions, core treatments, adjunct non-pharmacological interventions, pharmacological and surgical treatments. Methods: The literature was searched within health-economic/biomedical databases. Data extracted included: OA type, population characteristics, model setting/type/events, study perspective, comparators; and the reporting quality of the studies was assessed. The review protocol was registered at the International Prospective Register of Systematic Reviews (registration: CRD42018092937). Results: Eighty-eight studies were included. Pharmacological and surgical interventions were the focus in 51% and 44% studies, respectively. Twenty-four studies adopted a societal perspective (with increasing popularity after 2013), however most (63%) did not include indirect costs. Quality-adjusted life years (QALYs) was the most popular outcome measure since 2008. Markov models were used by 62% of studies, with increasing popularity since 2008. Until 2010, most studies used short-to-medium time horizons; subsequently a lifetime horizon became popular. Eighty-six percent of studies reported discount rate(s) (predominantly between 3% and 5%). Studies published after 2002 had a better coverage of OA-related adverse events (AEs). Reporting quality significantly improved after 2001. Conclusions: OA HEEMs have evolved and improved substantially over time, with focus shifting from short-to-medium-term pharmacological decision-tree models to surgical-focused lifetime Markov models. Indirect costs of OA are frequently not considered, despite using a societal perspective. There was lack of reporting sensitivity of model outcome to input parameters including discount rate, OA definition, and population parameters. Whilst the coverage of OA-related AEs has improved over time, it is still not comprehensive.

Using a qualitative design this study aimed to (1) explore the experience of people living with osteoarthritis (OA), (2) gain an understanding of their navigation of the health system and, (3) explore their opinions on the role of exercise and joint replacement surgery for the management of OA.Purposive sampling was used to recruit 26 participants with knee OA, aged 45 years and over, from Tasmania, Australia. Semi-structured interviews were audio-recorded, transcribed, coded, and thematically analysed to document participant understanding and experience of OA and their opinions on the role of exercise and surgery in managing OA.Of the 26 participants, 80% (n = 21) were female with a mean age of 66 years. The main theme identified was that individuals with knee OA were navigating a maze of OA treatments. Three related subthemes were that participants: (i) perceived their general practitioner did not have an ongoing role in their OA care, (ii) self-directed their management and, (iii) sampled from a 'smorgasbord' of treatment options, including low-value care options. Two other major themes were: the role of exercise for OA management, and surgery as a last resort.Our findings suggest that OA patients may not be choosing consistent, high-value care for their OA. This highlights the importance of an evidence-based multi-disciplinary approach to guide patients to self-manage their OA and support their navigation of the health system. Reducing emphasis on the pathway to surgery and streamlining access to conservative management strategies may assist people to receive high-value care.

Context Vitamin D deficiency is a common, modifiable determinant of musculoskeletal health. Objective There are limited data that examine the longitudinal change in population 25-hydroxyvitamin D (25[OH]D) and none that evaluate the long-term skeletal outcomes of longitudinal vitamin D status. Methods A prospective cohort analysis was conducted of community-dwelling adults aged 50 to 80 years who had 25(OH)D assessed by radioimmunoassay and bone mineral density (BMD) by dual-energy x-ray absorptiometry at baseline (n = 1096), 2.5 (n = 870), and 10 (n = 565) years. Sun exposure was quantified by questionnaire and supplement use at clinic review. 25(OH)D less than 50 nmol/L was considered deficient. Participants were provided with their 25(OH)D results. Results Over 10 years 25(OH)D increased (52.2 ± 17.0 to 63.5 ± 23.6 nmol/L, P Conclusions Population 25(OH)D concentration increased because of a combination of increased sun exposure and supplement use. Maintaining or achieving vitamin D sufficiency was associated with less BMD loss over 10 years.

Background This study aims to describe the relationships between physical activity (PA), body composition, and multimorbidity over 10 years. Method Participants (N = 373; 49% women; average age 61.3 ± 6.7 years) were followed for 10 years. Multimorbidity was defined by self-report as the presence of 2 or more of 12 listed chronic conditions. PA (steps per day) at baseline was assessed by pedometer, handgrip strength (HGS) by dynamometer, and appendicular lean mass (ALM) and total body fat mass by dual-energy x-ray absorptiometry. Relative HGS and ALM were calculated by dividing each body mass index (BMI). Regression cubic splines were used to assess evidence for a nonlinear relationship. Results After 10 years, 45% participants had multimorbidity. There was a nonlinear relationship between PA and multimorbidity—PA was associated with lower multimorbidity risk among individuals who engaged in Discussion These findings highlight the potential clinical importance of maintaining adequate levels of PA and of reducing adiposity and maintaining muscle function for minimizing the risk of multimorbidity in older adults.

Objective To describe the status of and identify factors associated with physical activity promotion by podiatrists. Design Cross sectional survey. Method In 2016−17 Australian podiatrists were invited to complete an online survey. Items assessed by Likert scale included; frequency of assessing and promoting physical activity and podiatrists’ intentions, attitudes, social norms, confidence, barriers, role beliefs and perceived knowledge and skills regarding the promotion of physical activity. Data were analysed using descriptive statistics, exploratory factor analysis and structural equation modelling. Results Of 316 respondents, 62% reported always/or often giving general and 39% specific physical activity advice. Attitudes to physical activity promotion were mostly positive and 83% agreed it was part of their role. Many believed they have the knowledge 62%) and skills to promote physical activity. Most podiatrists were confident to carry out basic physical activity promotion activities (83%), but fewer were confident assessing physical activity levels (54%), providing specific advice (47%), monitoring patient physical activity levels (49%) and carrying out physical activity counselling (41%). Modelling revealed intention to promote physical activity was most strongly influenced by experiential beliefs (β = 0.35, 95%CI 0.20−0.51) and instrumental beliefs (β = 0.27, 95%CI 0.15−0.40), whereas physical activity promotion was influenced by intention (β = 0.45, 95%CI 0.35−0.55) and behavioural control (β = 0.43, 95%CI 0.33−0.53). Conclusion Physical activity promotion is feasible and regularly practiced in the podiatry setting, however current practice appears suboptimal. Attitudes and behavioural control appear influential in engagement and deserve consideration when designing strategies to improve delivery in podiatric practice.

Background Current pharmacologic therapies for patients with osteoarthritis are suboptimal. Objective To determine the efficacy of Curcuma longa extract (CL) for reducing knee symptoms and effusion-synovitis in patients with symptomatic knee osteoarthritis and knee effusion-synovitis. Design Randomized, double-blind, placebo-controlled trial. (Australian New Zealand Clinical Trials Registry: ACTRN12618000080224). Setting Single-center study with patients from southern Tasmania, Australia. Participants 70 participants with symptomatic knee osteoarthritis and ultrasonography-defined effusion-synovitis. Intervention 2 capsules of CL (n = 36) or matched placebo (n = 34) per day for 12 weeks. Measurements The 2 primary outcomes were changes in knee pain on a visual analogue scale (VAS) and effusion-synovitis volume on magnetic resonance imaging (MRI). The key secondary outcomes were change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and cartilage composition values. Outcomes were assessed over 12 weeks. Results CL improved VAS pain compared with placebo by -9.1 mm (95% CI, -17.8 to -0.4 mm [P = 0.039]) but did not change effusion-synovitis volume (3.2 mL [CI, -0.3 to 6.8 mL]). CL also improved WOMAC knee pain (-47.2 mm [CI, -81.2 to -13.2 mm]; P = 0.006) but not lateral femoral cartilage T2 relaxation time (-0.4 ms [CI, -1.1 to 0.3 ms]). The incidence of adverse events was similar in the CL (n = 14 [39%]) and placebo (n = 18 [53%]) groups (P = 0.16); 2 events in the CL group and 5 in the placebo group may have been treatment related. Limitation Modest sample size and short duration. Conclusion CL was more effective than placebo for knee pain but did not affect knee effusion-synovitis or cartilage composition. Multicenter trials with larger sample sizes are needed to assess the clinical significance of these findings. Primary funding source University of Tasmania and Natural Remedies Private Limited.

Objective To describe the association between change in subchondral bone marrow lesions (BMLs) and change in tibiofemoral cartilage volume and knee symptoms in patients with symptomatic knee OA. Methods In total, 251 participants (mean 61.7 years, 51% female) were included. Tibiofemoral cartilage volume was measured at baseline and 24 months, and BML size at baseline, 6 and 24 months. Knee pain and function scores were evaluated at baseline, 6 and 24 months. Change in total and compartment-specific BML size was categorized according to the Least Significance Criterion. Linear mixed-effects models were used to evaluate the associations of change in BMLs over 6 and 24 months with change in cartilage volume over 24 months and knee symptoms over 6 and 24 months. Results Total BML size enlarged in 26% of participants, regressed in 31% and remained stable in 43% over 24 months. Compared with stable BMLs in the same compartment, enlarging BMLs over 24 months were associated with greater cartilage loss (difference: −53.0mm3, 95% CI: −100.0, −6.0), and regressing BMLs were not significantly associated with reduced cartilage loss (difference: 32.4mm3, 95% CI: −8.6, 73.3) over 24 months. Neither enlargement nor regression of total BML size over 6 and 24 months was associated with change in knee pain and function over the same time intervals. Conclusions In subjects with symptomatic knee osteoarthritis and BMLs, enlarging BMLs may lead to greater cartilage loss but regressing lesions are not associated with reduced cartilage loss while neither is associated with change in knee symptoms.

This study evaluated whether zoledronic acid (ZA) inhibited the progression of abdominal aortic calcification (AAC) over 3 years in 502 postmenopausal women with osteoporosis. AAC progressed in a similar proportion of participants in the ZA (29%) and placebo (31%) groups, suggesting no effect of ZA on AAC progression. Bisphosphonate use is associated with reduced risk of all-cause mortality and cardiovascular events. The underlying mechanisms are uncertain but may include effects on vascular calcification. This study aimed to evaluate the effect of zoledronic acid (ZA) on abdominal aortic calcification (AAC) in postmenopausal women with osteoporosis. This was a post hoc analysis of the HORIZON Pivotal Fracture Trial that included 502 postmenopausal women (mean age 72.5 years) with osteoporosis (234 received ZA and 268 placebo). AAC scores (range, 0–8) were assessed from paired spine X-rays at baseline and after 3 years. Progression of AAC was defined as any increase in AAC score. The association between change in hip and femoral neck bone mineral density and change in AAC score was also assessed. At baseline, 292 (58.2%) participants had AAC (i.e., AAC score > 0), with AAC scores similar in the two intervention groups (median [interquartile range], 1 [0 to 2] for both; p = 0.98). Over 3 years, AAC progressed in a similar proportion of participants in both groups (ZA 29% and placebo 31%; p = 0.64). Change in bone mineral density and change in AAC score were not correlated. Once-yearly zoledronic acid did not affect progression of AAC over 3 years in postmenopausal women with osteoporosis. ClinicalTrials.gov identifier: NCT00049829

Summary Objective To describe the association of subchondral and systemic bone mineral density (BMD) with knee and hip replacements (KR and HR, respectively) due to osteoarthritis. Design 1,095 participants (mean age 63 years, 51% female) were included. At baseline, subchondral BMD of the medial and lateral tibia in three regions of interest (ROI) for the right knee, and systemic BMD of the lumbar spine, femoral neck, total hip and whole-body, were measured using dual-energy X-ray absorptiometry. Subchondral BMD of the hip was not measured. Competing risk regression models were used to estimate sub-distribution hazard ratios (SHRs) of KR/HR per one standard deviation (SD) higher in BMD measures, with adjustment of potential confounders. Results Over 12.2 years, 79 (7.2%) participants underwent a KR and 56 (5.1%) an HR due to osteoarthritis. For the right side, medial subchondral BMD in ROI-3 was associated with an increased risk of KR (SHR 1.95 per SD; 95% Confidence Interval [CI], 1.57 to 2.43). In contrast, systemic BMD was not associated with the risk of KR, but higher BMD at the lumbar spine (1.42, 1.07 to 1.88) and whole-body (1.29, 1.00 to 1.66) were associated with an increased risk of HR at both sides. Conclusions Subchondral BMD is positively associated with an increased risk of KR and systemic BMD with an increased risk of HR, suggesting a role of BMD in the progression of osteoarthritis.

Summary Background & aims Aging is characterized by progressive decline in physiologic reserves and functions as well as prolonged inflammation, increasing susceptibility to disease. Diet plays an important role in maintaining health, and reducing morbidity and mortality, especially in older populations. This study was designed to determine prospective associations between dietary inflammatory index (DII®) scores and bone health, sarcopenia-related outcomes, falls risk and incident fractures in community-dwelling Australian older adults. Methods A total of 1098 [51% male; age (mean ± SD) 63.0 ± 7.5 years] non-institutionalized older adults who participated in the Tasmanian Older Adult Cohort Study (TASOAC) at baseline, 768 at 5 years, and 566 at 10 years follow-up were included in this analysis. Baseline energy-adjusted DII (E-DII) scores were calculated using a validated Food Frequency Questionnaire. Changes in bone mineral density (BMD) and appendicular lean mass (ALM) were measured over ten years using dual-energy x-ray absorptiometry. Ten-year changes in hand grip, knee extensor and whole lower-limb muscle strength and quality were assessed by dynamometers and change in falls risk score using the Physical Profile Assessment (PPA). Incident fractures at any site and non-vertebral fractures over 10 years were self-reported. Results The E-DII range was −3.48 to +3.23 in men and −3.80 to +2.74 in women. Higher E-DII score (indicating a more pro-inflammatory diet) was associated with lower total hip (B: −0.009; 95% CI: −0.017, 0.000) and lumbar spine BMD (B: −0.013; 95% CI: −0.024, −0.002), and higher falls risk score (B: 0.040; 95% CI: 0.002, 0.078) over 10 years in men. Women with higher E-DII scores had higher whole lower-limb muscle quality over 10 years (B: 0.109; 95% CI: 0.002, 0.215). For every unit increase in E-DII score, incident fracture rates increased by 9.0% in men (IRR: 1.090; 95% CI: 1.011, 1.175) and decreased by 12.2% in women (IRR: 0.878; 95% CI: 0.800, 0.964) in a fully adjusted model. Conclusion Higher E-DII scores were associated with lower bone density, higher falls risk, and increased incidence of fractures in community-dwelling older men, but decreased fracture incidence in women, over 10 years. This suggests pro-inflammatory diets may be more detrimental to musculoskeletal health in older men than in women. Additional studies are warranted to elucidate these sex differences.

To identify subgroups of community-dwelling older adults and to assess their longitudinal associations with long-term osteoarthritis (OA) outcomes. 1046 older adults aged 50–80 years were studied. At baseline, body mass index (BMI), pedometer-measured ambulatory activity (AA), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) determined knee pain and information on comorbidities were obtained. Tibial cartilage volume and bone-marrow lesions (BMLs) were assessed using MRI at baseline and 10 years and total knee replacements (TKR) by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry. Latent class analysis was used to determine participant subgroups, considering baseline BMI, AA, pain and comorbidities, and linear mixed-effects or log-binomial models were used to assess the associations. Three subgroups/classes were identified: subgroup 1 (43%): Normal/overweight participants with higher AA, lower pain and lower comorbidities; subgroup 2 (32%): Overweight participants with lower AA, mild pain and higher comorbidities; subgroup 3 (25%): Obese participants with lower AA, mild pain and higher comorbidities. Subgroup 3 had greater cartilage volume loss (β − 60.56 mm3, 95% CI − 105.91, − 15.21) and a higher risk of TKR (RR 3.19, 95% CI 1.75, 5.81), compared to subgroup 1. Subgroup 2 was not associated with cartilage volume change (β 13.06 mm3, 95% CI − 30.87, 57.00) or risk of TKR (RR 1.16, 95% CI 0.56, 2.36), compared to subgroup 1. Subgroup membership was not associated with worsening BMLs. Our findings suggest the existence of homogeneous subgroups of participants and support the utility of identifying patterns of characteristics/risk factors that may cluster together and using them to identify subgroups of people who may be at a higher risk of developing and/or progressing OA.

To evaluate the effect of annual infusions of zoledronic acid (ZA) with or without a single injection of methylprednisolone, compared to placebo, on quantitative magnetic resonance imaging 3-D bone area and bone shape in participants with symptomatic knee osteoarthritis (OA).This was a post-hoc analysis of the ZAP2 trial. Active appearance modelling was used to assess bone area (mmAt baseline 65% of participants demonstrated an OA shape. Treatment with ZA plus methylprednisolone but not ZA alone, compared to placebo, was associated with significantly slower expansion in bone area at the medial femoral (-33.9 mmZA plus methylprednisolone may retard expansion of bone area over 24 months, but ZA alone may not. Neither ZA with or without methylprednisolone slowed progression of bone shape over 6 or 24 months.

Objective Using a qualitative design this study aimed to 1) explore the attitudes towards and understanding of osteoarthritis (OA) held by Tasmanian general practitioners (GPs) and orthopaedic surgeons, 2) gain a deeper understanding of conservative and surgical management and 3) identify key barriers and challenges. Design Purposive sampling was used to recruit 17 ​GPs and 10 surgeons from Tasmania, Australia. Semi-structured interviews were audio-recorded, transcribed, coded, and thematically analysed to document understanding of OA, management and treatment decision making. Results GPs and surgeons had a shared understanding of the cause and management of OA which aligned well with evidence-based best practice. Most GPs acknowledged that severity of disease on an X-Ray does not correlate well with symptoms, although some GPs reported always using imaging to support their diagnosis. Conservative management was highly supported by all interviewees, focussing on exercise and/or physiotherapy. Key treatment barriers included managing poor patient understanding of OA, unrealistic expectations for treatment, lack of patient motivation and scepticism towards exercise, and cost and accessibility of conservative treatment options. Surgery was considered a suitable option when conservative management options had been exhausted. Conclusion This study uniquely interviewed GPs and surgeons from the same population, capturing two crucial areas of OA management. Some key barriers to treatment were identified and options for improving treatment include creating opportunities for increased patient education about OA, enhanced accessibility to OA conservative management programs along with improved reimbursement models supporting conservative management as first-line OA treatment.

Musculoskeletal pain is common and typically occurs at multiple sites. Pain has been shown to be associated with falls risk; however, whether an increased risk for falls associated with multisite pain (MSP) translates into an increased risk of fractures has not been investigated. This study aimed to examine the association of number of painful sites with prevalent and incident fractures. Data from a longitudinal population-based study of older adults (mean age 63 years) were utilized. Follow-up was performed at 2.6, 5.1, and 10.7 years later, respectively. Presence/absence of pain at the neck, back, hands, shoulders, hips, knees, and feet was assessed by questionnaire at baseline. Participants were classified into three groups according to the total number of painful sites: zero to two, three to four, and five to seven. Fractures were self-reported at each time point. BMD was measured by DXA. Falls risk was calculated based on the Short-Form Physiological Profile Assessment. Log-binomial regression was used for the analyses. There were 450 fractures at baseline and 154 new fractures reported during a mean follow-up period of 10.7 years (range 9.2 to 12.5 years). In multivariable analyses, number of painful sites was associated with prevalent fractures at any and nonvertebral site. Furthermore, participants with five to seven painful sites had an increased risk of incident fractures at any site (RR 1.69; 95% CI, 1.13 to 2.53); major site, including the femur, radius, ulnar, vertebral, rib, and humerus (RR 2.17; 95% CI 1.12 to 4.22); and vertebral site (RR 6.44, 95% CI, 1.64 to 25.33) compared with those with pain at zero to two sites. These associations remained statistically significant after further adjustment for falls risk and BMD. Pain at multiple sites was associated with incident fracture risk in a dose-response manner, suggesting that widespread pain is an independent contributor to fracture risk. The potential for pain management in fracture prevention warrants further exploration. © 2019 American Society for Bone and Mineral Research.

To identify serum biomarker(s) for predicting knee cartilage volume loss over time, we studied 139 knee osteoarthritis (OA) patients from a previous 24-month clinical trial cohort. Targeted metabolomic profiling was performed on serum collected at baseline. The pairwise metabolite ratios as proxies for enzymatic reaction were calculated and used in the analysis. Cartilage volume loss between baseline and 24 months was assessed quantitatively by magnetic resonance imaging (MRI). Data revealed an association between the serum ratio of lysophosphatidylcholine 18:2 (lysoPC 18:2) to phosphatidylcholine 44:3 (PC44:3) and the cartilage volume loss in the lateral compartment (β = −0.21 ± 0.04, p = 8.53*10−7) and with joint degradation markers, COMP (r = 0.32, p = 0.0002) and MMP1 (r = 0.26, p = 0.002). The significance remained after adjustment for age, sex, BMI, diabetes, hypertension, dyslipidemia, and the treatment taken in the original study. As the ratio indicated the over activation of the conversion pathway of PC to lysoPC catalyzed by phospholipase A2 (PLA2), we assessed and found that a specific PLA2, PLA2G5, was significantly increased in human OA cartilage and synovial membrane (85% and 19% respectively, both p

Aims: This study aims to describe the associations of low muscle mass, handgrip (HGS) and lower-limb muscle strength (LMS) with health-related quality of life (HRQoL) over 10 years in community-dwelling older adults. Methods: Participants (N = 1002; 51% women; mean age 63 ± 7.4 years) were prospectively followed for 10 years. HRQoL was measured using the validated assessment of quality of life (AQoL) instrument. Appendicular lean mass (ALM) was assessed using dual energy X-ray absorptiometry and normalized to body mass index (BMI). HGS and LMS were assessed using dynamometers. Low ALM/BMI (ALM/BMI LOW ), LMS (LMS LOW ) and HGS (HGS LOW ) at baseline were defined as the lowest 20% of the sex-specific distribution for each measure. Linear mixed effect regression models, adjusting for confounders, were used to estimate the association between ALM/BMI LOW , LMS LOW , and HGS LOW at baseline and HRQoL over 10 years. Results: Participants with LMS LOW (β = -0.061, 95% CI: -0.089, -0.033) and women (β = -0.089, 95% CI: -0.129, -0.049) but not men (β = -0.023, 95% CI: -0.064, 0.019) with HGS LOW had clinically meaningful reductions in HRQoL over 10 years compared to those with normal strength. There was a weaker but statistically significant association between ALM/BMI LOW and 10-year HRQoL (β = -0.038, 95% CI: -0.068, -0.008). Conclusions: Lower-limb muscle strength and handgrip strength (in women only), which can be easily measured in clinical practice, appear more important than muscle mass for HRQoL.

To investigate the longitudinal association between objectively measured ambulatory activity (AA) and knee MRI-detected osteophytes (OPs), and to test whether this relationship was modified by common risk factors for OA including sex, obesity, disease severity and knee injury history.408 community-dwelling adults aged 51-81 years were assessed at baseline and 2.7 years. T1-weighted fat-suppressed MRI was used to evaluate knee OPs at both time points. AA was assessed at baseline by pedometers and categorized as: less active (≤7499 steps per day), moderately active (7500-9999 steps per day) and highly active (≥10,000 steps per day).Statistically significant interactions were detected between knee OA risk factors and AA on increases in MRI-detected OPs (all P 0.05). In stratified analyses, being moderately active, compared to being less active, was protective against an increase in MRI-detected OPs (score change of ≥1) in females (relative risk (RR) = 0.42, 95%CI, 0.25-0.70, P 0.01), those who were obese (RR = 0.50, 95%CI, 0.30-0.83, P 0.01), those with radiographic OA (ROA) (RR = 0.68, 95%CI, 0.47-0.97, P = 0.02) and those with a history of knee injury (RR = 0.27, 95%CI, 0.08-0.88, P = 0.02) in almost every knee compartment, after adjustment for confounders. No statistically significant associations were found in males, non-obese, non-ROA or non-injury groups.Being moderately active is protective against an increase in MRI-detected OPs in females, those with ROA, those who are obese and those with a history of knee injury. These findings suggest that being moderately active is beneficial for individuals who are at higher risk of knee OA.

Summary Objective To describe associations between presence of patellar tendon enthesis (PTE) abnormalities and symptoms, structural abnormalities, and total knee replacement (TKR) in older adult cohort. Methods PTE abnormalities (presence of abnormal bone signal and/or bone erosion), were measured on T2-weighted magnetic resonance (MR) images at baseline in 961 community-dwelling older adults. Knee pain and function limitation were assessed using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Bone marrow lesions (BMLs), cartilage volume and defects score, and infrapatellar fat pad (IPFP) area were measured using validated methods. Incidence of TKR was determined by data linkage. Results Participants with abnormal PTE bone signal and/or erosion was 20%. Cross-sectionally, presence of PTE abnormalities was associated with greater pain intensity while going up and down stairs (β = 0.22 (95% confidence interval (CI); 0.03, 0.41)), greater risk of femoral BMLs (RR = 1.46 (1.12, 1.90)) and worse tibial cartilage defects score (RR = 1.70 (1.16, 2.47), and smaller IPFP area (β = −0.27 (−0.47, −0.06) cm2), after adjustment of confounders. Longitudinally, presence of baseline PTE abnormalities was associated with a deleterious increase in tibial BML size (RR = 1.52 (1.12, 2.05)) over 10.7 years but not symptoms, other structural changes, or TKR. Conclusion PTE abnormalities are common in older adults. Presence of cross-sectional but not longitudinal associations suggests they are commonly co-exist with other knee structural abnormalities but may not play a major role in symptom development or structural change, excepting tibial BMLs.

Objective To investigate the impact of total number and patterns of comorbidities on health-related quality of life (HRQoL) and identify the most prevalent and influential comorbidity patterns in people with OA over 10 years. Methods Participants from the Tasmanian Older Adult Cohort aged 50–80 years, with self-reported OA and data on comorbidities and HRQoL were included. Participants were interviewed at baseline (n = 398), 2.5 (n = 304), 5 (n = 269) and 10 years (n = 191). Data on the self-reported presence of 10 chronic comorbidities were collected at baseline. HRQoL was assessed using the Assessment of Quality of Life-4-Dimensions. The long-term impacts of the number and of the nine most prevalent combinations of cardiovascular (CVD), non-OA musculoskeletal (Ms), metabolic and respiratory comorbidities on HRQoL over 10 years were analysed using linear mixed regressions. Results Compared with comorbidity-free OA participants, the health state utility (HSU) of those with 2 or ≥3 comorbidities was respectively −0.07 and −0.13 units lower over 10 years, largely driven by reduced scores for independent living, social relationships and psychological wellness. Comorbidity patterns including ‘CVD+Ms’ were most influential, and associated with up to 0.13 units lower HSU, mostly through negative impacts on independent living (up to −0.12), psychological wellness (up to −0.08) and social relationship (up to −0.06). Conclusion Having more comorbidities negatively impacted OA patients’ long-term HRQoL. OA patients with CVD and non-OA musculoskeletal conditions had the largest HSU impairment, and therefore optimal management and prevention of these conditions may yield improvements in OA patients’ HRQoL.

Background To describe demographic and clinical factors associated with the presence and incidence of depression and explore the temporal relationship between depression and joint symptoms in patients with symptomatic knee osteoarthritis (OA). Methods Three hundred ninety-seven participants were selected from a randomized controlled trial in people with symptomatic knee OA and vitamin D deficiency (age 63.3 ± 7.1 year, 48.6% female). Depression severity and knee joint symptoms were assessed using the patient health questionnaire (PHQ-9) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), respectively, at baseline and 24 months. Results The presence and incidence of depression was 25.4 and 11.2%, respectively. At baseline, having younger age, a higher body mass index (BMI), greater scores of WOMAC pain (PR: 1.05, 95%CI:1.03, 1.07), dysfunction (PR: 1.02, 95%CI:1.01, 1.02) and stiffness (PR: 1.05, 95%CI: 1.02, 1.09), lower education level, having more than one comorbidity and having two or more painful body sites were significantly associated with a higher presence of depression. Over 24 months, being female, having a higher WOMAC pain (RR: 1.05, 95%CI: 1.02, 1.09) and dysfunction score (RR: 1.02, 95%CI: 1.01, 1.03) at baseline and having two or more painful sites were significantly associated with a higher incidence of depression. In contrast, baseline depression was not associated with changes in knee joint symptoms over 24 months. Conclusion Knee OA risk factors and joint symptoms, along with co-existing multi-site pain are associated with the presence and development of depression. This suggests that managing common OA risk factors and joint symptoms may be important for prevention and treatment depression in patients with knee OA. Trial registration ClinicalTrials.gov identifier: NCT01176344. Anzctr.org.au identifier: ACTRN12610000495022.

Current pharmacologic therapies for patients with osteoarthritis are suboptimal.To determine the efficacy ofRandomized, double-blind, placebo-controlled trial. (Australian New Zealand Clinical Trials Registry: ACTRN12618000080224).Single-center study with patients from southern Tasmania, Australia.70 participants with symptomatic knee osteoarthritis and ultrasonography-defined effusion-synovitis.2 capsules of CL (The 2 primary outcomes were changes in knee pain on a visual analogue scale (VAS) and effusion-synovitis volume on magnetic resonance imaging (MRI). The key secondary outcomes were change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and cartilage composition values. Outcomes were assessed over 12 weeks.CL improved VAS pain compared with placebo by -9.1 mm (95% CI, -17.8 to -0.4 mm [Modest sample size and short duration.CL was more effective than placebo for knee pain but did not affect knee effusion-synovitis or cartilage composition. Multicenter trials with larger sample sizes are needed to assess the clinical significance of these findings.University of Tasmania and Natural Remedies Private Limited.

Background Hip effusion-synovitis may be relevant to osteoarthritis (OA) but is of uncertain etiology. The aim of this study was to describe the cross-sectional and longitudinal associations of hip effusion-synovitis with clinical and structural risk factors of OA in older adults. Methods One hundred ninety-six subjects from the Tasmanian Older Adult Cohort (TASOAC) study with a right hip STIR (Short T1 Inversion Recovery) Magnetic Resonance Imaging (MRI) on two occasions were included. Hip effusion-synovitis CSA (cm2) was assessed quantitatively. Hip pain was determined by WOMAC (Western Ontario and McMaster Universities Osteoarthritis) while hip bone marrow lesions (BMLs), cartilage defects (femoral and/or acetabular) and high cartilage signal were assessed on MRI. Joint space narrowing (0–3) and osteophytes (0–3) were measured on x-ray using Altman’s atlas. Results Of 196 subjects, 32% (n = 63) had no or a small hip effusion-synovitis while 68% (n = 133) subjects had a moderate or large hip effusion-synovitis. Both groups were similar but those with moderate or large hip effusion-synovitis were older, had higher BMI and more hip pain. Cross-sectionally, hip effusion-synovitis at multiple sites was associated with presence of hip pain [Prevalence ratio (PR):1.42 95%CI:1.05,1.93], but not with severity of hip pain. Furthermore, hip effusion-synovitis size associated with femoral defect (βeta:0.32 95%CI:0.08,0.56). Longitudinally, and incident hip cartilage defect (PR: 2.23 95%CI:1.00, 4.97) were associated with an increase in hip effusion-synovitis CSA. Furthermore, independent of presence of effusion-synovitis, hip BMLs predicted incident (PR: 1.62 95%CI: 1.13, 2.34) and worsening of hip cartilage defects (PR: 1.50 95%CI: 1.20, 1.86). While hip cartilage defect predicted incident (PR: 1.11 95%CI: 1.03, 1.20) and worsening hip BMLs (PR: 1.16 95%CI: 1.04, 1.30). Conclusions Hip effusion-synovitis at multiple sites (presumably reflecting extent) may be associated with hip pain. Hip BMLs and hip cartilage defects are co-dependent and predict worsening hip effusion-synovitis, indicating causal pathways between defects, BMLs and effusion-synovitis.

Objective To describe the impact of OA on health-related quality of life (HRQoL) in the forms of health state utilities (HSUs) and health-dimension scores, and to compare the longitudinal changes in HRQoL for people with and without OA, using an Australian population-based longitudinal cohort. Methods Participants of the Tasmanian Older Adult Cohort with data on OA diagnosis and HRQoL were included [interviewed at baseline (n = 1093), 2.5 years (n = 871), 5 years (n = 760) and 10 years (n = 562)]. HRQoL was assessed using the Assessment of Quality of Life four-dimensions and analysed using multivariable linear mixed regressions. Results Compared with participants without OA, HSUs for those with OA were 0.07 (95% confidence interval: 0.09, 0.05) units lower on average over 10 years. HSUs for participants with knee and/or hip OA were similar to those with other types of OA at the 2.5 year follow-up and then diverged, with HSUs of the former being up to 0.09 units lower than the latter. Those with OA had lower scores for psychological wellness, independent living and social relationships compared with those without OA. Independent living and social relationships were mainly impacted by knee and/or hip OA, with the effect on the former increasing over time. Conclusion Interventions to improve HRQoL should be tailored to specific OA types, health dimensions, and times. Support for maintaining psychological wellness should be provided, irrespective of OA type and duration. However, support for maintaining independent living could be more relevant to knee and/or hip OA patients living with the disease for longer.

Summary Objectives To examine the cross-sectional and longitudinal associations of dietary patterns with knee symptoms and structures in patients with knee osteoarthritis (OA). Methods Participants with symptomatic knee OA were recruited from a randomised, placebo-controlled trial conducted in Tasmania (N = 259) and Victoria (N = 133). Diet was assessed by the Anti-Cancer Council of Victoria food frequency questionnaire. Factor analysis was used to identify dietary patterns. Knee symptoms were assessed using Western Ontario and McMaster Universities Arthritis Index (WOMAC) and structures using MRI. Multivariable linear regressions were used to examine associations. Results Three dietary patterns (“high-fat”, “healthy” and “mixed”) were identified in whole sample. Participants with higher “healthy pattern” score had lower total WOMAC, pain, function and stiffness scores at baseline but the associations were not significant over 24 months. Three (“western”, “vegetable and meat” and “mediterranean”) and two (“processed” and “vegetable”) patterns were identified in Tasmania and Victoria, respectively. Cross-sectionally, only “mediterranean pattern” and “vegetable pattern” scores were significantly and negatively associated with total WOMAC or function scores. Longitudinally, participants with higher “western pattern” had worsening function (β: 0.35, 95%CI: 0.03, 0.67) and total WOMAC (β: 0.40, 95%CI: 0.07, 0.72) scores; furthermore, “vegetable pattern” was associated with decreased WOMAC stiffness score (β: −0.47, 95%CI: −0.93, −0.02). In contrast, dietary patterns were largely not associated with structural changes. Conclusion Some healthy dietary patterns were associated with reduced joint symptoms but dietary patterns were not associated with joint structure in this sample with knee OA. Further studies are required to confirm these findings.

Objective To describe associations between hand abnormalities on MRI or radiographs (X-ray) and pain and function in a cross-sectional study of community-based older adults. Methods Distal and proximal interphalangeal index finger joints (n=221) were examined using MRI, X-ray, and hand examination. Hand pain, function, and stiffness were assessed using Australian/Canadian hand osteoarthritis index (AUSCAN) questionnaire. Grip strength was assessed using dynamometer. Models were adjusted for age, sex, and other MRI or X-ray abnormalities. Results Absence of collateral ligament (CLs) on MRI (relative risk; RR=3.15 (95% confidence interval 1.33, 7.50), and joint space narrowing (JSN) on X-ray (RR=2.96 (1.33, 6.58)) was associated with having a painful joint after adjustment for confounders. JSN was also associated with tender joints (RR=2.19 (1.01, 4.76)). Effusion-synovitis was associated with better AUSCAN pain scores (OR=0.51 (0.28, 0.94)) and JSN with worse AUSCAN pain scores (odds ratio; OR=1.67 (1.13, 2.48)). Absent CLs were also associated with stiffer joints (OR=3.12 (1.26, 7.70)) and weaker grip strength (β=-1.69 (-2.95, -0.43)) independent of pain and other features; JSN was also associated with weaker grip strength (β=-0.87 (-1.62, -0.14)). No other MRI or X-ray abnormalities were associated with pain or function independent of age, sex or pain. Conclusion Most MRI abnormalities were not associated with pain and function cross-sectionally. Absent CLs and JSN were associated with painful joints and weak grip strength independent of pain and other imaging features. JSN was also associated with tender joints and absent CLs with stiff joints. Unexpectedly, effusions were associated with reduced odds of pain.

This study aims to assess whether older adults with low muscle mass or strength, in the presence of obesity, have an increased risk of knee (TKR) and hip replacement (THR) over 13 years. 1082 community-dwelling older adults (51% women; mean age 62.9 ± 7.5 years) were studied at baseline and multiple time points over 13 years. The incidence of TKR and THR was determined by data linkage to National Joint Replacement Registry. Appendicular lean and fat mass were measured using DXA. Lower-limb muscle strength (LMS) was assessed by dynamometer. Low muscle mass and strength were defined as the lowest sex-specific tertiles for appendicular lean mass (adjusted for height and total body fat mass) and lower-limb strength, respectively. Obesity was defined as the highest sex-specific tertile for total body fat mass. Competing risk regression models were used to estimate the sub-distribution hazard ratio (SHR) for TKR and THR. Over 13 years of follow-up, 6.8% (n = 74/1082) of the participants had a TKR and 4.7% (n = 50/1066) had THR. Participants with the combination of obesity and low muscle strength (SHR 3.36, 95% CI 1.50, 7.53) but low muscle mass (SHR 1.11, 95% CI 0.52, 2.40) had a significantly increased risk of TKR, compared to individuals with neither obesity nor low muscle mass/strength. However, obesity with low muscle strength did not lead to a significantly greater risk of TKR compared to having low muscle strength or obesity alone. There was no evidence for an association between obesity with low muscle mass or strength and THR (all p 0.05). This finding suggests that combining muscle and fat assessments to predict the future risk of TKR is no better than each condition on its own.

Aims To describe the associations between interindividual (between-person) and intraindividual (within-person) variability in physical activity (PA) and knee pain and functional limitation among older adults. We also investigated the potential bidirectional association of between-person and within-person variability in knee pain and functional limitation with PA. Method Participants (N = 1064; 51% women; mean age 63 ± 7.4 years) were measured at baseline, 2.5, and 5 years. PA was measured using pedometers. Knee pain and functional limitation were assessed using the WOMAC scale. A two-part hurdle model, with adjustment for confounders, estimated the association of between-person and within-person variability in PA with knee pain/functional limitation (as the outcome). Linear mixed effect regression models described the association of between-person and within-person variability in knee pain and functional limitation with PA (as the outcome). Results Between-person effects showed that participants with a higher 5-year average PA had lower average WOMAC scores (β= –1.17, 95% CI: –1.82, –0.51). Within-person effects showed that at time-points when participants had a higher PA level than average, they also had lower WOMAC scores (β= –0.85, 95% CI: –1.36, –0.35). Conversely, both between-person (β= –15.6, 95% CI: –22.5, –8.8) and within-person increase (β= –7.4, 95% CI: –13.5, –1.4) in WOMAC scores were associated with lower PA. Conclusion These findings suggest that PA and knee pain/dysfunctional contribute to the development of one another. Pain can lead to changes in inter- and intraindividual PA levels, but the reverse is also possible – changes in PA results in changes in inter- and intraindividual pain/dysfunctional levels.

Objective To identify factors associated with non-medical health professionals’ engagement in physical activity (PA) promotion. Methods Five electronic databases were searched for studies including practising health professionals (excluding medical doctors), a PA promotion practice measure, a test of association between potential influencing factors and PA promotion practice, and written in English. Two researchers independently screened studies and extracted data. Extracted data were synthesized in a tabular format with a narrative summary (thematic analysis). Results Thirty studies involving 7734 non-medical health professionals were included. Self-efficacy in PA promotion, positive beliefs in the benefits of PA, assessing patients’ PA, and PA promotion training were the main factors associated with engaging in PA promotion. Lack of remuneration was not associated. Common study limitations included a lack of information on non-responders, data collection by survey only and limited reliability or validity testing of measurements. Conclusions There are common factors influencing PA promotion, but the absence of studies from some health professions, limitations related to study measures, and the lack of randomised controlled intervention trials highlights the need for further research. Practice Implications The factors identified may prove useful for guiding the development of strategies to encourage greater engagement in PA promotion by health professionals.

Summary Objective To assess the efficacy of adalimumab in patients with erosive hand osteoarthritis (OA). Method Patients >50 years old, meeting the American College of Rheumatology (ACR) criteria for hand OA, with pain >50 on 100 mm visual analogue scale (VAS), morning stiffness >30 min and ≥1 erosive joint on X-ray with synovitis present on magnetic resonance imaging (MRI) were included in a randomised double-blind placebo-controlled crossover trial. Patients were randomised to adalimumab (40 mg subcutaneous injections every other week) or identical placebo injections for 12 weeks followed by an 8-week washout and then crossed over treatment groups for another 12 weeks. The primary outcome was change in VAS hand pain over 12 weeks. Secondary outcomes included change in Australian/Canadian Hand OA Index (AUSCAN) pain, function and stiffness subscales from baseline to 4, 8 and 12 weeks, change in MRI-detected synovitis and bone marrow lesions (BMLs) from baseline to 12 weeks and change in VAS from baseline to 4 and 8 weeks. Results We recruited 51 patients and 43 were randomised to either Group 1 ( N = 18, active then placebo) or Group 2 ( N = 25, placebo then active). At 12 weeks there was no difference between the groups on the primary outcome measure (mean decrease in VAS pain of 3.2 mm standard deviation (SD 16.7) for adalimumab vs 0.8 mm (SD 29.6) for placebo). The adjusted treatment effect was −0.7 mm (95% confidence interval (CI) −9.3 to 8.0), P = 0.87. No statistically significant differences were found for any secondary outcomes. Conclusion Adalimumab did not show any effect on pain, synovitis or BMLs in patients with erosive hand OA with MRI-detected synovitis as compared to placebo after 12 weeks. Clinical trial registration number ACTRN12612000791831.

The aim of this study was to determine whether vitamin D supplementation and maintaining vitamin D sufficiency are associated with changes in inflammatory and metabolic biomarkers in patients with knee osteoarthritis (OA) and vitamin D deficiency. A total of 413 participants with symptomatic knee OA and vitamin D deficiency were enrolled in a randomised, placebo-controlled trial and received 1·25 mg vitamin D3 or placebo monthly for 24 months across two sites. In this post hoc analysis, 200 participants from one site (ninety-four from the placebo group and 106 from the vitamin D group; mean age 63·1 (sd 7·3) years, 53·3 % women) were randomly selected for measurement of serum levels of inflammatory and metabolic biomarkers at baseline and 24 months using immunoassays. In addition, participants were classified into two groups according to serum 25-hydroxyvitamin D (25(OH)D) levels at months 3 and 24: (1) not consistently sufficient (25(OH)D≤50 nmol/l at either month 3 or 24, n 61), and (2) consistently sufficient (25(OH)D>50 nmol/l at both months 3 and 24, n 139). Compared with placebo, vitamin D supplementation had no significant effect on change in serum high-sensitive C-reactive protein, IL-6, IL-8, IL-10, leptin, adiponectin, resistin, adipsin and apelin. Being consistently vitamin D sufficient over 2 years was also not associated with changes in these biomarkers compared with not being consistently sufficient. Vitamin D supplementation and maintaining vitamin D sufficiency did not alter serum levels of inflammatory and metabolic biomarkers over 2 years in knee OA patients who were vitamin D insufficient, suggesting that they may not affect systemic inflammation in knee OA patients.

Summary Objective To examine the association between ambulatory activity (AA), body composition measures and hip or knee joint replacement (JR) due to osteoarthritis. Design At baseline, 1082 community-dwelling older-adults aged 50–80 years were studied. AA was measured objectively using pedometer and body composition by dual-energy X-ray absorptiometry. The incidence of primary (first-time) JR was determined by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR). Log binomial regression with generalized estimating equations were used to estimate the risk of JR associated with baseline AA and body composition measures, adjusting for age, sex, X-ray disease severity, and pain. Results Over 13 years of follow-up, 74 (6.8%) participants had a knee replacement (KR) and 50 (4.7%) a hip replacement (HR). AA was associated with a higher risk of KR (RR 1.09/1000 steps/day, 95% CI 1.01, 1.16) and a lower risk of HR (RR 0.90/1000 steps/day, 95% CI 0.81, 0.99). Body mass index (BMI) (RR 1.07/kg/m 2 , 95% CI 1.03, 1.12), total fat mass (RR 1.03/kg, 95% CI 1.01, 1.06), trunk fat mass (RR 1.05/kg, 95% CI 1.00, 1.09), and waist circumference (RR 1.02/cm, 95% CI 1.00, 1.04) were associated with a higher risk of KR. Body composition measures were not associated with HR. Conclusions An objective measure of AA was associated with a small increased risk of KR and a small reduced risk of HR. Worse body composition profiles were associated with KR, but not HR. Altogether this may suggest different causal pathways for each site with regard to habitual activity and obesity.

Relationships between objectively assessed free-living physical activity (PA) and changes in bone health over time are poorly understood in older adults. This study suggests these relationships are sex-specific and that body composition may influence the mechanical loading benefits of PA. To investigate associations of objectively assessed PA and bone health in community-dwelling older adults. This secondary analysis of a subset of the Tasmanian Older Adult Cohort study included participants with PA assessed utilising ActiGraph GT1M accelerometers over 7 days (N = 209 participants, 53% female; mean ± SD age 64.5 ± 7.2 years). Steps/day and PA intensity were estimated via established thresholds. Bone mineral content (BMC) was acquired at the total hip, lumbar spine, legs and whole body by DXA at baseline and approximately 2.2 years later. Relationships between PA and BMC were assessed by multivariable linear regression analyses adjusted for age, smoking status, height and total lean mass. Men with above-median total hip BMC completed significantly less steps per day, but there was no significant difference in PA intensity compared with those with below-median BMC. There were no significant differences in PA in women stratified by median BMC. In women, steps/day were positively associated with leg BMC (B = 0.178; P = 0.017), and sedentary behaviour was negatively associated with leg BMC (− 0.165; 0.016) at baseline. After adjustment for confounders including lean mass and height, higher sedentary behaviour at baseline was associated with declines in femoral neck BMC (− 0.286; 0.011) but also with increases in pelvic BMC (0.246; 0.030) in men and increases in total hip BMC (0.215; 0.032) in women, over 2.2 years. No other significant longitudinal associations were observed after adjustment for body composition. Associations of accelerometer-determined sedentary behaviour and PA with bone health in older adults differ by sex and anatomical site and are mediated by body composition.