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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.

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.

To determine the independent associations of potential clinical, symptom, physical activity, and psychological factors with chronic plantar heel pain.Case-control.We investigated associations by comparing 220 participants with chronic (more than 3 months in duration) plantar heel pain to 100 age- and sex-matched controls, who were recruited randomly from the electoral roll. Exposures measured were waist girth, body mass index, body composition, clinical measures of foot and leg function, physical activity via accelerometry, depression and pain catastrophizing, symptoms of prolonged morning stiffness anywhere in the body, and multisite pain. Data were analyzed using multivariable conditional logistic regression.Waist girth (centimeters) (odds ratio [OR] = 1.06; 95% confidence interval [CI]: 1.03, 1.09), ankle plantar flexor strength (kilograms) (OR = 0.98; 95% CI: 0.97, 0.99), pain at multiple sites (pain at 1 other site: OR = 2.76; 95% CI: 1.29, 5.91; pain at 4 or more other sites: OR = 10.45; 95% CI: 3.66, 29.81), and pain catastrophizing status (none, some, or catastrophizer) (some: OR = 2.91; 95% CI: 1.33, 6.37; catastrophizer: OR = 6.79; 95% CI: 1.91, 24.11) were independently associated with chronic plantar heel pain. There were univariable but not independent associations with morning stiffness, first metatarsophalangeal joint extension range of motion, depression, and body mass index. There were no significant associations with physical activity or body composition (bioelectrical impedance analysis).Waist girth, ankle plantar flexor strength, multisite pain, and pain catastrophizing, but not foot-specific factors, were independently associated with chronic plantar heel pain. Of these 4 factors, 3 (waist girth, multisite pain, and pain catastrophizing) were central or systemic associations.

Objective To investigate the longitudinal associations of serum inflammatory markers and adipokines with joint symptoms and structures in participants with knee OA. Methods Two hundred participants (46.5% female, mean age 63.1 years, mean BMI 29.5 kg/m2) from Tasmania, part of the VIDEO (Vitamin D Effect on OA) study, were randomly selected in the current study. Serum levels of 19 biomarkers, scores of WOMAC and MRI-assessed knee structures were evaluated at baseline and month 24. The patterns of biomarkers were derived from principal component analysis and their association with knee symptoms and structures were examined using adjusted generalized estimating equations. Results Five components explained 78% of the total variance. IL-1β, -2, -4, -6, -8, -17 A, -17 F, -21, -22 and -23 loaded the highest on the first component, which was associated with increased bone marrow lesions (BMLs) and WOMAC dysfunction score. IL-10, -12 and GM-CSF loaded on the second component, which was associated with increased cartilage volume, and decreased effusion synovitis and WOMAC scores. Leptin, adipsin and CRP loaded on the third component, which was positively associated with WOMAC scores. Resistin loaded on the fourth component, which was associated with increased BMLs and cartilage defects. Apelin-36 and adiponectin loaded on the fifth component, which was associated with increased BMLs. Conclusion Various inflammatory and metabolic components were associated differently with joint symptoms and structural changes in knee OA, suggesting a complex inflammatory and metabolic interrelationship in the pathogenesis of knee OA.

Objective The present study was undertaken to determine whether vitamin D supplementation or maintaining sufficient vitamin D level reduces foot pain over 2 years in patients with symptomatic knee osteoarthritis (OA). Methods A post hoc study was conducted from a randomized, double-blind, placebo-controlled trial named the Vitamin D Effect on Osteoarthritis (VIDEO) study. Symptomatic knee OA patients with serum 25-hydroxyvitamin D levels between 12.5 nmoles/liter and 60 nmoles/liter were included and randomly allocated to either monthly vitamin D3 or placebo treatment (1:1) for 2 years. Manchester Foot Pain and Disability Index (MFPDI) was used to evaluate foot pain and disabling foot pain was defined as at least 1 of the 10 functional limitation items (items 1-9 and 11) being documented as on "most/every day(s)" in the last month. A repeated-measures, mixed-effects model was used to analyze the change of MFPDI scores between groups adjusting for potential confounders. Results A total of 413 patients with a mean age of 63.2 years (49.7% males) were enrolled and 340 completed the study. The mean MFPDI score was 22.8 ± 7.3, with 23.7% of participants having disabling foot pain at baseline. There were significant differences in MFPDI scores change between groups over 2 years, with more improvements in the vitamin D group than in the placebo group (-0.03 versus 1.30; P = 0.013) and more improvement in those maintaining sufficient vitamin D levels (n = 226) than those who did not (n = 114) (-0.09 versus 2.19; P = 0.001). Conclusion Vitamin D supplementation and maintenance of sufficient vitamin D levels may improve foot pain in those with knee OA.

Background and purpose: This study was undertaken to identify clinically meaningful comorbidity patterns and their associations with the demographic/clinical characteristics of people with multiple sclerosis (MS). Methods: We conducted latent class analysis to identify clinically distinct comorbidity patterns in MS using the 15 most common comorbidities among 1518 Australian Multiple Sclerosis Longitudinal Study participants. The associations between demographic/clinical characteristics and comorbidity patterns were examined using log-binomial and multinomial logistic regression. Results: Five distinct comorbidity patterns were identified: "minimally diseased class" (30.8%), consisting of participants with no or one comorbidity; "metabolic class" (22.7%); "mental health-allergy class" (21.7%); "nonmetabolic class" (7.6%); and "severely diseased class" (7.0%), consisting of participants with higher prevalence of these comorbidities. The relative probabilities of being assigned to comorbidity classes compared to the minimally diseased class were significantly increased for participants who were older (metabolic: relative risk ratio [RRR] = 1.09, 95% confidence interval [CI] = 1.06-1.11; nonmetabolic: RRR = 1.07, 95% CI = 1.04-1.11; severely diseased: RRR = 1.04, 95% CI = 1.01-1.08), female (nonmetabolic: RRR = 5.35, 95% CI = 1.98-14.42; severely diseased: RRR = 2.21, 95% CI = 1.02-4.77), and obese (metabolic: RRR = 4.06, 95% CI = 2.45-6.72; mental health-allergy: RRR = 1.57, 95% CI = 1.00-2.46; severely diseased: RRR = 4.53, 95% CI = 2.21-9.29) and who had moderate disability (mental health-allergy: RRR = 2.32, 95% CI = 1.47-3.64; severely diseased: RRR = 2.65, 95% CI = 1.16-6.04). Conclusions: Comorbidity patterns exist in MS. Women, people who were older, people who were obese, and people who had higher disability levels were more likely to be in classes with higher levels of comorbidity. These findings may offer opportunities for designing more personalised approaches to comorbidity prevention and treatment.

The Australian Health Economics Model of Osteoporosis (AusHEMO) has shown good face, internal and cross validities, and can be used to assist healthcare decision-making in Australia. This study aimed to document and validate the risk engine of the Australian Health Economics Model of Osteoporosis (AusHEMO). AusHEMO is a state-transition microsimulation model. The fracture risks were simulated using fracture incidence rates from the Dubbo Osteoporosis Epidemiology Study. The AusHEMO was validated regarding its face, internal and cross validities. Goodness-of-fit analysis was conducted and Lin’s coefficient of agreement and mean absolute difference with 95% limits of agreement were reported. The development of AusHEMO followed general and osteoporosis-specific health economics guidelines. AusHEMO showed good face validity regarding the model’s structure, evidence, problem formulation and results. In addition, the model has been proven good internal and cross validities in goodness-of-fit test. Lin’s coefficient was 0.99, 1 and 0.94 for validation against the fracture incidence rates, Australian life expectancies and residual lifetime fracture risks, respectively. In summary, the development of the risk engine of AusHEMO followed the best practice for osteoporosis disease modelling and the model has been shown to have good face, internal and cross validities. The AusHEMO can be confidently used to predict long-term fracture-related outcomes and health economic evaluations when costs data are included. Health policy-makers in Australia can use the AusHEMO to select which osteoporosis interventions such as medications and public health interventions represent good value for money.

Objective To describe the associations of blood pressure and arterial stiffness with knee cartilage volume in patients with knee OA. Methods A secondary analysis was performed on the data from participants in a randomized controlled trial that identified the effects of vitamin D supplementation on knee structures and symptoms among patients with symptomatic knee OA. Brachial and central blood pressure, arterial stiffness indicators and knee cartilage volume were measured at baseline and the 2 year follow-up. Associations were assessed using generalized estimating equations. Results Among 231 participants (average age 63.2 years), 48.9% were females. Higher supine systolic and diastolic pressures were significantly associated with lower tibial cartilage volume (systolic: lateral β −6.23, medial β −5.14, total β −11.35 mm3/mmHg; diastolic: lateral β −10.25, medial β −11.29, total β −21.50 mm3/mmHg). Higher supine systolic pressure was associated with lower femoral cartilage volume (lateral β −17.35, total β −28.31 mm3/mmHg). Central systolic pressure and arterial stiffness indicators (including pulse wave velocity, central pulse pressure and peripheral pulse pressure) were largely not associated with knee cartilage volume; however, higher augmentation index was associated with lower tibial and femoral cartilage volume (tibial: medial β −8.24, total β −19.13 mm3/%; femoral: lateral β −23.70, medial β −26.42, total β −50.12 mm3/%). Conclusions Blood pressure and arterial stiffness are associated with knee cartilage volume at several sites in knee OA patients. This supports that blood pressure and arterial stiffness may involve in the progression of knee OA.

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.

To derive dietary patterns and examine their longitudinal associations with sociodemographic and lifestyle factors in the Tasmanian Older Adult Cohort. This is a corrected analysis of a retracted paper. We followed 1098 adults aged ≥50 years for 5 years. Dietary intake was assessed using a validated food frequency questionnaire. Baseline dietary patterns were identified using exploratory factor analysis and scores at each time point calculated using the weighted sum score method. Associations of energy-adjusted dietary pattern scores with participant characteristics were assessed using linear mixed-effects models. The four dietary patterns identified were: fruit and vegetable (vegetables, potatoes, fruits); animal protein (poultry, red meats, fish); snack (snacks, sweets, nuts); western (meat pies, hamburgers, pizzas). Fruit and vegetable pattern scores were lower in men and current smokers at baseline. Animal protein scores were lower in older and retired people but higher in men and smokers at baseline. The sex difference in animal protein score increased over time (p = 0.012). At baseline, snack score was positively associated with age and physical activity, but lower in men and current smokers. The effect of age on snack score lessened over time (p = 0.035). Western scores were lower in older people but higher in men, current smokers and those living in disadvantaged areas at baseline. The effect of age on western score reduced over time (p = 0.001). The higher scores for healthy and/or lower scores for unhealthy patterns in men, smokers, retirees and those experiencing social disadvantage suggest these could be target groups for interventions to improve diet quality in older adults.

Little is known about the change in prevalence of comorbidities during the disease course of people with multiple sclerosis (MS) and whether the prevalences vary by MS onset type. To calculate the change in prevalence of comorbidities between symptom onset and the time of study, to compare the prevalences of comorbidities with those in the Australian population at the time of study and to examine onset-type differences. Comorbidity data from 1518 participants of the Australian MS Longitudinal Study and Australian population comparator data (2014–2015 National Health Survey) were used. The change in prevalence between time points and prevalence ratios (PR) at the time of study (crude, age and sex adjusted, and stratified by onset type) was calculated. Comorbidities were common, and those with the largest increases in prevalence between MS symptom onset and the time of study were depression (+ 26.9%), anxiety (+ 23.1%), hypertension (+ 21.9%), elevated cholesterol (+ 16.3%), osteoarthritis (+ 17.1%), eye diseases (+ 11.6%), osteoporosis (+ 10.9%) and cancer (+ 10.3%). Compared to the general population and after age and sex adjustment, participants had a significantly higher prevalence for 14/19 comorbidities at the time of study. The associations were strongest for anaemia, cancer (both PR > 4.00), anxiety, depression, migraine (all PR > 3.00), psoriasis and epilepsy (both PR > 2.00). No significant differences were seen by onset type. Comorbidities are common at MS symptom onset and increase with MS duration. Having MS may thus contribute to accrual of comorbidities. This emphasises the importance of optimal screening for and management of comorbidities in early MS and throughout the disease course.

More research is needed to understand the contribution of comorbidities to MS symptomatology. To examine the dose–response relationship between the number of comorbidities and severity of MS symptoms and to assess the relative contribution of comorbidity groups and individual comorbidities to the severity of each symptom. We surveyed 1223 participants of the Australian MS Longitudinal Study for the presence of 30 comorbidities and the severity of 13 MS symptoms (0–10 scale). The associations between comorbidities and symptoms were assessed using negative binomial regression. The relative contributions of comorbidities to the severity of symptoms were assessed using general dominance analysis. Higher number of comorbidities was most strongly associated with a higher severity of pain and feelings of anxiety and depression (ratios of means ≥ 0.12 per comorbidity increase). Comorbidities explained between 3.7% (spasticity) and 22.0% (feelings of anxiety) of the total variance of symptom severity. Mental health and musculoskeletal disorders contributed most strongly to the severity of the most common symptoms in MS. Our findings support that early recognition and optimal management of comorbidities, particularly of mental health and musculoskeletal disorders, could have a positive impact on the severity of symptoms of people with MS.

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 In this study of 695 Australian older adults (aged ≥50 years), we found that men and women had a similar trajectory of health-related quality of life (HRQoL) recovery following fragility fracture at any skeletal site. These results provide us with critical knowledge that improves our understanding of health outcomes post-fracture. Introduction Mortality is higher in men than that in women following a fragility fracture, but it is unclear whether recovery of patient-reported outcomes such as health-related quality of life (HRQoL) differs between sexes. This study aimed to identify sex differences in HRQoL recovery 12 months post-fracture. Methods Data were from the Australian arm of the International Costs and Utilities Related to Osteoporotic Fractures Study (AusICUROS). Participants recruited to AusICUROS were adults aged ≥50 years who sustained a fragility fracture. HRQoL was measured using the EQ-5D-3L at three time-points post-fracture: within 2 weeks (including pre-fracture recall) and at 4 and 12 months. Multivariate logistic regression analyses were undertaken, adjusting for confounders including age, education, income, and healthcare utilization post-fracture. Results Overall, 695 AusICUROS participants (536 women, 77.1%) were eligible for analysis with fractures at the hip (n = 150), distal forearm (n = 261), vertebrae (n = 61), humerus (n = 52), and other skeletal sites (n = 171). At the time of fracture, men were younger, reported a higher income, and were more likely to be employed, compared with women. For all fracture sites combined, there were no differences between men and women in recovery to pre-fracture HRQoL at 12-month follow-up (adjusted OR = 1.09; 95% CI: 0.75–1.61). When stratified by fracture site, no significant sex differences were seen for hip (OR = 1.02; 95% CI: 0.42–2.52), distal forearm (OR = 1.60; 95% CI: 0.68–3.78), vertebral (OR = 2.28; 95% CI: 0.61–8.48), humeral (OR = 1.62; 95% CI: 0.16–9.99), and other fractures (OR = 1.00; 95% CI: 0.44–2.26). Conclusion Community-dwelling men and women who survived the 12 months following fragility fracture had a similar trajectory of HRQoL recovery at any skeletal site.

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.

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.

Background and objectives: Although nutrition is important to bone health, the impact of different dietary patterns on bone density and fracture is unclear. The aim of this study was to synthesise conflicting evidence from observational studies to determine associations of empirically derived dietary patterns with bone density and fracture in healthy adults. Method: A systematic review (PROSPERO CRD42017071676) with meta-analysis where possible (for hip fracture) and otherwise with best-evidence synthesis. Results: Twenty-one studies were included in the best-evidence synthesis and four in the meta-analysis. Meta-analysis demonstrated a protective association between 'healthy' pattern score and hip fracture (risk ratio 0.73; 95% confidence interval: 0.56, 0.96; I2 = 95%) for highest compared to lowest 'healthy' pattern score category. In best-evidence synthesis, there was conflicting evidence for associations of both pattern scores with bone density at all sites and total fractures and for 'Western' score and hip fracture. No study reported detrimental effects of 'healthy' patterns, or beneficial effects of 'Western' patterns. Discussion: The results suggest that general practitioners promoting a 'healthy' dietary pattern is, at worst, unlikely to be detrimental for bone health and, at best, may reduce hip fracture.

Finding appropriate pharmacological options to treat osteoarthritis (OA) remain challenging. We aimed to determine the efficacy and safety of all types of turmeric extracts for the management of knee OA. Sixteen RCTs of up to 16 weeks duration including 1810 adults with knee OA were included. Eleven RCTs compared the efficacy of turmeric extracts with placebo and five with active comparators (NSAIDs). The overall risk bias of included RCTs was moderate. Turmeric extracts significantly reduced knee pain (SMD − 0.82, 95% CI − 1.17 to − 0.47, I2 = 86.23%) and improved physical function (SMD − 0.75, 95% CI − 1.18 to − 0.33, I2 = 90.05%) compared to placebo but had similar effects compared to NSAIDs. BMI was the major contributor to heterogeneity in the placebo-controlled studies (explained 37.68% and 67.24%, respectively, in the models) and modified the effects of the turmeric on pain and physical function with less improvement with higher BMI (SMD 0.26 95% CI 0.04 to 0.48; SMD 0.48 95% CI 0.21 to 0.74). No significant between-group differences were reported for either biochemical markers or imaging outcomes. Turmeric extracts had 12% fewer adverse events than NSAIDs and similar rates to placebo. Turmeric extract is a safe and effective option for the symptomatic management of knee OA, compared to placebo or NSAIDs. However, current evidence from short-term studies is heterogeneous and has moderate risk of bias leading to some uncertainty about the true effect.

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.

Summary Background & aims The evidence of benefiting from a high-quality diet for knee osteoarthritis (OA) joint structures, symptoms, and systemic abnormalities is limited. Clarifying the relationship between diet quality and knee OA could provide useful information for knee OA management. To investigate the associations between diet quality and knee joint structures, symptoms, lower limb muscle strength, depressive symptoms, and quality of life in people with knee OA. Methods This study was a post-hoc, exploratory analysis using data from a randomized controlled trial in symptomatic knee OA participants with a follow-up time of 24 months. In brief, eligible participants of the original study were aged 50–79 years, had symptomatic knee OA, and had a pain of 20–80 mm on a 100-mm visual analog scale. After excluding the patients without information on diet quality, 392 participants were included in this post-hoc analysis. Diet quality was assessed at baseline using the Australian Recommended Food Score (ARFS) which includes subscores of vegetable, fruit, grain, dairy products, fat, and alcohol. Knee joint structures (including cartilage volume, cartilage defect, bone marrow lesions, and effusion-synovitis volume assessed by magnetic resonance imaging), OA symptoms, lower limb muscle strength, depressive symptoms, and quality of life were assessed at baseline and follow up. Mixed-effects models were used to assess the associations of diet quality with those outcomes. Results Diet quality mainly reflect diet variety within the core food was not associated with knee structures and OA symptoms, but was associated with greater lower limb muscle strength (β = 0.66, P = 0.001), lower depressive symptom (β = -0.08, P = 0.001), and better quality of life (β = -0.06, P = 0.002). In further analyses of food group-based sub-scores, only the vegetable sub-score had the similar associations with lower limb muscle strength (β = 1.03, P = 0.004), depressive symptom (β = -0.17, P Conclusions Higher diet quality, mainly vegetable diet quality, is associated with greater lower limb muscle strength, less depressive symptoms, and higher quality of life in knee OA patients, suggesting higher diet quality may have protective effects on knee OA.

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.

Background The effect of vitamin D supplementation on postural muscles of the trunk is of particular interest because low 25‐hydroxyvitamin D [25(OH) D] levels are associated with decreased postural balance and increased risk of falls. Understanding the role of vitamin D supplementation plays in trunk muscle function of older adults is necessary, as this is a potentially modifiable factor to improve postural muscle function and decrease the risk of falling of older adults. The objective of this randomized controlled trial was to evaluate the effect of 12 months of vitamin D supplementation compared with placebo, on morphology and function of the trunk muscles of adults aged 50 to 79 years with low serum 25(OH) D levels. Methods This was a secondary analysis of a randomized, placebo‐controlled, and double‐blind clinical trial conducted between June 2010 and December 2013 in Tasmania, Australia. The clinical trial was registered with the Australian New Zealand clinical trial registration agency, ClinicalTrials.gov identifier: NCT01176344; Australian New Zealand Clinical Trials Registry: ACTRN 12610000495022. Participants were aged 50–79 years with ongoing symptoms of knee osteoarthritis and with low serum [25(OH) D] (12.5 to 60 nmol/L, 5.2 to 24 ng/mL). Participants were randomly assigned to either monthly 50 000 IU oral vitamin D3 (n = 104) or an identical placebo (n = 113) for 24 months as per clinical trial protocol. The primary outcomes in this pre‐specified secondary analysis were between‐group differences in change in size of rectus abdominis, transversus abdominis, internal oblique, external oblique, and lumbar multifidus muscles and function (assessed by change in thickness on contraction) of these muscles (excepting rectus abdominis) from baseline to 12 months. Muscle size was assessed using ultrasound imaging. Results Of 217 participants (mean age 63 years, 48% women), 186 (85.7%) completed the study. There were no significant between‐group differences in change in size or function of the abdominal or multifidus muscles after 12 months of vitamin D supplementation. Conclusions A monthly dose of 50 000 IU of vitamin D3 alone for 12 months does not affect the size or ability to contract trunk muscles of independent community‐dwelling older adults with symptomatic knee osteoarthritis and low serum 25(OH) D levels regardless of body mass index status or degree of vitamin D deficiency. An effect of vitamin D supplementation on other aspects of trunk muscle function such as strength, power, or physical function cannot be ruled out.

Knee osteoarthritis (OA) is the most common form of OA which affects knee joints and there is currently no disease-modifying treatment available for OA. Therefore, an ideal strategy to prevent the development of OA is to identify and intervene at the modifiable risk factors for the development and progression of OA. Early-life factors such as obesity and malalignment may affect the mechanical aspect of the knee (i.e. alterations in normal knee kinematics) and could be the risk factor for the development of knee OA in later life. Identifying early-life (gestational factors, congenital defects, childhood, adolescence, early adulthood) factors which affect the development of knee OA in later stages of the life may help to develop targeted prevention programs in early-life itself to prevent the development of knee OA. Hence, this systematic review protocol provides the method to be used to comprehensively summarise the existing evidence on early life modifiable risk factors associated with the development and progression of knee OA.

To describe the associations of baseline dietary pattern scores with falls risk, bone mineral density (BMD), and incident fractures measured over 10 years in older adults. Dietary patterns were identified using exploratory factor analysis. Femoral neck (FN), hip, and lumbar spine (LS) BMD were measured using dual-energy X-ray absorptiometry, falls risk z-score using the Physiological Profile Assessment, and incident fractures by self-report. Linear mixed-effects models and log-binomial regression were used to estimate associations between baseline dietary pattern z-scores and outcomes. Of 1098 participants at baseline, 567 were retained over 10 years. Four dietary patterns were derived: fruit and vegetable (FV), animal protein (AP), snack, and Western. FV pattern reduced falls risk at baseline by β = 0.05–0.08/SD and the annual decreases of FN and hip BMD were less for higher Western or AP pattern scores in all populations and women. The annual increase in LS of the entire population was greater with higher scores of FV, AP, and Western patterns (all β = 0.001 g/cm2/year/SD, p

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.

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.

The aim of this study was to evaluate the effect of zoledronic acid (ZA) and denosumab on low back pain (LBP) and Modic change (MC) over 6 months. Adults aged ≥40 years with significant LBP for at least 6 months duration and MC (type 1, 2, or mixed) were randomized to receive ZA (5 mg/100 mL), denosumab (60 mg), or placebo. LBP was measured monthly by visual analogue scale (VAS) and the LBP Rating Scale (RS). MC was measured from MRIs of T12 -S1 vertebrae at screening and 6 months. A total of 103 participants with moderate/severe LBP (mean VAS = 57 mm; mean RS = 18) and median total MC area 538 mm2 were enrolled. Compared to placebo, LBP reduced significantly at 6 months in the ZA group for RS (-3.3; 95% CI, -5.9 to -0.7) but not VAS (-8.2; 95% CI, -18.8 to +2.4) with similar findings for denosumab (RS, -3.0; 95% CI, -5.7 to -0.3; VAS, -10.7; 95% CI, -21.7 to +0.2). There was little change in areal MC size overall and no difference between groups with the exception of denosumab in those with type 1 Modic change (-22.1 mm2 ; 95% CI, -41.5 to -2.7). In post hoc analyses, both medications significantly reduced VAS LBP in participants with milder disc degeneration and non-neuropathic pain, and denosumab reduced VAS LBP in those with type 1 MC over 6 months, compared to placebo. Adverse events were more frequent in the ZA group. These results suggests a potential therapeutic role for ZA and denosumab in MC-associated LBP.

Introduction This study aimed to determine if beneficial effects of individualized feedback of fracture risk on osteoporosis preventive behaviors and bone mineral density observed in a 2-year trial were sustained long-term. Methods This was a 10-year follow-up of a 2-year RCT in 470 premenopausal women aged 25–44 years, who were randomized to one of two educational interventions (the Osteoporosis Prevention and Self-Management Course [OPSMC] or an osteoporosis information leaflet) and received tailored feedback of their relative risk of fracture in later life (high versus normal risk groups). Bone mineral density of lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry. Physical activity, dietary calcium intake, calcium and vitamin D supplements, and smoking status were measured by questionnaires. Results From 2 to 12 years, the high-risk group had a smaller decrease in femoral neck bone mineral density (β=0.023, 95% CI=0.005, 0.041 g/cm2) but similar lumbar spine bone mineral density change as the normal-risk group. They were more likely to use calcium (relative risk=1.66, 95% CI=1.22, 2.24) and vitamin D supplements (1.99, 95% CI=1.27, 3.11). The OPSMC had no effects on bone mineral density change. Both high-risk (versus normal-risk) and the OPSMC groups (versus leaflet) had a more favorable pattern of smoking behavior change (relative risk=1.85, 95% CI=0.70, 4.89 and relative risk=2.27, 95% CI=0.86, 6.01 for smoking cessation; relative risk=0.33, 95% CI=0.13, 0.80 and relative risk=0.28, 95% CI=0.10, 0.79 for commenced or persistent smoking). Conclusions Feedback of high fracture risk to younger women was associated with long-term improvements in osteoporosis preventive behaviors and attenuated femoral neck bone mineral density loss. Therefore, this could be considered as a strategy to prevent osteoporosis. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) NCT00273260.

Background/AimThe clinical relevance of MRI knee abnormalities in athletes is unclear. This study aimed to determine the prevalence of MRI knee abnormalities in Australian Rules Football (ARF) players and describe their associations with pain, function, past and incident injury and surgery history.Methods75 male players (mean age 21, range 16–30) from the Tasmanian State Football League were examined early in the playing season (baseline). History of knee injury/surgery and knee pain and function were assessed. Players underwent MRI scans of both knees at baseline. Clinical measurements and MRI scans were repeated at the end of the season, and incident knee injuries during the season were recorded.ResultsMRI knee abnormalities were common at baseline (67% bone marrow lesions, 16% meniscal tear/extrusion, 43% cartilage defects, 67% effusion synovitis). Meniscal tears/extrusion and synovial fluid volume were positively associated with knee symptoms, but these associations were small in magnitude and did not persist after further accounting for injury history. Players with a history of injury were at a greater risk of having meniscal tears/extrusion, effusion synovitis and greater synovial fluid volume. In contrast, players with a history of surgery were at a greater risk of having cartilage defects and meniscal tears/extrusion. Incident injuries were significantly associated with worsening symptoms, BML development and incident meniscal damage.ConclusionsMRI abnormalities are common in ARF players, are linked to a previous knee injury and surgery history, as well as incident injury but do not dictate clinical symptomatology.

The objective of this study was to investigate the associations of knee structural abnormalities with different patterns of pain. A total of 891 participants (average age 63 years; range 50 to 80 years) participated in this study. Presence of pain at the neck, back, hands, shoulders, hips, knees, and feet was assessed by questionnaire. Participants were categorized as having no pain at any site (no pain), pain only at the knee (KP), pain at other sites but not the knee (OP), and pain at the knee and other sites (KOP). T1-weighted or T2-weighted MRI of the right knee was performed to measure cartilage defects, bone marrow lesions (BMLs), and effusion-synovitis. Osteophytes and joint space narrowing were assessed by X-ray. KP, KOP, and OP were, respectively, present in 3, 43, and 42% of the participants. In multivariable analyses, KOP was associated with the presence of cartilage defects, BMLs, and osteophytes (OR 3.57 (95% CI 1.78 to 7.14), 2.37 (1.27 to 4.43), and 2.87 (1.10 to 7.51), respectively) in those with radiographic knee OA. KP was also associated with presence of these structural abnormalities as well as effusion-synovitis, and these associations were much stronger. The associations between structural abnormalities and KOP were weaker than those with KP in those with radiographic knee OA. This suggests that mechanisms mediating the association between structural pathology, localized, and generalized pain may be different, and central sensitization is possibly involved in generalized pain. Pain at other sites needs to be considered in the management and treatment of OA-related pain.

Summary Objective To develop a measure of knee joint effusion-synovitis volume and to examine the effect of vitamin D supplementation on effusion-synovitis in people with knee osteoarthritis (OA) and low vitamin D levels over 24 months. Method Symptomatic knee OA patients with low 25-(OH)D levels (12.5–60 nmol/l) were recruited for a multi-centre, randomised, placebo-controlled and double-blind trial. Participants (age 63 ± 7 years, 208 females) were allocated to either 50,000 IU monthly vitamin D 3 ( n = 209) or placebo ( n = 204) for 24 months. Knee effusion-synovitis volume in suprapatellar and other regions was measured on magnetic resonance imaging (MRI) using OsiriX software. The intra-class correlation coefficients (ICCs) were used to test inter- and intra-rater reliabilities. The least significant change criterion was used to define the increase/decrease in effusion-synovitis volume. Result The reproducibilities of effusion-synovitis volume measurement were high with ICCs ranging from 0.93 to 0.99. Over 24 months, effusion-synovitis volume remained stable in the vitamin D group but increased in placebos with a significant between-group difference (−1.94 ml, 95% confidence interval (CI): −3.54, −0.33). This effect was evident in those with baseline effusion-synovitis and with suprapatellar effusion-synovitis. The proportion with an increase in effusion-synovitis volume was lower in the vitamin D group than placebo (risk ratio (RR): 0.87, 95% CI: 0.77, 0.97). Conclusion This highly reproducible effusion-synovitis volume measurement could be a promising outcome measure in OA trials. Vitamin D supplementation could retard the progression of effusion-synovitis which can potentially benefit people with an inflammatory OA phenotype.

Poor balance is a risk factor for falls and fracture in older adults, but little is known about modifiable factors affecting balance in younger women. This study aimed to examine whether lower limb muscle strength (LMS) in young women and changes in LMS are independent predictors of balance in middle age. This was an observational 10-year follow-up of 470 women aged 25 to 44 years at baseline who had previously participated in a 2-year population-based randomized controlled trial of osteoporosis education interventions. Linear regression was used to examine the association between baseline LMS (by dynamometer) and change in LMS over 12 years with balance at 12 years (timed up and go test [TUG], step test [ST], functional reach test [FRT], and lateral reach test [LRT]). LMS declined by a mean of 17.3 kg over 12 years. After adjustment for potential confounders, baseline and change in LMS were independently beneficially associated with TUG (β = -0.008 sec/kg, 95% confidence interval [CI] -0.01 to -0.006, and β = -0.006 sec/kg, 95% CI -0.009 to -0.003 for baseline and change, respectively), FRT (β = 0.057 cm/kg, 95% CI 0.030 to 0.084, and β = 0.071 cm/kg, 95% CI 0.042 to 0.101, respectively), and LRT (β = 0.030 cm/kg, 95% CI 0.012 to 0.049, and β = 0.022 cm/kg, 95% CI 0.002 to 0.043, respectively) 12 years later. There was an association between baseline LMS and ST (β = 0.044 steps/kg, 95% CI 0.022 to 0.067) but not between change in LMS and ST. Among young women, greater LMS at baseline and slower decline over time are both associated with better balance in midlife. Analogous to the contributions of peak bone mass and bone loss to fracture risk in older adults, this suggests that both improvement of muscle strength in younger age and prevention of age-related loss of muscle strength could be potentially useful strategies to improve balance and reduce falls in later life.

OBJECTIVE Pain is common in the elderly. Knee pain may predict knee cartilage loss, but whether generalized pain is associated with knee cartilage loss is unclear. This study, therefore, aimed to determine whether pain at multiple sites predicts knee cartilage volume loss among community-dwelling older adults, and, if so, to explore potential mechanisms. METHODS Data from the prospective Tasmanian Older Adult Cohort study was utilized (n = 394, mean age 63 years, range 52-79 years). Experience of pain at multiple sites was assessed using a questionnaire at baseline. T1-weighted fat-saturated magnetic resonance imaging of the right knee was performed to assess the cartilage volume at baseline and after 2.6 years. Linear regression modeling was used with adjustment for potential confounders. RESULTS The median number of painful sites was 3 (range 0-7). There was a dose-response relationship between the number of painful sites and knee cartilage volume loss in the lateral and total tibiofemoral compartments (lateral β = -0.28% per annum; total β = -0.25% per annum, both P for trend

Summary Objective To describe cross-sectional and longitudinal associations between serum levels of interleukin (IL) - 6, IL-17A, IL-17F, IL-23 and knee bone marrow lesions (BMLs) in patients with knee osteoarthritis (OA). Design Patients ( n = 192) with symptomatic knee OA (mean 63 years, range 50–79, female 53%) were assessed at baseline and after 24 months. At each time point, serum IL-6, IL-17A, IL-17F and IL-23 were measured using Bio-Plex ® Multiplex Immunoassays with Luminex xMAP technology. Knee BMLs were scored using the modified whole organ MRI score (WORMS) from T2 weighted fat-suppressed fast spin echo magnetic resonance imaging (MRI). Multivariable linear regression and log binominal regression were used to determine the associations between cytokines and BMLs. Results Baseline IL-6 (quarters) were significantly associated with total knee BMLs ( P P = 0.05 for the trend), after adjustment for confounders. Baseline IL-17F and IL-23 (highest quarters vs others) was associated with an increase in BML score in females ( P = 0.04 for IL-17F; P = 0.01 for IL-23), but not in males, in multivariable analyses. In contrast, IL-17A was not significantly associated with BMLs in either females or males. Conclusion IL-6 is associated with increased knee BMLs in both females and males with OA. Serum IL-17F and IL-23 predicted increased knee BML scores in females only, suggesting that inflammation is involved in BML pathogenesis in knee OA, especially in women. Trail registration ClinicalTrials.gov identifier: NCT01176344; Australian New Zealand Clinical Trials Registry: ACTRN12610000495022.

Data linking cumulative lifetime vitamin D status with skeletal outcomes are lacking. We show that increasing cumulative sun exposure was associated with higher bone mineral density in younger males and protective against fractures in females independent of current vitamin D. This supports the concept that cumulative sun exposure is an important contributor to skeletal health. While low 25-hydroxyvitamin D levels are associated with increased fracture risk, this reflects only recent sun exposure. The Beagley-Gibson (BG) method utilises microtopographical skin changes to quantify cumulative lifetime ultraviolet radiation (sun) exposure. This study aimed to describe the relationship between BG grade, BMD, falls risk and fractures in older adults. Eight hundred thirty-five community-dwelling adults aged 53–83 years had silicone casts from the dorsum of both hands graded by the BG method. BMD was measured using DXA and falls risk using the short form of the Physiological Profile Assessment. Vertebral deformities and symptomatic fractures were assessed by DXA and questionnaire, respectively. The relationship between BG grade, spine BMD and vertebral fracture varied depending upon sex. In females, increasing grade was associated with lower vertebral fracture prevalence (OR = 0.44/grade, p = 0.018) and fewer fractures (OR = 0.82/grade, p = 0.021), particularly major fractures (OR = 0.75/grade, p = 0.03). In males, increasing grade was associated with more DXA-detected vertebral deformities (RR = 1.28/grade, p = 0.001), but not symptomatic fractures. These relationships were independent of BMD, falls risk, smoking and current 25-hydroxyvitamin D. BG grade was not associated with falls risk. For BMD, there were interactions between BG grade and both age and sex and a positive trend with hip BMD in younger males. BG grade demonstrated beneficial associations with fracture outcomes in females and BMD in younger males independent of current 25-hydroxyvitamin D. These data support the concept that cumulative ultraviolet radiation exposure is an important determinant of skeletal health. The association with vertebral deformities in males may reflect outdoor physical trauma in younger life.

We have found that early-life exposures are associated with areal bone mineral density (aBMD) at ages 8 and 16 years. This study aimed to assess whether these associations persist into young adulthood when peak bone mass (PBM) is achieved and extend this analysis to microarchitecture. Participants were followed from perinatal period to 25 years old (n = 201). Outcomes were total body, spine, and hip aBMD (by dual-energy X-ray absorptiometry [DXA]), and cortical and trabecular bone measures at the distal radius and tibia (by high-resolution peripheral quantitative computed tomography [HRpQCT]). Early-life exposures including breastfeeding, maternal smoking during pregnancy, and birth weight. Sex, weight, height, vegetables, fruit and calcium intake at age 25 years were regarded as potential confounders in the analysis. There were significant interactions between period of gestation and early-life exposures for bone measures, so all analyses were stratified by period of gestation. Breastfeeding was beneficially associated with hip and total body aBMD, total, cortical and trabecular volumetric BMD (vBMD), cortical thickness, porosity, trabecular number (Tb.N), separation (Tb.Sp), and bone volume fraction (Tb.BV/TV) at radius and/or tibia at age 25 years in participants born prematurely (β ranged from -0.92 to 0.94), but there were no associations in those born at term. Maternal smoking had no association with any DXA/HRpQCT measures in those born prematurely but was detrimentally associated with inner transitional zone porosity and Tb.N (β = 0.40 and β = -0.37, respectively) in those full-term participants. Associations of birth weight with bone measures did not persist after adjustment for weight gain since birth. Breastfeeding was associated with a lower risk of lower limb fractures and maternal smoking had a deleterious association with upper limb fractures. In conclusion, breastfeeding and maternal smoking may have effects on peak bone microarchitecture whereas the association with birth weight is countered by subsequent growth. © 2020 American Society for Bone and Mineral Research.

Background Clinical trials evaluating the effect of calcium supplementation on bone loss in lactating women have been small, with inconsistent results. Objectives We aimed to determine the effect of calcium supplementation on bone mineral density (BMD) in lactating women. Methods An electronic search of databases was conducted from inception to January 2020. Two authors screened studies, extracted data, and assessed the risk of bias of eligible studies. Percentage change in BMD was pooled using random-effects models and reported as weighted mean differences (WMDs) with 95% CIs. Risk of bias was assessed using the Cochrane risk of bias tool. Results Five randomized controlled trials including 567 lactating women were included. All had a high risk of bias. Mean baseline calcium intake ranged from 562 to 1333 mg/d. Compared with control groups (placebo/no intervention), calcium supplementation (600/1000 mg/d) had no significant effect on BMD at the lumbar spine (WMD: 0.74%; 95% CI: -0.10%, 1.59%; I2 = 47%; 95% CI: 0%, 81%; n = 527 from 5 trials) or the forearm (WMD: 0.53%; 95% CI: -0.35%, 1.42%; I2 = 55%; 95% CI: 0%, 85%; n = 415 from 4 trials). BMD at other sites was assessed in single trials: calcium supplementation had a small to moderate effect on total-hip BMD (WMD: 3.3%; 95% CI: 1.5%, 5.1%) but no effect on total body or femoral neck BMD. Conclusions Overall, the meta-analysis indicates that calcium supplementation does not provide clinically important benefits for BMD in lactating women. However, there was adequate dietary intake before supplementation in some studies, and others did not measure baseline calcium intake. Advising lactating women to meet the current recommended calcium intakes (with supplementation if dietary intake is low) is warranted unless new high-certainty evidence to the contrary from robust clinical trials becomes available. More research needs to be done in larger samples of women from diverse ethnic and racial groups.This systematic review was registered at www.crd.york.ac.uk/prospero as CRD42015022092.

This study reported that the transitional zones in older adults were enlarged at the expense of the compact-appearing cortex with a greater porosity in all cortical sub-compartments. The magnitude of differences in areal and volumetric bone mineral density (aBMD, vBMD) between older and younger groups was similar. Aging is strongly associated with bone loss, but little is known about magnitudes of differences in bone microarchitectures, aBMD, and vBMD from peak bone mass (PBM) to senescence. We aimed to describe differences in aBMD, vBMD, and bone microarchitecture parameters at the distal radius between older and young adults. We compared 201 participants, aged 62–89 years (female 47%) and 196 participants, aged 24–28 years (female 38%). Bone microarchitecture parameters at distal radius were measured using high-resolution peripheral computed tomography (HRpQCT). aBMD was measured using dual-energy X-ray absorptiometry (DXA). Unpaired t tests and chi-square tests were used to compare differences in means and proportions as appropriate. Older adults had thinner compact-appearing cortices with larger (cross-sectional area: outer 30.96 mm2 vs. 28.38 mm2, inner 36.34 mm2 vs. 32.93 mm2) and thicker (outer 0.57 mm vs. 0.54 mm, inner 0.71 mm vs. 0.65 mm) transitional zones compared with young adults (all p

ObjectivesPoor health literacy (HL) is associated with poorer health outcomes in diabetes but little is known about its effects on foot disease. This study was aimed to determine the associations between HL and diabetic foot disease.DesignThis is a cross-sectional analysis of baseline data from a prospective study of foot disease.SettingAttendees of the Royal Hobart Hospital’s Diabetes outpatient clinics.Participants222 people with type 1 or type 2 diabetes aged >40 years and without a history of foot disease, psychotic disorders or dementia.MeasuresOutcomes were peripheral neuropathy, peripheral arterial disease and foot deformity according to published guidelines. The exposure, HL, was measured using the short form Test of Functional Health Literacy in Adults (S-TOFHLA) and the Health Literacy Questionnaire (HLQ). Covariates included demographic characteristics, medical history, psychological measures and foot care behaviour.ResultsOf 222 participants, 204 had adequate HL. (Mean (SD) S-TOFHLA scores were 31.9 (6.7)), mean(SD) HLQ scores were 134.4 (18.4)). In univariable but not multivariable analyses, higher S-TOFHLA scores were associated with lower overall risk for foot disease (OR 0.96, 95% CI 0.93 to 0.99) and loss of protective sensation (OR 0.95, 95% CI 0.91 to 0.995).ConclusionsThese data provide little support for clinically important impacts of HL on risk factors for diabetic foot disease. However, in the absence of longitudinal data, such effects cannot be ruled out. Longitudinal studies measuring incident foot disease are needed to properly judge the potential for interventions improving HL to reduce the incidence of diabetic foot disease.

Associations between physical activity and time spent sedentary and musculoskeletal outcomes remain unclear in middle-aged adults. This study aimed to describe associations between objectively-measured physical activity and sedentary time and musculoskeletal health outcomes in middle-aged women. This cross-sectional study from a population-based sample of 309 women (age 36 to 57 years) examined associations of total physical activity (accelerometer counts/min of wear time), and time spent sedentary, in light physical activities and moderate-to-vigorous physical activities (MVPA) (by Actigraph GT1M accelerometer) with lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) (by dual-energy X-ray absorptiometry), lower limb muscle strength (LMS), and functional mobility and balance tests (timed up and go test [TUG], functional reach test [FRT], lateral reach test [LRT], and step test [ST]) using linear regression. Total physical activity was beneficially associated with FN BMD (values are β; 95% CI) (0.011 g/cm2 ; 95% CI, 0.003 to 0.019 g/cm2 ), LMS (2.13 kg; 95% CI, 0.21 to 4.06 kg), and TUG (-0.080 s; 95% CI, -0.129 to -0.030 s), after adjustment for confounders. MVPA was also beneficially associated with FN BMD (0.0050 g/cm2 ; 95% CI, 0.0007 to 0.0094 g/cm2 ), LMS (1.48 kg; 95% CI, 0.45 to 2.52 kg), ST (0.12 steps; 95% CI, 0.02 to 0.23 steps), and TUG (-0.043 s; 95% CI, -0.070 to -0.016 s). Associations between MVPA and LMS, TUG and ST persisted after further adjustment for sedentary time. Only TUG was associated with sedentary time, with a detrimental effect (0.075 s; 95% CI, 0.013 to 0.137 s) and this did not persist after further adjustment for MVPA. Light physical activity was not associated with any outcome. MVPA appears more important than light physical activity or sedentary time for many musculoskeletal outcomes in middle-aged women. This needs to be considered when developing interventions to improve habitual physical activity that aim to improve musculoskeletal health. © 2016 American Society for Bone and Mineral Research.

Purpose: To compare the performance of low muscle mass and function with falls risk, incident fracture and mortality over 10 years.1041 participants (50% women; mean age 63±7.5 years) were prospectively followed for 10 years. Falls risk was measured using the Physiological Profile Assessment, fractures were self-reported and mortality was ascertained from the death registry. Appendicular lean mass (ALM) was assessed using dual energy X-ray absorptiometry. Four anthropometric: (ALM/height2, ALM/body mass index, ALM/weight×100, a residuals method of ALM on height and total body fat) and four performance-based measures: (handgrip strength, lower-limb muscle strength, upper and lower-limb muscle quality) were examined. Participants in the lowest 20% of the sex-specific distribution for each anthropometric and performance-based measure were classified has having low muscle mass or function. Regression analyses were used to estimate associations between each anthropometric and performance-based measure at baseline and 10-year falls risk, incident fractures and mortality.Mean falls risk z-score at 10 years was 0.64 (SD 1.12), incident fractures and mortality over 10 years were 16% and 14% respectively. All baseline performance-based measures were significantly associated with higher falls risk score at 10 years. Low handgrip (RR 1.55, 95% CI: 1.09, 2.20) and ALM/body mass index (RR 1.54, 95% CI: 1.14, 2.08) were the only significant predictors of fracture and mortality respectively.Low handgrip strength, a simple and inexpensive test could be considered in clinical settings for identifying future falls and fractures. ALM/ body mass index could be most suitable in estimating 10-year mortality risk, but requires specialised equipment.

Background and purpose The Beagley–Gibson (BG) grading system utilizes microtopographical skin changes to generate an individualized, objective estimate of cumulative, lifetime ultraviolet radiation (UVR) exposure. However, predictors of BG grade are ill-defined, particularly in older populations. The aim of this cross-sectional study was to describe the factors associated with skin damage as measured by the BG method in 835 community-dwelling older adults. Methods Study participants aged 53–83 years had silicone casts taken from the dorsum of both hands and graded by the BG method. Lifetime sun exposure, skin phenotypic traits and smoking status were assessed by questionnaire. 25-hydroxyvitamin D and melanin density were measured using radioimmunoassay and spectrophotometry, respectively. Ordered logistic regression was used to compute a single odds ratio (OR) by taking BG grade as the outcome variable. Results Higher 25-hydroxyvitamin D was associated with increasing BG grade (OR = 1.39, P = 0.02) in adjusted analysis. Age (OR = 1.14, P < 0.001), occupational sun exposure (OR = 1.62, P < 0.001), ability to tan (OR = 1.40, P < 0.001), melanin density (OR=0.79, P = 0.001), lifetime leisure time sun exposure (OR = 1.21, P = 0.004), current smoking (OR = 1.82, P = 0.007), propensity to sunburn (OR = 1.18, P = 0.016), and waist–hip ratio (OR = 1.10, P = 0.02) were independent predictors of BG grade. Hair colour, number of sunburns, body mass index and gender were not independent predictors of BG grade. Conclusions Beagley–Gibson skin cast grade is a biologically relevant marker of UVR exposure in older adults influenced by both intrinsic and extrinsic factors.

OBJECTIVE: To describe associations between serum high-sensitivity C-reactive protein (hsCRP), knee bone marrow lesions (BMLs), and knee pain, cross-sectionally and longitudinally, in patients with knee osteoarthritis (OA). METHODS: Patients (n = 192) with symptomatic knee OA (mean age 63 years, range 50-79, women 53%) were assessed at baseline and after 24 months. Serum hsCRP was measured using enzyme-linked immunosorbent assay. Knee BMLs were scored using the modified Whole-Organ Magnetic Resonance Imaging (MRI) Score from T2-weighted fat-supressed fast spin-echo MRI. Knee pain was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index. RESULTS: Quartiles of baseline serum hsCRP were associated with the presence of knee BMLs (prevalence ratio 1.07 per quartile [95% confidence interval (95% CI) 1.00, 1.15]) and total knee pain scores (β 13.66 per quartile [95% CI 2.26, 25.07]) in multivariable analyses. Longitudinally, higher baseline hsCRP was associated with an increase in BML score (risk ratio 1.37 per quartile [95% CI 1.10, 1.70]), and change in hsCRP was positively associated with change in BML score (β 0.19 [95% CI 0.05, 0.34]) in adjusted analyses. Baseline hsCRP was not associated with change in total knee pain, but change in hsCRP was positively and significantly associated with change in total knee pain (β 4.71 [95% CI 0.48, 8.94]). This became nonsignificant after adjustment for changes in BML score. CONCLUSION: In patients with knee OA, serum hsCRP is associated with knee BML scores and, to a lesser extent, pain both cross-sectionally and longitudinally, suggesting that inflammation is linked with BMLs and their associated pain.

It is currently recommended in Australia that nursing home residents are supplemented daily with 1000 IU vitamin D as they are at an increased risk of fractures. Historically, supplementation has been low, and current supplementation prevalence is not known. The aim of this study was to determine the prevalence of vitamin D supplementation amongst nursing home residents in Tasmania, Australia. Resident data, including demographics, medical conditions and medications (including vitamin D and calcium supplement use), exercise and sun exposure, were obtained from residents’ files and staff in consenting nursing homes. Dietary calcium intake was estimated from the weekly menu of one nursing home and total calcium intake estimated from this and calcium supplement use. The prevalence of vitamin D supplementation was compared by resident characteristics and fracture risk factors. Of 811 residents, 409 (50 %) received daily vitamin D supplementation of at least 1000 IU. Residents receiving vitamin D supplementation were slightly younger (mean 83 vs. 85 years for supplemented and unsupplemented groups, respectively, p = 0.003) and more likely to have osteoporosis (29 vs. 22 % for supplemented and unsupplemented groups, respectively, p = 0.019). Only 43 % of residents with osteoporosis received vitamin D supplements. Most residents (86 %) did not have regular sunlight exposure. The median estimated total calcium intake of 800 ± 275 mg daily was below guideline recommendations of 1000–1300 mg daily. The prevalence of vitamin D supplementation in nursing home residents was relatively low, suggesting poor adherence to the relevant clinical guidelines. Additionally, most residents do not access sunlight. Interventions addressing this evidence–practice gap are needed.

Purpose The aim of this study was to determine and compare risk factors associated with incident fractures in older adults with and without obesity, defined by both body mass index (BMI) and body fat percentage. Methods 1,099 older adults (mean ± standard deviation age = 63.0 ± 7.5) years, participated in this prospective cohort study. Obesity status at baseline was defined by BMI (≥30 kg/m2) obtained by anthropometry and body fat percentage (≥30% for men and ≥40% for women) assessed by dual-energy X-ray absorptiometry (DXA). Total hip and lumbar spine areal bone mineral density (aBMD) were assessed by DXA up to five years. Incident fractures were self-reported up to 10 years. Results Prevalence of obesity was 28% according to BMI and 43% according to body fat percentage. Obese older adults by BMI, but not body fat percentage, had significantly higher aBMD at the total hip and spine compared with non-obese (both p-value 0.05). Mediation analysis confirmed that aBMD meditated the effects of BMI, but not body fat percentage, on all incident fractures. Higher baseline falls risk score was the only consistent predictor of increased likelihood of incident fracture in obese individuals only, according to both BMI and body fat percentage (both p-value

Background:Weight, dietary patterns, vitamin D, physical activity and grip strength have been suggested to be associated with bone loss in older adults. However, studies have yet been performed to investigate the associations between these factors and radial bone microarchitecture.Objectives:This study aimed to describe the associations of weight, dietary patterns, serum 25-hydroxyvitamin D (25(OH)D) concentrations, physical activity and grip strength with bone measures in older adults.Methods:Cross-sectional data on 201 older adults (mean age 72 years, female 46%) from a population-based cohort study were analysed. Weight, dietary patterns, serum 25(OH)D concentrations, physical activity (steps per day), grip strength were collected and analysed from baseline to 10-year follow-up. Areal bone mineral density (aBMD) at spine, hip and whole body were measured by dual-energy X-ray absorptiometry (DXA). Radial cortical and trabecular bone microarchitectures were measured by high-resolution peripheral computed tomography (HRpQCT). Multivariable linear regression was used to analyse associations of study factors with bone measures.Results:Weight was positively associated with radial bone area (total: β=0.18, 95% CI: 0.07, 0.29; cortical: β=0.12, 95% CI: 0.03, 0.21; trabecular: β=0.18, 95% CI: 0.05, 0.32), and was inversely associated with compact cortical volumetric bone mineral density (vBMD) (β= -0.19, 95% CI: -0.37, -0.01) and trabecular thickness (β= -0.25, 95% CI: -0.43, -0.07). Ten-year changes in weight were not significantly associated with bone measures, apart from radial trabecular separation (β= 0.15, 95%CI: 0.009, 0.28). Western dietary pattern scores were inversely associated with radial vBMD (total: β= -0.17, 95% CI: -0.32, -0.01; cortical: β= -0.19, 95% CI: -0.34, -0.04; compact cortical: β= -0.19, 95% CI: -0.34, -0.04; outer transitional zone: β= -0.20, 95% CI: -0.35, -0.06), and were positively associated with cortical porosity (cortical: β= 0.18, 95% CI: 0.03, 0.33; compact cortical: β= 0.19, 95% CI: 0.04, 0.34; outer transitional zone: β= 0.20, 95% CI: 0.06, 0.35). Steps per day were not significantly associated with bone measures, apart from inner transitional zone area and thickness (β= 0.12, 95% CI: 0.003, 0.24; β= 0.19, 95% CI: 0.05, 0.33). Healthy food pattern scores, serum 25(OH)D and grip strength were not significantly associated with radial HRpQCT measures.Conclusion:Higher weight, but not weight change, was beneficial for radial cortical and trabecular bone area but also associated with worse compact cortical vBMD and trabecular thickness. Higher western dietary pattern scores had adverse effects on radial vBMD and cortical porosity while physical activity had inconsistent associations.Disclosure of Interests:None declared

Background:Pharmacological therapies are limited, associated with off-target effects, are frequently contraindicated, and only modestly effective for pain in osteoarthritis (OA). Effusion and synovitis are common in OA and are associated with symptomatic and structural progression of OA.Curcuma longa(Turmeric) extract has anti-inflammatory effects and is gaining popularity in the treatment of OA despite the lack of high-quality evidence.Objectives:The CurKOA trial aimed to determine the efficacy ofCurcuma longaextract for reducing knee symptoms and effusion-synovitis in patients with symptomatic knee OA and knee effusion-synovitis.Methods:In this randomised, double-blind, placebo-controlled trial, participants with significant knee pain (≥ 40 mm on a 100-mm visual analog scale [VAS]), symptomatic knee OA (by ACR criteria) and ultrasound defined effusion-synovitis were randomised to receiveCurcuma longaextract (80% aqueous based extract standardized to turmerosaccharides + 20% curcuminoids, 2 × 500 mg capsules/day) or identical placebo for 12 weeks. Knee MRI scans were obtained at baseline and 12 weeks. Coprimary outcomes were changes in knee pain assessed by VAS and change in knee effusion-synovitis volume assessed by MRI over 12 weeks.Results:Among 70 participants (36 receivedCurcuma longa, 34 received placebo, age 61.8±8.6 years, 56% female),Curcuma longasignificantly improved VAS knee pain compared to placebo (-9.11mm, 95% confidence interval [CI] [- 17.79 to -0.44]) over 12 weeks, equivalent to a standardised effect size of 0.50. There was no significant between group difference in change in effusion-synovitis volume (3.24 mL [-0.33, 6.82]). There were significantly greater reductions in WOMAC knee pain (-47.22mm [-81.22, -13.22]), WOMAC function (-112.26mm [-222.79 to -1.74]) and significantly more OARSI-OMERACT treatment responders (63% treatment vs. 38% placebo [Risk Ratio=1.64 (1.00 to 2.70)]) in theCurcuma longagroup compared to the placebo group. There was no significant between-group difference in lateral femoral cartilage T2 relaxation time (-0.38 ms [- 1.10 to 0.34]) assessed from compositional MRI. The incidence of adverse events was similar in theCurcuma longa(n=14 (39%)) and placebo (n=18 (53%)) groups over 12 weeks (P=0.24).Conclusion:An extract ofCurcuma longasignificantly improved knee pain in an inflammatory phenotype of knee OA patients over 12 weeks compared to placebo but had no effect on knee effusion-synovitis and cartilage composition assessed using MRI. The moderate effect size of the treatment supports the use ofCurcuma longaextract for the symptomatic management of knee OA.Figure 1.Change in VAS and WOMAC subscale scores in treatment and control groups over the course of the study. (VAS = Visual analog scale, WOMAC = Western Ontario and McMaster University Index, CL = Curcuma longa extract)Disclosure of Interests:None declared

IMPORTANCE: A proof-of-principle study suggested that intravenous zoledronic acid may reduce knee pain and the size of bone marrow lesions in people with knee osteoarthritis, but data from large trials are lacking. OBJECTIVE: To determine the effects of intravenous zoledronic acid on knee cartilage volume loss in patients with symptomatic knee osteoarthritis and bone marrow lesions. DESIGN, SETTING, AND PARTICIPANTS: A 24-month multicenter, double-blind placebo-controlled randomized clinical trial conducted at 4 sites in Australia (1 research center and 3 hospitals). Adults aged 50 years or older with symptomatic knee osteoarthritis and subchondral bone marrow lesions detected by magnetic resonance imaging (MRI) were enrolled from November 2013 through September 2015. The final date of follow-up was October 9, 2017. INTERVENTIONS: Intravenous infusion with either 5 mg of zoledronic acid in a 100-mL saline solution (n = 113) or a placebo saline solution (n = 110) at baseline and 12 months. MAIN OUTCOMES AND MEASURES: The primary outcome was absolute change in tibiofemoral cartilage volume assessed using MRI over 24 months (the minimum clinically important difference [MCID] has not been established). Three prespecified secondary outcomes were change in knee pain assessed by a visual analog scale (0 [no pain] to 100 [unbearable pain]; MCID, 15) and the Western Ontario and McMaster Universities Osteoarthritis Index (0 [no pain] to 500 [unbearable pain]; MCID, 75) over 3, 6, 12, 18, and 24 months and change in bone marrow lesion size over 6 and 24 months (the MCID has not been established). RESULTS: Of 223 participants enrolled (mean age, 62.0 years [SD, 8.0 years]; 52% were female), 190 (85%) completed the trial. Change in tibiofemoral cartilage volume was not significantly different between the zoledronic acid group and the placebo group over 24 months (−878 mm(3) vs −919 mm(3); between-group difference, 41 mm(3) [95% CI, −79 to 161 mm(3)]; P = .50). No significant between-group differences were found for any of the prespecified secondary outcomes, including changes in knee pain assessed by a visual analog scale (−11.5 in the zoledronic acid group vs −16.8 in the placebo group; between-group difference, 5.2 [95% CI, −2.3 to 12.8]; P = .17), changes in knee pain assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (−37.5 vs −58.0, respectively; between-group difference, 20.5 [95% CI, −11.2 to 52.2]; P = .21), and changes in bone marrow lesion size (−33 mm(2) vs −6 mm(2); between-group difference, −27 mm(2) [95% CI, −127 to 73 mm(2)]; P = .60) over 24 months. Adverse events were more common with zoledronic acid than with placebo (96% vs 83%, respectively) and consisted mainly of acute reactions (defined as symptoms within 3 days of administration of infusion; 87% vs 56%). CONCLUSIONS AND RELEVANCE: Among patients with symptomatic knee osteoarthritis and bone marrow lesions, yearly zoledronic acid infusions, compared with placebo, did not significantly reduce cartilage volume loss over 24 months. These findings do not support the use of zoledronic acid in the treatment of knee osteoarthritis. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12613000039785

Summary Objective To describe the value of radiographic- and magnetic resonance imaging (MRI)-defined tibiofemoral osteoarthritis (ROA and MRI-OA, respectively) and in combination for predicting tibial cartilage loss, knee pain and disability and total knee replacement (TKR) in a population-based cohort. Design A radiograph and 1.5T MRI of the right knee was performed. ROA and MRI-OA at baseline were defined according to the Osteoarthritis Research Society International atlas and a published Delphi exercise, respectively. Tibial cartilage volume was measured over 2.6 and 10.7 years. Knee pain and disability were assessed at baseline, 2.6, 5.1 and 10.7 years. Right-sided TKRs were assessed over 13.5 years. Results Of 574 participants (mean 62 years, 49% female), 8% had ROA alone, 15% had MRI-OA alone, 13% had both ROA and MRI-OA. Having ROA (vs. no ROA) and MRI-OA (vs. no MRI-OA) predicted greater tibial cartilage loss over 2.6 years (−75.9 and −86.4 mm3/year) and higher risk of TKR over 13.5 years (Risk Ratio [RR]: 15.0 and 10.9). Only MRI-OA predicted tibial cartilage loss over 10.7 years (−7.1 mm3/year) and only ROA predicted onset and progression of knee symptoms (RR: 1.32–1.88). In participants with both MRI-OA and ROA, tibial cartilage loss was the greatest (over 2.6 years: −116.1 mm3/year; over 10.7 years: −11.2 mm3/year), and the onset and progression of knee symptoms (RR: 1.75–2.89) and risk of TKR (RR: 50.9) were the highest. Conclusions The Delphi definition of MRI-OA is not superior to ROA for predicting structural or symptomatic OA progression but, combining MRI-OA and ROA has much stronger predictive validity.