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Objective: To investigate the variation in the distribution and the natural history of hand pain over 6 weeks in individuals with symptomatic hand osteoarthritis. Design: Patient-reported outcome data were collected at baseline and weekly for 6 weeks from community-based participants enrolled in a randomised controlled trial. Participants were grouped based on location of significant pain (Visual Analogue Scale, VAS≥40/100 ​mm) (both carpometacarpal (CMC) and interphalangeal (IP), CMC only, and IP only). Results: At baseline, of the 106 participants, 55(51.9 %) had pain in both CMC and IP joints, 28(26.4 %) in IP joints only, and 16(15.1 %) in CMC joint only. Those with CMC and IP pain had significantly higher VAS pain [68.1 (2.6) vs 59.3 (3.5) vs 51.2 (4.7)]; Australian Canadian Osteoarthritis Hand Index, (AUSCAN) pain [290.1 (15.7) vs 225.3 (21.2) vs 237.9 (28.4)], stiffness [57.1 (3.7) vs 44.6 (5.0) vs 32.2 (6.7)] and functional limitation [527.5 (30.9) vs 356.0 (41.7) vs 433.3 (55.7)]; and pain sensitization [PainDETECT score 11.1 (1.1) vs 8.1 (1.8) vs 5.8 (1.9)] compared to those with IP or CMC only pain, respectively. All groups showed improvement in outcomes over 6 weeks without significant inter-group differences. Conclusion: In a population with significant hand pain, pain in both CMC and IP joints was most common and identified a more severe phenotype than pain in IP or CMC only with higher pain, more functional limitation and pain sensitization. These data have the potential to inform clinical management of patients with hand pain and patient selection in clinical trials.

Objectives: This study aimed at systematically review the evidence for the efficacy of Tumor Necrosis Factor (TNF) inhibitors on symptoms and structural outcomes in hand osteoarthritis. Methods: Three databases were searched for randomized controlled trials examining the efficacy of TNF inhibitors in hand osteoarthritis. Two authors extracted data and assessed the risk of bias. The mean difference (MD) was calculated, and a random-effects meta-analysis was performed. Results: Four studies were identified involving 276 participants. Meta-analysis showed that TNF inhibitors had no effect on pain at 4–6 weeks (MD -0.93, 95%CI -7.41 to 5.55; 2 studies) and 24–26 weeks (MD -3.82, 95%CI -11.46 to 3.83; 2 studies) and no effect on grip strength at 12 months (MD -0.35, 95%CI -1.08 to 0.37; 2 studies). There was limited evidence for the effect of TNF inhibitors on structural outcomes at 12 months. Subgroup analysis from 2 studies showed beneficial effect of TNF inhibitors on reducing the progression of structural outcomes in hand OA patients with signs of inflammation but not in those without inflammation. The certainty of the evidence was low for the effect of TNF inhibitor on pain and moderate for the effect on grip strength. Conclusion: This study found no effect of TNF inhibitors on clinical outcomes in hand osteoarthritis over the short term (

Abstract Background Knee replacements are increasingly performed in older adults but uncertainty remains regarding their benefits in the context of age-related decline in physical function and other comorbidities. This study aimed to examine (1) the effect of knee replacement on functional outcomes in the context of age-related decline in physical function and (2) the factors associated with minimal important improvement in physical function after knee replacement in community-dwelling older adults aged ≥ 70 years. Methods This cohort study was performed within the ASPREE trial, with 889 participants undergoing knee replacement during the trial and 858 age- and sex-matched controls without knee or hip replacement identified from 16,703 Australian participants aged ≥ 70 years. Health-related quality of life was assessed annually using the SF-12, including its physical and mental component summary (PCS and MCS). Gait speed was measured biennially. Multiple linear regression and analysis of covariance were used to adjust for potential confounders. Results Participants with knee replacement had significantly lower pre- and post-replacement PCS scores and gait speed compared with age- and sex-matched controls. Participants with knee replacement had significant improvement in PCS score following knee replacement (mean change 3.6, 95% CI 2.9–4.3) while PCS score remaining unchanged in age- and sex-matched controls (-0.02, 95% CI -0.6 to 0.6) during follow-up period. The greatest improvements were observed for bodily pain and physical function. Following knee replacement, 53% of participants experienced minimal important improvement in PCS score (increased by ≥ 2.7), while 24% experienced worsened PCS score (reduced by > 2.7). Participants experiencing improved PCS score postoperatively had significantly lower PCS and higher MCS scores pre-surgery. Conclusions Although community-based older adults experienced a significant improvement in PCS scores after knee replacement, their postoperative physical functional status remained significantly lower than age- and sex-matched controls. The degree of preoperative physical function impairment was a strong predictor of functional improvement, suggesting that this could be an important consideration when identifying older people most likely to benefit from knee replacement surgery.

Objective: To examine the efficacy and safety of topical corticosteroid over 6 weeks in patients with symptomatic hand osteoarthritis. Design: In a randomized, double-blind, placebo-controlled trial, community-based participants with hand osteoarthritis were randomly assigned (1:1) to topical Diprosone OV (betamethasone dipropionate 0.5 ​mg/g in optimised vehicle, n=54) or placebo (plain paraffin, n=52) ointment to painful joints 3 times daily for 6 weeks. Primary outcome was pain reduction [assessed by 100 ​mm visual analogue scale (VAS)] at 6 weeks. Secondary outcomes included changes in pain and function using the Australian Canadian Osteoarthritis Hand Index (AUSCAN), Functional Index for Hand Osteoarthritis (FIHOA), and Michigan Hand Outcomes Questionnaire (MHQ) at 6 weeks. Adverse events were recorded. Results: Of 106 participants (mean age 64.2 years, 85.9% female), 103 (97.2%) completed the study. Change in VAS at 6 weeks was similar in the Diprosone OV and placebo groups (−19.9 vs. −20.9, adjusted difference 0.6, 95% CI -8.9 to 10.2). There were no significant between-group differences in change in AUSCAN pain [adjusted difference 25.8 (−16.0 to 67.5)], AUSCAN function [21.2 (−55.0 to 97.4)], FIHOA [-0.1 (−1.7 to 1.5)], or MHQ [-1.2 (−6.0 to 3.6)]. Incidence of adverse events was 16.7% in Diprosone OV and 19.2% in placebo group. Conclusions: Topical Diprosone OV ointment, although well-tolerated, was no better than placebo in improving pain or function over 6 weeks in patient with symptomatic hand osteoarthritis. Future studies should consider examining joints with synovitis and whether delivery approaches enhancing transdermal penetration of corticosteroids into joints are effective in hand osteoarthritis. Trial registration: ACTRN 12620000599976. Registered May 22, 2020.

Abstract Background There is an unmet need for treatments for knee osteoarthritis (OA). Effusion-synovitis is a common inflammatory phenotype of knee OA and predicts knee pain and structural degradation. Anti-inflammatory therapies, such as diacerein, may be effective for this phenotype. While diacerein is recommended for alleviating pain in OA patients, evidence for its effectiveness is inconsistent, possibly because studies have not targeted patients with an inflammatory phenotype. Therefore, we will conduct a multi-centre, randomised, placebo-controlled double-blind trial to determine the effect of diacerein on changes in knee pain and effusion-synovitis over 24 weeks in patients with knee OA and magnetic resonance imaging (MRI)-defined effusion-synovitis. Methods We will recruit 260 patients with clinical knee OA, significant knee pain, and MRI-detected effusion-synovitis in Hobart, Melbourne, Adelaide, and Perth, Australia. They will be randomly allocated to receive either diacerein (50mg twice daily) or identical placebo for 24 weeks. MRI of the study knee will be performed at screening and after 24 weeks of intervention. The primary outcome is improvement in knee pain at 24 weeks as assessed by a 100-mm visual analogue scale (VAS). Secondary outcomes include improvement in volumetric (ml) and semi-quantitative (Whole-Organ Magnetic Resonance Imaging Score, 0–3) measurements of effusion-synovitis using MRI over 24 weeks, and improvement in knee pain (VAS) at 4, 8, 12, 16, and 20 weeks. Intention-to-treat analyses of primary and secondary outcomes will be performed as the primary analyses. Per protocol analyses will be performed as the secondary analyses. Discussion This study will provide high-quality evidence to determine whether diacerein improves pain, changes disease trajectory, and slows disease progression in OA patients with effusion-synovitis. If diacerein proves effective, this has the potential to significantly benefit the substantial proportion (up to 60%) of knee OA patients with an inflammatory phenotype. Trial registration Australian and New Zealand Clinical Trial Registry ACTRN12618001656224 . Registered on 08 October 2018.

Abstract Aims To investigate whether the associations between cartilage defects and cartilage volumes with changes in knee symptoms were mediated by osteophytes. Methods Data from the Vitamin D Effects on Osteoarthritis (VIDEO) study were analyzed as a cohort. The Western Ontario and McMaster Universities Osteoarthritis Index was used to assess knee symptoms at baseline and follow-up. Osteophytes, cartilage defects, and cartilage volumes were measured using magnetic resonance imaging at baseline. Associations between cartilage morphology and changes in knee symptoms were assessed using linear regression models, and mediation analysis was used to test whether these associations were mediated by osteophytes. Results A total of 334 participants (aged 50 to 79 years) with symptomatic knee osteoarthritis were included in the analysis. Cartilage defects were significantly associated with change in total knee pain, change in weight-bearing pain, and change in non-weight-bearing pain after adjustment for age, sex, body mass index, and intervention. Cartilage volume was significantly associated with change in weight-bearing pain and change in physical dysfunction after adjustment. Lateral tibiofemoral and patellar osteophyte mediated the associations of cartilage defects with change in total knee pain (49–55%) and change in weight-bearing pain (61–62%) and the association of cartilage volume with change in weight-bearing pain (27–30%) and dysfunction (24–25%). Both cartilage defects and cartilage volume had no direct effects on change in knee symptoms. Conclusions The significant associations between cartilage morphology and changes in knee symptoms were indirect and were partly mediated by osteophytes.

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

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

Abstract Background Hallux valgus is a common and disabling condition. This randomised pilot and feasibility trial aimed to determine the feasibility of conducting a parallel group randomised trial to evaluate the effectiveness of a nonsurgical intervention for reducing pain associated with hallux valgus. Methods Twenty‐eight community‐dwelling women with painful hallux valgus were randomised to receive either a multifaceted, nonsurgical intervention (footwear, foot orthoses, foot exercises, advice, and self‐management) or usual care (advice and self‐management alone). Outcome measures were obtained at baseline, 4, 8 and 12 weeks. The primary outcome was feasibility, evaluated according to demand (recruitment rate and conversion rate), acceptability, adherence, adverse events, and retention rate. Limited efficacy testing was conducted on secondary outcome measures including foot pain, foot muscle strength, general health‐related quality of life, use of cointerventions, and participants' perception of overall treatment effect. Results Between July 8, 2021, and April 22, 2022, we recruited and tested 28 participants (aged 44 to 80 years, mean 60.7, standard deviation 10.7). This period encompassed two COVID‐related stay‐at‐home orders (July 16 to July 27, and August 5 to October 21, 2021). The predetermined feasibility thresholds were met for retention rate, foot pain, mental health‐related quality of life, and use of cointerventions, partly met for acceptability, adverse events, and muscle strength, and not met for demand (recruitment rate or conversion rate), adherence, physical health‐related quality of life and perception of overall treatment effect. Conclusion In its current form, a randomised trial of footwear, foot orthoses, foot exercises, advice and self‐management for relieving pain associated with hallux valgus is not feasible, particularly due to the low adherence with the intervention. However, it is difficult to determine whether the trial would be feasible under different circumstances, particularly due to COVID‐19 stay‐at‐home orders. Future trials will need to consider improving the aesthetics of the footwear and making the exercise program less burdensome. Trial registration Australian and New Zealand Clinical Trial Registry (ACTRN12621000645853).

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

Objective: While targeting obesity is central to osteoarthritis management, recent meta-analyses demonstrate only modest effects of weight loss on symptoms, and little on structure. The World Health Organisation recommends that effective management of obesity include prevention of weight gain, weight maintenance and weight loss. Therefore, we systematically reviewed the recommendations and approaches for management of obesity in clinical practice guidelines (CPGs) for osteoarthritis. Design: Nine databases were searched (01.01.2010–15.03.2022) to identify guidelines informing the non-pharmacological management of osteoarthritis. Three reviewers appraised guidelines according to the AGREE II instrument, and independently extracted data on their characteristics. One author extracted and summarised guideline recommendations on weight management. This systematic review is registered on PROSPERO (CRD42021274195). Results: Of the included fifteen CPGs (median AGREE II domain score 78.7%), weight loss was recommended for knee (12 of 13) and hip (10 of 11) but not hand (0 of 4) osteoarthritis. Combination approaches of diet and/or exercise were recommended for overweight or obese individuals in knee (8 of 12) and hip (4 of 10) osteoarthritis. Two guidelines specified ≥5% weight loss. One guideline specified strategies for maintenance of lost weight; none specifically recommended preventing weight gain. There was discordance between strength of recommendation for weight loss and level of evidence (3 of 15). Conclusion: Most CPGs for knee and hip osteoarthritis recommend weight loss to manage obesity in osteoarthritis. As steady weight accumulation is common in adults, preventing weight gain should also be considered as it is a missed opportunity to improve outcomes in osteoarthritis.

Abstract Background Hand osteoarthritis is a common and disabling problem without effective therapies. Accumulating evidence suggests the role of local inflammation in causing pain and structural progression in hand osteoarthritis, and hand osteoarthritis with synovitis is a commonly encountered clinical phenotype. Methotrexate is a well-established, low-cost, and effective treatment for inflammatory arthritis with a well-described safety profile. The aim of this multicentre, randomised, double-blind, placebo-controlled trial is to determine whether methotrexate reduces pain over 6 months in patients with hand osteoarthritis and synovitis. Methods Ninety-six participants with hand osteoarthritis and synovitis will be recruited through the Osteoarthritis Clinical Trial Network (Melbourne, Hobart, Adelaide, and Perth), and randomly allocated in a 1:1 ratio to receive either methotrexate 20 mg or identical placebo once weekly for 6 months. The primary outcome is pain reduction (assessed by 100 mm visual analogue scale) at 6 months. The secondary outcomes include changes in physical function and quality of life assessed using Functional Index for Hand Osteoarthritis, Australian Canadian Osteoarthritis Hand Index, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, Short-Form-36, tender and swollen joint count, and grip strength, and structural progression assessed using progression of synovitis and bone marrow lesions from magnetic resonance imaging and radiographic progression at 6 months. Adverse events will be recorded. The primary analysis will be by intention to treat, including all participants in their randomised groups. Discussion This study will provide high-quality evidence to address whether methotrexate has an effect on reducing pain over 6 months in patients with hand osteoarthritis and synovitis, with major clinical and public health importance. While a positive trial will inform international clinical practice guidelines for the management of hand osteoarthritis, a negative trial would be highly topical and change current trends in clinical practice. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000877381. Registered 15 June 2017, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373124

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

Abstract Background To examine the association between circulating 25(OH)D concentrations and incidence of total hip replacement for osteoarthritis in a prospective cohort study. Methods This study examined a random sample of 2651 participants in the Melbourne Collaborative Cohort Study who had 25(OH)D concentrations measured from dried blood spots collected in 1990-1994. Participants who underwent total hip replacement for osteoarthritis between January 2001 and December 2018 were identified by linking the cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of total hip replacement for osteoarthritis in relation to 25(OH)D concentrations, adjusted for confounders. Results Eighty-six men and eighty-seven women had a total hip replacement for osteoarthritis. Compared with men in the lowest (1st) quartile of 25(OH)D concentration, the HR for total hip replacement was 2.32 (95% CI 1.05, 5.13) for those in the 2nd quartile, 2.77 (95% CI 1.28, 6.00) for those in the 3rd quartile, and 1.73 (95% CI 0.75, 4.02) for those in the highest quartile of 25(OH)D concentrations (p for trend 0.02). There was little evidence of an association in women. Conclusions Higher circulating 25(OH)D concentrations were associated with an increased risk of total hip replacement for osteoarthritis in men but not in women. Although the underlying mechanism warrants further investigation, our findings highlight the need to determine the optimal levels of circulating 25(OH)D to reduce the risk of hip osteoarthritis.

Abstract Background There has been immense interest and debate regarding the effectiveness of antibiotic treatment for chronic low back pain. Two randomised controlled trials have examined the efficacy of antibiotics for chronic low back pain with disc herniation and Modic changes, but have reported conflicting results. The aim of this double-blind, randomised, placebo-controlled trial is to determine the efficacy of antibiotic treatment in a broader patient subgroup of chronic low back pain with disc herniation and investigate whether the presence of Modic changes predicts response to antibiotic therapy. Methods One hundred and seventy individuals with chronic low back pain will be recruited through hospital and private medical and allied health clinics; advertising in national, community and social media; and posting of flyers in community locations. They will be randomly allocated to receive either amoxicillin-clavulanate (500 mg/125 mg) twice per day for 90 days or placebo. The primary outcome measure of pain intensity will be assessed using the Low Back Pain Rating scale and a 100-mm visual analogue scale at 12 months. Secondary measures of self-reported low back disability and work absence and hindrance will also be examined, and an economic analysis will be conducted. Intention-to-treat analyses will be performed. Discussion There is uncertainty about whether antibiotic treatment is effective for chronic low back pain and, if effective, which patient subgroup is most likely to respond. We will conduct a clinical trial to investigate the efficacy of antibiotics compared with placebo in individuals with chronic low back pain and a disc herniation. Our findings will provide high-quality evidence to assist in answering these questions. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12615000958583 . Registered on 11 September 2015

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

ObjectivePopulations with knee osteoarthritis (KOA) are at increased risk of cardiovascular disease, due to higher prevalence of risk factors including dyslipidaemia, where statins are commonly prescribed. However, the effect of statins on muscles and symptoms in this population is unknown. Thus, this study examined the effect of atorvastatin on muscle properties in patients with symptomatic KOA.DesignPost-hoc analysis of a 2-year multicentre randomised, double-blind, placebo-controlled trial.SettingAustralian community.ParticipantsParticipants aged 40–70 years (mean age 55.7 years, 55.6% female) with KOA who met the American College of Rheumatology clinical criteria received atorvastatin 40 mg daily (n = 151) or placebo (n = 153).Main outcome measuresLevels of creatinine kinase (CK), aspartate transaminase (AST), and alanine transaminase (ALT) at 1, 6, 12, and 24 months; muscle strength (by dynamometry) at 12 and 24 months; vastus medialis cross-sectional area (CSA) on magnetic resonance imaging at 24 months; and self-reported myalgia.ResultsThere were no significant between-group differences in CK and AST at all timespoints. The atorvastatin group had higher ALT than placebo group at 1 (median 26 vs. 21, p = 0.004) and 6 (25 vs. 22, p = 0.007) months without significant between-group differences at 12 and 24 months. Muscle strength increased in both groups at 24 months without between-group differences [mean 8.2 (95% CI 3.5, 12.9) vs. 5.9 (1.3, 10.4), p = 0.49]. Change in vastus medialis CSA at 24 months favoured the atorvastatin group [0.11 (−0.10, 0.31) vs. −0.23 (−0.43, −0.03), p = 0.02] but of uncertain clinical significance. There was a trend for more myalgia in the atorvastatin group (8/151 vs. 2/153, p = 0.06) over 2 years, mostly occurring within 6 months (7/151 vs. 1/153, p = 0.04).ConclusionsIn those with symptomatic KOA, despite a trend for more myalgia, there was no clear evidence of an adverse effect of atorvastatin on muscles, including those most relevant to knee joint health.

Abstract Background Arthritis, regardless of cause, has significant physical, social and psychological impacts on patients. We aimed to identify the non-healthcare needs perceived by patients with inflammatory arthritis (IA) and osteoarthritis (OA), and to determine if these differ. Methods We electronically searched MEDLINE, PsycINFO, EMBASE and CINAHL (1990–2020) systematically to identify non-healthcare-related needs of people with IA or OA. All citations were screened and quality appraised by two reviewers. Data was extracted by a single reviewer. Results The search identified 7853 citations, with 31 studies included (12 for OA, 20 for IA). Six areas of need emerged and these were similar in both group These were: 1) Assistance with activities of daily living especially related to a lack of independence; 2) Social connectedness: need for social participation; 3) Financial security: worry about financial security and increased costs of health-seeking behaviours; 4) Occupational needs: desire to continue work for financial and social reasons, facilitated by flexibility of workplace conditions/environment; 5) Exercise and leisure: including limitation due to pain; 6) Transportation: limitations in ability to drive and take public transport due to mobility concerns. Many areas of need were linked; e.g. loss of employment and requiring support from family was associated with a sense of “failure” and loss of identity, as social isolation. Conclusions This review highlights the pervasive impact of arthritis on peoples’ lives, regardless of aetiology, albeit with a limited evidence base. Improved identification and targeting of non-healthcare needs of people with arthritis is likely to improve person-centred care.

Abstract 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 .

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

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

Abstract Background Hallux valgus is a common and disabling condition. This randomised pilot and feasibility trial aims to determine the feasibility of conducting a fully‐powered parallel group randomised trial to evaluate the effectiveness of a multifaceted non‐surgical intervention for reducing pain associated with hallux valgus. Methods Twenty‐eight community‐dwelling women with painful hallux valgus will be randomised to receive either a multifaceted, non‐surgical intervention (footwear, foot orthoses, foot exercises, advice, and self‐management) or advice and self‐management alone. Outcome measures will be obtained at baseline, 4, 8 and 12 weeks. The primary outcome is feasibility, which will be evaluated according to demand, acceptability, adherence, adverse events, and retention rate. Limited efficacy testing will be conducted on secondary outcome measures including foot pain (the Manchester‐Oxford Foot Questionnaire), foot muscle strength (hand‐held dynamometry), general health‐related quality of life (the Short Form‐12), use of cointerventions, and participants' perception of overall treatment effect. Biomechanical testing will be conducted at baseline to evaluate the immediate effects of the footwear/orthotic intervention on pressure beneath the foot and on the medial aspect of the first metatarsophalangeal joint and hallux. Discussion This study will determine the feasibility of conducting a fully‐powered randomised trial of footwear, foot orthoses, foot exercises, advice and self‐management for relieving pain associated with hallux valgus and provide insights into potential mechanisms of effectiveness. Trial registration Australian and New Zealand Clinical Trial Registry (ACTRN12621000645853).

Abstract Objectives Low back pain is the largest contributor to disability worldwide. The role of body composition as a risk factor for back pain remains unclear. Our aim was to examine the relationship between fat mass and fat distribution on back pain intensity and disability using validated tools over 3 years. Methods Participants (aged 25–60 years) were assessed at baseline using dual-energy X-ray absorptiometry (DXA) to measure body composition. All participants completed the Chronic Pain Grade Scale at baseline and 3-year follow-up. Of the 150 participants, 123 (82%) completed the follow-up. Results Higher baseline body mass index (BMI) and fat mass (total, trunk, upper limb, lower limb, android, and gynoid) were all associated with high intensity back pain at either baseline and/or follow-up (total fat mass: multivariable OR 1.05, 95% CI 1.01–1.09, p

Abstract Objective To examine whether metformin use was associated with knee cartilage volume loss over 4 years and risk of total knee replacement over 6 years in obese individuals with knee osteoarthritis. Methods This study analysed the Osteoarthritis Initiative participants with radiographic knee osteoarthritis (Kellgren-Lawrence grade ≥ 2) who were obese (body mass index [BMI] ≥ 30 kg/m2). Participants were classified as metformin users if they self-reported regular metformin use at baseline, 1-year and 2-year follow-up (n = 56). Non-users of metformin were defined as participants who did not report the use of metformin at any visit from baseline to 4-year follow-up (n = 762). Medial and lateral cartilage volume (femoral condyle and tibial plateau) were assessed using magnetic resonance imaging at baseline and 4 years. Total knee replacement over 6 years was assessed. General linear model and binary logistic regression were used for statistical analyses. Results The rate of medial cartilage volume loss was lower in metformin users compared with non-users (0.71% vs. 1.57% per annum), with a difference of − 0.86% per annum (95% CI − 1.58% to − 0.15%, p = 0.02), after adjustment for age, gender, BMI, pain score, Kellgren-Lawrence grade, self-reported diabetes, and weight change over 4 years. Metformin use was associated with a trend towards a significant reduction in risk of total knee replacement over 6 years (odds ratio 0.30, 95% CI 0.07–1.30, p = 0.11), after adjustment for age, gender, BMI, Kellgren-Lawrence grade, pain score, and self-reported diabetes. Conclusions These data suggest that metformin use may have a beneficial effect on long-term knee joint outcomes in those with knee osteoarthritis and obesity. Randomised controlled trials are needed to confirm these findings and determine whether metformin would be a potential disease-modifying drug for knee osteoarthritis with the obese phenotype.

Abstract 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.

Background: Osteoarthritis (OA), the most common joint disease in the elderly, has no cure. Macroelements are vital in human health and their relationships with OA are not clear. Clarifying the relationships between macroelements and OA may assist knee OA management. Methods: This study was a post-hoc analysis using data from a two-year randomized controlled trial among 392 participants with knee OA. Dietary macroelements, including calcium, magnesium, potassium, and phosphorus were computed-based on a semi-quantitative food frequency questionnaire at baseline. Knee joint structures (including cartilage volume, cartilage defect, bone marrow lesions, and effusion-synovitis volume), OA symptoms, quality of life, and OA comorbid conditions (including lower limb muscle strength and depressive symptoms) were assessed at baseline and month 24. Western Ontario and McMaster Universities (WOMAC) Index and depressive symptoms were assessed at baseline and months 3, 6, 12, and 24. Quality of life and lower limb muscle strength were assessed at baseline and months 6, 12, and 24. All analyses were conducted using mixed-effects models. Results: Higher dietary magnesium and potassium were associated with fewer OA symptoms, higher quality of life, greater lower limb muscle strength, and fewer depressive symptoms, but not with knee joint structures. Higher dietary calcium and phosphorus was not associated with any of the OA-related outcomes, except that dietary phosphorus was associated with greater lower limb muscle strength. Conclusions: In the longitudinal analyses, higher dietary magnesium and potassium intake are associated with fewer OA symptoms, higher quality of life, and milder comorbid conditions in patients with knee OA, suggesting dietary magnesium and potassium may have beneficial effects on OA and could be used for knee OA management.

Abstract Background Bisphosphonates are a class of drugs that slow bone loss and are a promising candidate to treat knee osteoarthritis (OA) patients. In a pilot study, we demonstrated that zoledronic acid reduced knee pain and size of subchondral bone marrow lesions (BMLs) over 6 months in knee OA patients with significant knee pain and BMLs. A longer, larger study is required to assess whether decreases in BML size will translate to reductions in cartilage loss over time. We are currently conducting a multicentre, randomised, double-blind, placebo-controlled trial over 24 months that aims to compare the effect of annual infusions of zoledronic acid to placebo on knee structural change (assessed using magnetic resonance imaging (MRI)) and knee pain in knee OA patients. Methods Two hundred sixty-four patients with clinical knee OA, significant knee pain and subchondral BMLs present on MRI will be recruited in Hobart, Melbourne, Sydney and Adelaide. They will be randomly allocated to the two arms of the study, receiving an annual identical intravenous infusion of either 100 mL of fluid containing zoledronic acid (5 mg/100 mL) or placebo (0.9% NaCl 100 mL), at baseline and 1 year later. MRI of the study knee will be performed at screening, month 6 and 24. Knee structure, symptoms and function will be assessed using validated methods. The primary outcome is absolute change in tibiofemoral cartilage volume (mm3) over 24 months. Secondary outcomes include improvement in knee pain over 3, 6, 12, 18, and 24 months and reductions in BML size over 6 and 24 months. The primary analyses will be intention-to-treat analyses of primary and secondary outcomes. Per protocol analyses will be performed as the secondary analyses. Discussion This study will provide high-quality evidence to assess whether zoledronic acid has a novel disease modifying effect in OA by slowing cartilage loss and reducing pain. If zoledronic acid proves effective, it suggests great potential for cost savings through a delay or reduced need for joint replacement surgery, and potential for great improvements in quality of life for OA suffers. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN12613000039785, registered on 14 January 2013.

Abstract Background In higher income countries, work-related squatting and heavy lifting have been associated with increased arthritis risk. Here, we address the paucity of data regarding associations between arthritis and work-related physical stressors in lower- and middle-income countries. Methods Data were extracted from the Study on global AGEing and adult health (SAGE) Wave 1 (2007–10) for adults (aged ≥50 years) from Ghana, India, Russia and South Africa for whom detailed occupation data was available (n = 21,389; 49.2% women). Arthritis cases were identified using a symptom-defined algorithm (current) and self-reported doctor-diagnosis (lifetime). A sex-specific Job Exposure Matrix was used to classify work-related stressors: heavy physical work, kneeling/squatting, heavy lifting, arm elevation and awkward trunk posture. Using the International Standard Classification of Occupations, we linked SAGE and the Job Exposure Matrix. Logistic regression was used to investigate associations between arthritis and work-related stressors, adjusting for age (10 year age groupings), potential socioeconomic-related confounders, and body mass index. Excess exposure risk due to two-way interactions with other risk factors were explored. Results Doctor-diagnosed arthritis was associated with heavy physical work (adjusted odds ratios [OR] 1.12, 95%CI 1.01–1.23), awkward trunk posture (adjusted OR 1.23, 95%CI 1.12–1.36), kneeling or squatting (adjusted OR 1.25, 95%CI 1.12–1.38), and arm elevation (adjusted OR 1.66, 95%CI 1.37–2.00). Symptom-based arthritis was associated with kneeling or squatting (adjusted OR 1.27, 95%CI 1.08–1.50), heavy lifting (adjusted OR 1.33, 95%CI 1.11–1.58), and arm elevation (adjusted OR 2.16, 95%CI 1.63–2.86). Two-way interactions suggested excess arthritis risk existed for higher body mass index, and higher income or education. Conclusions Minimization of occupational health risk factors is common practice in higher income countries: attention should now be directed toward reducing work-related arthritis burden in lower- and middle-income countries.

Abstract Background There is a well-recognised relationship between body weight, plantar pressures and foot pain, but the temporal association between these factors is unknown. The aim of this study was to investigate the relationships between increasing weight, plantar pressures and foot pain over a two-year period. Methods Fifty-one participants (33 women and 18 men) completed the two-year longitudinal cohort study. The sample had a mean (standard deviation (SD)) age of 52.6 (8.5) years. At baseline and follow-up, participants completed the Manchester Foot Pain and Disability Index questionnaire, and underwent anthropometric measures, including body weight, body mass index, and dynamic plantar pressures. Within-group analyses examined differences in body weight, foot pain and plantar pressures between baseline and follow up, and multivariate regression analysis examined associations between change in body weight, foot pain and plantar pressure. Path analysis assessed the total impact of both the direct and indirect effects of change in body weight on plantar pressure and pain variables. Results Mean (SD) body weight increased from 80.3 (19.3), to 82.3 (20.6) kg, p = 0.016 from baseline to follow up. The change in body weight ranged from −16.1 to 12.7 kg. The heel was the only site to exhibit increased peak plantar pressures between baseline and follow up. After adjustment for age, gender and change in contact time (where appropriate), there were significant associations between: (i) change in body weight and changes in midfoot plantar pressure (B = 4.648, p = 0.038) and functional limitation (B = 0.409, p = 0.010), (ii) plantar pressure change in the heel and both functional limitation (B = 4.054, p = 0.013) and pain intensity (B = 1.831, p = 0.006), (iii) plantar pressure change in the midfoot and both functional limitation (B = 4.505, p = 0.018) and pain intensity (B = 1.913, p = 0.015). Path analysis indicated that the effect of increasing body weight on foot-related functional limitation and foot pain intensity may be mediated by increased plantar pressure in the midfoot. Conclusions These findings suggest that as body weight and plantar pressure increase, foot pain increases, and that the midfoot may be the most vulnerable site for pressure-related pain.

Abstract Background Osteoarthritis has a high prevalence in people with high bone mineral density (BMD). Nevertheless, whether high systemic BMD predates early structural features of knee osteoarthritis is unclear. This study examined the association between systemic BMD and knee cartilage defect progression and cartilage volume loss in middle-aged people without clinical knee disease. Methods Adults (n = 153) aged 25–60 years had total body, lumbar spine, and total hip BMD assessed by dual-energy X-ray absorptiometry at baseline (2005–2008), and tibial cartilage volume and tibiofemoral cartilage defects assessed by magnetic resonance imaging at baseline and follow up (2008–2010). Results Higher spine BMD was associated with increased risk for progression of medial (OR = 1.45, 95% CI 1.10, 1.91) and lateral (OR = 1.30, 95% CI 1.00, 1.67) tibiofemoral cartilage defects. Total hip BMD was also positively associated with the progression of medial (OR = 1.63, 95% CI 1.10, 2.41) and lateral (OR = 1.53, 95% CI 1.08, 2.18) tibiofemoral cartilage defects. Greater total body, spine, and total hip BMD were associated with increased rate of lateral tibial cartilage volume loss (for every 1 g/10 cm2 increase in total body BMD: B = 0.44%, 95% CI 0.17%, 0.71%; spine BMD: 0.17%, 95% CI 0.04%, 0.30%; total hip BMD: 0.29%, 95% CI 0.13%, 0.45%), with no significant associations for medial tibial cartilage volume loss. Conclusion In middle-aged people without clinical knee disease, higher systemic BMD was associated with increased early knee cartilage damage. Further work is needed to clarify the effect of systemic BMD at different stages of the pathway from health through to disease in knee osteoarthritis, as new therapies targeting bone are developed for the management of knee osteoarthritis.

Abstract Objective: To examine 25(OH)D testing patterns and frequency among general practitioners in a major community health service. Method: A clinical audit of patient records at a community health centre in Melbourne was undertaken. Patients aged 18 years and above were included. Univariate and multivariate logistic regression was used to examine the association between vitamin D testing and socio‐demographic characteristics while Poisson regression was used for the frequency of testing. Results: There were 1,217 patients tested for serum 25(OH)D. The community health centre was served by 12 general practitioners and an infectious disease specialist. The odds of vitamin D testing showed a positive, albeit weak, association with age (OR 1.01, 95%CI 1.00–1.02, p