Publications by authors named "Anita E Wluka"

178 Publications

Associations between diet quality and knee joint structures, symptoms and systemic abnormalities in people with symptomatic knee osteoarthritis.

Clin Nutr 2021 Mar 17;40(5):2483-2490. Epub 2021 Mar 17.

Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, China; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia; Department of Rheumatology and Immunology, Arthritis Research Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, China; School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. Electronic address:

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 < 0.001), and quality of life (β = -0.14, P < 0.001).

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.
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http://dx.doi.org/10.1016/j.clnu.2021.03.011DOI Listing
March 2021

Effect of atorvastatin on knee cartilage volume in patients with symptomatic knee osteoarthritis: results from a randomised placebo-controlled trial.

Arthritis Rheumatol 2021 Apr 12. Epub 2021 Apr 12.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, 3004, Australia.

Objective: To determine whether atorvastatin compared to placebo slows tibial cartilage volume loss in patients with symptomatic knee osteoarthritis in a multicentre, randomised, double-blind, placebo-controlled trial.

Methods: Participants aged 40-70 years were randomised to oral atorvastatin 40 mg (n=151) or matching placebo (n=153) once daily. Primary endpoint: annual percentage change in tibial cartilage volume assessed using magnetic resonance imaging (MRI) over two years. Pre-specified secondary endpoints: progression of cartilage defects and bone marrow lesions assessed using MRI, and change in Western Ontario and McMaster Universities Osteoarthritis Index pain, stiffness and function over two years.

Results: Of 304 participants (mean age 55.7 years, 55.6% female), 248 (81.6%) completed the trial. Annual change in tibial cartilage volume differed minimally between the atorvastatin and placebo groups (-1.66% vs. -2.17%, difference 0.50%, 95%CI -0.17% to 1.17%). There were no significant differences in progression of cartilage defects (odds ratio 0.86, 95%CI 0.52-1.41) or bone marrow lesions (odds ratio 1.00, 95%CI 0.62-1.63), change in pain [-36.0 vs. -29.5, adjusted difference -2.7, 95%CI -27.1 to 21.7), stiffness (-14.2 vs. -11.8, adjusted difference -0.2, 95%CI -12.2 to 11.8), or function [-89.4 vs. -87.5, adjusted difference 0.3, 95%CI -83.1 to 83.6). Incidence of adverse events was similar in atorvastatin (n=57, 37.7%) and placebo (n=52, 34.0%) groups.

Conclusion: Oral atorvastatin 40 mg once daily, compared with placebo, did not significantly reduce cartilage volume loss over two years in patients with symptomatic knee osteoarthritis. These findings do not support use of atorvastatin in the treatment of knee osteoarthritis.
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http://dx.doi.org/10.1002/art.41760DOI Listing
April 2021

Person-centred care in osteoarthritis and inflammatory arthritis: a scoping review of people's needs outside of healthcare.

BMC Musculoskelet Disord 2021 Apr 9;22(1):341. Epub 2021 Apr 9.

Department of Epidemiology and Preventative Medicine, School of Public Health and Preventative Medicine, Monash University, Melbourne, Victoria, Australia.

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.
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http://dx.doi.org/10.1186/s12891-021-04190-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035722PMC
April 2021

Endorsement of the domains of knee and hip osteoarthritis (OA) flare: A report from the OMERACT 2020 inaugural virtual consensus vote from the flares in OA working group.

Semin Arthritis Rheum 2021 Mar 20. Epub 2021 Mar 20.

Department of Physical Therapy, The University of British Columbia, Arthritis Research Canada, Canada.

Objective: Towards developing an instrument to measure knee and hip osteoarthritis (KHOA) flare, the Outcome Measures in Rheumatology (OMERACT) Flares in OA Working Group first sought to identify and define relevant domains of flare in KHOA.

Methods: Guided by OMERACT Filter 2.1, candidate domains were identified from data generated in interviews, in English or French, with persons with KHOA and health professionals (HPs) who treat OA. The first and second rounds of an online Delphi process with patients and HPs, including researchers, selected relevant domains. The third round provided agreement on the selected domains and their definitions. At the virtual OMERACT 2020 workshop, the proposed domains and their definitions were discussed in facilitated breakout groups with patients and HPs. Participants then voted, with consensus set at ≥70%.

Results: Qualitative interviews characterizing OA flare were completed with 29 persons with KHOA and 16 HPs. Content was analyzed and grouped into nine clusters. These candidate domains were included in two Delphi rounds, completed by 91 patients and 165 HPs then 50 patients and 116 HPs, per round, respectively. This resulted in selecting five relevant domains. A final Delphi round, completed by 38 patients and 89 HPs, provided agreement on these domains and their definitions. The OMERACT virtual vote included 27 patients and 106 HPs. The domains and their definitions were endorsed with ≥98% agreement. Domains include: Pain, Swelling, Stiffness, Psychological aspects, and Impact of symptoms, all defined "during flare".

Conclusion: Using OMERACT methodology, we have developed five domains of KHOA flare that were highly endorsed by patients and HPs.
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http://dx.doi.org/10.1016/j.semarthrit.2021.03.010DOI Listing
March 2021

Associations of blood pressure and arterial stiffness with knee cartilage volume in patients with knee osteoarthritis.

Rheumatology (Oxford) 2021 Feb 12. Epub 2021 Feb 12.

Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.

Objective: To describe the associations of blood pressure and arterial stiffness with knee cartilage volume in patients with knee osteoarthritis (OA).

Method: A secondary analysis was performed on the data from participants of a randomized controlled trial, which 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 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/percent. Femoral: Lateral β -23.70, medial β -26.42, total β -50.12 mm3/percent).

Conclusions: Blood pressure and arterial stiffness are associated with knee cartilage volume at several sites among knee OA patients. This supports that blood pressure and arterial stiffness may involve in the progression of knee OA.
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http://dx.doi.org/10.1093/rheumatology/keab092DOI Listing
February 2021

Effect of low-dose amitriptyline on low back pain with a neuropathic component: a post hoc analysis.

Spine J 2021 Jan 16. Epub 2021 Jan 16.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne 3004, Australia.

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http://dx.doi.org/10.1016/j.spinee.2021.01.012DOI Listing
January 2021

Depression in patients with knee osteoarthritis: risk factors and associations with joint symptoms.

BMC Musculoskelet Disord 2021 Jan 7;22(1):40. Epub 2021 Jan 7.

Department of Rheumatology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

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 .
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http://dx.doi.org/10.1186/s12891-020-03875-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791830PMC
January 2021

Obesity defined by body mass index and waist circumference and risk of total knee arthroplasty for osteoarthritis: A prospective cohort study.

PLoS One 2021 7;16(1):e0245002. Epub 2021 Jan 7.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

Objective: To examine the risk of total knee arthroplasty (TKA) due to osteoarthritis associated with obesity defined by body mass index (BMI) or waist circumference (WC) and whether there is discordance between these measures in assessing this risk.

Methods: 36,784 participants from the Melbourne Collaborative Cohort Study with BMI and WC measured at 1990-1994 were included. Obesity was defined by BMI (≥30 kg/m2) or WC (men ≥102cm, women ≥88cm). The incidence of TKA between January 2001 and December 2018 was determined by linking participant records to the National Joint Replacement Registry.

Results: Over 15.4±4.8 years, 2,683 participants underwent TKA. There were 20.4% participants with BMI-defined obesity, 20.8% with WC-defined obesity, and 73.6% without obesity defined by either BMI or WC. Obesity was classified as non-obese (misclassified obesity) in 11.7% of participants if BMI or WC alone was used to define obesity. BMI-defined obesity (HR 2.69, 95%CI 2.48-2.92), WC-defined obesity (HR 2.28, 95%CI 2.10-2.48), and obesity defined by either BMI or WC (HR 2.53, 95%CI 2.33-2.74) were associated with an increased risk of TKA. Compared with those without obesity, participants with misclassified obesity had an increased risk of TKA (HR 2.06, 95%CI 1.85-2.30). 22.7% of TKA in the community can be attributable to BMI-defined obesity, and a further 3.3% of TKA can be identified if WC was also used to define obesity.

Conclusions: Both BMI and WC should be used to identify obese individuals who are at risk of TKA for osteoarthritis and should be targeted for prevention and treatment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245002PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790262PMC
January 2021

Rates, costs and determinants of lumbar spine imaging in population-based women born in 1973-1978: Data from the Australian Longitudinal Study on Women's Health.

PLoS One 2020 3;15(12):e0243282. Epub 2020 Dec 3.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

Objective: There are concerns that lumbar spine imaging represents low value care. Our aim was to examine the use of lumbar spine imaging [radiography, computed tomography (CT), magnetic resonance imaging (MRI)] over 20 years, and costs and person-level characteristics of imaging in a large cohort of Australian women.

Methods: The Australian Longitudinal Study on Women's Health (ALSWH) is a longitudinal population-based survey of women randomly selected from national health insurance scheme (Medicare) database. This study examined 13458 women born in 1973-1978 who consented to link their ALSWH and Medical Benefits Scheme records. Self-reported data on demographics, body mass index, depression, physical and mental health, and back pain were collected in each survey performed in 1996, 2000, 2003, 2006, 2009, 2012, and 2015. Data on lumbar spine imaging from 1996 to 2015 were obtained from the Medical Benefits Scheme database.

Results: 38.9% of women underwent some form of lumbar spine imaging over 20 years. While radiography increased from 1996 to 2011 and decreased thereafter, CT and MRI continued to increase from 1996 to 2015. In women with self-reported back pain, depression and poorer physical health were associated with imaging, with no significant differences in types of imaging. Based on imaging rates in ALSWH, the estimated costs for Australian women aged 30-39 years were AU$51,735,649 over 2011-2015.

Conclusions: Lumbar spine imaging was common in population-based Australian women, with rates increasing over 20 years. Depression and poor physical health were associated with lumbar spine imaging. Raising awareness of this in clinicians is likely to result in significant cost savings if clinical guidelines are followed, with the potential of freeing resources for high value care and health outcomes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243282PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714143PMC
January 2021

The association between change in bone marrow lesion size and change in tibiofemoral cartilage volume and knee symptoms.

Rheumatology (Oxford) 2020 Nov 30. Epub 2020 Nov 30.

Menzies Institute for Medical Research, University of Tasmania, TAS, Hobart.

Objective: To describe the association between change in subchondral bone marrow lesions (BMLs) and change in tibiofemoral cartilage volume and knee symptoms in patients with symptomatic knee OA.

Methods: In total, 251 participants (mean 61.7 years, 51% female) were included. Tibiofemoral cartilage volume was measured at baseline and 24 months, and BML size at baseline, 6 and 24 months. Knee pain and function scores were evaluated at baseline, 6 and 24 months. Change in total and compartment-specific BML size was categorized according to the Least Significance Criterion. Linear mixed-effects models were used to evaluate the associations of change in BMLs over 6 and 24 months with change in cartilage volume over 24 months and knee symptoms over 6 and 24 months.

Results: Total BML size enlarged in 26% of participants, regressed in 31% and remained stable in 43% over 24 months. Compared with stable BMLs in the same compartment, enlarging BMLs over 24 months were associated with greater cartilage loss (difference: -53.0mm3, 95% CI: -100.0, -6.0), and regressing BMLs were not significantly associated with reduced cartilage loss (difference: 32.4mm3, 95% CI: -8.6, 73.3) over 24 months. Neither enlargement nor regression of total BML size over 6 and 24 months was associated with change in knee pain and function over the same time intervals.

Conclusions: In subjects with symptomatic knee osteoarthritis and BMLs, enlarging BMLs may lead to greater cartilage loss but regressing lesions are not associated with reduced cartilage loss while neither is associated with change in knee symptoms.
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http://dx.doi.org/10.1093/rheumatology/keaa716DOI Listing
November 2020

Effect of Stem Cell Injections on Osteoarthritis-related Structural Outcomes: A Systematic Review.

J Rheumatol 2020 Oct 1. Epub 2020 Oct 1.

SMH is the recipient of National Health and Medical Research Council (NHMRC) Early Career Fellowship (APP1142198). LC is the recipient of an Australian Postgraduate Award and Arthritis Foundation Scholarship. AEW and YW are the recipients of NHMRC Translating Research into Practice Fellowship (APP1150102 and APP1168185, respectively). J. Gong, BBiomedSc (Hons), J. Fairley, MBBS, F.M. Cicuttini, MBBS, FRACP, PhD, S.M. Hussain, MBBS, MPH, PhD, L. Chou, MBBS, FRACP, A.E. Wluka, MBBS, FRACP, PhD, Y. Wang, MBBS, MMed, PhD, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University; R. Vashishtha, BDS, MPH, Center for Alcohol Policy Research, School of Psychology and Public Health, La Trobe University, Melbourne, Australia. The authors have no conflicts of interest. Address correspondence to Dr. Y. Wang, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC 3004, Australia. Email: Accepted for publication September 24, 2020.

Objective: To systematically review the evidence for the efficacy of mesenchymal stem cell (MSC) injections in improving osteoarthritis (OA)-related structural outcomes.

Methods: Ovid Medline and EMBASE were searched from their inceptions to April 2020 using MeSH terms and key words. Independent reviewers extracted data and assessed methodological quality. Qualitative evidence synthesis was performed due to the heterogeneity of interventions and outcome measures.

Results: Thirteen randomized controlled trials (phase I or II) were identified: 10 in OA populations and 3 in populations at risk of OA, with low (n = 9), moderate (n = 3), or high (n = 1) risk of bias. Seven studies used allogeneic MSCs (4 bone marrow, 1 umbilical cord, 1 placenta, 1 adipose tissue), 6 studies used autologous MSCs (3 adipose tissue, 2 bone marrow, 1 peripheral blood). Among the 11 studies examining cartilage outcomes, 10 found a benefit of MSCs on cartilage volume, morphology, quality, regeneration, and repair, assessed by magnetic resonance imaging, arthroscopy, or histology. The evidence for subchondral bone was consistent in all 3 studies in populations at risk of OA, showing beneficial effects. Sixteen unpublished, eligible trials were identified by searching trial registries, including 8 with actual or estimated completion dates before 2016.

Conclusion: Our systematic review of early-phase clinical trials demonstrated consistent evidence of a beneficial effect of intraarticular MSC injections on articular cartilage and subchondral bone. Due to the heterogeneity of MSCs, modest sample sizes, methodological limitations, and potential for publication bias, further work is needed before this therapy is recommended in the management of OA.
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http://dx.doi.org/10.3899/jrheum.200021DOI Listing
October 2020

Association between increased signal intensity at the proximal patellar tendon and patellofemoral geometry in community-based asymptomatic middle-aged adults: a cross-sectional study.

BMC Musculoskelet Disord 2020 Aug 22;21(1):571. Epub 2020 Aug 22.

School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC, 3004, Australia.

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.
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http://dx.doi.org/10.1186/s12891-020-03589-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443287PMC
August 2020

Effects of vitamin D supplementation on disabling foot pain in patients with symptomatic knee osteoarthritis.

Arthritis Care Res (Hoboken) 2020 Jul 5. Epub 2020 Jul 5.

Department of Rheumatology, the third Affiliated Hospital of SUN YAT-SEN University, Guangzhou, China.

Objectives: This study aims to determine whether vitamin D supplementation or maintaining sufficient vitamin D level reduces foot pain over two years in patients with symptomatic knee 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 nmol/L to 60 nmol/L 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 one of the 10 functional limitation items (items 1-9,11) being documented as on 'most/every day(s)' in the last month. A repeated-measure mixed effect 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% participants having disabling foot pain at baseline. There were significant differences in MFPDI scores change between groups over 2 years, with more improvements in vitamin D group than in placebo group (-0.03 vs. 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 vs. 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.
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http://dx.doi.org/10.1002/acr.24371DOI Listing
July 2020

Association between hip muscle cross-sectional area and hip pain and function in individuals with mild-to-moderate hip osteoarthritis: a cross-sectional study.

BMC Musculoskelet Disord 2020 May 21;21(1):316. Epub 2020 May 21.

School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Rd, Melbourne, VIC, 3004, Australia.

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.
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http://dx.doi.org/10.1186/s12891-020-03348-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240926PMC
May 2020

Effect of Intravenous Zoledronic Acid on Tibiofemoral Cartilage Volume Among Patients With Knee Osteoarthritis With Bone Marrow Lesions: A Randomized Clinical Trial.

JAMA 2020 04;323(15):1456-1466

Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.

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 mm3 vs -919 mm3; between-group difference, 41 mm3 [95% CI, -79 to 161 mm3]; 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 mm2 vs -6 mm2; between-group difference, -27 mm2 [95% CI, -127 to 73 mm2]; 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.
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http://dx.doi.org/10.1001/jama.2020.2938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175085PMC
April 2020

Correspondence: Reply to Hopayian.

J Physiother 2020 01 16;66(1):65. Epub 2019 Dec 16.

Department of Epidemiology and Preventative Medicine, School of Public Health and Preventative Medicine, Monash University, Melbourne.

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http://dx.doi.org/10.1016/j.jphys.2019.11.015DOI Listing
January 2020

The bulge sign - a simple physical examination for identifying progressive knee osteoarthritis: data from the Osteoarthritis Initiative.

Rheumatology (Oxford) 2020 06;59(6):1288-1295

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

Objective: To examine whether the presence of bulge sign or patellar tap was associated with frequent knee pain, progression of radiographic OA (ROA) and total knee replacement (TKR).

Methods: This study included 4344 Osteoarthritis Initiative participants examined at baseline for bulge sign and/or patellar tap. The clinical signs were categorized as no (none at baseline and 2 years), resolved (present at baseline only), developed (present at 2 years only) and persistent (present at both time points). Frequent knee pain and progression of ROA over 4 years and TKR over 6 years were assessed. Binary logistic regression was used to examine the associations.

Results: A total of 12.7% of participants had bulge sign only, 2.0% had patellar tap only and 3.3% had both. A positive baseline bulge sign was associated with an increased risk of frequent knee pain [OR 1.31 (95% CI 1.04, 1.64), P = 0.02] and TKR [OR 1.47 (95% CI 1.06, 2.05), P = 0.02]. Developed bulge sign was associated with an increased risk of frequent knee pain [OR 1.75 (95% CI 1.34, 2.29), P < 0.001] and progressive ROA [OR 1.67 (95% CI 1.11, 2.51), P = 0.01]. Persistent bulge sign was associated with an increased risk of frequent knee pain [OR 1.60 (95% CI 1.09, 2.35), P = 0.02], progressive ROA [OR 1.84 (95% CI 1.01, 3.33), P = 0.045] and TKR [OR 2.13 (95% CI 1.23, 3.68), P = 0.007]. Patellar tap was not examined for its association with joint outcomes due to its low prevalence.

Conclusion: The presence of bulge sign identifies individuals at increased risk of frequent knee pain, progression of ROA and TKR. This provides clinicians with a quick, simple, inexpensive method for identifying those at higher risk of progressive knee OA who should be targeted for therapy.
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http://dx.doi.org/10.1093/rheumatology/kez443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244780PMC
June 2020

Higher Serum Levels of Resistin Are Associated With Knee Synovitis and Structural Abnormalities in Patients With Symptomatic Knee Osteoarthritis.

J Am Med Dir Assoc 2019 10 20;20(10):1242-1246. Epub 2019 Aug 20.

Clinical Research Centre, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China; Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. Electronic address:

Objective: Resistin acts as an endogenous ligand of Toll-like receptor (TLR)-4 that triggers major inflammatory pathways and mediates inflammatory processes. The role of resistin in osteoarthritis (OA) pathogenesis is unclear. The aim of this study is to describe the longitudinal associations of serum levels of resistin with knee synovitis measures and structural abnormalities in patients with knee OA.

Design: A prospective cohort study.

Setting And Participants: Patients (n = 200) with symptomatic knee OA (mean age 63.1 years, range 49-79; female 46.5%) participated.

Measures: All measures were performed at baseline and 2 years later. Serum resistin was measured using enzyme-linked immunosorbent assay. Infrapatellar fat pad (IPFP) high signal intensity alteration and effusion synovitis were measured from magnetic resonance imaging (MRI). Knee structures including cartilage volume, cartilage defects, and bone marrow lesions (BMLs) were also assessed by MRI semiquantitatively or quantitatively. Linear or logistic mixed effects regression analyses were used in longitudinal analyses.

Results: Serum resistin was positively associated with high signal intensity alteration measures of IPFP as well as the presence [relative risk = 1.06, 95% confidence interval (CI) 1.02, 1.10] and volume (β = 0.77, 95% CI 0.01, 1.53) of effusion synovitis in multivariable analyses. Serum levels of resistin were also positively associated with higher tibiofemoral cartilage defect (β = 1.98, 95% CI 0.34, 3.57) and BML scores (β = 3.18, 95% CI 0.99, 5.37) after adjustment for covariates.

Conclusion And Implications: Higher serum levels of resistin are associated with knee synovitis surrogate measures and structural abnormalities, suggesting that obesity may promote OA not only by increasing weight loading on joints but also by triggering 1 or more inflammatory pathways.
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http://dx.doi.org/10.1016/j.jamda.2019.07.001DOI Listing
October 2019

High baseline fat mass, but not lean tissue mass, is associated with high intensity low back pain and disability in community-based adults.

Arthritis Res Ther 2019 07 5;21(1):165. Epub 2019 Jul 5.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Rd, Melbourne, Victoria, 3004, Australia.

Objectives: Low back pain is the largest contributor to disability worldwide. The role of body composition as a risk factor for back pain remains unclear. Our aim was to examine the relationship between fat mass and fat distribution on back pain intensity and disability using validated tools over 3 years.

Methods: Participants (aged 25-60 years) were assessed at baseline using dual-energy X-ray absorptiometry (DXA) to measure body composition. All participants completed the Chronic Pain Grade Scale at baseline and 3-year follow-up. Of the 150 participants, 123 (82%) completed the follow-up.

Results: Higher baseline body mass index (BMI) and fat mass (total, trunk, upper limb, lower limb, android, and gynoid) were all associated with high intensity back pain at either baseline and/or follow-up (total fat mass: multivariable OR 1.05, 95% CI 1.01-1.09, p < 0.001). There were similar findings for all fat mass measures and high levels of back disability. A higher android to gynoid ratio was associated with high intensity back pain (multivariable OR 1.04, 95% CI 1.01-1.08, p = 0.009). There were no associations between lean mass and back pain.

Conclusions: This cohort study provides evidence for the important role of fat mass, specifically android fat relative to gynoid fat, on back pain and disability.
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http://dx.doi.org/10.1186/s13075-019-1953-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612201PMC
July 2019

People with low back pain want clear, consistent and personalised information on prognosis, treatment options and self-management strategies: a systematic review.

J Physiother 2019 07 18;65(3):124-135. Epub 2019 Jun 18.

Department of Epidemiology and Preventative Medicine, School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia. Electronic address:

Question: What health information needs are perceived by people with low back pain?

Design: Systematic review of publications examining perceived health information needs related to low back pain identified through Medline, EMBASE, CINAHL and PsycINFO (1990 to 2018).

Participants: Adults with low back pain of any duration.

Data Extraction And Analysis: Two reviewers independently extracted descriptive data regarding study design and methodology, and assessed risk of bias. Aggregated findings of the perceived needs of people with low back pain regarding health information were meta-synthesised.

Results: Forty-one studies (34 qualitative, four quantitative and three mixed-methods) were identified. Two major areas of perceived health information needs for low back pain emerged. The first major area was needs related to information content: general information related to low back pain, its cause and underlying pathology; strong desire for diagnosis and imaging; prognosis, future disability and effect on work capacity; precipitants and management of flares; general management approaches; self-management strategies; prevention; and support services. The second major area of needs related to how the information was delivered. People with low back pain wanted clear, consistent information delivered in suitable tone and understandable language.

Conclusion: Available data suggest that the information needs of people with low back pain are centred around their desire for a diagnosis, potentially contributing to expectations for and overuse of imaging. People with low back pain expressed a strong desire for clear, consistent and personalised information on prognosis, treatment options and self-management strategies, related to healthcare and occupational issues. To correct unhelpful beliefs and optimise delivery of evidence-based therapy, patient and healthcare professional education (potentially by an integrated public health approach) may be warranted.
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http://dx.doi.org/10.1016/j.jphys.2019.05.010DOI Listing
July 2019

Vascular Pathology and Osteoarthritis: A Systematic Review.

J Rheumatol 2020 05 1;47(5):748-760. Epub 2019 Jun 1.

From the School of Public Health and Preventive Medicine, Monash University, Alfred Hospital, Melbourne; Australian National University (ANU) College of Health and Medicine, Canberra; The Alfred Hospital, Melbourne, Australia.

Objective: Vascular pathology (changes in blood vessels) and osteoarthritis (OA) are both common chronic conditions associated with aging and obesity, but whether vascular pathology is a risk factor for OA is unclear. The aim of this study was to systematically review the evidence for an association between vascular pathology and risk of joint-specific OA.

Methods: Scopus, Ovid Medline, and EMBASE were searched from inception to February 2019. MeSH terms and keywords were used to identify studies examining the association between vascular pathology and OA. Two reviewers independently extracted the data and assessed the methodological quality. Qualitative evidence synthesis was performed.

Results: Fifteen studies with high (n = 3), fair (n = 3), or low (n = 9) quality were included. Features of vascular pathology included atherosclerosis, vascular stiffness, and endothelial dysfunction in different vascular beds. There was evidence for an association between vascular pathology and risk of hand OA in women but not men, and between vascular pathology and risk of knee OA in both men and women. Only 2 studies examined hip OA showing no association between vascular pathology and risk of hip OA.

Conclusion: There is evidence suggesting an association between vascular pathology and risk of hand and knee OA, with a potential causal relationship for knee OA. Based on the limited evidence, it is hard to conclude an association for hip OA. Further stronger evidence is needed to determine whether there is a causal relationship.
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http://dx.doi.org/10.3899/jrheum.181236DOI Listing
May 2020

Association between metformin use and disease progression in obese people with knee osteoarthritis: data from the Osteoarthritis Initiative-a prospective cohort study.

Arthritis Res Ther 2019 05 24;21(1):127. Epub 2019 May 24.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, Victoria, 3004, Australia.

Objective: To examine whether metformin use was associated with knee cartilage volume loss over 4 years and risk of total knee replacement over 6 years in obese individuals with knee osteoarthritis.

Methods: This study analysed the Osteoarthritis Initiative participants with radiographic knee osteoarthritis (Kellgren-Lawrence grade ≥ 2) who were obese (body mass index [BMI] ≥ 30 kg/m). 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.
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http://dx.doi.org/10.1186/s13075-019-1915-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534888PMC
May 2019

Associations of Joint Line Tenderness and Patellofemoral Grind With Long-Term Knee Joint Outcomes: Data From the Osteoarthritis Initiative.

Arthritis Care Res (Hoboken) 2020 06 15;72(6):778-786. Epub 2020 May 15.

School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

Objective: To examine whether joint line tenderness and patellofemoral grind from physical examination were associated with cartilage volume loss, worsening of radiographic osteoarthritis, and the risk of total knee replacement.

Methods: This study examined 4,353 Osteoarthritis Initiative participants. For each measurement of joint line tenderness and patellofemoral grind, the patterns were defined as no (none at baseline and at 1 year), fluctuating (present at either time point), and persistent (present at both time points). Cartilage volume loss and worsening of radiographic osteoarthritis over 4 years were assessed using magnetic resonance imaging and radiographs, and total knee replacement over 6 years was assessed.

Results: A total of 35.0% of participants had joint line tenderness, and 15.8% had patellofemoral grind. Baseline patellofemoral grind, but not joint line tenderness, was associated with increased cartilage volume loss (1.08% per year versus 0.96% per year; P = 0.02) and an increased risk of total knee replacement (odds ratio [OR] 1.55 [95% confidence interval (95% CI) 1.11-2.17]; P = 0.01). While the patterns of joint line tenderness were not significantly associated with joint outcomes, participants with persistent patellofemoral grind had an increased rate of cartilage volume loss (1.30% per year versus 0.90% per year; P < 0.001) and an increased risk of total knee replacement (OR 2.10 [95% CI 1.30-3.38]; P = 0.002) compared with those participants without patellofemoral grind.

Conclusion: Patellofemoral grind, but not joint line tenderness, may represent a clinical marker associated with accelerated cartilage volume loss over 4 years and an increased risk of total knee replacement over 6 years. This simple clinical examination may provide clinicians with an inexpensive way to identify those at higher risk of disease progression who should be targeted for surveillance and management.
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http://dx.doi.org/10.1002/acr.23906DOI Listing
June 2020

Vitamin D supplements for trunk muscle morphology in older adults: secondary analysis of a randomized controlled trial.

J Cachexia Sarcopenia Muscle 2019 02 22;10(1):177-187. Epub 2018 Nov 22.

Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.

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.
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http://dx.doi.org/10.1002/jcsm.12364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438333PMC
February 2019

Patients' perceived needs for medical services for non-specific low back pain: A systematic scoping review.

PLoS One 2018 8;13(11):e0204885. Epub 2018 Nov 8.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

Background: An improved understanding of patients' perceived needs for medical services for low back pain (LBP) will enable healthcare providers to better align service provision with patient expectations, thus improving patient and health care system outcomes. Thus, we aimed to identify the existing literature regarding patients' perceived needs for medical services for LBP.

Methods: A systematic scoping review was performed of publications identified from MEDLINE, EMBASE, CINAHL and PsycINFO (1990-2016). Descriptive data regarding each study, its design and methodology were extracted and risk of bias assessed. Aggregates of patients' perceived needs for medical services for LBP were categorised.

Results: 50 studies (35 qualitative, 14 quantitative and 1 mixed-methods study) from 1829 were relevant. Four areas of perceived need emerged: (1) Patients with LBP sought healthcare from medical practitioners to obtain a diagnosis, receive management options, sickness certification and legitimation for their LBP. However, there was dissatisfaction with the cursory and superficial approach of care. (2) Patients had concerns about pharmacotherapy, with few studies reporting on patients' preferences for medications. (3) Of the few studies which examined the patients' perceived need of invasive therapies, these found that patients avoided injections and surgeries (4) Patients desired spinal imaging for diagnostic purposes and legitimation of symptoms.

Conclusions: Across many different patient populations with data obtained from a variety of study designs, common themes emerged which highlighted areas of patient dissatisfaction with the medical management of LBP, in particular, the superficial approach to care perceived by patients and concerns regarding pharmacotherapy. Patients perceive unmet needs from medical services, including the need to obtain a diagnosis, the desire for pain control and the preference for spinal imaging. These issues need to be considered in developing approaches for the management of LBP in order to improve patient outcomes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204885PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6224057PMC
April 2019

Efficacy of Low-Dose Amitriptyline for Chronic Low Back Pain: A Randomized Clinical Trial.

JAMA Intern Med 2018 11;178(11):1474-1481

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Alfred Hospital, Melbourne, Australia.

Importance: Antidepressants at low dose are commonly prescribed for the management of chronic low back pain and their use is recommended in international clinical guidelines. However, there is no evidence for their efficacy.

Objective: To examine the efficacy of a low-dose antidepressant compared with an active comparator in reducing pain, disability, and work absence and hindrance in individuals with chronic low back pain.

Design, Setting, And Participants: A double-blind, randomized clinical trial with a 6-month follow-up of adults with chronic, nonspecific, low back pain who were recruited through hospital/medical clinics and advertising was carried out.

Intervention: Low-dose amitriptyline (25 mg/d) or an active comparator (benztropine mesylate, 1 mg/d) for 6 months.

Main Outcomes And Measures: The primary outcome was pain intensity measured at 3 and 6 months using the visual analog scale and Descriptor Differential Scale. Secondary outcomes included disability assessed using the Roland Morris Disability Questionnaire and work absence and hindrance assessed using the Short Form Health and Labour Questionnaire.

Results: Of the 146 randomized participants (90 [61.6%] male; mean [SD] age, 54.8 [13.7] years), 118 (81%) completed 6-month follow-up. Treatment with low-dose amitriptyline did not result in greater pain reduction than the comparator at 6 (adjusted difference, -7.81; 95% CI, -15.7 to 0.10) or 3 months (adjusted difference, -1.05; 95% CI, -7.87 to 5.78), independent of baseline pain. There was no statistically significant difference in disability between the groups at 6 months (adjusted difference, -0.98; 95% CI, -2.42 to 0.46); however, there was a statistically significant improvement in disability for the low-dose amitriptyline group at 3 months (adjusted difference, -1.62; 95% CI, -2.88 to -0.36). There were no differences between the groups in work outcomes at 6 months (adjusted difference, absence: 1.51; 95% CI, 0.43-5.38; hindrance: 0.53; 95% CI, 0.19-1.51), or 3 months (adjusted difference, absence: 0.86; 95% CI, 0.32-2.31; hindrance: 0.78; 95% CI, 0.29-2.08), or in the number of participants who withdrew owing to adverse events (9 [12%] in each group; χ2 = 0.004; P = .95).

Conclusions And Relevance: This trial suggests that amitriptyline may be an effective treatment for chronic low back pain. There were no significant improvements in outcomes at 6 months, but there was a reduction in disability at 3 months, an improvement in pain intensity that was nonsignificant at 6 months, and minimal adverse events reported with a low-dose, modest sample size and active comparator. Although large-scale clinical trials that include dose escalation are needed, it may be worth considering low-dose amitriptyline if the only alternative is an opioid.

Trial Registration: anzctr.org.au Identifier: ACTRN12612000131853.
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http://dx.doi.org/10.1001/jamainternmed.2018.4222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248203PMC
November 2018

Knee effusion volume assessed by magnetic resonance imaging and progression of knee osteoarthritis: data from the Osteoarthritis Initiative.

Rheumatology (Oxford) 2019 02;58(2):246-253

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

Objective: To examine whether baseline knee joint effusion volume and the change in effusion volume over 1 year are associated with cartilage volume loss, progression of radiographic OA (ROA) over 4 years and risk of total knee replacement over 6 years.

Methods: This study included 4115 Osteoarthritis Initiative participants with knee joint effusion volume quantified by MRI at baseline. The change in effusion volume over 1 year was assessed. Cartilage volume loss and progression of ROA over 4 years were assessed using MRI and X-ray and total knee replacement over 6 years was assessed. Multiple linear regression and binary logistic regression were used for data analyses.

Results: Baseline knee effusion volume (per 5 ml) was positively associated with a loss of medial and lateral cartilage volume [regression coefficient 0.13%/year (95% CI 0.10, 0.17) and 0.13%/year (95% CI 0.10, 0.16), respectively, both P < 0.001], progression of ROA [odds ratio (OR) 1.28 (95% CI 1.20, 1.37), P < 0.001], and risk of knee replacement [OR 1.12 (95% CI 1.05, 1.20), P = 0.001]. A 5 ml increase in knee effusion volume over 1 year was positively associated with medial cartilage volume loss [regression coefficient 0.09%/year (95% CI 0.04, 0.15), P = 0.001], progression of ROA [OR 1.21 (95% CI 1.11, 1.33), P < 0.001] and risk of knee replacement [OR 1.24 (95% CI 1.12, 1.37), P < 0.001].

Conclusions: Knee joint effusion volume assessed from MRI provides a continuous and sensitive measure that was associated with cartilage volume loss, progression of ROA and risk of total knee replacement. It may provide a method to identify individuals with an inflammatory OA phenotype who are at higher risk of disease progression.
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http://dx.doi.org/10.1093/rheumatology/key274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343462PMC
February 2019

Patients' perceived health information needs in inflammatory arthritis: A systematic review.

Semin Arthritis Rheum 2019 04 18;48(5):900-910. Epub 2018 Aug 18.

Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Australia. Electronic address:

Objectives: To identify the breadth of the literature regarding patients' perceived health information needs related to inflammatory arthritis care.

Methods: A systematic scoping review of MEDLINE, EMBASE, CINAHL and PsycINFO was performed to identify relevant articles (1990 -2016) examining patients' perceived needs relating to health information in inflammatory arthritis. Data and themes were identified and categorised and risk of bias assessed.

Results: Twenty nine studies (11 quantitative, 14 qualitative and 4 mixed methods) from 4121 identified articles were relevant for inclusion. Most focussed on rheumatoid arthritis. Key findings included: (1) Reasons for seeking health information often focussed on gaining ownership over their condition and facilitating self-management. (2) Demographic differences in information needs were inconsistent, but women and younger patients generally reported more needs. (3) Desired information content was broad, and included targeted and practical information covering disease treatment and psychosocial wellbeing. (4) Preferred information delivery method was consultation with a Rheumatologist; however group sessions had advantages for psychosocial issues while written information provided useful supplementation. (5) Barriers to meeting health information needs were around timely access.

Conclusions: Patients with inflammatory arthritis have high information needs, desiring practical and individualised information. When developing strategies to meet patients' information needs, aligning patient expectations with delivery methods that are accessible, cost-effective and flexible may help to optimize patient outcomes.
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http://dx.doi.org/10.1016/j.semarthrit.2018.07.014DOI Listing
April 2019

Association Between Quantitatively Measured Infrapatellar Fat Pad High Signal-Intensity Alteration and Magnetic Resonance Imaging-Assessed Progression of Knee Osteoarthritis.

Arthritis Care Res (Hoboken) 2019 05;71(5):638-646

University of Tasmania, Hobart, Tasmania, and Monash University, Melbourne, Victoria, Australia, and Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Objective: To describe the cross-sectional and longitudinal associations between quantitative measures of infrapatellar fat pad (IPFP) signal-intensity alteration and knee structural abnormalities in patients with symptomatic knee osteoarthritis (OA).

Methods: A total of 261 patients (mean ± SD age 63.0 ± 7.2 years) with symptomatic knee OA were selected from a randomized controlled trial with a follow-up of 2 years. IPFP signal-intensity alterations at baseline were quantitatively measured on T2-weighted fat-saturated magnetic resonance imaging using MATLAB. These quantitative measures included the SD of whole IPFP signal intensity measurement, the upper quartile value of high signal intensity (UQ ), the ratio of volume of high signal-intensity alteration to volume of whole IPFP (percentage ), and the clustering effect of high signal intensity (clustering-factor ). Cartilage volume and defects and bone marrow lesions (BMLs) were assessed using validated measures.

Results: Higher baseline SD of the IPFP, UQ , and clustering-factor were associated with greater loss of tibial cartilage volume and larger increases in tibiofemoral cartilage defects over 2 years. Patients with high and medium tertiles of clustering-factor had greater loss of cartilage volume per annum compared with those with a low tertile (for high 4.9%, for medium 4.6%, and for low 3.3% annually). Baseline percentage and clustering-factor were positively and significantly associated with increases in tibiofemoral BMLs over 2 years. Cross-sectional associations between IPFP measures and knee structures were similar but more consistent.

Conclusion: Quantitative measures of increased signal intensity in the IPFP were associated with knee structural abnormalities in the tibiofemoral compartment, suggesting that these measurements could be used as an additional entry criterion to enrich studies for faster progressors of knee OA.
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May 2019

A protocol for a multicentre, randomised, double-blind, placebo-controlled trial to compare the effect of annual infusions of zoledronic acid to placebo on knee structural change and knee pain over 24 months in knee osteoarthritis patients - ZAP2.

BMC Musculoskelet Disord 2018 Jul 18;19(1):217. Epub 2018 Jul 18.

Menzies Institute for Medical Research, University of Tasmania, Private Bag 23, Hobart, TAS, 7000, Australia.

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 (mm) 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.
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http://dx.doi.org/10.1186/s12891-018-2143-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052532PMC
July 2018