The association of comorbidities with sleep quality among Australians with multiple sclerosis: Insights from the Australian Multiple Sclerosis Longitudinal Study.

BACKGROUND: Comorbidities and poor sleep quality are prevalent among individuals with multiple sclerosis (MS). Our understanding of the effects of comorbidities on sleep quality in MS remains limited. OBJECTIVES: The objectives were to investigate whether the number and presence of specific comorbidities have associations with sleep quality and to assess the relative contribution of comorbidity groups to sleep quality. METHODS: We collected data on sleep quality (using Pittsburgh Sleep Quality Index (PSQI)) and presence of comorbidities in people with MS (n = 1597). Associations between comorbidities and sleep quality were examined using linear regression and dominance analysis. RESULTS: Having more comorbidities was associated with poorer sleep quality (p for trend < 0.001). All 13 groups of comorbidities explained 12.9% of the variance in PSQI from which half of the variance was contributed by mental health disorders. In total, 16 of the 28 comorbidities were associated with significantly worse sleep quality, with the strongest associations seen for 'other autoimmune diseases' (ß = 1.98), depression (ß = 1.76), anxiety (ß = 1.72) and rheumatoid arthritis (ß = 1.62). CONCLUSIONS: Many individual comorbidities are associated with poorer sleep quality, with mental health disorders making the largest relative contribution. Optimal management of comorbidities that make the greatest contributions could have the largest benefit for improving sleep in MS.

Krill Oil for Knee Osteoarthritis: A Randomized Clinical Trial.

Importance: Knee osteoarthritis is disabling, with few effective treatments. Preliminary evidence suggested that krill oil supplementation improved knee pain, but effects on knee osteoarthritis remain unclear. Objective: To evaluate efficacy of krill oil supplementation, compared with placebo, on knee pain in people with knee osteoarthritis who have significant knee pain and effusion-synovitis. Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled clinical trial in 5 Australian cities. Participants with clinical knee osteoarthritis, significant knee pain, and effusion-synovitis on magnetic resonance imaging were enrolled from December 2016 to June 2019; final follow-up occurred on February 7, 2020. Interventions: Participants were randomized to 2 g/d of krill oil (n = 130) or matching placebo (n = 132) for 24 weeks. Main Outcomes and Measures: The primary outcome was change in knee pain as assessed by visual analog scale (range, 0-100; 0 indicating least pain; minimum clinically important improvement = 15) over 24 weeks. Results: Of 262 participants randomized (mean age, 61.6 [SD, 9.6] years; 53% women), 222 (85%) completed the trial. Krill oil did not improve knee pain compared with placebo (mean change in VAS score, -19.9 [krill oil] vs -20.2 [placebo]; between-group mean difference, -0.3; 95% CI, -6.9 to 6.4) over 24 weeks. One or more adverse events was reported by 51% in the krill oil group (67/130) and by 54% in the placebo group (71/132). The most common adverse events were musculoskeletal and connective tissue disorders, which occurred 32 times in the krill oil group and 42 times in the placebo group, including knee pain (n = 10 with krill oil; n = 9 with placebo), lower extremity pain (n = 1 with krill oil; n = 5 with placebo), and hip pain (n = 3 with krill oil; n = 2 with placebo). Conclusions and Relevance: Among people with knee osteoarthritis who have significant knee pain and effusion-synovitis on magnetic resonance imaging, 2 g/d of daily krill oil supplementation did not improve knee pain over 24 weeks compared with placebo. These findings do not support krill oil for treating knee pain in this population. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12616000726459; Universal Trial Number: U1111-1181-7087.

Using qualitative free-text data to investigate the lived experience of the COVID-19 pandemic for a large cohort of Australians with different multiple sclerosis related disability levels.

BACKGROUND: No large-scale qualitative studies have investigated the lived experience of people living with multiple sclerosis (PwMS) during the pandemic according to their disability level. We used qualitative research methods to investigate the lived experience of a large cohort of Australians living with differing multiple sclerosis (MS)-related disability levels during the COVID-19 pandemic. We also provided useful contextualisation to existing quantitative work. METHODS: This was a retrospective survey-based mixed-methods cohort study. A quality-of-life study was conducted within the Australian MS Longitudinal Study during the pandemic. Disability severity was calculated using the Patient Determined Disease Steps. Qualitative free-text data regarding COVID-19 impacts was collected/analysed for word frequency and also thematically (inductively/deductively using sophisticated grounded theory) using NVivo software. We also triangulated word frequency with emerging themes. RESULTS: N=509 PwMS participated providing n=22 530 words of COVID-19-specific data. Disability severity could be calculated for n=501 PwMS. The word 'working' was important for PwMS with no disability, and 'support' and 'isolation' for higher disability levels. For PwMS with milder disability, thematic analysis established that multitasking increased stress levels, particularly if working from home (WFH) and home-schooling children. If not multitasking, WFH was beneficial for managing fatigue. PwMS with severe disability raised increased social isolation as a concern including prepandemic isolation. CONCLUSIONS: We found negative impacts of multitasking and social isolation for PwMS during the pandemic. WFH was identified as beneficial for some. We recommend targeted resourcing decisions for PwMS in future pandemics including child-care relief and interventions to reduce social isolation and suggest that these could be incorporated into some form of advanced care planning. As the nature of work changes postpandemic, we also recommend a detailed investigation of WFH for PwMS including providing tailored employment assistance.

Validation of the EQ-5D-5L and psychosocial bolt-ons in a large cohort of people living with multiple sclerosis in Australia.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory, neurodegenerative disease of the central nervous system which results in disability over time and reduced quality of life. To increase the sensitivity of the EQ-5D-5L for psychosocial health, four bolt-on items from the AQoL-8D were used to create the nine-item EQ-5D-5L-Psychosocial. We aimed to externally validate the EQ-5D-5L-Psychosocial in a large cohort of people with MS (pwMS) and explore the discriminatory power of the new instrument with EQ-5D-5L/AQoL-8D. METHODS: A large representative sample from the Australian MS Longitudinal Study completed the AQoL-8D and EQ-5D-5L (including EQ VAS) and both instruments health state utilities (HSUs) were scored using Australian tariffs. Sociodemographic/clinical data were also collected. External validity of EQ-5D-5L-Psychosocial scoring algorithm was assessed with mean absolute errors (MAE) and Spearman's correlation coefficient. Discriminatory sensitivity was assessed with an examination of ceiling/floor effects, and disability severity classifications. RESULTS: Among 1683 participants (mean age: 58.6 years; 80% female), over half (55%) had moderate or severe disability. MAE (0.063) and the distribution of the prediction error were similar to the original development study. Mean (± standard deviation) HSUs were EQ-5D-5L: 0.58 ± 0.32, EQ-5D-5L-Psychosocial 0.62 ± 0.29, and AQoL-8D: 0.63 ± 0.20. N = 157 (10%) scored perfect health (i.e. HSU = 1.0) on the EQ-5D-5L, but reported a mean HSU of 0.90 on the alternative instruments. The Sleep bolt-on dimension was particularly important for pwMS. CONCLUSIONS: The EQ-5D-5L-Psychosocial is more sensitive than the EQ-5D-5L in pwMS whose HSUs approach those reflecting full health. When respondent burden is taken into account, the EQ-5D-5L-Psychosocial is preferential to the AQoL-8D. We suggest a larger confirmatory study comparing all prevalent multi-attribute utility instruments for pwMS.

Intravenous bisphosphonates do not improve knee pain or bone marrow lesions in people with knee osteoarthritis: a meta-analysis.

OBJECTIVE: To summarize effects of intravenous bisphosphonates (IVBP) in patients with symptomatic knee OA and bone marrow lesions (BMLs), using a meta-analysis of randomized controlled trials (RCTs). METHODS: Literature databases were searched for placebo-controlled RCTs of IVBPs for knee OA from inception, and included validated pain and function scales, BML size and incidence of adverse events. Efficacy was compared using standardized mean differences (SMD) and risk ratios (RR) with fixed-effect or random-effects models. Methodological quality was assessed using the Cochrane risk of bias tool, heterogeneity was assessed by I2 statistics. RESULTS: We included 428 patients in four RCTs of 2-24 months duration; most patients (84%) received zoledronic acid (ZA). Risk of bias was low-moderate. IVBP had large effect sizes on pain within 3 months [SMD = -2.33 (95% CI: -3.02, -1.65)] mainly driven by neridronate (resulting in substantial heterogeneity, I2 = 92%) with no effect for ZA alone. Differences in knee function were statistically significant at 3 months [SMD = -0.22 (-0.43, -0.01), I2 = 0.2%]. Effect sizes for pain did not reach statistical significance at any other time point. IVBPs improved a semi-quantitative measure of BML size within 6 months [SMD = -0.52 (-0.89, -0.14), I2 = 0%] but not at 12 months or two years. Adverse events [RR = 1.19 (1.00, 1.41) I2 = 52%], occurred more frequently with IVBP. CONCLUSION: ZA has no effect on knee pain, possibly a short-term effect on BML size and higher rates of adverse events. Neridronate may improve pain in the short term, but this is based on a single trial.

Poor sleep and multiple sclerosis: associations with symptoms of multiple sclerosis and quality of life.

BACKGROUND: Sleep difficulties are common in people with multiple sclerosis (MS), but whether associations between poor sleep quality and quality of life are independent of MS symptoms, obesity and other MS-related factors remains unclear. METHODS: Cross-sectional analyses of data from the Australian MS Longitudinal Study (n=1717). Sleep was assessed using the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and International Restless Legs Syndrome Study Group Rating Scale; health-related quality of life using the Assessment of Quality-of-Life 8-D. RESULTS: Poor sleep quality was common (67%), and more common than in community samples. Sleep measures clustered independently within MS symptoms. The clusters 'fatigue and cognitive', 'feelings of anxiety and depression', 'pain and sensory', were independently associated with poor sleep quality. Quality-of-Life utility scores were a clinically meaningful 0.19 units lower in those with poor sleep. Sleep quality, daytime sleepiness and restless leg syndrome were associated with reduced quality of life, independent of MS-related symptoms and body mass index. CONCLUSION: Poor sleep quality is common in MS and was strongly associated with worse health-related quality of life, independent of other MS symptoms and did not cluster with other common MS symptoms. Improving sleep quality may substantially improve quality of life in people with MS.

Association between diet quality in adolescence and adulthood and knee symptoms in adulthood: a 25-year cohort study.

We aimed to describe associations between diet quality in adolescence and adulthood and knee symptoms in adulthood. Two hundred seventy-five participants had adolescent diet measurements, 399 had adult diet measurements and 240 had diet measurements in both time points. Diet quality was assessed by Dietary Guidelines Index (DGI), reflecting adherence to Australian Dietary Guidelines. Knee symptoms were collected using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Data were analysed using zero-inflated negative binomial regressions. The overall adolescent DGI was not associated with adult knee symptoms, although lower intake of discretionary foods (e.g. cream, alcohol, bacon and cake) in adolescence was associated with lower pain (mean ratio (MR) 0·96) and dysfunction (MR 0·94). The overall adult DGI was not associated with knee symptoms; however, limiting saturated fat was associated with lower WOMAC (Pain: MR 0·93; stiffness: MR 0·93; dysfunction: MR 0·91), drinking water was associated with lower stiffness (MR 0·90) and fruit intake was associated with lower dysfunction (MR 0·90). Higher DGI for dairy products in adulthood was associated with higher WOMAC (Pain: MR 1·07; stiffness: MR 1·13; dysfunction: MR 1·11). Additionally, the score increases from adolescence to adulthood were not associated with adult knee symptoms, except for associations between score increase in limiting saturated fat and lower stiffness (MR 0·89) and between score increase in fruit intake and lower dysfunction (MR 0·92). In conclusion, the overall diet quality in adolescence and adulthood was not associated with knee symptoms in adulthood. However, some diet components may affect later knee symptoms.

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

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.

Efficacy and Safety of Turmeric Extracts for the Treatment of Knee Osteoarthritis: a Systematic Review and Meta-analysis of Randomised Controlled Trials.

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

Bone Microarchitecture, Volumetric or Areal Bone Mineral Density for Discrimination of Vertebral Deformity in Adults: A Cross-sectional Study.

INTRODUCTION/BACKGROUND: Both areal bone mineral density (aBMD) and bone microarchitecture have been associated with vertebral deformity (VD), but there are limited data on the utility of bone microarchitecture measures in combination with aBMD in discriminating VD. This study aimed to describe whether radial bone microarchitecture measures alone or in combinations with radial volumetric bone mineral density (vBMD) or spine aBMD can improve discrimination of VD in adults. METHODS: Data on 196 subjects (mean age (standard deviation, SD) = 72 (7) years, female 46%) were utilized. VD of T4-L4 and spine aBMD were measured using dual-energy X-ray absorptiometry. VD was defined if anterior to posterior height ratio was more than 3-SD, 4-SD below, or >25% decrease compared with the sex-matched normal means. Bone microarchitecture parameters at distal radius were collected using high-resolution peripheral quantitative computed tomography and analyzed using StrAx. RESULTS: The strongest associations were seen for the cortical thickness (odds ratios (ORs): 2.63/SD decrease for 25% and 2.38/SD decrease for 3-SD criterion) and compact cortical area (OR: 3.33/SD decrease for 4-SD criterion). The area under the receiver operating characteristic curve (AUC) for spine aBMD for VD was 0.594, 0.597, and 0.634 for 25%, 3-SD and 4-SD criteria, respectively (all p < 0.05). Compact cortical area, cortical thickness and compact cortical thickness alone had the largest AUCs for VD (0.680-0.685 for 25% criterion, 0.659-0.674 for 3-SD criterion, and 0.699-0.707 for 4-SD criterion). Adding spine aBMD or radial vBMD to each cortical measure did not improve VD discrimination (∆ AUC 0.8%-2.1%). CONCLUSIONS: Cortical measures had the best utility for discriminating VD when used alone. Adding either spine aBMD or radial vBMD did not improve the utility of cortical measures.

Effectiveness of Curcuma longa Extract for the Treatment of Symptoms and Effusion-Synovitis of Knee Osteoarthritis : A Randomized Trial.

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

Association of body composition, physical activity and physical performance with knee cartilage thickness and bone area in young adults.

OBJECTIVE: To describe associations of body composition, physical activity and physical performance with knee cartilage thickness and subchondral bone area in young adults. METHODS: Body composition, physical activity and physical performance were measured 4-5 years prior to knee MRI. Cartilage thickness and bone area were measured quantitatively from MRI. Associations were assessed using linear regression analysis, with mediators being identified using mediation analysis. RESULTS: Participants (n = 186) were 31-41 years of age when the MRI was acquired and 48% were female. Greater lean mass was positively associated with cartilage thickness [ß = 6.52 µm/kg (95% CI 0.86, 12.18)] and bone area [ß = 13.37 mm2/kg (95% CI 5.43, 21.31)]. Physical performance measures were positively associated with cartilage thickness [long jump: ß = 2.44 µm/cm (95% CI 0.70, 4.18); hand grip strength: 7.74 µm/kg (95% CI 1.50, 13.98); physical work capacity: 1.07 µm/W (95% CI 0.29, 1.85)] and bone area [long jump: ß = 3.99 mm2/cm (95% CI 0.64, 7.34); hand grip strength: 19.06 mm2/kg (95% CI 7.21, 30.92); leg strength: 3.18 mm2/kg (95% CI 1.09, 5.28); physical work capacity: 3.15 mm2/W (95% CI 1.70, 4.60)]. Mediation analysis suggested these associations were mediated by lean mass (effect mediated: 27-95%). CONCLUSION: Greater lean mass and better physical performance measured 4-5 years prior were associated with greater knee cartilage thickness and subchondral bone area in young adults, and the associations of physical performance were largely mediated by lean mass. These findings suggest lean mass may play an important role in maintaining knee joint health in young adults.

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

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.

Association of adiposity measures in childhood and adulthood with knee cartilage thickness, volume and bone area in young adults.

OBJECTIVE: To describe the associations of childhood and adulthood adiposity measures with knee cartilage thickness, volume and bone area in young adults. METHODS: Childhood and adulthood adiposity measures (weight, height, waist circumference and hip circumference) of 186 participants were collected in 1985 (aged 7-15 years) and during 2004-2006 (aged 26-36 years). Knee magnetic resonance imaging was conducted during 2008-2010 (aged 31-41 years) and cartilage thickness, volume and bone area were measured using a quantitative approach (Chondrometrics, Germany). Linear regressions were used to examine the above associations. RESULTS: The prevalence of overweight was 7.6% in childhood and 42.1% in adulthood. Childhood weight (ß = - 5.57 mm2/kg) and body mass index (BMI) (ß = - 11.55 mm2/kg/m2) were negatively associated with adult patellar bone area, whereas adult weight was positively associated with bone area in medial femorotibial compartment (MFTC) (ß = 3.37 mm2/kg) and lateral femorotibial compartment (LFTC) (ß = 2.08 mm2/kg). Adult waist-hip ratio (WHR) was negatively associated with cartilage thickness (MFTC: ß = - 0.011; LFTC: ß = - 0.012 mm/0.01 unit), volume (Patella: ß = - 20.97; LFTC: ß = - 21.71 mm3/0.01 unit) and bone area (Patella: ß = - 4.39 mm2/0.01 unit). The change in WHR z-scores from childhood to adulthood was negatively associated with cartilage thickness (MFTC: ß = - 0.056 mm), volume (patella: - 89.95; LFTC: - 93.98 mm3), and bone area (patella: - 20.74 mm2). All p-values < 0.05. CONCLUSIONS: Childhood weight and BMI were negatively but adult weight was positively associated with adult bone area. Adult WHR and the change in WHR from childhood to adulthood were negatively associated with cartilage thickness, volume, and bone area. These suggest early-life adiposity measures may affect knee structures in young adults.

How Do MRI-Detected Subchondral Bone Marrow Lesions (BMLs) on Two Different MRI Sequences Correlate with Clinically Important Outcomes?

The aim of this study is to describe the association of bone marrow lesions (BMLs) present on two different MRI sequences with clinical outcomes, cartilage defect progression, cartilage volume loss over 2.7 years, and total knee replacement (TKR) over 13.3 years. 394 participants (50-80 years) were assessed at baseline and 2.7 years. BML presence at baseline was scored on T1-weighted fat-suppressed 3D gradient-recalled acquisition (T1) and T2-weighted fat-suppressed 2D fast spin-echo (T2) sequences. Knee pain, function, and stiffness were assessed using WOMAC. Cartilage volume and defects were assessed using validated methods. Incident TKR was determined by data linkage. BMLs were mostly present on both MRI sequences (86%). BMLs present on T2, T1, and both sequences were associated with greater knee pain and functional limitation (odds ratio = 1.49 to 1.70; all p < 0.05). Longitudinally, BMLs present on T2, T1, and both sequences were associated with worsening knee pain (ß = 1.12 to 1.37, respectively; p < 0.05) and worsening stiffness (ß = 0.45 to 0.52, respectively; all p < 0.05) but not worsening functional limitation or total WOMAC. BMLs present on T2, T1, and both sequences predicted site-specific cartilage defect progression (relative risk = 1.22 to 4.63; all p < 0.05) except at the medial tibial and inferior patellar sites. Lateral tibial and superior patellar BMLs present on T2, T1, and both sequences predicted site-specific cartilage volume loss (ß = - 174.77 to - 140.67; p < 0.05). BMLs present on T2, T1, and both sequences were strongly associated with incident TKR. BMLs can be assessed on either T2- or T1-weighted sequences with no clinical predictive advantage of either sequence.

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.

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.

Associations of dietary patterns with bone mass, muscle strength and balance in a cohort of Australian middle-aged women.

Influences of dietary patterns on musculoskeletal health are poorly understood in middle-aged women. This cross-sectional analysis from a cohort of 347 women (aged 36-57 years) aimed to examine associations between dietary patterns and musculoskeletal health outcomes in middle-aged women. Diet was measured by the Cancer Council of Victoria FFQ. Total body bone mineral content (TB BMC), femoral neck and lumbar spine bone density (dual-energy X-ray absorptiometry), lower limbs muscle strength (LMS) and balance tests (timed up and go test, step test, functional reach test (FRT) and lateral reach test) were also measured. Exploratory factor analysis was used to identify dietary patterns and scores for each pattern generated using factor loadings with absolute values ≥0·20. Associations between food pattern scores and musculoskeletal outcomes were assessed using multivariable linear regression. Three dietary patterns were identified: 'Healthy' (high consumption of a plant-based diet - vegetables, legumes, fruit, tomatoes, nuts, snacks, garlic, whole grains and low intake of high-fat dairy products), 'high protein, high fat' (red meats, poultry, processed meats, potatoes, cruciferous and dark-yellow vegetables, fish, chips, spirits and high-fat dairy products) and 'Processed foods' (high intakes of meat pies, hamburgers, beer, sweets, fruit juice, processed meats, snacks, spirits, pizza and low intake of cruciferous vegetables). After adjustment for confounders, Healthy pattern was positively associated with LMS, whereas Processed foods pattern was inversely associated with TB BMC and FRT. The associations were not significant after accounting for multiple comparisons. There were no associations with any other outcomes. These results suggest that maintaining a healthy diet could contribute to bone acquisition, muscle strength and balance in adult life. However, while they provide some support for further investigating dietary strategies for prevention of age-related loss of muscle and deterioration in balance, the exploratory nature of the analyses means that confirmation in longitudinal studies and/or trials with pre-specified hypotheses is needed.

Associations of Sarcopenic Obesity and Dynapenic Obesity with Bone Mineral Density and Incident Fractures Over 5-10 Years in Community-Dwelling Older Adults.

The purpose of this study is to determine whether low muscle mass (sarcopenia) or strength (dynapenia), in the presence of obesity, are associated with increased risk for osteoporosis and non-vertebral fracture over 5-10 years in community-dwelling older adults. N = 1089 volunteers (mean ± SD age 62 ± 7 years; 51 % female) participated at baseline and 761 attended follow-up clinics (mean 5.1 ± 0.5 years later). Total body, total hip and spine BMD, and appendicular lean and total fat mass were assessed by DXA. Sarcopenic obesity and dynapenic obesity were defined as the lowest sex-specific tertiles for appendicular lean mass or lower-limb strength, respectively, and the highest sex-specific tertile for total fat mass. Fractures were self-reported on three occasions over 10.7 ± 0.7 years in 563 participants. Obese alone participants had significantly higher BMD at all sites compared with non-sarcopenic non-obese. Sarcopenic obese and dynapenic obese men had lower spine and total body BMD, respectively, and sarcopenic obese women had lower total hip BMD, compared with obese alone (all P < 0.05). Sarcopenic obese men had higher non-vertebral fracture rates compared to non-sarcopenic non-obese (incidence rate ratio: 3.0; 95 % CI 1.7-5.5), and obese alone (3.6; 1.7-7.4). Sarcopenic obese women had higher fracture rates compared with obese alone (2.8; 1.4-5.6), but this was non-significant after adjustment for total hip BMD. Sarcopenic and dynapenic obese older adults may have increased risk of osteoporosis and non-vertebral fracture relative to obese alone counterparts. Sarcopenic and dynapenic obese individuals potentially represent a subset of the obese older adult population who require closer monitoring of bone health during ageing.

Change in knee structure and change in tibiofemoral joint space width: a five year longitudinal population-based study.

BACKGROUND: Change in knee cartilage volume is frequently used as a proxy for change in knee joint space width over time, but longitudinal data on these associations is limited. We aimed to determine whether change in knee cartilage volume, new or worsening meniscal extrusion (ME), meniscal tears and cartilage defects over 2.4 years correlated with change in joint space width (JSW) over 5 years in older community dwelling adults. METHODS: Participants (n = 153) had their right knee imaged using MR imaging and x-ray at baseline, and after 2.4 years (MRI) and 5 years (x-ray). Cartilage volume, cartilage defects, meniscal extrusions and meniscal tears were assessed on sagittal T1-weighted fat-suppressed MRI. JSW was assessed using standard fixed semi-flexed view radiographs, and scored on those with adequate alignment. RESULTS: Participants were 51-79 (mean 62) years old; 48% were female. Cartilage volume reduced over time (medial -134 ± 202 µL/year, lateral -106 ± 165 µL/year, p < 0.001), as did JSW (medial -0.05 ± 0.16 mm/year, lateral -0.12 ± 0.24 mm/year, p < 0.001). In multivariable analysis, the only consistent predictor of change in JSW was new or worsening ME (medial tibia R(2) 3.1%, p = 0.031; medial femur R(2) 3.2%, p = 0.024); change in cartilage volume correlated with change in JSW laterally (R(2) 4.8%, p = 0.007) and was borderline medially (R(2) 2.2%, p = 0.064); there was no association for meniscal tears or cartilage defects. The magnitude of these associations were similar albeit somewhat greater for ME in participants with radiographic OA (R(2) 6.2%, p = 0.017). CONCLUSION: Change in ME and cartilage volume weakly predict change in JSW, but the vast majority of the variation remains unexplained. Since MRI examines cartilage directly while radiographs examine it indirectly, these results cast doubt on the validity of using JSW as a proxy measure of cartilage loss.

Effect of bisphosphonate use in patients with symptomatic and radiographic knee osteoarthritis: data from the Osteoarthritis Initiative.

OBJECTIVES: Bisphosphonates have some reported beneficial effects in treating osteoarthritis (OA). This study examined the effects of bisphosphonate use on symptoms and structural progression of knee OA in participants from the NIH Osteoarthritis Initiative cohort. METHODS: People with typical OA trial entry criteria (KL2/3, minimum joint space width 2.5-5.0 mm and pain ≥4 on a numeric rating scale) were classified as bisphosphonate users (≥3 of the 5 years; n=55) or non-users (no use in the preceding 5 years or during follow-up; n=268). Annual data over 4 years were analysed using linear mixed modelling and generalised estimating equations. RESULTS: Bisphosphonate compliance was 85% at year 1, reducing to 76% by year 4. Numeric rating scale pain scores were significantly reduced among bisphosphonate users at years 2 and 3 (year 3, -0.9 vs -2.2, p=0.004), though not year 4, after adjustment for baseline pain and analgesic use. Differences in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and disability scores did not reach statistical significance at any time point. There was a trend to less joint space narrowing in bisphosphonate users over time (year 4, 0.51 vs 0.29 mm; p=0.06). CONCLUSIONS: Significant reduction in numeric rating scale pain was observed in the first 3 years with bisphosphonate use; diminution of effects by year 4 may reflect reduced compliance. Differences in results obtained using numeric rating scale and WOMAC may reflect different constructs measured by these tools. The beneficial trend on structural progression should be considered in terms of the sample size.