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.

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.

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.

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.

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.

Moderate vitamin D deficiency is associated with changes in knee and hip pain in older adults: a 5-year longitudinal study.

BACKGROUND: Vitamin D is important for bone, cartilage and muscle function but there are few studies on its association with joint pain. OBJECTIVE: To investigate whether serum vitamin D predicts change in knee and hip pain in older adults. METHODS: Longitudinal population-based cohort study of randomly selected older adults (n=769) aged 50-80 years (mean 62 years); 50% were male. Serum 25-hydroxyvitamin D (25-OHD) was assessed at baseline by radioimmunoassay, and pain at baseline, 2.6 and/or 5 years using the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) questionnaire. We used linear regression with adjustment for age, sex, body mass index and season, then further adjusted for potential structural mechanisms (radiographic osteoarthritis, bone marrow lesions, chondral defects and muscle strength). RESULTS: Mean total knee WOMAC score was 3.2 (range 0-39). 4.2% of participants had moderate vitamin D deficiency at baseline (25-OHD 12.5-25 nmol/l). 25-OHD <25 nmol/l predicted change in knee pain (using total WOMAC score) over 5 years (ß=2.41, p=0.002) with a similar effect size for hip pain over 2.4 years (ß=2.20, p=0.083). Results were consistent within pain subscales, and the association was independent of demographic, anthropometric and structural covariates. No association was present when 25-OHD was analysed as a continuous measure. CONCLUSIONS: Moderate vitamin D deficiency independently predicts incident, or worsening of, knee pain over 5 years and, possibly, hip pain over 2.4 years. Therefore correcting moderate vitamin deficiency may attenuate worsening of knee or hip pain in elderly people but giving supplements to those with a higher 25-OHD level is unlikely to be effective.

The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study.

OBJECTIVE: To estimate the global burden of hip and knee osteoarthritis (OA) as part of the Global Burden of Disease 2010 study and to explore how the burden of hip and knee OA compares with other conditions. METHODS: Systematic reviews were conducted to source age-specific and sex-specific epidemiological data for hip and knee OA prevalence, incidence and mortality risk. The prevalence and incidence of symptomatic, radiographic and self-reported hip or knee OA were included. Three levels of severity were defined to derive disability weights (DWs) and severity distribution (proportion with mild, moderate and severe OA). The prevalence by country and region was multiplied by the severity distribution and the appropriate disability weight to calculate years of life lived with disability (YLDs). As there are no deaths directly attributed to OA, YLDs equate disability-adjusted life years (DALYs). RESULTS: Globally, of the 291 conditions, hip and knee OA was ranked as the 11th highest contributor to global disability and 38th highest in DALYs. The global age-standardised prevalence of knee OA was 3.8% (95% uncertainty interval (UI) 3.6% to 4.1%) and hip OA was 0.85% (95% UI 0.74% to 1.02%), with no discernible change from 1990 to 2010. Prevalence was higher in females than males. YLDs for hip and knee OA increased from 10.5 million in 1990 (0.42% of total DALYs) to 17.1 million in 2010 (0.69% of total DALYs). CONCLUSIONS: Hip and knee OA is one of the leading causes of global disability. Methodological issues within this study make it highly likely that the real burden of OA has been underestimated. With the aging and increasing obesity of the world's population, health professions need to prepare for a large increase in the demand for health services to treat hip and knee OA.

The effect of FTO variation on increased osteoarthritis risk is mediated through body mass index: a Mendelian randomisation study.

OBJECTIVE: Variation in the fat mass and obesity-associated (FTO) gene influences susceptibility to obesity. A variant in the FTO gene has been implicated in genetic risk to osteoarthritis (OA). We examined the role of the FTO polymorphism rs8044769 in risk of knee and hip OA in cases and controls incorporating body mass index (BMI) information. METHODS: 5409 knee OA patients, 4355 hip OA patients and up to 5362 healthy controls from 7 independent cohorts from the UK and Australia were genotyped for rs8044769. The association of the FTO variant with OA was investigated in case/control analyses with and without BMI adjustment and in analyses matched for BMI category. A mendelian randomisation approach was employed using the FTO variant as the instrumental variable to evaluate the role of overweight on OA. RESULTS: In the meta-analysis of all overweight (BMI≥25) samples versus normal-weight controls irrespective of OA status the association of rs8044769 with overweight is highly significant (OR[CIs] for allele G=1.14 [01.08 to 1.19], p=7.5×10(-7)). A significant association with knee OA is present in the analysis without BMI adjustment (OR[CIs]=1.08[1.02 to 1.14], p=0.009) but the signal fully attenuates after BMI adjustment (OR[CIs]=0.99[0.93 to 1.05], p=0.666). We observe no evidence for association in the BMI-matched meta-analyses. Using mendelian randomisation approaches we confirm the causal role of overweight on OA. CONCLUSIONS: Our data highlight the contribution of genetic risk to overweight in defining risk to OA but the association is exclusively mediated by the effect on BMI. This is consistent with what is known of the biology of the FTO gene and supports the causative role of high BMI in OA.

Capsaicin for osteoarthritis pain.

UNLABELLED: Capsaicin appears to be effective for osteoarthritis pain but it is uncertain whether the effect has a dose response, is consistent across joints, or changes over time. METHODS: Randomized controlled trials of topical capsaicin use in OA were identified from PubMed, EMBASE, and ISI Web of Knowledge. Effect on pain scores, patient global evaluation of treatment effectiveness and application site burning were assessed by standardised mean differences (SMD), using RevMan. RESULTS: Five double-blind randomized controlled trials and one case-crossover trial of topical capsaicin use were identified. Formulations ranged from 0.025 to 0.075%, and trial durations from 4 to 12 weeks. Trials assessed OA of the knee (n = 3), hand (n = 1), and a mix of joints (n = 2). Capsaicin treatment efficacy (vs. placebo) for change in VAS pain score was moderate, at 0.44 (95% CI 0.25-0.62) over 4 weeks of treatment. There was no heterogeneity between studies, indicating no between-study differences, including effect of OA site or treatment concentration. Two studies reported treatment beyond 4 weeks, with divergent results. One study reported an effect size of -9 mm after 12 weeks, and maximal between-group differences at 4 weeks. A second study reported that between-group differences increased over time, up to 20 weeks. Capsaicin was reported as being safe and well-tolerated, with no systemic toxicity. Mild application site burning affected 35-100% of capsaicin-treated patients with a risk ratio of 4.22 (95% CI 3.25-5.48, n = 5 trials); incidence peaked in week 1, with incidence rates declining over time. CONCLUSIONS: Topical capsaicin treatment four times daily is moderately effective in reducing pain intensity up to 20 weeks regardless of site of application and dose in patients with at least moderate pain and clinical or radiologically defined OA, and is well tolerated.

Effects of individualized bone density feedback and educational interventions on osteoporosis knowledge and self-efficacy: a 12-yr prospective study.

This is 12-yr follow-up of a randomized controlled trial aimed to evaluate the long-term effects of bone density feedback and osteoporosis education on osteoporosis knowledge and self-efficacy. We examined the effects of feedback of bone density-defined fracture risk (high [T-score <0] vs normal [T-score ≥0] risk) and 2 different educational interventions (the group-based Osteoporosis Prevention and Self-Management Course [OPSMC] vs an osteoporosis leaflet) on osteoporosis knowledge and self-efficacy in women aged 25-44. Seventy-four percent (N = 347) of 470 participants at baseline participated at 12 yr. Overall, the scores were higher for osteoporosis knowledge but lower for self-efficacy at 12 yr. However, neither intervention had an effect on the change in knowledge (T-score, ß = 0.4, 95% confidence interval [CI] = -0.3 to 1.1; OPSMC, ß = 0.2, 95% CI = -0.5 to 0.9) or self-efficacy (T-score, ß = -1.1, 95% CI = -2.5 to 0.4; OPSMC, ß = -0.2, 95% CI = -1.6 to 1.3). Women in households with an unemployed main financial provider had a decrease in knowledge at 12 yr compared with those in households with an employed main financial provider in whom knowledge increased (ß = -1.95, 95% CI = -3.40 to -0.50), but there were no other predictors of change identified for knowledge or self-efficacy. In conclusion, beneficial effects of both OPSMC and feedback of high fracture risk on osteoporosis knowledge seen previously at 2 yr were not sustained after 12 yr although overall knowledge was still significantly higher than at baseline. Neither intervention improved osteoporosis self-efficacy. More frequent osteoporosis education and bone density feedback may be required to maintain knowledge, and other approaches to improve self-efficacy are necessary.