Improving telehealth for persons with multiple sclerosis - a cross-sectional study from the Australian MS longitudinal study.

PURPOSE: The COVID-19 pandemic impacted healthcare delivery, especially for people with chronic disease. We investigated telehealth use by persons with multiple sclerosis (MS) during the COVID-19 pandemic and their suggestions to improve their telehealth experience. METHODS: From persons with MS, we collected data on demographic, disease-related and social determinants of health, telehealth use during the COVID-19 pandemic, satisfaction with telehealth, and suggestions to improve telehealth. We conducted univariate log-binomial regression to establish factors associated with telehealth use versus no use, summarised experiences and suggestions for improvement with frequency tables, and conducted thematic analysis on free-text suggestions for improvement. RESULTS: Of 1,485 participants, 69.8% used telehealth during the first phase of the COVID-19 pandemic. Only small differences were observed for demographic, disease and social health determinants between telehealth users and non-users. Most participants who used telehealth had good or very good experiences (new providers:74.3%; existing providers:78.6%). The most common suggestion for improving telehealth experience was "guidance on preparing for telehealth sessions." Participants also wanted expansion in telehealth availability and utility. CONCLUSION: Persons with MS in Australia commonly used telehealth during the COVID-19 pandemic and were generally satisfied with their experiences. Implementing the suggested improvements will help optimise telehealth for persons with MS. REGISTRATION: N/A.

Australians with multiple sclerosis (MS) had good or very good experiences of telehealth during the first year of the pandemic.Telehealth is a useful consultation tool for many rehabilitation professions and may be appropriate for use across the whole MS population.To improve the delivery of rehabilitation through telehealth, provision of better guidance on preparing for telehealth consultations and provision of digital equipment to monitor their health is wanted by persons with MS.Rehabilitation professionals and researchers should take opportunities to identify if proficiency in the English language and cultural background may influence experiences with telehealth in persons with MS.

Zoledronic acid does not slow spinal radiographic progression of osteoarthritis in postmenopausal women with osteoporosis and radiographic osteoarthritis.

Introduction: Post hoc analyses of osteoporosis trials have suggested that alendronate and strontium ranelate may be associated with a reduction in the progression of spinal radiographic osteoarthritis (OA). We performed an analysis on a subgroup of participants in the horizon PFT trial (a 3-year randomized controlled trial (RCT) of yearly zoledronic acid (ZA) in postmenopausal women with osteoporosis), to evaluate the effect of ZA on the structural progression of spinal osteophytes (OPh) and disk space narrowing (DN). Methods: Paired lateral spinal X-rays (baseline and 36 months) were selected from the horizon PFT trial records restricted to those with radiographic OA at baseline. The X-rays were analyzed by two readers blinded to the treatment allocation. OPh and DN were scored separately using the Lane atlas (0-3 for increasing severity at each vertebral level) at all evaluable levels from T4-12 and L1-5. Results: A total of 504 sets of paired radiographs were included in the analysis, 245 in the ZA group and 259 in the placebo group. Overall, the rates of change of OPh and DN scores were low, and they were not statistically different between the groups (change in the whole spine OPh ZA 1.0 ± 1.6, placebo 0.8 ± 1.3, p = 0.1; DN ZA 0.3 ± 1.0, placebo 0.3 ± 0.8, p = 0.7). Conclusion: Yearly ZA for 3 years was not associated with a slowing of progression of OPh or DN in the thoracolumbar spine in patients with pre-existing radiographic OA.

Predictors of total hip replacement in community based older adults: a cohort study.

OBJECTIVE: The purpose of this study is to describe predictors of total hip replacement (THR) in community dwelling older adults. A better understanding of predictors of THR can aid in triaging patients and researching preventative strategies. DESIGN: At baseline, participants had assessment of radiographic OA and cam morphology (from pelvic radiographs), shape mode scores and hip bone mineral density (BMD; from dual energy X-ray absorptiometry (DXA)). After 2.6 and 5 years, participants reported hip pain using WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index), and had hip structural changes assessed using magnetic resonance imaging (MRI). Risk of THR was analysed using mixed-effect Poisson regression. RESULTS: Incidence of THR for OA over 14 years was 4.6% (37/801). As expected, WOMAC hip pain and hip radiographic OA both predicted risk of THR. Additionally, shape mode 2 score (decreasing acetabular coverage) (RR 1.83/SD; 95% CI 1.1-3.04), shape mode 4 score (non-spherical femoral head) (RR 0.59/SD; 95% CI 0.36-0.96), cam morphology (α > 60°) (RR 2.2/SD; 95% CI 1.33-3.36), neck of femur BMD (RR 2.09/SD, 95% CI 1.48-2.94) and bone marrow lesions (BMLs) increased risk of THR (RR 7.10/unit; 95% CI 1.09-46.29). CONCLUSION: In addition to hip pain and radiographic hip OA, measures of hip shape, cam morphology, BMD and BMLs independently predict risk of THR. This supports the role of hip bone geometry and structure in the pathogenesis of end stage hip OA and has identified factors that can be used to improve prediction models for THR.

The association between incident vertebral deformities, health-related quality of life and functional impairment: a 10.7-year cohort study.

We aimed to describe longitudinal changes in health-related quality of life (HRQoL) measures associated with incident vertebral deformities (VDs) over 10.7 years. Incident VDs are associated with clinically significant functional impairment in men, and reduction in overall HRQoL in older women. Increasing severity and number of incident VDs are associated with clinically meaningful functional impairment in men, but not women. INTRODUCTION: To describe associations between incident VD and changes in HRQoL and functional ability in older adults over 10.7 years. METHODS: Participants (n = 780) underwent whole-body dual-energy X-ray absorptiometry (DXA) scans at baseline, 2.5, 5.1 and 10.7 years later. VD was defined as ≥ 25% reduction in anterior height relative to posterior height of vertebrae from T4 to L4. An incident VD was defined as a new VD at any follow-up visit. Assessment of Quality of Life (AQoL-4D) questionnaire and Health Assessment Questionnaire-Disability Index (HAQ-DI) were used to assess HRQoL and functional impairment. Changes in AQoL and HAQ-DI associated with incident VD were analysed using multilevel mixed-effects linear regression. Log binomial regression was used to examine clinically relevant changes and effects of severity and number of VD. RESULTS: The incidence of VD was 37% over 10.7 years. In women, incident VDs were associated with annual reduction in AQoL utility score (ß = -0.005, 95% CI -0.008 to -0.002). Men had increased risk of clinically significant reduction in HAQ-DI (IRR = 1.76, 95% CI 1.07-2.89). Men had increased risk of clinically important functional impairment with increasing severity (IRR 1.76, 95% CI 1.04-2.95 for mild vs IRR 1.98, 95% CI 1.13-3.47 for moderate to severe VD) as well as number of incident VD (IRR 1.85, 95% CI 1.17-2.93 for one vs IRR 1.88, 95% CI 0.94-3.78 for ≥ 2 VDs). Such associations were not observed in women. CONCLUSIONS: Incident VDs are associated with clinically significant functional impairment in men, and reduction in overall HRQoL in older women. Increasing severity and number of incident VDs are associated with clinically meaningful functional impairment in men, but not women.

Once-yearly zoledronic acid and change in abdominal aortic calcification over 3 years in postmenopausal women with osteoporosis: results from the HORIZON Pivotal Fracture Trial.

This study evaluated whether zoledronic acid (ZA) inhibited the progression of abdominal aortic calcification (AAC) over 3 years in 502 postmenopausal women with osteoporosis. AAC progressed in a similar proportion of participants in the ZA (29%) and placebo (31%) groups, suggesting no effect of ZA on AAC progression. INTRODUCTION: Bisphosphonate use is associated with reduced risk of all-cause mortality and cardiovascular events. The underlying mechanisms are uncertain but may include effects on vascular calcification. This study aimed to evaluate the effect of zoledronic acid (ZA) on abdominal aortic calcification (AAC) in postmenopausal women with osteoporosis. METHODS: This was a post hoc analysis of the HORIZON Pivotal Fracture Trial that included 502 postmenopausal women (mean age 72.5 years) with osteoporosis (234 received ZA and 268 placebo). AAC scores (range, 0-8) were assessed from paired spine X-rays at baseline and after 3 years. Progression of AAC was defined as any increase in AAC score. The association between change in hip and femoral neck bone mineral density and change in AAC score was also assessed. RESULTS: At baseline, 292 (58.2%) participants had AAC (i.e., AAC score > 0), with AAC scores similar in the two intervention groups (median [interquartile range], 1 [0 to 2] for both; p = 0.98). Over 3 years, AAC progressed in a similar proportion of participants in both groups (ZA 29% and placebo 31%; p = 0.64). Change in bone mineral density and change in AAC score were not correlated. CONCLUSION: Once-yearly zoledronic acid did not affect progression of AAC over 3 years in postmenopausal women with osteoporosis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00049829.

Comparison of radiographic and MRI osteoarthritis definitions and their combination for prediction of tibial cartilage loss, knee symptoms and total knee replacement: a longitudinal study.

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

KARAOKE: Krill oil versus placebo in the treatment of knee osteoarthritis: protocol for a randomised controlled trial.

BACKGROUND: Knee osteoarthritis (OA) is a common and important cause of pain and disability, but interventions aimed at modifying structures visible on imaging have been disappointing. While OA affects the whole joint, synovitis and effusion have been recognised as having a role in the pathogenesis of OA. Krill oil reduces knee pain and systemic inflammation and could be used for targeting inflammatory mechanisms of OA. METHODS/DESIGN: We will recruit 260 patients with clinical knee OA, significant knee pain and effusion-synovitis present on MRI in five Australian cities (Hobart, Melbourne, Sydney, Adelaide and Perth). These patients will be randomly allocated to the two arms of the study, receiving 2 g/day krill oil or inert placebo daily for 6 months. MRI of the study knee will be performed at screening and after 6 months. Knee symptoms, function and MRI structural abnormalities will be assessed using validated methods. Safety data will be recorded. Primary outcomes are absolute change in knee pain (assessed by visual analog score) and change in size of knee effusion-synovitis over 24 weeks. Secondary outcomes include improvement in knee pain over 4, 8, 12, 16 and 20 weeks. The primary analyses will be intention-to-treat analyses of primary and secondary outcomes. Per protocol analyses adjusting for missing data and for treatment compliance will be performed as the secondary analyses. DISCUSSION: This study will provide high-quality evidence to assess whether krill oil 2 g/day reduces pain and effusion-synovitis size in older adults with clinical knee OA and knee effusion-synovitis. If krill oil is effective and confirmed to be safe, we will provide compelling evidence that krill oil improves pain and function, changes disease trajectory and slows disease progression in OA. Given the lack of approved therapies for slowing disease progression in OA, and moderate cost of krill oil, these findings will be readily translated into clinical practice. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12616000726459. Registered on 02 June 2016. Universal Trial Number (UTN) U1111-1181-7087.

Patellar tendon enthesis abnormalities and their association with knee pain and structural abnormalities in older adults.

OBJECTIVE: To describe associations between presence of patellar tendon enthesis (PTE) abnormalities and symptoms, structural abnormalities, and total knee replacement (TKR) in older adult cohort. METHODS: PTE abnormalities (presence of abnormal bone signal and/or bone erosion), were measured on T2-weighted magnetic resonance (MR) images at baseline in 961 community-dwelling older adults. Knee pain and function limitation were assessed using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Bone marrow lesions (BMLs), cartilage volume and defects score, and infrapatellar fat pad (IPFP) area were measured using validated methods. Incidence of TKR was determined by data linkage. RESULTS: Participants with abnormal PTE bone signal and/or erosion was 20%. Cross-sectionally, presence of PTE abnormalities was associated with greater pain intensity while going up and down stairs (ß = 0.22 (95% confidence interval (CI); 0.03, 0.41)), greater risk of femoral BMLs (RR = 1.46 (1.12, 1.90)) and worse tibial cartilage defects score (RR = 1.70 (1.16, 2.47), and smaller IPFP area (ß = -0.27 (-0.47, -0.06) cm2), after adjustment of confounders. Longitudinally, presence of baseline PTE abnormalities was associated with a deleterious increase in tibial BML size (RR = 1.52 (1.12, 2.05)) over 10.7 years but not symptoms, other structural changes, or TKR. CONCLUSION: PTE abnormalities are common in older adults. Presence of cross-sectional but not longitudinal associations suggests they are commonly co-exist with other knee structural abnormalities but may not play a major role in symptom development or structural change, excepting tibial BMLs.

Factors associated with prevalent and incident foot pain: data from the Tasmanian Older Adult Cohort Study.

OBJECTIVES: To describe factors associated with prevalent and incident foot pain in a population-based cohort of older adults (n = 1092). STUDY DESIGN: Longitudinal observational study. MAIN OUTCOME MEASURES: Prevalent foot pain, incident foot pain after 5 years. METHODS: Potential correlates included demographic factors, anthropometry, leg strength, metabolic factors, steps per day (using pedometer), pain at 6 other sites, and psychological wellbeing. Data were analysed using log binomial models. RESULTS: Participants were aged 50-80 years (mean 63 years), 49% male, mean body mass index (BMI) 27.8 ± 4.7 at baseline. The prevalence of foot pain at baseline was 38% and the incidence of new pain over 5 years was 20%. BMI, pain at other sites (neck, hands, knees, pain at three or more sites), and poorer psychological wellbeing were independently associated with baseline foot pain. Baseline BMI and pain in the neck, hands, and knees were independently associated with incident foot pain; but change in weight or BMI, total number of painful joints and psychological wellbeing were not. Self-reported diabetes and cigarette smoking were not associated with prevalent or incident foot pain. CONCLUSIONS: This study demonstrates that greater body weight and joint pain at multiple sites were consistently associated with prevalent foot pain and predict incident foot pain. Addressing excess body mass and taking a global approach to the treatment of pain may reduce the prevalence and incidence of foot pain in older adults.

Association of childhood adiposity measures with adulthood knee cartilage defects and bone marrow lesions: a 25-year cohort study.

OBJECTIVE: To describe the associations between childhood adiposity measures and adulthood knee cartilage defects and bone marrow lesions (BMLs) measured 25 years later. METHODS: 327 participants from the Australian Schools Health and Fitness Survey (ASHFS) of 1985 (aged 7-15 years) were followed up 25 years later (aged 31-41 years). Childhood measures (weight, height and skinfolds) were collected in 1985. Body mass index (BMI), overweight status and fat mass were calculated. Participants underwent 1.5 T knee magnetic resonance imaging (MRI) during 2008-2010, and cartilage defects and BMLs were scored from knee MRI scans. Log binomial regressions were used to examine the associations. RESULTS: Among 327 participants (47.1% females), 21 (6.4%) were overweight in childhood. Childhood adiposity measures were associated with the increased risk of adulthood patellar cartilage defects (Weight relative risk (RR) 1.05/kg, 95% confidence interval (CI) 1.01-1.09; BMI 1.10/kg/m2, 1.01-1.19; Overweight 2.22/yes, 1.21-4.08; fat mass 1.11/kg, 1.01-1.22), but not tibiofemoral cartilage defects. Childhood adiposity measures were not significantly associated with adulthood knee BMLs except for the association between childhood overweight status and adulthood patellar BMLs (RR 2.87/yes, 95% CI 1.10-7.53). These significant associations persisted after adjustment for corresponding adulthood adiposity measure. CONCLUSION: Childhood adiposity measures were associated with the increased risk of adulthood patellar cartilage defects and, to a lesser extent, BMLs, independent of adulthood adiposity measures. These results suggest that adiposity in childhood has long-term effects on patellar structural abnormalities in young adults.

A randomised double-blind placebo-controlled crossover trial of HUMira (adalimumab) for erosive hand OsteoaRthritis - the HUMOR trial.

OBJECTIVE: To assess the efficacy of adalimumab in patients with erosive hand osteoarthritis (OA). METHOD: Patients >50 years old, meeting the American College of Rheumatology (ACR) criteria for hand OA, with pain >50 on 100 mm visual analogue scale (VAS), morning stiffness >30 min and ≥1 erosive joint on X-ray with synovitis present on magnetic resonance imaging (MRI) were included in a randomised double-blind placebo-controlled crossover trial. Patients were randomised to adalimumab (40 mg subcutaneous injections every other week) or identical placebo injections for 12 weeks followed by an 8-week washout and then crossed over treatment groups for another 12 weeks. The primary outcome was change in VAS hand pain over 12 weeks. Secondary outcomes included change in Australian/Canadian Hand OA Index (AUSCAN) pain, function and stiffness subscales from baseline to 4, 8 and 12 weeks, change in MRI-detected synovitis and bone marrow lesions (BMLs) from baseline to 12 weeks and change in VAS from baseline to 4 and 8 weeks. RESULTS: We recruited 51 patients and 43 were randomised to either Group 1 (N = 18, active then placebo) or Group 2 (N = 25, placebo then active). At 12 weeks there was no difference between the groups on the primary outcome measure (mean decrease in VAS pain of 3.2 mm standard deviation (SD 16.7) for adalimumab vs 0.8 mm (SD 29.6) for placebo). The adjusted treatment effect was -0.7 mm (95% confidence interval (CI) -9.3 to 8.0), P = 0.87. No statistically significant differences were found for any secondary outcomes. CONCLUSION: Adalimumab did not show any effect on pain, synovitis or BMLs in patients with erosive hand OA with MRI-detected synovitis as compared to placebo after 12 weeks. CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12612000791831.

Associations between MRI-detected early osteophytes and knee structure in older adults: a population-based cohort study.

OBJECTIVES: To describe prevalence of osteophytes (OPs) detected only by magnetic resonance imaging (MRI) but not by standard X-ray in older adults and to evaluate longitudinal associations with knee structural changes. METHODS: 837 participants were randomly selected from the local community and had MRI scans to assess knee OPs and other structures. OPs detected only by MRI but not by standard X-ray were defined as MRI-detected early OPs (MRI-OPs for short). OPs detected by both MRI and X-ray were defined as established-OPs. RESULTS: The prevalence of MRI-OPs was 50% while the prevalence of established-OPs was 10% and no-OPs was 40% at total tibiofemoral (TF) compartment at baseline. Compared with no-OPs, participants with MRI-OPs had greater risks of increased cartilage defects in all TF compartments (RR 1.37, 95%CI 1.07-1.74) and bone marrow lesions (BMLs) only in medial TF compartment (RR 1.49, 95%CI 1.06-2.11), after adjustment for age, sex, BMI, cartilage defects, BMLs and/or joint space narrowing; participants with established-OPs had greater cartilage volume loss at total (ß -2.02, 95%CI -3.86, -0.17) and lateral tibial sites (ß -5.63, 95%CI -9.93, -1.32), greater risks of increased cartilage defects in total (RR 1.66, 95%CI 1.15-2.40) and medial TF compartments (RR 1.49, 95%CI 1.20-1.69) and BMLs in all TF compartments (RR 1.88, 95%CI 1.22-2.89), after adjustment for covariates. CONCLUSION: MRI-OPs were associated with changes in knee structures, and the associations were similar but not as prominent as those for established-OPs. These suggest MRI-OPs may have a role to play in knee early-stage osteoarthritic progression.

Pain in knee osteoarthritis is associated with variation in the neurokinin 1/substance P receptor (TACR1) gene.

BACKGROUND: Substance P (SP) is a pain- and inflammation-related neuropeptide which preferentially binds to the neurokinin receptor 1 (NK1 ). SP and NK1 receptors have been implicated in joint pain, inflammation and damage in animal models and human studies of osteoarthritis (OA). The aim of this study was to test if genetic variation at the neurokinin 1 receptor gene (TACR1) is associated with pain in individuals with radiographic knee OA. METHODS: Participants from the Genetics of OA and Lifestyle study were used for the discovery group (n = 1615). Genotype data for six SNPs selected to cover most variation in the TACR1 gene were used to test for an association with symptomatic OA. Replication analysis was performed using data from the Chingford 1000 Women Study, Hertfordshire Cohort Study, Tasmanian Older Adult Cohort Study and the Clearwater OA Study. In total, n = 1715 symptomatic OA and n = 735 asymptomatic OA individuals were analysed. RESULTS: Out of six SNPs tested in the TACR1 gene, one (rs11688000) showed a nominally significant association with a decreased risk of symptomatic OA in the discovery cohort. This was then replicated in four additional cohorts. After adjusting for age, gender, body mass index and radiographic severity, the G (minor) allele at rs11688000 was associated with a decreased risk of symptomatic OA compared to asymptomatic OA cases (p = 9.90 × 10-4 , OR = 0.79 95% 0.68-0.90 after meta-analysis). CONCLUSIONS: This study supports a contribution from the TACR1 gene in human OA pain, supporting further investigation of this gene's function in OA. SIGNIFICANCE: This study contributes to the knowledge of the genetics of painful osteoarthritis, a condition which affects millions of individuals worldwide. Specifically, a contribution from the TACR1 gene to modulating pain sensitivity in osteoarthritis is suggested.

Association between MRI-detected osteophytes and changes in knee structures and pain in older adults: a cohort study.

OBJECTIVE: To describe cross-sectional and longitudinal associations between magnetic resonance imaging (MRI)-detected osteophytes (OPs) and knee structural abnormalities and knee pain in older adults. METHOD: A prospective population-based cohort study of 895 participants aged 50-80 years (mean age 62 years, 50% female) was performed. T1-or T2-weighted fat suppressed MRI was used to assess knee OPs, cartilage volume, cartilage defects and bone marrow lesions (BMLs) at baseline and after 2.6 years. Radiographically-detected OPs were scored according to the Osteoarthritis Research Society International (OARSI) atlas. Knee pain was assessed using a self-administered questionnaire at baseline, 2.6 and 5 years later. RESULTS: 85% of participants had MRI-detected OPs at baseline, while 10% of participants had radiographically-detected OPs. Cross-sectionally, higher gardes of MRI-detected OPs in all compartments were significantly, independently and site-specifically associated with higher prevalences of cartilage defects and BMLs, lower cartilage volume and higher prevalence of knee pain. Longitudinally, higher gardes of baseline MRI-detected OPs site-specifically predicted greater risks of any increase in cartilage defects or BMLs, and loss of cartilage volume in medial and lateral tibiofemoral (LTF) and total compartments over 2.6 years in multivariable analyses. These significant associations were similar in those without radiographically-detected OPs. MTF and total OP scores were significantly associated with change in total knee pain over 2.6 and 5 years but these became non-significant after adjustment for cartilage defects and BMLs. CONCLUSION: MRI-detected knee OPs are common and appear to be clinically relevant to knee structural changes in older adults.

Cut-points for associations between vitamin D status and multiple musculoskeletal outcomes in middle-aged women.

This was the first study examining optimal vitamin D status for musculoskeletal health in middle-aged women. A 25-hydroxyvitamin D level of at least 29 to 33 nmol/L appears required for optimal musculoskeletal health, but the current cut-off of 50 nmol/L may be warranted. INTRODUCTION: This study aimed to determine whether cut-points exist for associations between serum 25-hydroxyvitamin D (25OHD) and musculoskeletal health outcomes in middle-aged women, below which greater 25OHD levels are associated with musculoskeletal health benefits and above which no such associations exist. METHODS: This is a cross-sectional study of 344 women aged 36-57 years. Cut-points for associations of serum 25OHD with lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD), lower limb muscle strength (LMS), timed up and go test (TUG), functional reach test (FRT), lateral reach test (LRT), and step test (ST) were explored using locally weighted regression smoothing and nonlinear least-squares estimation, and associations above and below the identified cut-points were estimated using segmented regression. RESULTS: The prevalence of low 25OHD was 28 % (<50 nmol/L). Significant cut-points (nmol/L) were identified for FN BMD 31 (95 % confidence interval (CI): 18, 43), LS BMD 31 (17, 45), TUG 30 (24, 36), ST 33 (24, 31), FRT 31 (18, 43), and LMS 29 (8, 49) but not LRT (42 (-8, 93). Below these cut-points, there were beneficial associations between higher 25OHD level and each outcome, while above the cut-points, there were no beneficial associations. CONCLUSIONS: In middle-aged women, there are thresholds for associations between serum 25OHD concentrations and bone density and most balance measures, suggesting that 25OHD levels of at least 29 to 33 nmol/L are required for optimal musculoskeletal health in this population. The current cut-off of 50 nmol/L may be higher than needed for some outcomes but appears warranted overall.

Cross-sectional and longitudinal associations between serum inflammatory cytokines and knee bone marrow lesions in patients with knee osteoarthritis.

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

Lower limb muscle strength is associated with poor balance in middle-aged women: linear and nonlinear analyses.

UNLABELLED: This was the first study investigating both linear associations between lower limb muscle strength and balance in middle-aged women and the potential for thresholds for the associations. There was strong evidence that even in middle-aged women, poorer LMS was associated with reduced balance. However, no evidence was found for thresholds. INTRODUCTION: Decline in balance begins in middle age, yet, the role of muscle strength in balance is rarely examined in this age group. We aimed to determine the association between lower limb muscle strength (LMS) and balance in middle-aged women and investigate whether cut-points of LMS exist that might identify women at risk of poorer balance. METHODS: Cross-sectional analysis of 345 women aged 36-57 years was done. Associations between LMS and balance tests (timed up and go (TUG), step test (ST), functional reach test (FRT), and lateral reach test (LRT)) were assessed using linear regression. Nonlinear associations were explored using locally weighted regression smoothing (LOWESS) and potential cut-points identified using nonlinear least-squares estimation. Segmented regression was used to estimate associations above and below the identified cut-points. RESULTS: Weaker LMS was associated with poorer performance on the TUG (ß -0.008 (95 % CI: -0.010, -0.005) second/kg), ST (ß 0.031 (0.011, 0.051) step/kg), FRT (ß 0.071 (0.047, 0.096) cm/kg), and LRT (ß 0.028 (0.011, 0.044) cm/kg), independent of confounders. Potential nonlinear associations were evident from LOWESS results; significant cut-points of LMS were identified for all balance tests (29-50 kg). However, excepting ST, cut-points did not persist after excluding potentially influential data points. CONCLUSIONS: In middle-aged women, poorer LMS is associated with reduced balance. Therefore, improving muscle strength in middle-age may be a useful strategy to improve balance and reduce falls risk in later life. Middle-aged women with low muscle strength may be an effective target group for future randomized controlled trials. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) NCT00273260.

Changes in quality of life associated with fragility fractures: Australian arm of the International Cost and Utility Related to Osteoporotic Fractures Study (AusICUROS).

UNLABELLED: We investigated change in health-related quality of life due to fracture in Australian adults aged over 50 years. Fractures reduce quality of life with the loss sustained at least over 12 months. At a population level, the loss was equivalent to 65 days in full health per fracture. PURPOSE: We aimed to quantify the change in health-related quality of life (HRQoL) that occurred as a consequence of a fracture using the EQ-5D-3 L questionnaire. METHODS: Adults aged ≥50 years with a low to moderate energy fracture were recruited from eight study centres across Australia. This prospective study included an 18-month follow-up of participants recruited within 2 weeks of a fracture (hip, wrist, humerus, vertebral and ankle). Information collected at baseline and 4, 12 and 18 months included characteristics of participants such as income level, education and prior fracture status. At 12 months post-fracture, the cumulative loss of quality of life was estimated using multivariate regression analysis to identify the predictors of HRQoL loss. RESULTS: Mean HRQoL for all participants before fracture was 0.86, with wrist fracture having the highest pre-fracture HRQoL (0.90), while vertebral fracture had the lowest (0.80). HRQoL declined to 0.42 in the immediate post-fracture period. Only participants with a wrist, humerus or ankle fracture returned to their pre-fracture HRQoL after 18 months. An increased loss of HRQoL over 12 months was associated with HRQoL prior to the fracture, hospitalisation, education and fracture site. The multiple regression explained 30 % of the variation in the cumulative HRQoL loss at 12 months post-fracture for all fractures. CONCLUSION: Low to moderate energy fractures reduce HRQoL, and this loss is sustained for at least 12 months or, in the case of hip and spine fractures, at least 18 months. At a population level, this represents an average loss of 65 days in full health per fragility fracture. This significant burden reinforces the need for cost-effective fracture prevention strategies.

Treatment with 4Jointz reduces knee pain over 12 weeks of treatment in patients with clinical knee osteoarthritis: a randomised controlled trial.

OBJECTIVE: To assess the efficacy of thrice daily topical 4Jointz utilizing Acteev technology (a combination of a standardized comfrey extract and a pharmaceutical grade tannic acid, 3.5 g/day) on osteoarthritic knee pain, markers of inflammation and cartilage breakdown over 12 weeks. PATIENTS AND METHODS: Adults aged 50-80 years (n = 133) with clinical knee OA were randomised to receive 4Jointz or placebo in addition to existing medications. Pain and function were measured using a visual analogue scale (VAS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) scale at baseline, 4, 8 and 12 weeks. Inflammation was measured analysing IL-6 expression and CTX-2 presence as representative for cartilage breakdown using ELISA, at baseline and 12 weeks. RESULTS: Pain scores significantly reduced in the group who received 4Jointz compared to the group who received placebo after 12 weeks using both the VAS (-9.9 mm, P = 0.034) and the KOOS pain scale (+5.7, P = 0.047). Changes in IL-6 and CTX-2 were not significant (-0.04, P = 0.5; -0.01, P = 0.68). Post-hoc analyses suggested that treatment may be most effective in women (VAS -16.8 mm, P = 0.008) and those with milder radiographic osteoarthritis (OA) (VAS -16.1 mm, P = 0.009). Rates of adverse events were similar in both groups, excepting local rash that was more common amongst participants receiving 4Jointz (21% vs 1.6%, IRR 13.2, P = 0.013), but only 26% (n = 4) of participants with rashes discontinued treatment. There were no changes in systemic blood results. CONCLUSIONS: Topical treatment using 4Jointz reduced pain but had no effect on inflammation or cartilage breakdown over 12 weeks of treatment. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials registry ACTRN12610000877088.