Pre-exercise and acute movement-evoked pain trajectories during a 24-week outdoor walking program for knee osteoarthritis (WALK).

Objectives: Exploring (1) pre-exercise and acute movement-evoked pain (AMEP) during an outdoor walking program in individuals with knee osteoarthritis (OA); and (2) comparing baseline physical performance and AMEP flares initiated by walking between participants with either a higher or lower attendance rate. Methods: Individuals with knee OA were prescribed a 24-week walking program, including one unsupervised walk and two supervised walk classes per week. Participants self-reported knee pain on a numerical rating scale (NRS; 0-10) before and after each supervised class. Mixed-effects models were used to investigate trajectories over time for pre-exercise pain and AMEP change (post-minus pre-exercise pain; positive value indicates flare-up). Baseline physical performance (6 tests) and AMEP flares were compared between participants with higher (attending ≥70% of supervised classes) and lower attendance rates. Results: Of 24 participants commencing the program, 7 (29%) withdrew. Over 24 weeks, pre-exercise pain improved by 1.20 NRS (95% CI -1.41 to -0.99), with estimated largest per class improvements during the first 8 weeks (-0.05 (-0.06 to -0.03) and plateauing around 20-weeks. The AMEP was estimated to improve by 0.19 NRS (95% CI -0.38 to -0.004) over 24-weeks, with improvements plateauing around 12-weeks. Participants with lower attendance (n â€‹= â€‹11) scored poorer on all physical performance tests and experienced a slight increase in AMEP during the first two weeks of the program. Conclusions: Participants improved in pre-exercise pain and AMEP in the first 20 and 12 weeks, respectively. Despite supervision, physical performance and AMEP flares may have contributed to lower attendance. Trial registration number: 12618001097235.

A pilot randomized controlled trial evaluating outdoor community walking for knee osteoarthritis: walk.

OBJECTIVES: To determine the feasibility of a randomized controlled trial (RCT) examining outdoor walking on knee osteoarthritis (KOA) clinical outcomes and magnetic resonance imaging (MRI) structural changes. METHOD: This was a 24-week parallel two-arm pilot RCT in Tasmania, Australia. KOA participants were randomized to either a walking plus usual care group or a usual care control group. The walking group trained 3 days/week. The primary outcome was feasibility assessed by changes being required to the study design, recruitment, randomization, program adherence, safety, and retention. Exploratory outcomes were changes in symptoms, physical performance/activity, and MRI measures. RESULTS: Forty participants (mean age 66 years (SD 1.4) and 60% female) were randomized to walking (n = 24) or usual care (n = 16). Simple randomization resulted in a difference in numbers randomized to the two groups. During the study, class sizes were reduced from 10 to 8 participants to improve supervision, and exclusion criteria were added to facilitate program adherence. In the walking group, total program adherence was 70.0% and retention 70.8% at 24 weeks. The walking group had a higher number of mild adverse events and experienced clinically important improvements in symptoms (e.g., visual analogue scale (VAS) knee pain change in the walking group: - 38.7 mm [95% CI - 47.1 to - 30.3] versus usual care group: 4.3 mm [- 4.9 to 13.4]). CONCLUSIONS: This study supports the feasibility of a full-scale RCT given acceptable adherence, retention, randomization, and safety, and recruitment challenges have been identified. Large symptomatic benefits support the clinical usefulness of a subsequent trial. TRIAL REGISTRATION NUMBER: 12618001097235. Key Points • This pilot study is the first to investigate the effects of an outdoor walking program on knee osteoarthritis clinical outcomes and MRI joint structure, and it indicates that a full-scale RCT is feasible. • The outdoor walking program (plus usual care) resulted in large improvements in self-reported knee osteoarthritis symptoms compared to usual care alone. • The study identified recruitment challenges, and the manuscript explores these in more details and provides recommendations for future studies.

Feasibility of 'parkrun' for people with knee osteoarthritis: A mixed methods pilot study.

Objective: To investigate the feasibility of 'parkrun' for people with knee osteoarthritis (OA) and examine its potential to improve symptoms and increase physical activity. Design: This uncontrolled mixed methods pilot study enrolled people with knee OA not meeting physical activity guidelines. Participants were asked to walk in four consecutive parkrun events supervised by an exercise physiologist/physiotherapist. Feasibility was assessed by recruitment data (numbers screened and time to enrol 15 participants), adherence to the protocol, acceptability (measured by confidence, enjoyment, difficulty ratings and qualitative interviews), and safety (adverse events). Secondary measures were changes in knee pain, function, stiffness, and physical activity levels. Results: Participants (n â€‹= â€‹17) were enrolled over 11 months and recruitment was slower than anticipated. Fourteen participants attended all four parkruns and three of these participants shortened the 5 â€‹km course to ∼3 â€‹km. Across all four parkruns, 75% of participants reported high confidence that they could complete the upcoming parkrun and the majority (87%) enjoyed participating. Most participants rated parkrun either "slightly difficult" (38.5%) or "moderately difficult" (35%) and two mild adverse events were reported. Participants showed improvements in knee pain, function, stiffness, and physical activity levels. Conclusions: This pilot study demonstrates parkrun's feasibility, acceptability, safety and, its potential to improve knee OA symptoms and physical activity levels. Participating in parkrun was acceptable and enjoyable for some, but not all participants. The scalability, accessibility and wide appeal of parkrun supports the development of larger programs of research to evaluate the use of parkrun for people with knee OA.

The cross-sectional and longitudinal associations of dietary patterns with knee symptoms and MRI detected structure in patients with knee osteoarthritis.

OBJECTIVES: To examine the cross-sectional and longitudinal associations of dietary patterns with knee symptoms and structures in patients with knee osteoarthritis (OA). METHODS: Participants with symptomatic knee OA were recruited from a randomised, placebo-controlled trial conducted in Tasmania (N = 259) and Victoria (N = 133). Diet was assessed by the Anti-Cancer Council of Victoria food frequency questionnaire. Factor analysis was used to identify dietary patterns. Knee symptoms were assessed using Western Ontario and McMaster Universities Arthritis Index (WOMAC) and structures using MRI. Multivariable linear regressions were used to examine associations. RESULTS: Three dietary patterns ("high-fat", "healthy" and "mixed") were identified in whole sample. Participants with higher "healthy pattern" score had lower total WOMAC, pain, function and stiffness scores at baseline but the associations were not significant over 24 months. Three ("western", "vegetable and meat" and "mediterranean") and two ("processed" and "vegetable") patterns were identified in Tasmania and Victoria, respectively. Cross-sectionally, only "mediterranean pattern" and "vegetable pattern" scores were significantly and negatively associated with total WOMAC or function scores. Longitudinally, participants with higher "western pattern" had worsening function (ß: 0.35, 95%CI: 0.03, 0.67) and total WOMAC (ß: 0.40, 95%CI: 0.07, 0.72) scores; furthermore, "vegetable pattern" was associated with decreased WOMAC stiffness score (ß: -0.47, 95%CI: -0.93, -0.02). In contrast, dietary patterns were largely not associated with structural changes. CONCLUSION: Some healthy dietary patterns were associated with reduced joint symptoms but dietary patterns were not associated with joint structure in this sample with knee OA. Further studies are required to confirm these findings.

Skin Photosensitivity is Associated with 25-Hydroxyvitamin D and BMD but not Fractures Independent of Melanin Density in Older Caucasian Adults.

Whether skin photosensitivity modulates sun exposure behaviours, consequent vitamin D status and skeletal health outcomes independently of constitutive pigmentation have not been systematically investigated. 1072 community-dwelling adults aged 50-80 years had skin photosensitivity quantified by questionnaire and melanin density by spectrophotometry. Bone mineral density (BMD), falls risk and 25-hydroxyvitamin D (25OHD) were measured using DXA, short form physiological profile assessment and radioimmunoassay, respectively. Sun exposure and symptomatic fractures were assessed by questionnaire. Participants were followed up at 2.5 (n = 879), 5 (n = 767) and 10 (n = 571) years. Higher resistance to sunburn and greater ability to tan were associated with reduced sun protection behaviours (RR 0.87, p < 0.001 & RR 0.88, p < 0.001), higher lifetime discretionary sun exposure in summer (RR 1.05, p = 0.001 & RR 1.07, p = 0.001) and winter (RR 1.07, p = 0.001 & RR 1.08, p = 0.02) and fewer lifetime sunburns (RR 0.86, p < 0.001 & RR 0.91, p = 0.001). Higher resistance to sunburn was associated with lower total body (ß = - 0.006, p = 0.047) and femoral neck (ß = - 0.006, p = 0.038) BMD, but paradoxically, fewer prevalent fractures (RR 0.94, p = 0.042). Greater ability to tan was associated with higher 25OHD (ß = 1.43, p = 0.04), lumbar spine (ß = 0.014, p = 0.046) and total body (ß = 0.013, p = 0.006) BMD, but not fracture or falls risk. These associations were independent of constitutive melanin density. Cutaneous photosensitivity was associated with sun exposure behaviours, cutaneous sequelae and, consequently, 25OHD and BMD in older Caucasian adults independent of constitutive melanin density. There was no consistent association with fracture outcomes, suggesting environmental factors are at least as important.

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.

Constitutive melanin density is associated with prevalent and short-term, but not long-term, incident fracture risk in older Caucasian adults.

Higher cutaneous melanin reduces vitamin D3 production. This may increase fracture risk. We found that cutaneous melanin density was associated with prevalent and short-term, but not long-term, incident fracture risk in older Caucasian adults. Melanin density either acts as a surrogate marker or its relationship with fracture changes with time. INTRODUCTION: Higher cutaneous melanin reduces vitamin D3 production. This may impact lifetime vitamin D status and increase fracture risk. This study aimed to describe the relationship between spectrophotometrically determined constitutive melanin density, prevalent and incident fractures in a cohort of exclusively older Caucasian adults. METHODS: 1072 community-dwelling adults aged 50-80 years had constitutive melanin density quantified using spectrophotometry. Participants were followed up at 2.5 (n = 879), 5 (n = 767), and 10 (n = 571) years after the baseline assessment. Prevalence and number of symptomatic fractures were assessed by questionnaire. RESULTS: Higher melanin density was independently associated with greater prevalence of any fracture (RR 1.08, p = 0.03), vertebral fracture (RR 1.41, p = 0.04) and major fracture (RR 1.12, p = 0.04) and the number of fractures (RR 1.09, p = 0.04) and vertebral fractures (RR 1.47, p = 0.04) in cross-sectional analysis. At the 2.5-year follow-up, higher melanin density was associated with incident fractures (RR 1.42, p = 0.01) and major fractures (RR 1.81, p = 0.01) and the number of incident fractures (RR 1.39, p = 0.02) and major fractures (RR 2.14, p = 0.01). The relationship between melanin density and incident fracture attenuated as the duration of follow-up increased and was not significant at the 5- or 10-year follow-up. CONCLUSIONS: Constitutive melanin density was associated with prevalent and short-term, but not long-term, incident fracture risk in older Caucasian adults. This suggests melanin density either acts as a surrogate marker for an unmeasured fracture risk factor or the relationship between melanin density and fracture changes with time.

The association of subchondral and systemic bone mineral density with osteoarthritis-related joint replacements in older adults.

OBJECTIVE: To describe the association of subchondral and systemic bone mineral density (BMD) with knee and hip replacements (KR and HR, respectively) due to osteoarthritis. DESIGN: 1,095 participants (mean age 63 years, 51% female) were included. At baseline, subchondral BMD of the medial and lateral tibia in three regions of interest (ROI) for the right knee, and systemic BMD of the lumbar spine, femoral neck, total hip and whole-body, were measured using dual-energy X-ray absorptiometry. Subchondral BMD of the hip was not measured. Competing risk regression models were used to estimate sub-distribution hazard ratios (SHRs) of KR/HR per one standard deviation (SD) higher in BMD measures, with adjustment of potential confounders. RESULTS: Over 12.2 years, 79 (7.2%) participants underwent a KR and 56 (5.1%) an HR due to osteoarthritis. For the right side, medial subchondral BMD in ROI-3 was associated with an increased risk of KR (SHR 1.95 per SD; 95% Confidence Interval [CI], 1.57 to 2.43). In contrast, systemic BMD was not associated with the risk of KR, but higher BMD at the lumbar spine (1.42, 1.07 to 1.88) and whole-body (1.29, 1.00 to 1.66) were associated with an increased risk of HR at both sides. CONCLUSIONS: Subchondral BMD is positively associated with an increased risk of KR and systemic BMD with an increased risk of HR, suggesting a role of BMD in the progression of osteoarthritis.

The effect of weight loss on the progression of meniscal extrusion and size in knee osteoarthritis: a post-hoc analysis of the Intensive Diet and Exercise for Arthritis (IDEA) trial.

OBJECTIVE: Weight loss has beneficial effects on clinical outcomes in knee osteoarthritis (OA), but the mechanism is still unclear. Since meniscus extrusion is associated with knee pain, this study assessed whether weight loss by diet and/or exercise is associated with less progression in meniscus extrusion measures over time. DESIGN: The Intensive Diet and Exercise for Arthritis trial (IDEA) was a prospective, single-blind, randomized-controlled trial including overweight and obese older adults with knee pain and radiographic OA. Participants were randomized to 18-month interventions: exercise only, diet only or diet + exercise. In a random subsample of 105 participants, MRIs were obtained at baseline and follow-up. The medial and lateral menisci were segmented and quantitative position and size measures were obtained, along with semiquantitative extrusion measures. Linear and log-binomial regression were used to examine the association between change in weight and change in meniscus measures. Between-group differences were analyzed using an analysis of covariance. RESULTS: Weight loss was associated with less progression over time of medial meniscus extrusion as measured by the maximum (ß: -24.59 µm, 95%CI: -41.86, -7.33) and mean (ß: -19.08 µm, 95%CI: -36.47, -1.70) extrusion distances. No relationships with weight loss were observed for lateral meniscus position, medial or lateral meniscus size or semiquantitative measures. Change in meniscus position and size did not differ significantly between groups. CONCLUSIONS: Weight loss was associated with beneficial modifications of medial meniscus extrusion over 18 months. This may be one of the mechanisms by which weight loss translates into a clinical benefit. CLINICAL TRIAL REGISTRATION: NCT00381290.

Ambulatory activity interacts with common risk factors for osteoarthritis to modify increases in MRI-detected osteophytes.

OBJECTIVE: To investigate the longitudinal association between objectively measured ambulatory activity (AA) and knee MRI-detected osteophytes (OPs), and to test whether this relationship was modified by common risk factors for OA including sex, obesity, disease severity and knee injury history. METHODS: 408 community-dwelling adults aged 51-81 years were assessed at baseline and 2.7 years. T1-weighted fat-suppressed MRI was used to evaluate knee OPs at both time points. AA was assessed at baseline by pedometers and categorized as: less active (≤7499 steps per day), moderately active (7500-9999 steps per day) and highly active (≥10,000 steps per day). RESULTS: Statistically significant interactions were detected between knee OA risk factors and AA on increases in MRI-detected OPs (all P < 0.05). In stratified analyses, being moderately active, compared to being less active, was protective against an increase in MRI-detected OPs (score change of ≥1) in females (relative risk (RR) = 0.42, 95%CI, 0.25-0.70, P < 0.01), those who were obese (RR = 0.50, 95%CI, 0.30-0.83, P < 0.01), those with radiographic OA (ROA) (RR = 0.68, 95%CI, 0.47-0.97, P = 0.02) and those with a history of knee injury (RR = 0.27, 95%CI, 0.08-0.88, P = 0.02) in almost every knee compartment, after adjustment for confounders. No statistically significant associations were found in males, non-obese, non-ROA or non-injury groups. CONCLUSIONS: Being moderately active is protective against an increase in MRI-detected OPs in females, those with ROA, those who are obese and those with a history of knee injury. These findings suggest that being moderately active is beneficial for individuals who are at higher risk of knee OA.

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.

Predictors of pain severity trajectory in older adults: a 10.7-year follow-up study.

OBJECTIVES: To identify distinct pain trajectories over 10.7 years and to examine predictors of identified pain trajectories in an older population and those with radiographic knee osteoarthritis (ROA). METHODS: 963 participants (aged 50-80 years) from a population-based cohort had baseline demographic, psychological, lifestyle and comorbidities data collected. T1-and T2-weighted magnetic resonance imaging (MRI) of the right knee was performed to measure knee structural pathology-cartilage defects, bone marrow lesions (BMLs) and effusion-synovitis. Group-based trajectory modelling (GBTM) was applied to identify trajectories of knee pain over 10.7 years measured by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: Three distinct pain trajectories were defined: 'Minimal pain' (n = 501, 52%), 'Mild pain' (n = 329, 34%) and 'Moderate pain' (n = 165, 14%). In multivariable analysis, having cartilage defects, BMLs and effusion-synovitis were associated with an increased risk of being in the 'Mild pain' (relative risk [RR]: 1.40 to 1.92) and 'Moderate pain' trajectory (RR: 1.72 to 2.26), compared with the 'Minimal pain' trajectory. Being obese and having more painful sites were associated with 'Mild pain' and 'Moderate pain' trajectories, while unemployment, lower education level and presence of emotional problems were associated with 'Moderate pain' trajectory group. Similar results were found for those with ROA. CONCLUSION: Distinct pain trajectories identified suggest that homogeneous subgroups exist, which might be useful for phenotypic assessment for pain management, particularly in knee osteoarthritis. Structural pathology was associated with worse pain trajectories, suggesting that peripheral stimuli are critical for the development and maintenance of pain severity. Environmental and psychological factors may exacerbate pain perception.

Constitutive melanin density is associated with higher 25-hydroxyvitamin D and potentially total body BMD in older Caucasian adults via increased sun tolerance and exposure.

Greater skin pigmentation reduces dose equivalent cutaneous vitamin D3 production, potentially impacting lifetime vitamin D status and fracture risk. We show that melanin density was positively associated with 25-hydroxyvitamin D and total body bone mineral density. These relationships were partially explained by greater sun exposure due to more permissive skin phenotype. INTRODUCTION: Higher cutaneous melanin reduces vitamin D3 production. This may impact lifetime vitamin D status and increase fracture risk. This study aimed to describe the relationship between spectrophotometrically determined constitutive melanin density, osteoporotic risk factors and potential intermediaries in a cohort of exclusively older Caucasian adults. METHODS: One thousand seventy-two community-dwelling adults aged 50-80 years had constitutive melanin density quantified using spectrophotometry. Sun exposure, skin phenotype, non-melanoma skin cancer (NMSC) prevalence and smoking status were assessed by questionnaire. Bone mineral density (BMD), falls risk, physical activity and 25-hydroxyvitamin D were measured using DXA, the short form Physiological Profile Assessment, pedometer and radioimmunoassay, respectively. RESULTS: Higher melanin density was independently associated with greater ability to tan (RR = 1.27, p < 0.001), less propensity to sunburn (RR = 0.92, p < 0.001), fewer lifetime sunburns (RR = 0.94, p = 0.01), current smoking (RR = 1.41, p < 0.001), female sex (RR = 1.24, p < 0.001) and less photodamage (RR = 0.98, p = 0.01). The associations between melanin density and sun exposure (RR = 1.05-1.11, p < 0.001-0.01), sun protection behaviours (RR = 0.89, p < 0.001) and NMSC prevalence (RR = 0.75, p = 0.001) were no longer significant after taking into account skin phenotype and sun exposure, respectively. 25-Hydroxyvitamin D was strongly associated with higher melanin density (ß = 1.71-2.05, p = 0.001). The association between melanin density and total body BMD (ß = 0.007, p = 0.04) became non-significant after adjustment for 25-hydroxyvitamin D. There was no association between melanin density and physical activity, falls risk or BMD at other sites. CONCLUSIONS: Our data support a model of higher constitutive melanin density underpinning a less photosensitive skin phenotype, permitting greater sun exposure with fewer sequelae and yielding higher 25-hydroxyvitamin D and, potentially, total body BMD.

The relationship between objectively assessed physical activity and bone health in older adults differs by sex and is mediated by lean mass.

Relationships between objectively assessed free-living physical activity (PA) and changes in bone health over time are poorly understood in older adults. This study suggests these relationships are sex-specific and that body composition may influence the mechanical loading benefits of PA. INTRODUCTION: To investigate associations of objectively assessed PA and bone health in community-dwelling older adults. METHODS: This secondary analysis of a subset of the Tasmanian Older Adult Cohort study included participants with PA assessed utilising ActiGraph GT1M accelerometers over 7 days (N = 209 participants, 53% female; mean ± SD age 64.5 ± 7.2 years). Steps/day and PA intensity were estimated via established thresholds. Bone mineral content (BMC) was acquired at the total hip, lumbar spine, legs and whole body by DXA at baseline and approximately 2.2 years later. Relationships between PA and BMC were assessed by multivariable linear regression analyses adjusted for age, smoking status, height and total lean mass. RESULTS: Men with above-median total hip BMC completed significantly less steps per day, but there was no significant difference in PA intensity compared with those with below-median BMC. There were no significant differences in PA in women stratified by median BMC. In women, steps/day were positively associated with leg BMC (B = 0.178; P = 0.017), and sedentary behaviour was negatively associated with leg BMC (- 0.165; 0.016) at baseline. After adjustment for confounders including lean mass and height, higher sedentary behaviour at baseline was associated with declines in femoral neck BMC (- 0.286; 0.011) but also with increases in pelvic BMC (0.246; 0.030) in men and increases in total hip BMC (0.215; 0.032) in women, over 2.2 years. No other significant longitudinal associations were observed after adjustment for body composition. CONCLUSIONS: Associations of accelerometer-determined sedentary behaviour and PA with bone health in older adults differ by sex and anatomical site and are mediated by body composition.

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.

The association between ambulatory activity, body composition and hip or knee joint replacement due to osteoarthritis: a prospective cohort study.

OBJECTIVE: To examine the association between ambulatory activity (AA), body composition measures and hip or knee joint replacement (JR) due to osteoarthritis. DESIGN: At baseline, 1082 community-dwelling older-adults aged 50-80 years were studied. AA was measured objectively using pedometer and body composition by dual-energy X-ray absorptiometry. The incidence of primary (first-time) JR was determined by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR). Log binomial regression with generalized estimating equations were used to estimate the risk of JR associated with baseline AA and body composition measures, adjusting for age, sex, X-ray disease severity, and pain. RESULTS: Over 13 years of follow-up, 74 (6.8%) participants had a knee replacement (KR) and 50 (4.7%) a hip replacement (HR). AA was associated with a higher risk of KR (RR 1.09/1000 steps/day, 95% CI 1.01, 1.16) and a lower risk of HR (RR 0.90/1000 steps/day, 95% CI 0.81, 0.99). Body mass index (BMI) (RR 1.07/kg/m2, 95% CI 1.03, 1.12), total fat mass (RR 1.03/kg, 95% CI 1.01, 1.06), trunk fat mass (RR 1.05/kg, 95% CI 1.00, 1.09), and waist circumference (RR 1.02/cm, 95% CI 1.00, 1.04) were associated with a higher risk of KR. Body composition measures were not associated with HR. CONCLUSIONS: An objective measure of AA was associated with a small increased risk of KR and a small reduced risk of HR. Worse body composition profiles were associated with KR, but not HR. Altogether this may suggest different causal pathways for each site with regard to habitual activity and obesity.

Prospective Associations of Low Muscle Mass and Function with 10-Year Falls Risk, Incident Fracture and Mortality in Community-Dwelling Older Adults.

OBJECTIVES: Purpose: To compare the performance of low muscle mass and function with falls risk, incident fracture and mortality over 10 years. METHODS: 1041 participants (50% women; mean age 63±7.5 years) were prospectively followed for 10 years. Falls risk was measured using the Physiological Profile Assessment, fractures were self-reported and mortality was ascertained from the death registry. Appendicular lean mass (ALM) was assessed using dual energy X-ray absorptiometry. Four anthropometric: (ALM/height2, ALM/body mass index, ALM/weight×100, a residuals method of ALM on height and total body fat) and four performance-based measures: (handgrip strength, lower-limb muscle strength, upper and lower-limb muscle quality) were examined. Participants in the lowest 20% of the sex-specific distribution for each anthropometric and performance-based measure were classified has having low muscle mass or function. Regression analyses were used to estimate associations between each anthropometric and performance-based measure at baseline and 10-year falls risk, incident fractures and mortality. RESULTS: Mean falls risk z-score at 10 years was 0.64 (SD 1.12), incident fractures and mortality over 10 years were 16% and 14% respectively. All baseline performance-based measures were significantly associated with higher falls risk score at 10 years. Low handgrip (RR 1.55, 95% CI: 1.09, 2.20) and ALM/body mass index (RR 1.54, 95% CI: 1.14, 2.08) were the only significant predictors of fracture and mortality respectively. CONCLUSIONS: Low handgrip strength, a simple and inexpensive test could be considered in clinical settings for identifying future falls and fractures. ALM/ body mass index could be most suitable in estimating 10-year mortality risk, but requires specialised equipment.

The relationship between cumulative lifetime ultraviolet radiation exposure, bone mineral density, falls risk and fractures in older adults.

Data linking cumulative lifetime vitamin D status with skeletal outcomes are lacking. We show that increasing cumulative sun exposure was associated with higher bone mineral density in younger males and protective against fractures in females independent of current vitamin D. This supports the concept that cumulative sun exposure is an important contributor to skeletal health. INTRODUCTION: While low 25-hydroxyvitamin D levels are associated with increased fracture risk, this reflects only recent sun exposure. The Beagley-Gibson (BG) method utilises microtopographical skin changes to quantify cumulative lifetime ultraviolet radiation (sun) exposure. This study aimed to describe the relationship between BG grade, BMD, falls risk and fractures in older adults. METHODS: Eight hundred thirty-five community-dwelling adults aged 53-83 years had silicone casts from the dorsum of both hands graded by the BG method. BMD was measured using DXA and falls risk using the short form of the Physiological Profile Assessment. Vertebral deformities and symptomatic fractures were assessed by DXA and questionnaire, respectively. RESULTS: The relationship between BG grade, spine BMD and vertebral fracture varied depending upon sex. In females, increasing grade was associated with lower vertebral fracture prevalence (OR = 0.44/grade, p = 0.018) and fewer fractures (OR = 0.82/grade, p = 0.021), particularly major fractures (OR = 0.75/grade, p = 0.03). In males, increasing grade was associated with more DXA-detected vertebral deformities (RR = 1.28/grade, p = 0.001), but not symptomatic fractures. These relationships were independent of BMD, falls risk, smoking and current 25-hydroxyvitamin D. BG grade was not associated with falls risk. For BMD, there were interactions between BG grade and both age and sex and a positive trend with hip BMD in younger males. CONCLUSIONS: BG grade demonstrated beneficial associations with fracture outcomes in females and BMD in younger males independent of current 25-hydroxyvitamin D. These data support the concept that cumulative ultraviolet radiation exposure is an important determinant of skeletal health. The association with vertebral deformities in males may reflect outdoor physical trauma in younger life.

Predictors of Beagley-Gibson skin cast grade in older adults.

BACKGROUND AND PURPOSE: The Beagley-Gibson (BG) grading system utilizes microtopographical skin changes to generate an individualized, objective estimate of cumulative, lifetime ultraviolet radiation (UVR) exposure. However, predictors of BG grade are ill-defined, particularly in older populations. The aim of this cross-sectional study was to describe the factors associated with skin damage as measured by the BG method in 835 community-dwelling older adults. METHODS: Study participants aged 53-83 years had silicone casts taken from the dorsum of both hands and graded by the BG method. Lifetime sun exposure, skin phenotypic traits and smoking status were assessed by questionnaire. 25-hydroxyvitamin D and melanin density were measured using radioimmunoassay and spectrophotometry, respectively. Ordered logistic regression was used to compute a single odds ratio (OR) by taking BG grade as the outcome variable. RESULTS: Higher 25-hydroxyvitamin D was associated with increasing BG grade (OR = 1.39, P = 0.02) in adjusted analysis. Age (OR = 1.14, P < 0.001), occupational sun exposure (OR = 1.62, P < 0.001), ability to tan (OR = 1.40, P < 0.001), melanin density (OR=0.79, P = 0.001), lifetime leisure time sun exposure (OR = 1.21, P = 0.004), current smoking (OR = 1.82, P = 0.007), propensity to sunburn (OR = 1.18, P = 0.016), and waist-hip ratio (OR = 1.10, P = 0.02) were independent predictors of BG grade. Hair colour, number of sunburns, body mass index and gender were not independent predictors of BG grade. CONCLUSIONS: Beagley-Gibson skin cast grade is a biologically relevant marker of UVR exposure in older adults influenced by both intrinsic and extrinsic factors.