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Objective: To determine the effect of zoledronic acid (ZA) on the risk of total knee replacement (TKR) in patients with symptomatic knee osteoarthritis and without severe joint space narrowing (JSN). Methods: We included 222 participants (mean age 62 years, 52% female) from the two‐year Zoledronic Acid for Osteoarthritis Knee Pain trial (113 received 5 mg of ZA annually and 109 received placebo) conducted between November 2013 and October 2017. Primary TKR were identified until February 22, 2022. The effect of ZA on TKR risk was evaluated using Cox proportional hazard regression models. Because the treatment effect failed the proportional hazards assumption, a time‐varying coefficients analysis for treatment was conducted by splitting the study into two periods (ie, within and after two years of randomization). Results: Over a mean follow‐up of seven years, 39% and 30% of participants had any TKR in the ZA and placebo groups, and 28% and 18% had TKR in the study knee, respectively. Use of ZA was associated with a higher risk of TKR in any knee (hazard ratio [HR] 4.2, 95% confidence interval [CI] 1.2–14.7) and showed a trend in the study knee (HR 6.8, 95%CI 0.9–53.9) during the trial. In the posttrial period, the risk of TKR was similar in the ZA and the placebo groups for any knee (HR 1.2, 95%CI 0.5–1.8) and the study knee (HR 1.4, 95%CI 0.5–2.2). Conclusion: These results suggest that ZA is not protective against TKR in patients with symptomatic knee osteoarthritis and without severe JSN. [ABSTRACT FROM AUTHOR]

We examined the longitudinal associations of accelerometer-measured physical activity and sedentary time with leg muscle strength (LMS), balance, and falls in middle-aged women. This was a 5-year cohort study among 308 women aged 36–56 years. We used linear mixed-effects models to examine associations of baseline and change in accelerometer-measured sedentary time, light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) with baseline and 5-year change in LMS and balance (timed up and go test [TUG], functional reach test [FRT], lateral reach test [LRT], and step test [ST]), and negative binomial/Poisson and log-binomial regression as appropriate to assess associations with falls after 5-year follow-up. Greater baseline MVPA was associated with better baseline LMS (β = 4.65 kg/SD, 95% CI: 1.37, 7.93) and TUG (β = −0.09 s/SD, 95% CI: –0.18, –0.01) but not with change in them over 5 years. Baseline MVPA was not associated with FRT at baseline but associated with a greater decrease in FRT (β = −0.87 cm/SD, 95% CI: –1.57, –0.17). Increased MVPA over 5 years was associated with less deterioration in FRT (β = 0.88 cm/SD, 95% CI: 0.14, 1.61). Increased sedentary time over 5 years was associated with a larger decrease in FRT (β = −0.82 cm/SD, 95% CI: –1.58, –0.07). Higher baseline LPA was associated with higher falls risk (IRR = 1.27, 95% CI: 1.02, 1.57). Higher baseline MVPA may benefit LMS and balance, while increasing MVPA in the medium term has little effect on change in these outcomes in mid-life. Detrimental association of LPA with falls may be due to greater exposures to environmental hazards. Highlights Our study for the first time examined the longitudinal associations of objectively measured physical activity and sedentary time with leg muscle strength, balance and falls in middle-aged women. Higher baseline moderate-to-vigorous physical activity (MVPA) may be beneficial for muscle strength and balance at baseline but increasing MVPA in the medium term has little effect on change in LMS or balance outcomes in middle-aged women. Higher baseline light physical activity (LPA) was associated with an increased risk of falls. The detrimental association of LPA with falls may be due to a greater exposure to environmental hazards in midlife, which needs to be clarified in future research. [ABSTRACT FROM AUTHOR]

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 I 2 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, I 2 = 92%) with no effect for ZA alone. Differences in knee function were statistically significant at 3 months [SMD = − 0.22 (− 0.43, − 0.01), I 2 = 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), I 2 = 0%] but not at 12 months or two years. Adverse events [RR = 1.19 (1.00, 1.41) I 2 = 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. [ABSTRACT FROM AUTHOR]

Objective: The effect of physical activity on the risk of developing knee osteoarthritis (OA) is unclear. We undertook this study to examine the relationship between recreational physical activity and incident knee OA outcomes using comparable physical activity and OA definitions. Methods: Data were acquired from 6 global, community‐based cohorts of participants with and those without knee OA. Eligible participants had no evidence of knee OA or rheumatoid arthritis at baseline. Participants were followed up for 5–12 years for incident outcomes including the following: 1) radiographic knee OA (Kellgren‐Lawrence [K/L] grade ≥2), 2) painful radiographic knee OA (radiographic OA with knee pain), and 3) OA‐related knee pain. Self‐reported recreational physical activity included sports and walking/cycling activities and was quantified at baseline as metabolic equivalents of task (METs) in days per week. Risk ratios (RRs) were calculated and pooled using individual participant data meta‐analysis. Secondary analysis assessed the association between physical activity, defined as time (hours per week) spent in recreational physical activity and incident knee OA outcomes. Results: Based on a total of 5,065 participants, pooled RR estimates for the association of MET days per week with painful radiographic OA (RR 1.02 [95% confidence interval (95% CI) 0.93–1.12]), radiographic OA (RR 1.00 [95% CI 0.94–1.07]), and OA‐related knee pain (RR 1.00 [95% CI 0.96–1.04]) were not significant. Similarly, the analysis of hours per week spent in physical activity also showed no significant associations with all outcomes. Conclusion: Our findings suggest that whole‐body, physiologic energy expenditure during recreational activities and time spent in physical activity were not associated with incident knee OA outcomes. [ABSTRACT FROM AUTHOR]

Background: A socioeconomic gradient exists in the utilisation of total hip replacements (THR) and total knee replacements (TKR) for osteoarthritis. However, the relations between socioeconomic status (SES) and time to THR or TKR is unknown. Aim: To describe the association between SES and time to THR and TKR. Methods: One thousand and seventy‐two older adults residing in Tasmania, Australia, were studied. Incident primary THR and TKR were determined by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry. At baseline, each participant's area‐level SES was determined using the Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) from the Australian Bureau of Statistics' 2001 census data. The IRSAD was analysed in two ways: (i) categorised into quartiles, whereby quartile 1 represented the most socioeconomically disadvantaged group; and (ii) the cohort dichotomised at the quartile 1 cut‐point. Results: The mean age was 63.0 (±7.5) years and 51% were women. Over the median follow up of 12.9 (interquartile range: 12.2–13.9) years, 56 (5%) participants had a THR and 79 (7%) had a TKR. Compared with the most disadvantaged quartile, less disadvantaged participants were less likely to have a THR (i.e. less disadvantaged participants had a longer time to THR; hazard ratio (HR): 0.56; 95% confidence interval (CI) 0.32, 1.00) but not TKR (HR: 0.90; 95% CI 0.53, 1.54). However, the former became non‐significant after adjustment for pain and radiographic osteoarthritis, suggesting that the associations may be mediated by these factors. Conclusions: The present study suggests that time to joint replacement was determined according to the symptoms/need of the participants rather than their SES. [ABSTRACT FROM AUTHOR]

Objective To investigate the impact of total number and patterns of comorbidities on health-related quality of life (HRQoL) and identify the most prevalent and influential comorbidity patterns in people with OA over 10 years. Methods Participants from the Tasmanian Older Adult Cohort aged 50–80 years, with self-reported OA and data on comorbidities and HRQoL were included. Participants were interviewed at baseline (n  = 398), 2.5 (n  = 304), 5 (n  = 269) and 10 years (n  = 191). Data on the self-reported presence of 10 chronic comorbidities were collected at baseline. HRQoL was assessed using the Assessment of Quality of Life-4-Dimensions. The long-term impacts of the number and of the nine most prevalent combinations of cardiovascular (CVD), non-OA musculoskeletal (Ms), metabolic and respiratory comorbidities on HRQoL over 10 years were analysed using linear mixed regressions. Results Compared with comorbidity-free OA participants, the health state utility (HSU) of those with 2 or ≥3 comorbidities was respectively −0.07 and −0.13 units lower over 10 years, largely driven by reduced scores for independent living, social relationships and psychological wellness. Comorbidity patterns including 'CVD+Ms' were most influential, and associated with up to 0.13 units lower HSU, mostly through negative impacts on independent living (up to −0.12), psychological wellness (up to −0.08) and social relationship (up to −0.06). Conclusion Having more comorbidities negatively impacted OA patients' long-term HRQoL. OA patients with CVD and non-OA musculoskeletal conditions had the largest HSU impairment, and therefore optimal management and prevention of these conditions may yield improvements in OA patients' HRQoL. [ABSTRACT FROM AUTHOR]

Objective: To determine whether atorvastatin slows tibial cartilage volume loss in patients with symptomatic knee osteoarthritis (OA) in a multicenter, randomized, double‐blind, placebo‐controlled trial. Methods: Participants ages 40–70 years were randomized to receive oral atorvastatin (40 mg once daily) (n = 151) or matching placebo (n = 153). The primary end point was annual percentage change in tibial cartilage volume over 2 years, assessed using magnetic resonance imaging (MRI). The prespecified secondary end points were progression of cartilage defects and bone marrow lesions over 2 years, which were assessed using MRI and change in Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index pain, stiffness, and function scores. Results: A total of 248 of 304 participants (81.6%) completed the trial (mean age 55.7 years; 55.6% women). The annual change in tibial cartilage volume differed minimally between the atorvastatin and placebo groups (mean change –1.66% versus –2.17%, between‐group difference 0.50% [95% confidence interval (95% CI) –0.17%, 1.17%]). There were no significant differences in the progression of cartilage defects (odds ratio [OR] 0.86 [95% CI 0.52, 1.41]) or progression of bone marrow lesions (OR 1.00 [95% CI 0.62, 1.63]). Moreover, there were no significant differences in change in WOMAC pain, stiffness, or function scores over 2 years between the atorvastatin and placebo groups (mean change in pain score –36.0 versus –29.5, adjusted difference –2.7 [95% CI –27.1, 21.7]; mean change in stiffness score –14.2 versus –11.8, adjusted difference –0.2 [95% CI –12.2, 11.8]; mean change in function score –89.4 versus –87.5, adjusted difference 0.3 [95% CI –83.1, 83.6]). The incidence of adverse events (AEs) was similar between the atorvastatin and placebo groups (57 [37.7%] versus 52 [34.0%] experiencing AEs). Conclusion: Treatment with oral atorvastatin (40 mg once daily), compared to placebo, did not significantly reduce cartilage volume loss over 2 years in patients with symptomatic knee OA. These findings do not support the use of atorvastatin for the treatment of knee OA. [ABSTRACT FROM AUTHOR]

* OBJECTIVE: To determine the independent associations of potential clinical, symptom, physical activity, and psychological factors with chronic plantar heel pain. * DESIGN: Case-control. * METHODS: We investigated associations by comparing 220 participants with chronic (more than 3 months in duration) plantar heel pain to 100 age- and sex-matched controls, who were recruited randomly from the electoral roll. Exposures measured were waist girth, body mass index, body composition, clinical measures of foot and leg function, physical activity via accelerometry, systemdepression and pain catastrophizing, symptoms of prolonged morning stiffness anywhere in the body, and multisite pain. Data were analyzed using multivariable conditional logistic regression. * RESULTS: Waist girth (centimeters) (odds ratio [OR] = 1.06; 95% confidence interval ICI]: 1.03, 1.09), ankle plantar flexor strength (kilograms) (OR - 0.98; 95% Cl: 0.97,0.99), pain at multiple sites (pain at 1 other site : OR = 2.76 ; 95 % Cl : 1. 29, 591; pain at 4 or more other sites: OR = 10.45; 95% Cl: 3.66, 29.81), and pain catastrophizing status (none, some, or catastrophizer) (some: OR = 2.91: 95% Cl: 1.33, 6.37: catastrophizer OR = 6.79; 95% Cl: 1.91,24.11) were independently associated with chronic plantar heel pair. There were univariable but not independent associations with morning stiffness, first metatarsophalangeal joint extension range of motion, depression, and body mass index. There were no significant associations with physical activity or body composition (bioelectrical impedance analysis) * CONCLUSION: Waist girth, ankle plantar flexor strength, multisite pain, and pain catasheel trophizing, but not foot-specific factors, were independently associated with chronic plantar heel pain. Of these 4 factors, 3 (waist girth, multisite pain, and pain catastrophizing) were central or systemic associations. [ABSTRACT FROM AUTHOR]

Objective To describe the impact of OA on health-related quality of life (HRQoL) in the forms of health state utilities (HSUs) and health-dimension scores, and to compare the longitudinal changes in HRQoL for people with and without OA, using an Australian population-based longitudinal cohort. Methods Participants of the Tasmanian Older Adult Cohort with data on OA diagnosis and HRQoL were included [interviewed at baseline (n  = 1093), 2.5 years (n  = 871), 5 years (n  = 760) and 10 years (n  = 562)]. HRQoL was assessed using the Assessment of Quality of Life four-dimensions and analysed using multivariable linear mixed regressions. Results Compared with participants without OA, HSUs for those with OA were 0.07 (95% confidence interval: 0.09, 0.05) units lower on average over 10 years. HSUs for participants with knee and/or hip OA were similar to those with other types of OA at the 2.5 year follow-up and then diverged, with HSUs of the former being up to 0.09 units lower than the latter. Those with OA had lower scores for psychological wellness, independent living and social relationships compared with those without OA. Independent living and social relationships were mainly impacted by knee and/or hip OA, with the effect on the former increasing over time. Conclusion Interventions to improve HRQoL should be tailored to specific OA types, health dimensions, and times. Support for maintaining psychological wellness should be provided, irrespective of OA type and duration. However, support for maintaining independent living could be more relevant to knee and/or hip OA patients living with the disease for longer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: To examine associations of education and occupation with handgrip strength (HGS), lower limb strength (LLS) and appendicular lean mass (ALM). Methods: Measures of HGS, LLS and ALM (dual‐energy X‐ray absorptiometry) were ascertained at baseline in 1090 adults (50‐80 years, 51% women), ~3 and 5 years. Education and occupation were self‐reported, the latter categorised as high‐skilled white collar (HSWC), low‐skilled white collar (LSWC) or blue collar. Separate general estimating equations were performed. Results: The highest education group had greater HGS than the middle (0.33 psi) and lowest (0.48 psi) education groups, and 0.34 kg greater ALM than the lowest education group. HGS was 0.46 psi greater for HSWC than LSWC groups. Compared to LSWC groups, LLS was 5.38 and 7.08 kg greater in HSWC and blue‐collar groups. Blue‐collar and HSWC groups each had ~ 0.60‐0.80kg greater ALM than LSWC. Conclusion: Progressive muscle loss can be prevented by targeted intervention; thus, we suggest clinical attention be directed towards specific social groups. [ABSTRACT FROM AUTHOR]

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 [β = 6.52 μm/kg (95% CI 0.86, 12.18)] and bone area [β = 13.37 mm2/kg (95% CI 5.43, 21.31)]. Physical performance measures were positively associated with cartilage thickness [long jump: β = 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: β = 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. [ABSTRACT FROM AUTHOR]

Objective To examine the association of metabolic syndrome (MetS) and its components with knee cartilage volume loss and bone marrow lesion (BML) change. Methods Longitudinal data on 435 participants from a population-based cohort study were analysed. Blood pressure, glucose, triglycerides and high-density lipoprotein (HDL) were collected. MetS was defined based on the National Cholesterol Education Program–Adult Treatment Panel III criteria. MRI of the right knee was performed to measure cartilage volume and BML. Radiographic knee OA was assessed by X-ray and graded using the Altman atlas for osteophytes and joint space narrowing. Results Thirty-two percent of participants had MetS and 60% had radiographic knee OA. In multivariable analysis, the following were independently associated with medial tibial cartilage volume loss: MetS, β = −0.30%; central obesity, β = −0.26%; and low HDL, β = −0.25% per annum. MetS, hypertriglyceridaemia and low HDL were also associated with higher risk of BML size increase in the medial compartment (MetS: relative risk 1.72, 95% CI 1.22, 2.43; hypertriglyceridaemia: relative risk 1.43, 95% CI 1.01, 2.02; low HDL: relative risk 1.67, 95% CI 1.18, 2.36). After further adjustment for central obesity or BMI, MetS and low HDL remained statistically significant for medial tibial cartilage volume loss and BML size increase. The number of components of MetS correlated with greater cartilage volume loss and BML size increase (both P for trend <0.05). There were no statistically significant associations in the lateral compartment. Conclusion MetS and low HDL are associated with medial compartment cartilage volume loss and BML size increase, suggesting that targeting these factors has the potential to prevent or slow knee structural change. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy and safety of lesinurad in combination with febuxostat in a 12-month phase III trial in patients with tophaceous gout. Methods Patients with serum urate (UA) ≥8.0 mg/dl (≥6.0 mg/dl with urate-lowering therapy) and ≥1 measurable target tophus were given febuxostat 80 mg/day for 3 weeks before randomization to receive lesinurad (200 or 400 mg daily) or placebo in addition to the febuxostat. The primary end point was the proportion of patients achieving a serum UA level of <5.0 mg/dl (month 6). The key secondary end point was the proportion of patients with complete resolution of ≥1 target tophus (month 12). Other end points included the percentage change in total target tophi area. Safety assessments included adverse events and laboratory data. Results Patients (n = 324) were predominantly male, with a mean age of 54.1 years. Significantly more patients achieved the serum UA target by month 6 with the addition of lesinurad 400 mg (76.1%; P < 0.0001), but not 200 mg (56.6%; P = 0.13), to the febuxostat therapy as compared with febuxostat alone (46.8%). At all other time points, significantly more patients in the lesinurad 200 mg group achieved the serum UA target. The number of patients with complete tophus resolution was not different between groups. Treatment with lesinurad (200 mg and 400 mg) plus febuxostat reduced the total target tophi area as compared with febuxostat alone (50.1% and 52.9% versus 28.3%, respectively; P < 0.05). Safety was generally comparable with that of febuxostat alone, except for higher rates of predominantly reversible elevations in the serum creatinine level, particularly with lesinurad 400 mg. Conclusion Treatment with lesinurad in combination with febuxostat demonstrated superior lowering of serum UA levels as compared with febuxostat alone, with clinically relevant added effects on tophi and an acceptable safety profile with lesinurad 200 mg in patients with tophaceous gout warranting additional therapy. [ABSTRACT FROM AUTHOR]

Objective. To identify novel biomarker(s) for predicting advanced knee OA. Methods. Study participants were derived from the Newfoundland Osteoarthritis Study and the Tasmania Older Adult Cohort Study. All knee OA cases were patients who underwent total knee replacement (TKR) due to primary OA. Metabolic profiling was performed on fasting plasma. Four thousand and eighteen plasma metabolite ratios that were highly correlated with that in SF in our previous study were generated as surrogates for joint metabolism. Results. The discovery cohort included 64 TKR cases and 45 controls and the replication cohorts included a cross-sectional cohort of 72 TKR cases and 76 controls and a longitudinal cohort of 158 subjects, of whom 36 underwent TKR during the 10-year follow-up period. We confirmed the previously reported association of the branched chain amino acids to histidine ratio with advanced knee OA (P = 9.3 x 10-7) and identified a novel metabolic marker--the lysophosphatidylcholines (lysoPCs) to phosphatidylcholines (PCs) ratio--that was associated with advanced knee OA (P = 1.5 x 10-7) after adjustment for age, sex and BMI. When the subjects of the longitudinal cohort were categorized into two groups based on the optimal cut-off of the ratio of 0.09, we found the subjects with the ratio ≽0.09 were 2.3 times more likely to undergo TKR than those with the ratio <0.09 during the 10-year follow-up (95% CI: 1.2, 4.3, P = 0.02). Conclusion. We identified the ratio of lysoPCs to PCs as a novel metabolic marker for predicting advanced knee OA. Further studies are required to examine whether this ratio can predict early OA change. [ABSTRACT FROM AUTHOR]

Objectives. The aim was to determine the non-melanoma skin cancer (NMSC) risk in patients with RA or PsA exposed to MTX and other DMARDs. Methods. Information on medication was collected on 405 patients with RA or PsA in two private rheumatology practices and was matched to comprehensive histologically confirmed cancer registry data for the years 1978-2005. Relative risks (RRs) were estimated by logarithmic binomial modelling, and standardized incidence ratios (SIRs) were calculated from year-, sex- and age-specific rates of NMSC for the local population. Results. Compared with no MTX usage, any MTX usage was associated with a higher rate of at least one histopathologically confirmed NMSC (SIR 4.64, 95% CI: 0.67, 33.2). The SIR was 4.81 (95% CI: 3.60, 6.29) for those receiving a cumulative dose >8000 mg compared with SIR 2.31 (95% CI: 1.58, 2.36) for <5000 mg. An increased risk was shown for both basal cell carcinomas and squamous cell carcinomas, with an apparent dose--response relationship for basal cell carcinomas but not for squamous cell carcinomas. There was an increased risk of NMSC in patients taking CSA (RR = 2.51, 95% CI: 1.23, 5.13) and D-Pen (RR 3.49, 95% CI: 1.34, 4.63) in addition to MTX, but not for patients taking AZA or LEF. Conclusion. MTX, and concurrent MTX and CSA or D-Pen use, is associated with an increased risk of NMSC. These results should encourage greater clinical vigilance for NMSC in treated patients with RA and PsA. [ABSTRACT FROM AUTHOR]

Objectives. Conflicting reports of the effect of physical activity on knee cartilage may be due to the heterogeneity of populations examined and, in particular, the underlying health of the knee joint. This study examined the influence of recreational and occupational physical activity on cartilage volume loss. Methods. A total of 250 participants with no significant musculoskeletal disease were recruited. A gender-specific median cartilage volume split was used to define people in the lowest and highest 50% of baseline cartilage volume. Baseline recreational and occupational activity was examined by questionnaire, while cartilage volume was assessed by MRI at baseline and 2.4 years later. Results. Significant interactions were demonstrable between physical activity and cartilage volume loss based on stratification of baseline cartilage volume (all P ≤ 0.03). There was a dose-response relationship between frequently performed baseline occupational activities and medial cartilage volume loss in both the low (B = 0.2% per annum, 95% CI: 0.0, 0.04% per annum) and high (B = -0.2% per annum, 95% CI: -0.4, 0.0% per annum) baseline cartilage volume groups (P = 0.001 for interaction). Individuals with low baseline cartilage volume who were active in their occupation and/or recreational activity had greater medial cartilage volume loss than their more inactive counterparts (2.4% per annum vs 1.5% per annum, P = 0.02). Conclusion. Whereas people with less baseline cartilage volume are more at risk of structural knee damage with either heavy occupational or recreational workloads or both, individuals with high baseline cartilage volume may advantageously modify their risk for knee OA by participating in more frequent occupational physical activities. [ABSTRACT FROM AUTHOR]

Objective To describe the natural history of quantitatively measured knee effusion-synovitis and the longitudinal associations between effusion-synovitis and knee structural factors, including cartilage defects, cartilage volume, subchondral bone marrow lesions, and meniscal pathology, in older adults. Methods A total of 406 subjects (with a mean age of 63 years, 50% women) were randomly selected at baseline and followed up 2.7 years later. T2- or T1-weighted fat saturation magnetic resonance imaging was used to assess knee effusion-synovitis maximal area, cartilage defects, cartilage volume, bone marrow lesions, and meniscal pathology at baseline and follow-up. Multivariable generalized linear regression was performed to analyze the associations between the maximal area of effusion-synovitis and other joint structural factors after adjustment for age, sex, body mass index, tibial bone area, and/or radiographic osteoarthritis (OA). Results Over 2.7 years of follow-up, the size of effusion-synovitis increased in 29%, remained stable in 50%, and decreased in 22% of the participants. Baseline effusion-synovitis maximal area was significantly associated with changes in knee cartilage defects (β = 0.18 [95% confidence interval (95% CI)] 0.07, 0.29), bone marrow lesions (β = 0.17 [95% CI 0.05, 0.30]), and cartilage volume (β = −0.40 [95% CI −0.71, −0.09]) but not with change in meniscal pathology. In contrast, baseline structural measures were not associated with change or increase in effusion-synovitis maximal area. Conclusion Our findings indicate that knee effusion-synovitis is not static in older adults. It is predictive of, but not predicted by, other structural abnormalities, suggesting a potential role in early knee OA changes. [ABSTRACT FROM AUTHOR]

Objective. Cartilage loss is a key pathological feature of OA and can be assessed indirectly using radiography or directly through MRI. A number of cross-sectional studies have suggested that primary generalized osteoarthritis (PGOA) may be a distinct disease, but despite the high frequency of involvement of the hip and the knee joints in OA, very few studies have looked at the radiographic association between these two joints, and none has done so using MRI. The aim of this study was to examine the association of hip and knee cartilage measured by both radiography and MRI.Methods. We studied 151 participants from the Tasmanian Older Adult Cohort (TASOAC) study, who were selected randomly from the southern Tasmanian electoral rolls. MRI was used to assess hip and knee cartilage volume and radiography was used to assess joint space narrowing (JSN). Correlation analyses were used to compare cartilage volume measurements and JSN.Results. In adjusted analysis, there was a consistent, positive association between knee and hip cartilage volume that was best for total knee cartilage volume (r = 0.16–0.40, all P < 0.05). In contrast, there was at best a weak correlation, depending on the site, between hip and knee JSN (r = −0.01 to 0.21).Conclusion. Hip and knee cartilage volume are more strongly associated than hip and knee JSN, suggesting a commonality of cartilage volume at different anatomic sites. The weaker radiographic association may reflect less measurement error with MRI or the contribution of multiple structures to joint space in the knee. [ABSTRACT FROM PUBLISHER]

Objective. To systematically review the evidence for association between serum 25-hydroxyvitamin D (25-(OH)D) and OA and the effect of vitamin D therapy on OA.Methods. An English Medline, EMBASE and Cochrane Library search for vitamin D and OA from January 1980 to June 2012 was performed. Randomized controlled trials (RCTs), cohort, case–control and cross-sectional studies in adults were included. The methodological quality of the selected studies was assessed and a best-evidence synthesis was used to summarize the results due to the heterogeneity of the studies.Results. Of the 86 evaluated articles, 2 RCTs and 13 observational studies were included in the final analyses. The number of participants ranged from 64 to 1644 (0–100% women). The RCTs were only reported in abstract form and showed inconsistent results, most likely due to variations in their study design. There was insufficient or limited evidence for associations between 25-(OH)D and hand or hip OA. For knee radiographic OA as assessed by the Kellgren and Lawrence (KL) score, there was moderate evidence showing that low levels of 25-(OH)D were associated with increased progression of radiographic OA. Strong evidence for an association between 25-(OH)D and cartilage loss was apparent when joint space narrowing and changes in cartilage volume were considered collectively as cartilage loss.Conclusion. 25-(OH)D appears to be implicated in structural changes of knee OA rather than symptoms, and further well-designed RCTs are required to determine whether vitamin D supplementation can slow disease progression. There is insufficient evidence for other sites. [ABSTRACT FROM PUBLISHER]

Objective Although there is evidence for a beneficial effect of increased quadriceps strength on knee symptoms, the effect on knee structure is unclear. We undertook this study to examine the relationship between change in vastus medialis cross-sectional area (CSA) and knee pain, tibial cartilage volume, and risk of knee replacement in subjects with symptomatic knee osteoarthritis (OA). Methods One hundred seventeen subjects with symptomatic knee OA underwent magnetic resonance imaging of the knee at baseline and at 2 and 4.5 years. Vastus medialis CSA was measured at baseline and at 2 years. Tibial cartilage volume was measured at baseline and at 2 and 4.5 years. Knee pain was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index at baseline and at 2 years. The frequency of knee joint replacement over 4 years was determined. Regression coefficients (B) and odds ratios were determined along with 95% confidence intervals (95% CIs). Results After adjusting for confounders, baseline vastus medialis CSA was inversely associated with current knee pain (r = −0.16, P = 0.04) and with medial tibial cartilage volume loss from baseline to 2 years (B coefficient −10.9 [95% CI −19.5, −2.3]), but not with baseline tibial cartilage volume. In addition, an increase in vastus medialis CSA from baseline to 2 years was associated with reduced knee pain over the same time period (r = 0.24, P = 0.007), reduced medial tibial cartilage loss from 2 to 4.5 years (B coefficient −16.8 [95% CI −28.9, −4.6]), and reduced risk of knee replacement over 4 years (odds ratio 0.61 [95% CI 0.40, 0.94]). Conclusion In a population of patients with symptomatic knee OA, increased vastus medialis size was associated with reduced knee pain and beneficial structural changes at the knee, suggesting that management of knee pain and optimizing vastus medialis size are important in reducing OA progression and subsequent knee replacement. [ABSTRACT FROM AUTHOR]

Objectives. There have been no reported studies of the association between parity and cartilage in young individuals. The aim of this study was to describe the association between parity, cartilage volume and cartilage defects in women aged 31–41 years.Methods. Cross-sectional study of 144 women, mean age 36 years and BMI 25 kg/m2, who were participants in an established prospective study. Parity was assessed using a questionnaire. Knee (medial tibial, lateral tibial and patellar) cartilage volume, cartilage defects (grade 0–4 depending on the severity of cartilage thickness loss at tibial and patellar sites) and tibial bone area were assessed using T1-weighted fat-suppressed MRI.Results. The prevalence of cartilage defects (grade &geq;2) in this population was 13%. Parity was associated with a higher risk of cartilage defects at the patellar [prevalence ratio (PR) per birth 1.52, 95% CI 1.05, 2.21; PR parous vs nulliparous 1.93, 95% CI 0.66, 5.65], but not tibial sites, after adjustment for confounders including age, BMI, smoking, physical activity, knee injury and tibial bone area. This association between parity and patellar cartilage defects was stronger for those women who had three or more births (vs nulliparous, PR 5.27, 95% CI 1.39, 20.01). There were no significant associations between parity and cartilage volume.Conclusion. Parity was associated with knee cartilage defects primarily at the patellar site in this sample of young women. This association was more apparent with increasing number of live births, suggesting a possible adverse effect of parity on knee cartilage. [ABSTRACT FROM PUBLISHER]

• In addition to inter-individual differences, intra-individual variability in physical activity is associated with knee pain and functional limitation. • When participants engaged in more physical activity than their average level, they had lower knee pain and functional limitation. • Conversely, having higher functional limitations compared with an individual's average was associated with lower levels of physical activity. To describe the associations between interindividual (between-person) and intraindividual (within-person) variability in physical activity (PA) and knee pain and functional limitation among older adults. We also investigated the potential bidirectional association of between-person and within-person variability in knee pain and functional limitation with PA. Participants (N = 1064; 51% women; mean age 63 ± 7.4 years) were measured at baseline, 2.5, and 5 years. PA was measured using pedometers. Knee pain and functional limitation were assessed using the WOMAC scale. A two-part hurdle model, with adjustment for confounders, estimated the association of between-person and within-person variability in PA with knee pain/functional limitation (as the outcome). Linear mixed effect regression models described the association of between-person and within-person variability in knee pain and functional limitation with PA (as the outcome). Between-person effects showed that participants with a higher 5-year average PA had lower average WOMAC scores (β= –1.17, 95% CI: –1.82, –0.51). Within-person effects showed that at time-points when participants had a higher PA level than average, they also had lower WOMAC scores (β= –0.85, 95% CI: –1.36, –0.35). Conversely, both between-person (β= –15.6, 95% CI: –22.5, –8.8) and within-person increase (β= –7.4, 95% CI: –13.5, –1.4) in WOMAC scores were associated with lower PA. These findings suggest that PA and knee pain/dysfunctional contribute to the development of one another. Pain can lead to changes in inter- and intraindividual PA levels, but the reverse is also possible – changes in PA results in changes in inter- and intraindividual pain/dysfunctional levels. [ABSTRACT FROM AUTHOR]

To determine the effect of vitamin D supplementation and maintaining sufficient serum vitamin D on depressive symptoms in patients with knee osteoarthritis (OA) and vitamin D deficiency. A prespecified secondary analysis of a multicentre, randomized, double-blind, placebo-controlled trial. Participants were randomly assigned to receive oral vitamin D 3 (50,000 IU, n = 209) or placebo (n = 204) monthly for 24 months. In addition, participants who completed the trial were classified into 2 groups according to their serum 25(OH)D levels at month 3 and 24 as follows: not consistently sufficient (serum 25(OH)D ≤ 50 nmol/L at month 3 and/or 24), and consistently sufficient (serum 25(OH)D > 50 nmol/L at both month 3 and 24). Multilevel mixed-effect models were used to compare differences of change in PHQ-9 scores between groups. This clinical trial was conducted in participants with symptomatic knee OA and vitamin D deficiency from June 2010 to December 2013 in Tasmania and Victoria, Australia. The primary outcome was the depressive symptoms change over 24 months, which was measured using the Patient Health Questionnaire (PHQ-9, 0-27). Of 599 participants who were screened for eligibility, 413 participants were enrolled (mean age: 63.2 years; 50.3% female) and 340 participants (intervention n = 181, placebo n = 159, 82.3% retention rate) completed the study. The baseline prevalence of depression (PHQ-9 score ≥5) was 25.4%. Depressive symptoms improved more in the vitamin D supplementation group compared to the placebo group [β: −0.66, 95% confidence interval (CI): −1.22 to −0.11, P for difference =.02] and in the participants who maintained vitamin D sufficiency compared to those who did not (β: −0.73, 95% CI: −1.41 to −0.05, P for difference =.04) over 24 months. These findings suggest that vitamin D supplementation and maintaining adequate vitamin D levels over 24 months may be beneficial for depressive symptoms in patients with knee OA. [ABSTRACT FROM AUTHOR]