Risk of first hip fracture under treatment with zoledronic acid versus alendronate: a NOREPOS cohort study of 88,000 Norwegian men and women in outpatient care.

We aimed to investigate the risk of hip fracture associated with zoledronic acid treatment compared to alendronate on a population level. The risk of hip fracture was lower in women using zoledronic acid and higher in women who had discontinued treatment. The findings support the effectiveness of intravenous bisphosphonate. PURPOSE: To investigate whether zoledronic acid (ZOL) was associated with a lower risk of the first hip fracture than alendronate (ALN) in Norway using real-world data. METHODS: Nationwide data on drugs dispensed in outpatient pharmacies were individually linked with all hospital-treated hip fractures. Individuals aged 50-89 years without previous hip fracture were included at their first filling of a prescription for ALN or ZOL during 2005-2016. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) for first hip fracture by time-varying exposure to ZOL versus ALN were estimated in sex-stratified flexible parametric survival analyses. Covariates included time-varying accumulated ALN exposure and comorbidity level expressed by the prescription-based Rx-Risk Comorbidity Index, marital status, education, and residential urbanity. RESULTS: Of 75,250 women who initiated treatment, 72,614 (96.5%) were exposed to ALN and 6366 (8.5%) to ZOL. Of 12,739 men who initiated treatment, 12,311 (96.6%) were exposed to ALN and 784 (6.2%) to ZOL. In women, the HR for first hip fracture was 0.75 (95% CI: 0.61-0.91) for ZOL versus ALN. In men, the corresponding HR was 0.59 (95% CI: 0.32-1.07). Discontinued treatment was associated with increased risk compared with current ALN treatment in women (HR: 1.33; 95% CI: 1.24-1.42, men: HR 1.13 (95% CI: 0.95-1.35)). CONCLUSIONS: In women, the risk of first hip fracture when treated with ZOL was 25% lower than when treated with ALN. Discontinued treatment was associated with a 33% increase in hip fracture risk. Similar, albeit statistically non-significant, results were observed in men.

Automated segmentation of the median nerve in patients with carpal tunnel syndrome.

Machine learning and deep learning are novel methods which are revolutionizing medical imaging. In our study we trained an algorithm with a U-Net shaped network to recognize ultrasound images of the median nerve in the complete distal half of the forearm and to measure the cross-sectional area at the inlet of the carpal tunnel. Images of 25 patient hands with carpal tunnel syndrome (CTS) and 26 healthy controls were recorded on a video loop covering 15 cm of the distal forearm and 2355 images were manually segmented. We found an average Dice score of 0.76 between manual and automated segmentation of the median nerve in its complete course, while the measurement of the cross-sectional area at the carpal tunnel inlet resulted in a 10.9% difference between manually and automated measurements. We regard this technology as a suitable device for verifying the diagnosis of CTS.

Educational gradient in hip fracture incidence in Norway. The Norwegian Epidemiologic Osteoporosis Studies (NOREPOS).

Examining fracture dynamics by socioeconomic status may inform healthcare and prevention. We found a higher risk of hip fracture in men and women with lower educational level in Norway. However, by age 90 + years, the cumulative incidence was higher in those with higher education, due to their higher life expectancy. PURPOSE: Socioeconomic gradients are seen for several health outcomes in high-income countries. We aimed to examine possible educational gradients in risk of hip fracture in Norway and to describe the cumulative incidence of hip fracture by educational level. METHODS: In a population-wide cohort of Norwegians aged ≥ 50 years, information on attained education from Statistics Norway was linked to hospital-treated hip fractures and deaths during 2002-2019. We estimated relative fracture risk by educational level (primary, secondary or tertiary) in Cox proportional hazards regression. We also examined the cumulative incidence over attained age by gender and educational level in competing risk regression. RESULTS: The population included N = 1,389,858 individuals with 135,938 incident hip fractures. Compared with men who had attained tertiary education, hazard ratios (95% confidence intervals) for hip fracture were 1.44 (1.40, 1.49) in men with primary education only and 1.26 (1.22, 1.29) in men with secondary education. In women, the corresponding estimates were 1.28 (1.25, 1.31) and 1.16 (1.13, 1.19). In the age range 50 to 90 years, the highest cumulative incidence of hip fracture was seen in those with primary education. The gradient gradually diminished with advancing age and was reversed in the oldest (> 90 years) in both genders. CONCLUSIONS: There was a clear educational gradient in hip fracture incidence in both men and women in Norway, with a higher risk in people with lower education. Despite this, the cumulative incidence of hip fracture in old age was highest among people with higher education, due to their higher life expectancy.

Rheumatoid arthritis, disease-modifying antirheumatic drugs and risk of major osteoporotic fracture: prospective data from the HUNT Study, Norway.

OBJECTIVES: Rheumatoid arthritis has been associated with increased fracture risk. New treatments have improved the course of the disease substantially, but it is not clear if this influences fracture risk. We examined if rheumatoid arthritis, overall and according to disease-modifying antirheumatic drugs (DMARDs), is associated with a risk of major osteoporotic fractures. METHODS: Overall, 92 285 participants in the population-based Nord-Trndelag Health Study (HUNT), Norway were included and linked with hospital records for a validated rheumatoid arthritis diagnosis (n=605), type of DMARD treatment and fracture diagnosis. Participants were followed up until the first major osteoporotic fracture, death, emigration or end of follow-up. Cox regression was used to estimate HRs for fractures among individuals with rheumatoid arthritis, overall and by DMARD treatment, compared with participants without rheumatoid arthritis. RESULTS: A total of 9670 fractures were observed during follow-up, of which 88 were among those with rheumatoid arthritis. Compared with the reference group of participants without rheumatoid arthritis, those with the disease had an HR of fracture of 1.41 (95% CI 1.13 to 1.74). The association was largely similar for users of csDMARDs (HR 1.44; 95% CI 1.15 to 1.81), whereas the association for bDMARD users was weaker and less precise (HR 1.19; 95% CI 0.64 to 2.21). CONCLUSION: Participants with rheumatoid arthritis had a 40% higher risk of fracture than participants without the disease. A similar fracture risk was observed for conventional synthetic DMARD use, whereas there was weak evidence that the use of biological DMARDs may be associated with a somewhat lower fracture risk.

A meta-analysis of previous falls and subsequent fracture risk in cohort studies.

The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. INTRODUCTION: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). METHODS: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. RESULTS: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51) and men (HR 1.53, 95% CI 1.41-1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27-1.84) in men vs. HR 1.32 (95% CI 1.20-1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men. CONCLUSIONS: A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.

An atlas of genetic determinants of forearm fracture.

Osteoporotic fracture is among the most common and costly of diseases. While reasonably heritable, its genetic determinants have remained elusive. Forearm fractures are the most common clinically recognized osteoporotic fractures with a relatively high heritability. To establish an atlas of the genetic determinants of forearm fractures, we performed genome-wide association analyses including 100,026 forearm fracture cases. We identified 43 loci, including 26 new fracture loci. Although most fracture loci associated with bone mineral density, we also identified loci that primarily regulate bone quality parameters. Functional studies of one such locus, at TAC4, revealed that Tac4-/- mice have reduced mechanical bone strength. The strongest forearm fracture signal, at WNT16, displayed remarkable bone-site-specificity with no association with hip fractures. Tall stature and low body mass index were identified as new causal risk factors for fractures. The insights from this atlas may improve fracture prediction and enable therapeutic development to prevent fractures.

Exploring the impact of the national tender system on the use of costly drugs treating rheumatoid arthritis patients in ten rheumatology centers in Norway (2010-2019).

BACKGROUND: Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) are highly effective in treating rheumatoid arthritis (RA), albeit high drug cost has restricted their use in many countries. As a countermeasure, Norway implemented pharmaceutical tendering as a cost-reducing strategy. The aim of this study was to assess the annual proportion of different b/tsDMARDs registered to treat RA patients under the influence of a Norwegian pharmaceutical tendering between 2010 and 2019. METHOD: The data is collected from ten Norwegian outpatient centers. The included patients are categorized as naïve, non-naïve, and current b/tsDMARD users. 13 individual b/tsDMARDs are assessed and compared with the tender rankings from each year. Overview of subcutaneous (sc) with per oral vs. intravenous (iv) and biosimilars vs. non-biosimilar are also described. RESULT: The tender-winning b/tsDMARD was the most or second most used drug in nine out of ten years for naïve users, seven for non-naïve users, and twice for current users. The average sum of the highest and second highest proportion among naïve, non-naïve, and current b/tsDMARD users were 75%, 53%, and 50% during the ten years, respectively. The tender-winning drug was iv in eight out of ten years. However, the average total proportion of sc and per oral b/tsDMARDs was about 70% for naïve b/tsDMARD users, 50% for non-naïve b/tsDMARD users, and 60% for current b/tsDMARD users. The main contributors to sc and per oral b/tsDMARD were etanercept (reference and biosimilar) and certolizumab pegol. The main contributors to iv b/tsDMARD were rituximab reference and infliximab biosimilar. Despite low-ranking offers, rituximab reference (offered as a second-line drug) often achieved a high proportion among non-naïve and current b/tsDMARD users. After the introduction of biosimilars, their average proportion was about 40%, 40%, and 20% for naïve, non-naïve, and current b/tsDMARD users, respectively. CONCLUSION: Based on observed data, a higher tender rank was associated with a higher proportion among naïve and non-naïve b/tsDMARD users. However, in most cases, sc b/tsDMARDs achieved a higher proportion with lower tender ranks than iv b/tsDMARDs with higher tender ranks.

Changes of inflammation in patients with psoriatic arthritis after high intensity interval training assessed by ultrasound and MRI, a randomized controlled trial.

BACKGROUND: In psoriatic arthritis (PsA) there is a theoretical risk of increased disease activity related to strenuous physical activity, including exercise. We evaluated the effect of high intensity interval training (HIIT) on objective measures of inflammation in PsA assessed by ultrasound (US) of peripheral joints and entheses, and by bone marrow edema (BME) on MRI of the sacroiliac joints (SIJ) and spine. METHODS: We randomly assigned 67 PsA patients to an intervention group that performed structured HIIT for 11 weeks, or to a control group instructed not to change their physical exercise habits. Outcome measures included US evaluation of the total cohort and MRI in a subgroup of 41; both assessed at 3 months. We calculated the proportions with an increased US B-mode and power-doppler (PD) signal of joints and entheses and Spondyloarthritis-Research-Consortium-of-Canada (SPARCC)-BME score of the SIJ and spine for both groups. RESULTS: Proportions with an increased US B-mode score of the joints were 32% and 28% in HIIT and control groups, respectively. Corresponding proportions of PD scores of the joints were 7% and 10% and PD scores of entheses were 32% and 31%. The proportions with increased MRI BME of the SIJ were 6% in the HIIT group and 10% in the control group. Corresponding proportions were 6% and 5% for the MRI BME of the spine. CONCLUSION: In PsA patients with a low to moderate disease activity, there was no clear evidence of objectively measured increased inflammation after HIIT, as evaluated by US and MRI. TRIAL REGISTRATION: ClinicalTrials.gov NCT02995460 (16/12/2016).

Relative importance of inflammation and cardiorespiratory fitness for all-cause mortality risk in persons with rheumatoid arthritis: the population-based Trøndelag Health Study.

OBJECTIVE: Inflammation and reduced cardiorespiratory fitness (CRF) are associated with increased mortality rates in rheumatoid arthritis (RA). We aimed at directly comparing the relative importance of inflammation and reduced CRF as mediators of all-cause mortality in persons with RA compared with controls, quantifying direct and indirect (mediated) effects. METHODS: Persons with (n=223, cases) and without (n=31 684, controls) RA from the third survey of the Trøndelag Health Study (HUNT3, 2006-2008) were included. Inflammation was quantified using C reactive protein (CRP) and estimated CRF (eCRF) was calculated using published formulae. All-cause mortality was found by linkage to the Norwegian Cause of Death Registry, with follow-up from inclusion in HUNT3 until death or 31 December 2018. Data were analysed using standardised equation modelling, permitting complex correlations among variables. RESULTS: Persons with RA had increased all-cause mortality rates (24.1% vs 9.9%, p<0.001). Both eCRF (p<0.001) and CRP ≥3 mg/L (p<0.001) were mediators of this excess mortality, rendering the direct effect of RA non-significant (p=0.19). The indirect effect of RA mediated by eCRF (standardised coefficient 0.006) was approximately three times higher than the indirect effect mediated by CRP (standardised coefficient 0.002) in a model adjusted for other mortality risk factors. CONCLUSION: Even with CRP concentrations <3 mg/L in all patients with RA, excess mortality mediated by low CRF would still play an important role. Improved inflammation control in RA does not necessarily lead to better CRF. Therefore, our study strongly supports recommendations for development and implementation of exercise programmes aimed at improving CRF in persons with RA.

Discontinuation rate of sulfasalazine, leflunomide and methotrexate due to adverse events in a real-life setting (NOR-DMARD).

Objectives: MTX, LEF and SSZ are conventional synthetic DMARDs (csDMARDs) with a well-established role in the treatment of RA. We aimed to estimate and compare the relative risks for adverse events (AEs) and the discontinuation of these drugs owing to AEs. Methods: We included all 3339 patients from the NOR-DMARD study treated with MTX, LEF or SSZ in monotherapy. All reported AEs were compared between treatment groups using quasi-Poisson regression. In addition, drug retention rates were analysed using Kaplan-Meier estimates with Cox regression to control for possible confounders. We analysed drug retention rates and cumulative risk of discontinuation attributable to AEs using the Kaplan-Meier estimator. We assessed age, sex, baseline DAS in 28 joints with ESR (DAS28-ESR), seropositivity, prednisolone use, previous DMARD use, year of inclusion and co-morbidity as possible cofounders. Results: We found that the discontinuation rate attributable to AEs was significantly higher for LEF and SSZ than for MTX. After the first year, it was 13.7% (95% CI 12.2, 15.2), 39.6% (95% CI 34.8, 44) and 43.4% (95% CI 38.2, 48.1) for MTX, SSZ and LEF, respectively. Similar results were found when adjusting for confounders. The overall AEs were comparable across the treatment groups. The AE profile was as expected for each drug. Conclusion: Our work has shown a similar AE profile of csDMARDs to previous data. However, higher discontinuation rates for SSZ and LEF cannot be explained easily from AE profiles.

High physical activity in persons with psoriatic arthritis is associated with reduced visceral fat mass and percentage body fat: the Trøndelag Health study.

The associations of physical activity (PA) with body composition among persons with psoriatic arthritis (PsA) are not well described. The objective was to investigate associations of PA with visceral fat mass and percentage body fat in persons with PsA of different age groups. Persons with PsA (CASPAR criteria, n = 356), and controls (n = 47,470) from the Trøndelag Health Study (HUNT4, 2017-2019) were included. Visceral fat mass and percentage body fat measured using bioelectrical impedance were primary outcomes in multivariable linear regression analysis. PsA, PA (questionnaire data), and age were explanatory variables, with adjustment for sex, smoking, heart disease, lung disease, and height. An interaction term between PsA and age was included in both models. Persons with PsA had altered body composition, including higher visceral fat mass and percentage body fat, especially those < 40 years of age (p ≤ 0.01). Moderate or high PA was associated with significantly lower values of the primary outcomes. Differences were Moderate compared to low PA: 1.4 kg (95% CI 1.3, 1.5 kg) lower visceral fat mass, and 2.0% (95% CI 1.8, 2.1) lower percentage body fat. Differences were High compared to low PA: 3.2 kg (95% CI 3.1, 3.3) lower visceral fat mass and 5.0% (95% CI 4.8, 5.1%) lower percentage body fat. Persons with PsA had higher visceral fat mass and percentage body fat, especially if < 40 years, and PA was associated with lower values of both endpoints. Changes of body composition in persons with PsA may influence important health outcomes and should be addressed in clinical practice.

The association between rheumatoid arthritis and reduced estimated cardiorespiratory fitness is mediated by physical symptoms and negative emotions: a cross-sectional study.

OBJECTIVES: Persons with rheumatoid arthritis (RA) have lower cardiorespiratory fitness (CRF) than healthy individuals. We sought to identify variables explaining the association between RA status and reduced CRF. METHODS: RA patients recruited from two Norwegian hospitals and blood donors recruited as controls filled in questionnaires about physical activity, physical symptoms, and psychological factors. Estimated CRF (eCRF) was calculated from non-exercise models. The relationship between RA status and reduced eCRF was explored with structural equation modelling. The latent variables physical symptoms (based on morning stiffness, joint pain, and pain in neck, back, or hips) and negative emotions (based on Hospital Anxiety and Depression Scale's Depression score and Cohen's perceived stress scale) were included as possible mediators between RA status and eCRF in separate and combined models adjusted for age and sex. RESULTS: Two-hundred-and-twenty-seven RA patients and 300 controls participated. The patients were older and had lower eCRF than controls (age- and sex-adjusted mean difference: 1.7 mL/kg/min, p=0.002). Both latent variables were significant mediators of the association between RA and reduced eCRF when included in separate models. The latent variables mediated 74% of the total effect of RA on eCRF in the combined model. Standardized coefficients: direct effect of RA -0.024 (p=0.46), indirect effect through physical symptoms -0.034 (p=0.051), and indirect effect through negative emotions -0.034 (p=0.039). CONCLUSION: Both physical symptoms and negative emotions mediated the association between RA and reduced eCRF with similar effect sizes. To successfully increase CRF in RA patients, both physical and psychological factors should be addressed. Key Points • The RA patients in the present study had 1.7 mL/kg/min lower mean estimated cardiorespiratory fitness (CRF) compared to healthy controls. • Mediation analysis demonstrated that physical symptoms and negative emotions mediated 74% of the total negative effect of RA on estimated CRF in a combined, adjusted model. • This suggests that both physical and psychological factors should be addressed when supporting RA patients in improving their CRF.

Persons with rheumatoid arthritis have higher barriers to physical activity than controls: a cross-sectional study using the Facilitators and Barriers to Physical Activity Questionnaire (FasBarPAQ).

Facilitators and barriers to performing physical activity (PA) may vary among persons with rheumatoid arthritis (RA) as well as between RA patients and healthy individuals. Primary objective: To investigate associations of presence of RA and levels of stress and depression with scores for facilitators and barriers to PA, using a new questionnaire (FasBarPAQ). Secondary objectives: investigate inter-individual score differences in persons with RA, and associations with RA disease-specific variables. Persons with RA from two outpatient clinics (n = 203) and blood donor controls (n = 293) filled in the new 14-item FasBarPAQ questionnaire, the Hospital Anxiety and Depression Scale depression scale (HADS-D), Cohen's perceived stress scale, and questions regarding PA. Clinical data, and self-reported disease activity and physical function were collected for the persons with RA. Data were analyzed using linear and logistic regression. RA was associated with lower Facilitators scores (coefficient = - 1.30, p = 0.015), higher Barriers scores (coefficient = 2.36, p < 0.001) and lower Total Facilitators-Barriers scores (coefficient = - 3.67, p < 0.001). HADS-D ≥ 8 was associated with lower Total scores (coefficient = - 3.32, p = 0.022), and the two higher stress score tertiles were associated with higher Barriers and lower Total scores (p = 0.023 to p < 0.001). Persons with RA reported greatly varying facilitators and barriers profiles. Seropositivity and higher patient global assessment were associated with higher Barriers scores (coefficients = 1.79, p = 0.011; 0.60, p < 0.001) and lower Total scores (coefficients = - 3.60, p = 0.003; - 0.98, p < 0.001). Persons with RA had higher barriers and lower facilitators for PA, with varying individual profiles. The new FasBarPAQ questionnaire may be a useful screening tool for healthcare providers treating persons with RA.

Inflammation mediates approximately one quarter of excess relative all-cause mortality in persons with rheumatoid arthritis: the Trøndelag Health Study.

Inflammation may contribute to excess mortality in rheumatoid arthritis (RA) patients. We investigated associations to all-cause mortality of the inflammation markers high-sensitivity C-reactive protein (CRP), lactoferrin (neutrophil activation marker), and neopterin (monocyte activation marker). From the population-based Trøndelag Health Study (3rd wave 2006-2008), 316 RA patients and 43,579 controls were included. Lactoferrin and neopterin were quantified in a nested cohort (n = 283 RA patients, n = 3698 controls). Follow-up was until death found by linkage to the Norwegian Cause of Death Registry or 31.12.2018. All-cause mortality was analyzed using Cox regression and Cox regression-based mediation analysis. Having RA (hazard ratio (HR): 1.25, 95%CI: 1.00, 1.56, p = 0.048), and CRP ≥ 3 mg/L (HR: 1.50, 95%CI: 1.41, 1.60, p < 0.001) were associated with all-cause mortality. The overall excess relative mortality risk of having RA was 38%. CRP ≥ 3 mg/L mediated approximately 1/4 of this risk (p < 0.001). In the nested cohort, CRP ≥ 3 mg/L (HR: 1.51, 95%CI: 1.26, 1.80, p < 0.001) and neopterin (HR: 1.17, 95%CI: 1.01, 1.36, p = 0.031) were associated with all-cause mortality. In conclusion, CRP levels ≥ 3 mg/L mediated approximately a quarter of the 38% excess relative all-cause mortality risk associated with RA. Using definitions of RA remission with emphasis both on joint status and the level of general inflammation may help guide the most efficient treatment regimens.

Assessment of the genetic and clinical determinants of hip fracture risk: Genome-wide association and Mendelian randomization study.

Hip fracture is the clinically most important fracture, but the genetic architecture of hip fracture is unclear. Here, we perform a large-scale hip fracture genome-wide association study meta-analysis and Mendelian randomization study using five cohorts from European biobanks. The results show that five genetic signals associate with hip fractures. Among these, one signal associates with falls, but not with bone mineral density (BMD), while four signals are in loci known to be involved in bone biology. Mendelian randomization analyses demonstrate a strong causal effect of decreased femoral neck BMD and moderate causal effects of Alzheimer's disease and having ever smoked regularly on risk of hip fractures. The substantial causal effect of decreased femoral neck BMD on hip fractures in both young and old subjects and in both men and women supports the use of change in femoral neck BMD as a surrogate outcome for hip fractures in clinical trials.

Exercise Self-Efficacy and patient global assessment were associated with 6-min walk test distance in persons with rheumatoid arthritis.

INTRODUCTION: Low functional capacity is related to future loss of daily function and cardiovascular events. The present study explored the associations of patient-reported outcome measures (PROMs) and disease-specific measures with functional capacity as measured by the 6-min walk test (6MWT) in persons with rheumatoid arthritis (RA). METHODS: Seventy-nine participants from rheumatology outpatient clinics were included. The distance walked during the 6MWT (6MWD) was the dependent variable in multivariable regression analyses. Model 1 included the independent variables sex, age (in tertiles to improve model fit), and body mass index (BMI). Building on Model 1, Model 2 added smoking, patient global assessment (PGA), Exercise Self-Efficacy, Hospital Anxiety and Depression Scale's Depression score, and Cohen's Perceived Stress Scale score, whereas Model 3 added smoking, disease duration, present use of glucocorticosteroids, seropositivity, Disease Activity Score 28-C-Reactive Protein (DAS28-CRP), and a comorbidity variable. RESULTS: Median age was 65 years, 76% were female, and median 6MWD was 493 m. In Model 1, BMI and age were significantly associated with the 6MWD (R2 = 0.42). In Model 2, PGA and Exercise Self-Efficacy were also significantly associated with the 6MWD, with standardized regression coefficients of - 0.21 (p = 0.03) and 0.26 (p = 0.004) respectively (R2 = 0.54). The RA-specific variables in Model 3 were not significantly associated with the 6MWD (R2 = 0.49). CONCLUSION: The PROMs PGA and Exercise Self-Efficacy were significantly associated with functional capacity as measured by the 6MWT in persons with RA, whereas disease-specific measures such as DAS28-CRP and disease duration were not. Key Points • Functional capacity measured with the 6-minute walk test was significantly associated with body mass index, age, patient global assessment, and Exercise Self-Efficacy in persons with RA. • Patient-reported outcome measures explained more of the variation in functional capacity than objective or composite measures of disease and are relevant measures in clinical follow-up. • Techniques that enhance self-efficacy for exercise should be incorporated into clinical practice to promote physical activity.

Impact of Total Hip Replacements on the Incidence of Hip Fractures in Norway During 1999-2019. A Norwegian Epidemiologic Osteoporosis Studies (NOREPOS) Study.

The knowledge about why hip fracture rates in Norway have declined is sparse. Concurrent with decreasing hip fracture rates, the rates of total hip replacements (THRs) have increased. We wanted to investigate if hip fracture rates continued to decline, and whether the increase in THRs had any influence on this decline, assuming that living with a hip prosthesis precludes fracture of the operated hip. Information on hip fractures in Norway 1999-2019 was available from the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS) hip fracture database and population size were available in official population tables from Statistics Norway. Primary THRs (for any cause except hip fracture) 1989-2019 were obtained from the Norwegian Arthroplasty Register. We calculated the annual age-standardized incidence rates of hip fracture by sex for the period 1999-2019. The hip fracture rates in a scenario with no hip prostheses were calculated by subtracting 0.5 persons from the population at risk for each prevalent hip prosthesis, considering that each person has two hips at risk of fracture. We estimated how much of the decline could be attributed to the increased prevalence of hip prostheses. From 1999 to 2019, age-standardized incidence rates of hip fracture decreased by 27% in women and 20% in men. The rates remained stable in those under 70 years and decreased in those 70 years and above. Excluding replaced hips from the population at risk led to higher incidence rates, and this impact was considerably larger at higher ages. The increased prevalence of hip prostheses over the period accounted for approximately 18% (20% in women and 11% in men) of the observed decline in hip fracture rates. In conclusion, the incidence of hip fractures continued to decline, and the increasing number of people living with hip prostheses contributed significantly to the observed declining time trends. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Evaluating the Impact of High Intensity Interval Training on Axial Psoriatic Arthritis Based on MR Images.

High intensity interval training (HIIT) has been shown to benefit patients with psoriatic arthritis (PsA). However, magnetic resonance (MR) imaging has uncovered bone marrow edema (BME) in healthy volunteers after vigorous exercise. The purpose of this study was to investigate MR images of the spine of PsA patients for changes in BME after HIIT. PsA patients went through 11 weeks of HIIT (N = 19, 4 men, median age 52 years) or no change in physical exercise habits (N = 20, 8 men, median age 45 years). We acquired scores for joint affection and pain and short tau inversion recovery (STIR) and T1-weighted MR images of the spine at baseline and after 11 weeks. MR images were evaluated for BME by a trained radiologist, by SpondyloArthritis Research Consortium of Canada (SPARCC) scoring, and by extraction of textural features. No significant changes of BME were detected in MR images of the spine after HIIT. This was consistent for MR image evaluation by a radiologist, by SPARCC, and by texture analysis. Values of textural features were significantly different in BME compared to healthy bone marrow. In conclusion, BME in spine was not changed after HIIT, supporting that HIIT is safe for PsA patients.

Contribution of an extensive medication-based comorbidity index (Rx-Risk) in explaining the excess mortality after hip fracture in older Norwegians: a NOREPOS cohort study.

OBJECTIVES: Patients with hip fracture are typically characterised by extensive comorbidities and excess mortality. Methods that account for a wide range of comorbidities are needed when attempting to identify causal associations in registry-based studies. We aimed to study the association between the prescription-based Rx-Risk Comorbidity Index (abbreviated Rx-Risk) and mortality by history of hip fracture, and to quantify the contribution of Rx-Risk in explaining the excess mortality after hip fracture. SETTING: In this prospective study, we used nationwide registry data from outpatient care. Rx-Risk was based on filled prescriptions recorded in the Norwegian Prescription Database. Medications were mapped to 46 comorbidity categories by Anatomical Therapeutic Chemical code. Information on hip fractures during 1994-2013 was available from the Norwegian Epidemiologic Osteoporosis Studies hip fracture database, and year of death was obtained from Statistics Norway. We estimated 1-year mortality risk (January through December 2014) according to Rx-Risk score based on dispensed prescriptions in 2013, history of hip fracture, age and sex using Poisson regression. PARTICIPANTS: All individuals aged 65 years and older who were alive by the end of 2013 and had filled at least one prescription in an outpatient pharmacy in Norway in 2013 (n=735 968). RESULTS: Mortality increased exponentially with increasing Rx-Risk scores, and it was highest in persons with a history of hip fracture across the major range of Rx-Risk scores. Age- and sex-adjusted mortality risk difference according to history of hip fracture (yes vs no) was 4.4 percentage points (7.8% vs 3.4%). Adjustment for Rx-Risk score further attenuated this risk difference to 3.3 percentage points. CONCLUSIONS: History of hip fracture and comorbidity assessed by Rx-Risk are independent risk factors for mortality in the community-dwelling older population in Norway. Comorbidity explained a quarter of the excess mortality in persons with a history of hip fracture.

Use of the Behavioral Regulation in Exercise Questionnaire-2 to assess motivation for physical activity in persons with rheumatoid arthritis: an observational study.

Arthritis patients may show little motivation for physical activity (PA), resulting in a sedentary lifestyle. The primary objective of the study was to investigate whether motivation for PA and fulfillment of PA recommendations were associated with cardiorespiratory fitness in patients with RA. The exploratory objective was to study whether university students could be used as controls for RA patients in future studies of PA motivation. Peak oxygen uptake (VO2peak) was measured in 93 RA patients. The patients and 354 students filled in the Behavioral Regulation in Exercise Questionnaire-2 (BREQ-2). Data were analyzed using structural equation modeling with adjustment for age and sex. The BREQ-2 scores were also compiled to an overall motivational style "Relative Autonomy Index" as previously published. Mean VO2peak for the RA patients was 32.2 (SD: 9.6) mL × min-1 × kg-1. Only 29 patients (31%) fulfilled the current recommendations for PA. BREQ-2 scores were associated with measured VO2peak (standardized coefficient 0.33, p < 0.001). Whether a person fulfilled the current recommendations for PA was a significant mediator of this effect (standardized coefficients: mediated effect; 0.22, p = 0.001, remaining direct effect; 0.11, p = 0.18). The Relative Autonomy Index also significantly predicted measured VO2peak (standardized coefficient 0.30, p < 0.001). The underlying BREQ-2 factor structure was significantly different between RA patients and university students, and comparison of scores would not be adequate. Motivation for PA was significantly associated with measured VO2peak in RA patients. The effect was mediated by whether the patient fulfilled the current recommendations for PA. Addressing and stimulating motivation is important when intervening to increase PA and cardiovascular fitness in RA patients.