This population-based cohort study investigated the associations of parity, age at first birth, and breastfeeding duration with risk of major osteoporotic fractures in Norwegian women. Higher parity, higher age at first birth, and longer breastfeeding duration were associated with modestly reduced fracture risk. Reproductive factors may influence long-term bone health, yet studies on their associations with fracture risk have yielded inconsistent results. This study examined associations between parity, age at first birth, and lifetime breastfeeding duration with risk of major osteoporotic fractures in Norwegian women. We included 41,274 women aged ≥ 45 years in the Trøndelag Health Study (HUNT) linked with the Medical Birth Registry of Norway and hospital-based fracture records. We used Cox proportional hazards regression to estimate hazard ratios (HRs) with 95

We used Mendelian randomization to investigate whether genetic proxies of glucagon-like peptide-1 receptor (GLP1R) expression are associated with risk of psoriasis and psoriatic arthritis (PsA). Higher GLP1R expression was associated with reduced susceptibility to psoriasis and PsA, independent of metabolic traits, while no risk-reducing effects were observed for other immune-mediated inflammatory diseases. These results highlight a disease-specific association between GLP1 pathway activity and psoriatic disease.

Background: Up to one-third of people living with psoriasis develop psoriatic arthritis (PsA), and the majority have active psoriasis prior to the development of arthritis. Clinical risk factors, such as nail involvement, in conjunction with novel blood biomarkers, could improve PsA risk monitoring and early diagnosis. Objectives: The aim of the HIPPOCRATES Prospective Observational Study (HPOS— www.hpos.study ) is to follow a cohort living with psoriasis and identify risk factors for the development of PsA. Design: HPOS is a patient-driven online prospective European observational cohort. Methods: Adult participants with psoriasis but with no prior diagnosis of PsA are eligible. Participants are invited to provide consent and join the study online. They complete a semi-structured questionnaire to collect data on demographics, psoriasis, comorbidities, risk factors for PsA, and the Psoriasis Epidemiology Screening Tool screening questionnaire. Follow-up is conducted through a questionnaire every 6 months. The primary outcome is the new onset of PsA confirmed by a diagnosis from their doctor. The study will also collect peripheral blood samples from a subset of participants for biomarker identification. Ethics: This study follows the principles of the Declaration of Helsinki. To date, ethical approval has been granted by independent ethical committees in 10 countries. Discussion: Studying a cohort of individuals with psoriasis will allow us to identify risk factors for arthritis development and to develop a risk calculator. This can support focused efforts on screening, patient education, and even studies looking to delay or prevent the onset of arthritis. This study, run via remote online data collection, provides an efficient way to recruit a large cohort (25,000) across multiple countries. However, challenges have had to be addressed with some key changes in study design, ethical review, and recruitment strategies required for each individual country. Trial registration: HPOS, Clinicaltrials.gov ID: NCT05858528, IRAS number 325080; https://clinicaltrials.gov/study/NCT05858528?locStr=United%20Kingdom&country=United%20Kingdom&cond=Psoriasis&term=HPOS&aggFilters=status%3Anot%20rec&rank=1 .

In this meta-analysis of international cohorts, current smoking is confirmed as a significant BMD-independent predictor of future fracture with a stronger relationship in men than in women. A causative and reversible effect of smoking on fracture risk is suggested by past smoking having a significantly lower risk than current smoking. In this meta-analysis of international cohorts, the aim was to examine the relationship of current and past smoking with fracture risk to provide an update for future iterations of the FRAX tool. The risk of fracture associated with current and past smoking was estimated using an extended Poisson model applied separately to each of 58 prospective international cohort studies. Covariates included current time since start of follow up, current age, and in an additional model, BMD at the femoral neck. The results of the different studies were merged by using inverse-variance weighted β-coefficients. This analysis included a total of 1,691,024 participants (61.2

Psoriatic arthritis (PsA) and low physical activity (PA) negatively influence body composition. We examined the relative strength of associations of PA and PsA with body composition in individuals with PsA compared to controls, and comparing PA assessment by self-report versus a device. We analyzed data from 142 individuals with PsA and 23 858 controls who participated in the fourth survey of the Trøndelag Health study (HUNT4, 2017–2019). Standardized multivariable linear regression models were used to assess the relative strength of associations of PsA (CASPAR criteria) and PA with visceral fat mass and percentage body fat measured by bioelectrical impedance analysis. PA was either self-reported (exercise frequency, duration and intensity) or device-measured using accelerometers. Model fit was compared using Akaike’s Information Criterion and the Bayesian Information Criterion. Standardized regression coefficients for PsA had much smaller absolute values than those for performing PA in explaining variations in body composition (visceral fat mass: PsA: 0.017 to 0.019, PA: -0.14 to -0.31; percentage body fat: PsA 0.013 to 0.015, PA: -0.12 to -0.29). Unstandardized models showed that performing moderate to high levels of PA could compensate for the unfavorable body composition associated with PsA. Models with device-measured PA had substantially better fit than those with self-report, indicating that they better captured the variations in body composition. PA explained larger variations in body composition than PsA. Individuals with PsA should be informed that engaging in PA has a greater positive impact on body composition than the negative consequences of having PsA.

The relationship between bone mineral density (BMD) at the femoral neck and fracture risk was determined in a meta-analysis of primary data of 307205 men and women from 53 cohort studies. Low BMD was an important predictor of fracture risk, particularly for hip fracture. This study aimed to quantify the relationship between DXA-measured femoral neck BMD and fracture risk and examine the effect of age, sex, time since measurement, and initial BMD value on fracture risk, with a view to updating FRAX®. We studied 307,205 men and women from within 53 predominately population-based cohorts followed up for an average of 8.7 years and a total of 2,683,185 person-years. The association of BMD and fracture risk was examined using a Poisson model in each cohort separately by sex. Results were expressed as a gradient of risk (GR, hazard ratio/standard deviation decrease in BMD). The different studies were then merged using weighted coefficients. Most hip fractures arose in men and women with low bone mass or osteoporosis at baseline (73 = 0.12 for women and p = 0.89 for men). A significant decrease in GR for hip fracture was observed with increasing duration of follow-up, but the magnitude of the effect was modest compared with the effect of age. For other fracture outcomes, including non-hip major osteoporotic fracture, the gradient of risk was lower than for hip fracture. Femoral neck BMD is a risk factor for fracture of substantial importance, particularly for future hip fracture. The lower magnitude of association at older age is consistent with other non-skeletal factors contributing to hip fracture risk with advancing age. Its validation on an international basis supports its use in case finding strategies. Its use should, however, take account of the variations in predictive value of BMD with age, sex, length of follow-up, and BMD.

BACKGROUND:Psoriasis is recognized as a systemic inflammatory disease associated with metabolic dysregulation. Understanding these metabolic changes may reveal biomarkers to elucidate disease mechanisms and predict comorbidities. While previous studies have identified psoriasis-associated metabolites, findings are often limited by sample sizes and lack validation. OBJECTIVES:To identify circulating metabolites associated with psoriasis, including disease severity and psoriatic arthritis. Further, we investigated whether the metabolic signature was disease-specific compared to other immune-mediated inflammatory diseases (IMIDs). METHODS:We performed a cross-sectional analysis of 470,352 White/European individuals from the UK Biobank (n=453,428) and HUNT (n=16,924). Nuclear Magnetic Resonance spectroscopy was used to quantify metabolite levels, covering lipoprotein fractions and subfractions, fatty acids, and small-molecular metabolites. For each metabolite, we performed multivariable linear regression adjusting for age, sex, BMI, smoking status, and use of lipid-lowering medications. RESULTS:The metabolomic profile of psoriasis was largely consistent across the two populations. In the model adjusted for age and sex, 123 metabolic measures were associated with psoriasis. After full adjustment, only Glycoprotein acetyls (GlycA) remained associated with psoriasis (coefficient [95% CI]: 0.09 [0.07-0.11] in UK Biobank and 0.11 [0.06-0.17] in HUNT). In HUNT, severe psoriasis exhibited more pronounced metabolic alterations compared to non-severe psoriasis. Across both populations, phenylalanine levels were highly elevated in psoriatic arthritis compared to cutaneous psoriasis (0.44 [0.29-0.60] in UK Biobank and 0.47 [0.28-0.67] in HUNT). In comparisons across IMIDs, atopic dermatitis and cutaneous-limited psoriasis exhibited milder metabolic alterations, and psoriasis in HUNT showed a distinct lipoprotein profile. CONCLUSIONS:This large-scale study confirms metabolic alterations in individuals with psoriasis and highlights phenylalanine as a potential biomarker for joint involvement in psoriasis. The distinct metabolomic profile of psoriasis relative to other IMIDs suggests a potentially unique systemic profile. These findings offer a foundation for advancing biomarker research and mechanistic studies for psoriasis.

In the largest meta-analysis of international cohorts to date, a family history of fracture is confirmed as a significant BMD-independent predictor of future fracture risk. Parental and sibling histories of fracture carry the same significance for future fracture, including the impact of family hip fracture on future hip fracture risk. PURPOSE:We have undertaken a meta-analysis of international prospective cohorts to quantify the relationship between a family history of fracture and future fracture incidence. METHODS:The analysis dataset comprised 350,542 men and women from 42 cohorts in 29 countries followed for 2.8 million person-years. We investigated the relationship between family history of hip fracture or any fracture and the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture (MOF), and hip fracture alone using an extended Poisson model in each cohort. Models were adjusted for current age, sex, BMD, and follow-up time. RESULTS:As no difference in influence of family history of fracture was seen between genders, results are presented for men and women combined. A parental history of hip fracture was associated with a higher risk of incident fracture across all fracture outcome categories, with a stronger relationship with future hip fracture (hazard ratios (HR, 95% CI) for hip and MOF 1.37, 1.23-1.52 and 1.19, 1.12-1.27, respectively). Associations were slightly reduced but remained significant when additionally adjusted for BMD and did not vary by baseline offspring age, follow-up time, or parent affected. In a more limited analysis, parental history of any fracture or a sibling history of hip or any fracture showed similar associations to those observed with parental history of hip fracture. CONCLUSIONS:A family history of fracture is confirmed as a significant BMD-independent predictor of future fracture risk. While parental hip fracture appears the strongest factor for future hip fracture, a family history of other fractures might be appropriate for inclusion in future iterations of the FRAX tool.

This population study investigated the association between birth characteristics and fracture risk in 11,099 young adults (aged 19–54 years). Our findings indicate that birth weight, gestational age, and birth weight for gestational age were not associated with fractures in the wrist, humerus, hip, and spine in this population. Skeletal development starts during fetal life, and it is estimated that most bone formation occurs in the 3rd trimester. This study examined the association between birth characteristics and fractures of the wrist, humerus, hip, and spine, in young adults (19–54 years). 11.099 participants in the 3rd survey of the HUNT Study (2006–2008) were linked with the Medical Birth Registry of Norway and hospital records. Fractures of the wrist, humerus, hip, and spine were identified using ICD9/10 codes between 1988 and 2021. Follow-up was from date of participation in HUNT until a first fracture, emigration, death, or end of study. Cox regression was used to estimate hazard ratios (HR) of fracture associated with birth characteristics (95

BACKGROUND:Children with juvenile idiopathic arthritis (JIA) are at risk for impaired bone health. This study evaluates bone mineral density (BMD) and potential risk factors for reduced BMD. METHODS:In the NorJIA study, Norwegian children with JIA, and age-matched and sex-matched controls participated in a multicentre cohort study with clinical examinations, questionnaires, imaging and blood tests. BMD was measured using dual-energy X-ray absorptiometry and adjusted for bone age. Standard descriptive statistics and t-tests were used. RESULTS:205 children with JIA had BMD measured at two study visits, 2 years apart and 125 controls at the second visit. At visit 2, median age was 14.7 years (IQR 11.5-16.6). Median disease duration was 6.6 (IQR 4.7-10.4) years, 50.7% had used or were currently using biologic disease-modifying antirheumatic drugs and 25.9% had ever used systemic steroids. There were no substantial differences in BMD Z-scores between the JIA group and controls. Mean BMD Z-score L1-L4 in JIA was 0.0 (95% CI -0.1, 0.1) and in controls 0.1 (95% CI -0.1, 0.3). A robust association was seen between physical activity levels and BMD. In children with JIA, the mean BMD Z-score L1-L4 was -0.3 (95% CI -0.6, 0.0) in the low-activity group and 0.2 (95% CI 0.0, 0.4) in the high-activity group, with a similar trend in controls. Children with JIA were as physically active as controls. CONCLUSIONS:BMD Z-scores in JIA were similar to controls and positively associated with physical activity. This underlines the importance of early disease control, steroid-sparing medications and physical activity to optimise bone health. TRIAL REGISTRATION NUMBER:NCT03904459.

The relationship between rheumatoid arthritis (RA) and fracture risk was estimated in an international meta-analysis of individual-level data from 29 prospective cohorts. RA was associated with an increased fracture risk in men and women, and these data will be used to update FRAX®. RA is a well-documented risk factor for subsequent fracture that is incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between rheumatoid arthritis and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD) with a view to updating FRAX. The resource comprised 1,909,896 men and women, aged 20–116 years, from 29 prospective cohorts in which the prevalence of RA was 3

Background: Psoriasis is a systemic inflammatory disease associated with metabolic dysregulation. Understanding these metabolic changes may reveal biomarkers to elucidate disease mechanisms and predict comorbidities. While previous studies have identified psoriasis-associated metabolites, findings are often limited by sample sizes and lack validation. Objectives: We aimed to identify circulating metabolites associated with psoriasis, including cutaneous activity, severity, and psoriatic arthritis. Further, we investigated whether the signature was disease-specific compared to other immune-mediated inflammatory diseases (IMIDs). Methods: We performed a cross-sectional analysis of 270,848 White/European individuals from the UK Biobank (n=253,924) and HUNT (n=16,924). Both cohorts used nuclear magnetic resonance spectroscopy to quantify metabolite levels, covering lipoprotein fractions and subfractions, fatty acids, and small-molecular metabolites. For each metabolite, we performed multivariable linear regression adjusting for age, sex, BMI, smoking status, and use of lipid-lowering medications. Results: The metabolomic profile of psoriasis was largely consistent across cohorts. In the model adjusted for age and sex, 116 metabolic measures were associated with psoriasis in both cohorts. After full adjustment, only Glycoprotein acetyls (GlycA) remained associated with psoriasis (coefficient [95% CI]: 0.09 [0.07-0.11] in UK Biobank and 0.11 [0.06-0.17] in HUNT). Despite more substantial metabolic alterations in cutaneous-active psoriasis, GlycA was also elevated in HUNT participants reporting no active psoriasis rash (coefficient [95% CI]: 0.12 [0.04-0.20] in non-cutaneous-active and 0.11 [0.03-0.19] in cutaneous-active psoriasis). In HUNT, severe psoriasis exhibited more pronounced metabolic alterations compared to non-severe psoriasis. Across both cohorts, phenylalanine levels were highly elevated in psoriatic arthritis compared to cutaneous psoriasis (coefficient [95% CI]: 0.41 [0.20-0.62] in UK Biobank and 0.47 [0.28-0.67] in HUNT). All IMIDs showed elevated GlycA and reduced albumin, with milder changes in atopic dermatitis. Psoriasis in the HUNT cohort exhibited a distinct lipoprotein profile compared to other IMIDs. Conclusions: This large-scale, cross-cohort study confirms metabolic alterations in individuals with psoriasis and highlights elevated GlycA levels regardless of cutaneous activity. The distinct metabolomic profile of psoriasis relative to other IMIDs suggests a potentially unique systemic profile. These findings offer a foundation for advancing biomarker research and mechanistic studies for psoriasis. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research is funded by grants from the Liaison Committee for Education, Research and Innovation in Central Norway and the Joint Research Committee between St Olavs Hospital and the Faculty of Medicine and Health Sciences, NTNU - Norwegian University of Science and Technology. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The UK Biobank has been approved by the Northwest Multi-centre Research Ethics Committee (MREC) as a Research Tissue Bank (RTB) approval, granted in 2011 and renewed every 5 years. For more information, see: https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/about-us/ethics. The use of HUNT data has been approved by the Regional Committee for Medical and Health Research Ethics (REK), Central Norway, with application number 27420. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The UK Biobank data is available to researchers for all types of health-related research that is in the public interest. Data are available for approved researchers through the UK Biobank data-access protocol. For accessing the resource, this project has been approved with application number 40135. For more information, see: https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access. The HUNT data is stored in the HUNT databank (https://www.ntnu.edu/hunt/databank), and is accessible for researchers approved by the Regional Committee for Medical and Health Research Ethics. Researchers from other countries are welcome to apply in cooperation with a Norwegian Principal Investigator. For more information, see: http://www.ntnu.edu/hunt/data.

Psoriasis and psoriatic arthritis (PsA) are chronic immune-mediated inflammatory diseases associated with obesity, cardiometabolic disease, and mortality. The glucagon-like peptide-1 (GLP1) pathway has emerged as a key factor in the development of obesity and cardiometabolic disease. GLP1 receptor agonists demonstrably improve insulin resistance, dyslipidemia, obesity, and mortality, with emerging evidence suggesting potential benefit for psoriasis. To evaluate whether GLP1 biology influences psoriatic disease risk, we conducted a Mendelian randomization study. A 22-variant cis-eQTL genetic instrument for GLP1R expression in whole blood from the eQTLGen consortium was generated as a proxy for GLP1R pathway activity (n=31,684). Genetic proxies of GLP1R expression were associated with a lower risk of psoriasis (OR=0.723, 95% CI 0.678-0.771, p=1.08x10-22) and PsA (OR=0.483, 95% CI 0.402-0.580, p=5.33x10-15) in European-ancestry GWAS meta-analyses. Effects persisted after adjustment for genetic proxies of central adiposity, HbA1c, LDL cholesterol, and triglycerides, consistent with potential pathway effects on psoriatic disease, independent of metabolic effects. To determine the specificity of the observed effect, we conducted analyses of seven additional immune-mediated diseases (IMIDs). No protective effects were observed for other IMIDs, including acne and atopic dermatitis. In contrast, risk-increasing effects were observed for Crohn's disease (OR=1.242, 95% CI 1.107-1.395, p=2.35x10-04) and rheumatoid arthritis (OR=1.502, 95% CI 1.350-1.672, p=1.36x10-13). These findings provide genetic evidence of disease-specific, potentially direct immunomodulatory effects of GLP1R signaling on psoriasis and PsA risk, and support further mechanistic and therapeutic evaluation in randomized trials. ### Competing Interest Statement - B.O.A. leads a collaborative research project between NTNU and Novartis Norge AS with financial support from Novartis Norge AS. - C.H.S. reports grants from an MRC-funded stratified medicine consortium with multiple industry partners, grants from IMI (Horizon 2020)-funded European consortium with multiple industry partners, and others from AbbVie, Novartis, Pfizer, Sanofi, Boehringer Ingelheim and SOBI, outside the submitted work; and is Chair of UK guidelines on biologic therapy in psoriasis. - J.M.G has served as a consultant for AbbVie, Artax (DSMB), Bristol Myers Squibb, Boehringer Ingelheim, Celldex (DSMB), FIDE (which is sponsored by multiple pharmaceutical companies) GSK, Inmagene (DSMB), Lilly, Leo, Moonlake (DSMB), Janssen Biologics, Novartis Corp, UCB (DSMB), Neuroderm (DSMB), Oruka, Inc, Teva (DSMB; and receives research grants (to the Trustees of the University of Pennsylvania) from Amgen, Bristol Myers Squibb, and Pfizer Inc.; and received payment for continuing medical education work related to psoriasis that was supported indirectly pharmaceutical sponsors. Dr Gelfand is a Deputy Editor for the Journal of Investigative Dermatology receiving honoraria from the Society for Investigative Dermatology, is Chief Medical Editor for Healio Dermatology (receiving honoraria) and is a member of the Board of Directors for the International Psoriasis Council and the Medical Dermatology Society, receiving no honoraria. - All other authors have no conflicts of interest of disclosures to declare. ### Funding Statement - This work was funded by the International Psoriasis Council, National Psoriasis Foundation and the University of Pennsylvania Skin Biology and Diseases Resource-based Center - The above funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The primary analysis in this study utilised publicly available summary-level data from previously published GWAS. As these analyses did not involve individual participant data or direct contact with human subjects, this research was exempt from institutional ethical review. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Two-sample MR was performed using publicly available summary statistics that can be downloaded from the GWAS catalogue (https://www.ebi.ac.uk/gwas/) and/or can be downloaded from the GWAS catalogue obtained from the corresponding author of the GWAS on reasonable request. All data supporting the findings of this study are presented within the manuscript and the supplementary file. Additional details and code used for Mendelian randomization analyses are available from the corresponding author (ravi.ramessur{at}pennmedicine.upenn.edu) upon reasonable request.

The aim of this international meta-analysis was to quantify the predictive value of BMI for incident fracture and relationship of this risk with age, sex, follow-up time, and BMD. A total of 1 667 922 men and women from 32 countries (63 cohorts), followed for a total of 16.0 million person-years were studied. 293 325 had FN BMD measured (2.2 million person-years follow-up). An extended Poisson model in each cohort was used to investigate relationships between WHO-defined BMI categories (Underweight: <18.5 kg/m2; Normal: 18.5-24.9 kg/m2; Overweight: 25.0-29.9 kg/m2; Obese I: 30.0-34.9 kg/m2; Obese II: ≥35.0 kg/m2) and risk of incident osteoporotic, major osteoporotic and hip fracture (HF). Inverse-variance weighted β-coefficients were used to merge the cohort-specific results. For the subset with BMD available, in models adjusted for age and follow-up time, the hazard ratio (95% CI) for HF comparing underweight with normal weight was 2.35 (2.10-2.60) in women and for men was 2.45 (1.90-3.17). Hip fracture risk was lower in overweight and obese categories compared to normal weight [obese II vs normal: women 0.66 (0.55-0.80); men 0.91 (0.66-1.26)]. Further adjustment for FN BMD T-score attenuated the increased risk associated with underweight [underweight vs normal: women 1.69 (1.47-1.96); men 1.46 (1.00-2.13)]. In these models, the protective effects of overweight and obesity were attenuated, and in both sexes, the direction of association reversed to higher fracture risk in Obese II category [Obese II vs Normal: women 1.24 (0.97-1.58); men 1.70 (1.06-2.75)]. Results were similar for other fracture outcomes. Underweight is a risk factor for fracture in both men and women regardless of adjustment for BMD. However, while overweight/obesity appeared protective in base models, they became risk factors after additional adjustment for FN BMD, particularly in the Obese II category. This effect in the highest BMI categories was of greater magnitude in men than women. These results will inform the second iteration of FRAX®.

ObjectiveTo identify factors associated with two self-reported measures of physical activity (PA) in patients with rheumatoid arthritis (RA).MethodHospital outpatients with RA from central Norway filled in questionnaires about symptoms, psychological factors, and PA. Outcomes were two alternative self-reported measures of PA: (i) fulfilling the aerobic PA recommendations of >= 150 min/week at moderate intensity or >= 75 min/week at vigorous intensity; or (ii) being in the PA maintenance stage of the Stages of Exercise Behaviour Change framework. Logistic regression was applied to identify factors associated with PA. Step 1 included the independent variables sex, age, and smoking habits. Step 2a added self-reported function, joint pain during the past 6 months, and fatigue to Step 1. Step 2b added Exercise Self-Efficacy and the Relative Autonomy Index (RAI), calculated from the Behavioural Regulation in Exercise Questionnaire-2, to Step 1. Step 3 included all the mentioned independent variables. Steps 1-3 were analysed for each PA measure.ResultsIn total, 227 patients participated. The RAI had a statistically significant positive association with being physically active according to both PA definitions. Joint pain had a significant negative association with meeting the aerobic PA recommendations but was not associated with being in the PA maintenance stage.ConclusionThe degree of self-determined motivation was the most consistent variable associated with self-reported PA behaviour. Joint pain was associated with one of the two PA measures. Motivation and joint pain may be useful targets for intervention in clinical practice to improve PA engagement among patients with RA.

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.

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.