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Background: Our objective was to determine the survival and causes of death in a large and well-characterized cohort of patients with giant cell arteritis (GCA). Methods: This is a hospital-based, retrospective, observational cohort study including patients diagnosed with GCA in Western Norway during 1972–2012. Patients were identified through computerized hospital records using the International Classification of Diseases (ICD)-coding system. Medical records were reviewed. Patients were randomly assigned population controls matched on age, sex, and geography from the Central Population Registry of Norway (CPRN). Date and cause of death were obtained from the Norwegian Cause of Death Registry (NCoDR). The survival was analyzed using Kaplan-Meier methods with the Gehan-Breslow test and the causes of death using cumulative incidence and Cox models for competing risks. Results: We identified 881 cases with a clinical diagnosis of GCA of which 792 fulfilled the American College of Rheumatology (ACR) 1990 classification criteria. Among those fulfilling the ACR criteria, 528 were also biopsy-verified. Cases were matched with 2577 population controls. A total of 490 (56%) GCA patients and 1517 (59%) controls died during the study period. We found no difference in the overall survival of GCA patients compared to controls, p = 0.413. The most frequent underlying causes of death in both groups were diseases of the circulatory system followed by cancer. GCA patients had increased risk of dying of circulatory disease (HR 1.31, 95% CI 1.13–1.51, p

BACKGROUND A frequent observation in inflammatory conditions, including rheumatoid arthritis (RA), is low circulating amounts of pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B-6. Recently, a functional marker of vitamin B-6 status, the ratio of 3-hydroxykynurenine (HK): xanthurenic acid (XA) in plasma (HK: XA), was proposed. OBJECTIVE We investigated vitamin B-6 status in patients with RA before and after established treatment with TNFα inhibitors. METHODS We performed a longitudinal study of RA patients (n = 106, 36% men, median age 54 y) starting first treatment with a TNFα inhibitor (infliximab, etanercept, adalimumab, golimumab, or certolizumab). Clinical assessment (Disease Activity Score for 28 standard joints, DAS28), joint ultrasonography, and blood draw were performed at baseline and after 3 mo treatment. Plasma concentrations of PLP, HK, and XA were measured by liquid chromatography-tandem mass spectrometry. Associations of changes in vitamin B-6 markers with change in DAS28 were assessed by generalized additive models regression and with European League Against Rheumatism (EULAR) response categories by linear regression. RESULTS At baseline PLP was inversely correlated with CRP (ρ = -0.27, P = 0.007), whereas HK: XA correlated with DAS28 (ρ = 0.46, P

Immunogenicity is a frequent cause of secondary non-response to tumour necrosis factor (TNF) inhibitors. Drug level measurement and detection of antidrug antibodies have been shown to be cost effective and clinically relevant, and a large number of assays are available for these purposes. It is, however, difficult to compare assays and translate results into clinical meaningful information due to different methodological approaches and a lack of assay standardization. We have analysed infliximab drug levels and antidrug antibodies in 107 patient samples using enzyme-linked immunoassays (ELISA), immunofluorometric assays (IFMA) and reporter-gene assays (RGA). The RGA gave the lowest results for drug levels, whereas the IFMA detected the highest number of antidrug antibody positive sera. Applying individualized therapeutic ranges to each assay resulted in agreement among all three assays in 74% of samples for drug levels and 98% of samples for antidrug antibodies. We found that TNF inhibitor monitoring assays measure on different scales and that the agreement between quantitative results is limited. However, interassay differences can partially be overcome by assay-individualized translations of quantities into categories, which also is necessary for a meaningful clinical application. Our data demonstrate that assays should not be used interchangeably and that direct comparison of quantitative drug levels obtained with different assays should be avoided.

Accepted manuscript version. Published version available in Journal of Bone and Mineral Research, 2017;32(10):1981-1989

Summary Background TNF inhibitors have improved treatment of Crohn's disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriatic arthritis, and chronic plaque psoriasis, but are expensive therapies. The aim of NOR-SWITCH was to examine switching from originator infliximab to the less expensive biosimilar CT-P13 regarding efficacy, safety, and immunogenicity. Methods The study is a randomised, non-inferiority, double-blind, phase 4 trial with 52 weeks of follow-up. Adult patients on stable treatment with infliximab originator treated in a hospital setting for at least 6 months were eligible for participation. Patients with informed consent were randomised in a 1:1 ratio to either continued infliximab originator or to switch to CT-P13 treatment, with unchanged dosing regimen. Data were collected at infusion visits in 40 Norwegian study centres. Patients, assessors, and patient care providers were masked to treatment allocation. The primary endpoint was disease worsening during 52-week follow-up. 394 patients in the primary per-protocol set were needed to show a non-inferiority margin of 15%, assuming 30% disease worsening in each group. This trial is registered with ClinicalTrials.gov, number NCT02148640. Findings Between Oct 24, 2014, and July 8, 2015, 482 patients were enrolled and randomised (241 to infliximab originator, 241 to CT-P13 group; one patient was excluded from the full analysis and safety set for CT-P13) and 408 were included in the per-protocol set (202 in the infliximab originator group and 206 in the CT-P13 group). 155 (32%) patients in the full analysis set had Crohn's disease, 93 (19%) had ulcerative colitis, 91 (19%) had spondyloarthritis, 77 (16%) had rheumatoid arthritis, 30 (6%) had psoriatic arthritis, and 35 (7%) had chronic plaque psoriasis. Disease worsening occurred in 53 (26%) patients in the infliximab originator group and 61 (30%) patients in the CT-P13 group (per-protocol set; adjusted treatment difference −4·4%, 95% CI −12·7 to 3·9). The frequency of adverse events was similar between groups (for serious adverse events, 24 [10%] for infliximab originator vs 21 [9%] for CT-P13; for overall adverse events, 168 [70%] vs 164 [68%]; and for adverse events leading to discontinuation, nine [4%] vs eight [3%], respectively). Interpretation The NOR-SWITCH trial showed that switching from infliximab originator to CT-P13 was not inferior to continued treatment with infliximab originator according to a prespecified non-inferiority margin of 15%. The study was not powered to show non-inferiority in individual diseases. Funding Norwegian Ministry of Health and Care Services.

Higher hip fracture incidence in urban than in rural areas has been demonstrated, but urban–rural differences in posthip fracture mortality have been less investigated, and the results are disparate. Hence, the aims of the present register‐based cohort study were to examine possible urban–rural differences in short‐ and long‐term mortality in Norwegian hip fracture patients and their potential associations with sociodemographic variables, and to investigate possible urban–rural differences in excess mortality in hip fracture patients compared with the general population. Data were provided from the NOREPOS hip fracture database, the 2001 Population and Housing Census, and the National Registry. The urbanization degree in each municipality was determined by the proportion of inhabitants living in densely populated areas (rural: 2/3). Age‐adjusted mortality rates and standardized mortality ratios were calculated for hip fracture patients living in rural, semirural, and urban municipalities. A flexible parametric model was used to estimate age‐adjusted average and time‐varying HRs by category of urbanization with the rural category as reference. Among 96,693 hip fracture patients, urban residents had higher mortality than their rural‐dwelling counterparts. The HR of mortality in urban compared with rural areas peaked during the first 1 to 2 years postfracture with a maximum HR of 1.20 (95% CI, 1.10 to 1.30) in men and 1.15 (95% CI, 1.08 to 1.21) in women. The differences were significant during approximately 5 years after fracture. Adjusting for sociodemographic variables did not substantially change the results. However, absolute 30‐day mortality was not significantly different between urban and rural residents, suggesting that health‐care quality immediately postfracture does not vary by urbanization. The novel findings of a higher long‐term mortality in urban hip fracture patients might reflect disparities in health status or lifestyle, differences in posthip fracture health care or rehabilitation, or a combination of several factors. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Objective.To determine the risk of cancer in a large Norwegian cohort of patients with giant cell arteritis (GCA).Methods.This is a hospital-based, retrospective, observational cohort study including patients diagnosed with GCA in the Bergen Health Area during 1972–2012. Patients were identified through computerized hospital records using the International Classification of Diseases coding system. Medical records were reviewed. Each patient was randomly assigned population controls matched on age, sex, and geography from the Central Population Registry of Norway. Data on the occurrence of cancer were obtained from the Cancer Registry of Norway. The cumulative risk of malignancy was estimated using Kaplan-Meier methods and potential differences were analyzed using the Gehan-Breslow and log-rank tests.Results.We identified 881 cases with a clinical diagnosis of GCA, of which 792 fulfilled the American College of Rheumatology (ACR) 1990 classification criteria and 528 were biopsy-verified. Cases with no registered cancer prior to GCA diagnosis were included in a time-to-event analysis, with first cancer as the event (n = 767 with clinical GCA diagnosis, 686 fulfilling ACR criteria for GCA, 463 biopsy-verified). These cases were matched with previously cancer-free population controls (n = 1437, 1284, 895, respectively). We found no significant difference in the risk of malignancy after time of diagnosis/matching for GCA patients compared to population controls (p > 0.05).Conclusion.In this study of a large and well-characterized cohort of patients with GCA, there was no difference in the risk of malignancy in patients with GCA compared to matched population controls.

// Ingvild Eide Graff 1 , Jannike Oyen 1 , Marian Kjellevold 1 , Livar Froyland 1 , Clara Gram Gjesdal 2,3 , Bjorg Almas 4 , Grethe Rosenlund 5 and Oyvind Lie 1 1 National Institute of Nutrition and Seafood Research (NIFES), Bergen, Norway 2 Department of Rheumatology, Haukeland University Hospital, Bergen, Norway 3 Department of Clinical Science, University of Bergen, Bergen, Norway 4 Hormone Laboratory, Haukeland University Hospital, Bergen, Norway 5 Skretting Aquaculture Research Centre, Stavanger, Norway Correspondence to: Jannike Oyen, email: // Keywords : Atlantic salmon, bone health, vitamin D, vitamin K, bone biomarkers, Gerotarget Received : March 09, 2016 Accepted : June 09, 2016 Published : August 14, 2016 Abstract Suboptimal vitamin D status is common among humans, and might increase bone resorption with subsequent negative effects on bone health. Fatty fish, including Atlantic salmon, is an important dietary vitamin D source. However, due to a considerable change in fish feed composition, the contribution of vitamin D from salmon fillet has been reduced. The main objective was to investigate if intake of vitamin D 3 enriched salmon or vitamin D 3 tablets decreased bone biomarkers (urinary N-telopeptides, deoxypyridinoline, serum bone-specific alkaline phosphatase, and osteocalcin) compared to a low vitamin D 3 intake. The 122 healthy postmenopausal women included in this 12 weeks intervention trial were randomized into four groups: three salmon groups (150 grams/two times/week) and one tablet group (800 IU vitamin D and 1000 mg calcium/day). The salmon groups also received calcium supplements. The salmon had three different vitamin D 3 /vitamin K 1 combinations: high D 3 +high K 1 , low D 3 +high K 1 , or high D 3 +low K 1 . Increased intake of salmon containing high levels of vitamin D 3 (0.35-0.38 mg/kg/fillet) and supplements with the same weekly contribution had a positive influence on bone health as measured by bone biomarkers in postmenopausal women. Consequently, an increased level of vitamin D 3 at least to original level in feed for salmonids will contribute to an improved vitamin D 3 status and may improve human bone health.

The previously reported decline in age-adjusted hip fracture rates in Norway during 1999–2008 continued after 2008. The annual number of hip fractures decreased in women and increased in men. Norway has among the highest hip fracture incidence rates ever reported despite previously observed declining rates from 1999 through 2008. The aim of the present study was to investigate whether this downward trend continued through 2013, and to compare gender-specific trends in 5 year age-groups during three time periods: 1999–2003, 2004–2008, and 2009–2013. All hip fractures (cervical, trochanteric, and sub-trochanteric) admitted to Norwegian hospitals were retrieved. Annual age-standardized incidence rates of hip fracture per 10,000 person-years by gender were calculated for the period 1999–2013. Time trends were tested by age-adjusted Poisson regression. From 1999 through 2013 there were 140,136 hip fractures in persons aged 50 years and above. Age-adjusted hip fracture incidence rates declined by 20.4 % (95 % CI: 18.6–20.1) in women and 10.8 % (95 % CI: 7.8–13.8) in men, corresponding to an average annual age-adjusted decline of 1.5 % in women and 0.8 % in men. Except for the oldest men, hip fracture rates declined in all age-groups 70 years and older. The average annual number of fractures decreased in women (−0.3 %) and increased in men (+1.1 %). During the past 15 years, hip fracture rates have declined in Norway. The forecasted growing number of older individuals might, however, cause an increase in the absolute number of fractures, with a substantial societal economic and public health burden.

Fatigue occurs in all chronic inflammatory diseases, in cancer, and in some neurological conditions. Patients often regard fatigue as one of their most debilitating problems, but currently there is no established treatment and the mechanisms that lead to and regulate fatigue are incompletely understood. Our objective was to more completely understand the physiology of this phenomenon. Twenty-four patients with rheumatoid arthritis (RA) naïve to treatment with biological drugs were enrolled for the study. Fatigue was measured with a fatigue visual analogue scale (fVAS). Ethylenediaminetetraacetic acid (EDTA) plasma samples were subjected to gas chromatography-time-of-flight mass spectrometry (GC/MS-TOF)-based metabolite profiling. Obtained metabolite data were evaluated by multivariate data analysis with orthogonal projections to latent structures (OPLS) method to pinpoint metabolic changes related to fatigue severity. A significant multivariate OPLS model was obtained between the fVAS scores and the measured metabolic levels. Increasing fatigue scores were associated with a metabolic pattern characterized by down-regulation of metabolites from the urea cycle, fatty acids, tocopherols, aromatic amino acids, and hypoxanthine. Uric acid levels were increased. Apart from fatigue, we found no other disease-related variables that might be responsible for these changes. Our MS-based metabolomic approach demonstrated strong associations between fatigue and several biochemical patterns related to oxidative stress.

Following publication of the original article [1], the authors reported an error.

Aims and objectives To examine changes in patient-reported fatigue, over a twelve month period, in rheumatoid arthritis patients who commence biologic treatment, and to identify possible predictors for such changes. Background Fatigue is a burdensome symptom for patients with rheumatoid arthritis. Despite biologics being effective in reducing disease activity, patients still report fatigue. Design A longitudinal observational study. Methods A total of 48 patients were enrolled in the study. Fatigue was measured by the Fatigue Severity Scale. Independent samples T-tests were used to test gender differences, and paired samples T-tests were used to measure differences between repeated measures. Bivariate and multiple regression analyses were used to examine potential predictors for changes in fatigue, such as age, sex, Disease Activity Score 28, pain and physical and emotional well-being. Results Forty-seven patients completed the study. From baseline to 12-month follow-up, fatigue decreased significantly in both women and men. Analyses of predictors were performed step-wise, and the final model included sex and physical well-being. The results from this final step showed that female sex was the only significant predictor for changes in fatigue. Conclusion Patients commencing biologic therapy reported a significant reduction in fatigue. Female sex was a significant predictor of changes in fatigue. Relevance to clinical practice Despite improvements in pharmacological treatment, patients with rheumatoid arthritis still report fatigue. This is a multifaceted health problem encompassing personal and emotional factors in addition to the clinical factors directly connected to the disease.

Background A meta-analysis from 2014 reported a low but statistically significant increased malignancy risk among patients with giant cell arteritis (GCA), but individual epidemiological studies have shown conflicting results.1 Objectives To determine the risk of cancer in GCA patients during a 41 year period. Methods Hospital-based retrospective cohort study including patients diagnosed with GCA in Bergen Health Area during 1972–2012. Patients were identified through computerised hospital records using the International Classification of Diseases (ICD)-coding system. Clinical information was extracted from patients’ medical journals. We excluded patients if data were unavailable, if the reviewing rheumatologist found GCA to be an implausible diagnosis or if the American College of Rheumatology (ACR) 1990 classification criteria for GCA were not fulfilled. Each patient was matched for age, sex, and county of residence to 3 control subjects randomly selected from the Central Population Registry of Norway. Information on the occurrence of cancer was obtained from the Cancer Registry of Norway. The cumulative incidence of malignancy in cases and controls were estimated using Kaplan-Meier plots. Results The patient inclusion process and patient characteristics have been published previously.2 A total of 792 patients were included, 566 (71.5%) women (mean age 73.5 years, SD 8) and 226 (28.5%) men (mean age 72.1, SD 9). There were 2314 matched controls (excluding duplicate controls and control subjects which were also among the cases). The mean duration of follow-up for the GCA-patients was 7.2 years (SD 6.7). The mean duration of follow-up for the controls was 6.6 years (SD 6.1). The relative risk of malignancy during follow-up was higher for controls compared to cases during the majority of the observation period, but the overall difference was not statistically significant (p=0.060, figure 1). However, the subset of 528 patients (66.7%) with a positive temporal artery biopsy (TAB) had a statistically significant lower risk of malignancy compared to their matched controls (p=0.006). Conclusions We did not find a significant difference in the risk of malignancy in the overall GCA cohort compared to their matched controls. However, we found a statistically significant reduced risk of malignancy during follow-up for the subset of GCA-patients with a positive TAB. This is in contrast to the results of a meta-analysis which found an increased risk of malignancy in the subgroup with positive TAB. Further studies are required to determine whether this is a true difference, and what the potential causes may be. References [1] Ungprasert P, Sanguankeo A, Upala S, Knight EL. Risk of malignancy in patients with giant cell arteritis and polymyalgia rheumatica: a systematic review and meta-analysis. Semin Arthritis Rheum2014;44(3):366–70. [2] Brekke LK, Diamantopoulos AP, Fevang B-T, Aβmus J, Espero E, Gjesdal CG. Incidence of giant cell arteritis in Western Norway 1972–2012: a retrospective cohort study. Arthritis Research & Therapy2017;19:278. doi:10.1186/s13075-017-1479-6 Acknowledgements The study has used data from the Cancer Registry of Norway (CRN). The interpretation and reporting of these data are the sole responsibility of the authors, and no endorsement by CRN is intended nor should be inferred. Disclosure of Interest L. Brekke Grant/research support from: MSD, A. Diamantopoulos: None declared, B.-T. Fevang Consultant for: Lilly, Novartis, AbbVie, J. Assmus: None declared, C. Gjesdal: None declared

Background Giant cell arteritis (GCA) is the most common systemic vasculitis in adults. Objectives To determine the causes of death in GCA patients during a 41 year period. Methods Hospital-based retrospective cohort study including patients diagnosed with GCA in Bergen Health Area during 1972–2012. Patients were identified through computerised hospital records using the International Classification of Diseases (ICD)-coding system. Clinical information was extracted from patients’ medical journals. We excluded patients if data were unavailable, if the reviewing rheumatologist found GCA to be an implausible diagnosis or if the American College of Rheumatology (ACR) 1990 classification criteria for GCA were not fulfilled. Information on cause of death was obtained from the Norwegian Cause of Death Registry (NCoDR). We grouped causes of death according to the European Shortlist for Causes of Death 2012-version (COD-SL-2012). Statistics Norway (www.ssb.no) provided background population data (all deaths during 1972–2012 in the Norwegian population ≥50 years of age). Statistical comparison was performed using mid-p values. Results The patient inclusion process and patient characteristics have been published previously.1 A total of 792 patients were included, 566 (71.5%) females (mean age 73.5 years, SD 8) and 226 (28.5%) males (mean age 72.1, SD 9). 432 patients (54.5%) died during the study period (1 January 1972 – 31 December 2012). NCoDR had data on the cause of death for 431 of these. During the study period (1972–2012) there were 1635979 registered deaths in the general Norwegian population aged ≥50 years. The most frequent underlying causes of death in the overall study population were diseases of the circulatory system (53.4%), cancer (11.6%) and diseases of the respiratory system (10.0%). The most frequent causes of death in the general population were also diseases of the circulatory system (46.0%), cancer (22.8%) and diseases of the respiratory system (10.0%). The distribution of causes of death differed significantly between GCA-patients and the general Norwegian population (mid-p-value Conclusions The most frequent causes of death in our cohort of GCA-patients were diseases of the circulatory system, cancer and diseases of the respiratory system (including influenza and pneumonia). These were also the most frequent causes of death in the general Norwegian population aged ≥50 years, but the distribution of death causes differed significantly between GCA-patients and the general population. However, this might reflect differences in the composition of the populations that we were not able to adjust for. We aim to analyse this further by comparing our GCA-cohort with randomly selected age-, sex- and geographically matched control subjects. Reference [1] Brekke LK, Diamantopoulos AP, Fevang B-T, Assmus J, Espero E, Gjesdal CG. Incidence of giant cell arteritis in Western Norway 1972–2012: a retrospective cohort study. Arthritis Research & Therapy2017;19:278. doi:10.1186/s13075-017-1479-6 Disclosure of Interest L. Brekke Grant/research support from: MSD, A. Diamantopoulos: None declared, B.-T. Fevang Consultant for: Lilly, Novartis, AbbVie, J. Assmus: None declared, C. Gjesdal: None declared

The present study investigated the risk of incident hip fractures according to serum concentrations of vitamin K1 and 25-hydroxyvitamin D in elderly Norwegians during long-term follow-up. The results showed that the combination of low concentrations of both vitamin D and K1 provides a significant risk factor for hip fractures. This case-cohort study aims to investigate the associations between serum vitamin K1 and hip fracture and the possible effect of 25-hydroxyvitamin D (25(OH)D) on this association. The source cohort was 21,774 men and women aged 65 to 79 years who attended Norwegian community-based health studies during 1994–2001. Hip fractures were identified through hospital registers during median follow-up of 8.2 years. Vitamins were determined in serum obtained at baseline in all hip fracture cases (n = 1090) and in a randomly selected subcohort (n = 1318). Cox proportional hazards regression with quartiles of serum vitamin K1 as explanatory variable was performed. Analyses were further performed with the following four groups as explanatory variable: I: vitamin K1 ≥ 0.76 and 25(OH)D ≥ 50 nmol/l, II: vitamin K1 ≥ 0.76 and 25(OH)D

Hip fractures are associated with high excess mortality. Education is an important determinant of health, but little is known about educational inequalities in post-hip fracture mortality. Our objective was to investigate educational inequalities in post-hip fracture mortality and to examine whether comorbidity or family composition could explain any association. We conducted a register-based population study of Norwegians aged 50 years and older from 2002 to 2010. We measured total mortality according to educational attainment in 56,269 hip fracture patients (NORHip) and in the general Norwegian population. Both absolute and relative educational inequalities in mortality in people with and without hip fracture were compared. There was an educational gradient in post-hip fracture mortality in both sexes. Compared with those with primary education only, the age-adjusted relative risk (RR) of mortality in hip fracture patients with tertiary education was 0.82 (95% confidence interval [CI] 0.77-0.87) in men and 0.79 (95% CI 0.75-0.84) in women. Additional adjustments for Charlson comorbidity index, marital status, and number of children did not materially change the estimates. Regardless of educational attainment, the 1-year age-adjusted mortality was three- to fivefold higher in hip fracture patients compared with peers in the general population without fracture. The absolute differences in 1-year mortality according to educational attainment were considerably larger in hip fracture patients than in the population without hip fracture. Absolute educational inequalities in mortality were higher after hip fracture compared with the general population without hip fracture and were not mediated by comorbidity or family composition. Investigation of other possible mediating factors might help to identify new targets for interventions, based on lower educational attainment, to reduce post-hip fracture mortality.

Background Giant cell arteritis (GCA) is the most common systemic vasculitis in persons older than 50 years. The highest incidence rates of the disease have been reported in Scandinavian countries. Our objective was to determine the epidemiology of GCA in an expected high-incidence region during a 41-year period. Methods This is a hospital-based, retrospective, cohort study. Patients diagnosed with GCA in Bergen health area during 1972–2012 were identified through computerized hospital records (n = 1341). Clinical information was extracted from patients’ medical journals, which were reviewed by a standardized method. We excluded patients if data were unavailable (n = 253), if the reviewing rheumatologist found GCA to be an implausible diagnosis (n = 207) or if the American College of Rheumatology (ACR) 1990 classification criteria for GCA were not fulfilled (n = 89). Descriptive methods were used to characterize the sample. Incidence was analyzed by graphical methods and Poisson regression. Results A total of 792 patients were included. The average annual cumulative incidence of GCA was 16.7 (95% CI 15.5-18.0) per 100,000 of the population ≥ 50 years old. The corresponding incidence for biopsy-verified GCA was 11.2 (95% CI 10.2–12.3). The annual cumulative incidence increased with time in the period 1972–1992 (relative risk (RR) 1.1, p

BackgroundSarcopenia is prevalent in older persons and is a risk factor for falls, fractures, and mortality. The aim of this study was to determine a) the feasibility of determining sarcopenia in patients with acute hip fracture, b) the prevalence of sarcopenia and c) associations of sarcopenia with nutritional status and comorbidities.MethodsA multicenter cross-sectional study on sarcopenia in male and female patients with acute hip fracture. Participants were previously ambulatory and living in the community. Sarcopenia was assessed postoperatively with muscle mass estimated by anthropometry using triceps skinfold, arm circumference, height, weight and sex. Grip strength was measured by Jamar dynamometer and pre-fracture mobility was by self-report using the New Mobility Score.ResultsOut of 282 patients, 202 were assessed for sarcopenia of whom 74 (37%) were diagnosed as sarcopenic. Sarcopenia was associated with age, odds ratio (OR) 1.4 per 5 years, 95% confidence interval (CI) [1.1, 1.8], ASA Physical Status Classification System score, OR 2.3 per point, 95% CI [1.3, 4.3] and number of medications at discharge, OR 1.2 per medication, 95% CI [1.0, 1.3] and inversely associated with BMI, OR 0.8, 95% CI [0.7, 0.9] and serum albumin, OR 0.9, 95% CI [0.8,1.0].ConclusionsThirty-seven percent of assessed subjects were diagnosed with sarcopenia. Our data demonstrates that the prevalence of sarcopenia is associated with older age, malnutrition and comorbidities. Determining sarcopenia at the bedside was feasible in postoperative hip fracture patients by using grip strength, estimation of muscle mass by anthropometry and self-reported mobility.

Hip fractures are associated with increased mortality and their incidence in Norway is one of the highest worldwide. The aim of this nationwide study was to examine short- and long-term mortality after hip fractures, burden of disease (attributable fraction and potential years of life lost), and time trends in mortality compared to the total Norwegian population. Information on incident hip fractures between 1999 and 2008 in all persons aged 50. years and older was collected from Norwegian hospitals. Death and emigration dates of the hip fracture patients were obtained through 31 December 2010. Standardized mortality ratios (SMRs) were calculated and Poisson regression analyses were used for the estimation of time trends in SMRs. Among the 81,867 patients with a first hip fracture, the 1-year excess mortality was 4.6-fold higher in men, and 2.8-fold higher in women compared to the general population. Although the highest excess mortality was observed during the first two weeks post fracture, the excess risk persisted for twelve years. Mortality rates post hip fracture were higher in men compared to women in all age groups studied. In both genders aged 50. years and older, approximately 5% of the total mortality in the population was related to hip fractures. The largest proportion of the potential life-years lost was in the relatively young-old, i.e. less than 80. years. In men, the 1-year absolute mortality rates post hip fracture declined significantly between 1999 and 2008, by contrast, the mortality in women increased significantly relatively to the population mortality.

Summary The cytokine interferon gamma (IFN-γ) stimulates neopterin release and tryptophan degradation into kynurenines through the kynurenine pathway. High levels of neopterin were associated with increased hip fracture risk, as were some of the kynurenines, suggesting a role of IFN-γ-mediated inflammation in the processes leading to hip fracture. Introduction Low-grade systemic inflammation has been associated with bone loss and risk of fractures. Interferon gamma (IFN-γ) initiates macrophage release of neopterin and also stimulates degradation of tryptophan along the kynurenine pathway as part of cell-mediated immune activation. Plasma neopterin and the kynurenine/tryptophan ratio (KTR) are thus markers of IFN-γ-mediated inflammation. Risk of hip fracture was investigated in relation to markers of inflammation and metabolites in the kynurenine pathway (kynurenines). Methods Participants (71 to74 years, N = 3,311) in the community-based Hordaland Health Study (HUSK) were followed for hip fractures from enrolment (1998–2000) until 31 December 2009. Plasma C-reactive protein (CRP), neopterin, KTR, and six kynurenines were investigated as predictors of hip fracture, using Cox proportional hazards regression analyses. Results A hazard ratio (HR) of 1.9 (95 % confidence interval (CI) 1.3–2.7) for hip fracture was found in the highest compared to the lowest quartile of neopterin (p trend across quartiles

Summary In the large community-based Hordaland Health Study, low plasma dimethylglycine was associated with low bone mineral density in both middle-aged and elderly subjects and to an increased risk of subsequent hip fracture among the elderly. These associations seemed to be particularly strong among subjects exposed to nicotine. Introduction Dimethylglycine (DMG) is a product of the cho- line oxidation pathway and formed from betaine during the folate-independent remethylation of homocysteine (Hcy) to methionine. Elevated plasma DMG levels are associated with atherosclerotic cardiovascular disease and inflammation, which in turn are related to osteoporosis. High plasma total Hcy and low plasma choline are associated with low bone mineral density (BMD) and hip fractures, but the role of plas- ma DMG in bone health is unknown. Methods We studied the associations of plasma DMG with BMD among 5315 participants (46-49 and 71-74 years old) and with hip fracture among 3310 participants (71-74 years old) enrolled in the Hordaland Health Study. Results In age and sex-adjusted logistic regression models, subjects in the lowest versus highest DMG tertile were more likely to have low BMD (odds ratio (OR) 1.68, 95 % confi- dence interval (CI) 1.43-1.99). The association was stronger in participants exposed compared to those unexposed to nic- otine (OR 2.31, 95 % CI 1.73-3.07 and OR 1.43, 95 % CI 1.16-1.75, respectively, p interaction=0.008). In the older co- hort, Cox regression analyses adjusted for sex showed that low plasma DMG was associated with an increased risk of hip fracture (hazard ratio (HR) 1.70, 95 % CI 1.28-2.26). A trend toward an even higher risk was found among women exposed to nicotine (HR 3.41, 95 % CI 1.40-8.28). Conclusion Low plasma DMG was associated with low BMD and increased risk of hip fractures. A potential effect modification by nicotine exposure merits particular attention.

Objective: Stearoyl-coenzyme A desaturase-1 (SCD1) is a key enzyme in fatty acid and energy metabolism. Increased hepatic SCD1 activity is associated with obesity and obesity-related diseases. We examined the relations of two plasma SCD activity indices (16:1n-7/16:0, 18:1n-9/18:0) with body composition, and the association of lifestyle and dietary variables with the plasma SCD indices. Design and Methods: This population-based, cross-sectional study of 2021 elderly (71–74 y) men and women from the Hordaland Health Study in Western Norway was conducted using a validated food frequency questionnaire, body composition measurements by dual-energy X-ray absorptiometry and determination of the plasma fatty acid profile. Results: In multivariate regression analyses, plasma SCD indices were positively associated with BMI and body fat (P < 0.001 for both). From the 2.5th to 97.5th percentiles of plasma SCD-16 and SCD-18 indices, fat mass differed by about 8 kg and 5 kg, respectively. Intake of polyunsaturated fatty acids were negatively associated with SCD-16 (partial r = −0.30) and SCD-18 (partial r = −0.24) (P < 0.001 for both). Alcohol intake was positively associated with SCD-16 (partial r = 0.26) and SCD-18 (partial r = 0.16) (P < 0.001 for both), whereas coffee consumption and physical activity were inversely associated with SCD-16 (P = 0.026 and P = 0.006, respectively) and SCD-18 (P = 0.001 and P = 0.022, respectively). Conclusions: In this elderly population, plasma markers of SCD1 activity are associated with increased adiposity. Furthermore, modifiable dietary habits and lifestyle are associated with plasma SCD indices. These results suggest that SCD1 activity may be a promising target for weight control.

Background Second hip fracture risk is elevated after the first, however whether risk differs with age, by sex or over time is not well known. Objective To examine the risk of second hip fracture by sex, age and time after first hip fracture. Design Data on all hip fractures in subjects 50 years and older and treated in Norwegian hospitals during 1999–2008 were retrieved. Surgical procedure codes and additional diagnosis codes were used to define incident fractures. Survival analyses with and without adjustment for competing risk of death were used to estimate the risk of second hip fracture. Results Among the 81,867 persons who sustained a first hip fracture, 6161 women and 1782 men suffered a second hip fracture during follow-up. The overall age-adjusted hazard ratio (HR) of a second hip fracture did not differ between the sexes (women versus men, HR = 1.03; 95% confidence interval (CI): 0.98–1.09). Taking competing risk of death into account, the corresponding age-adjusted HR of a second hip fracture was 1.40 (95% CI: 1.33–1.47) in women compared to men. The greater risk in women was due to a higher mortality in men. Based on competing risk analyses, we estimate that 15% of women and 11% of men will have suffered a second hip fracture within 10 years after the first hip fracture. The ten-year cumulative incidence was above 10% in all age-groups, except in men 90 years and older. Conclusion Fracture preventive strategies have a large potential in both women and men who suffer their first hip fracture due to the high risk of another hip fracture.

Background: Choline is an important nutrient either obtained from a variety of foods or synthesized endogenously, and it is the precursor of betaine. We previously reported positive associations between plasma free choline and bone mineral density (BMD). Animal studies suggest an impact of dietary choline on bone metabolism, but the role of dietary intake of choline and betaine for human bone health is unknown.Objectives: The main aims were to examine the associations of dietary choline, choline species, and betaine with BMD and to study the relations between dietary and plasma free choline and betaine.Methods: Study subjects were participants in the Hordaland Health Study, including 2649 women and 1983 men (aged 46-49 or 71-74 y). BMD was measured by dual-energy X-ray absorptiometry, and dietary intake was obtained by using a validated 169-item food-frequency questionnaire. Risk associations were assessed by logistic regression and correlations by ρ (Spearman's bivariate rank order correlation).Results: Subjects in the lowest compared with the highest tertile of dietary total choline, free choline, glycerophosphocholine, phosphocholine, phosphatidylcholine, and sphingomyelin had a higher risk of low-femoral neck BMD, defined as the lowest BMD quintile. Particularly strong associations were found among middle-aged men for intake of free choline (OR: 1.83; 95% CI: 1.24, 2.69; P = 0.002) and glycerophosphocholine (OR: 2.13; 95% CI: 1.43, 3.16; P < 0.001) and among elderly women for total choline (OR: 1.96; 95% CI: 1.33, 2.88; P = 0.001) and phosphatidylcholine (OR: 1.94; 95% CI: 1.33, 2.84: P = 0.001) intake. No significant associations were observed between dietary betaine and BMD. Dietary total choline, free choline, glycerophosphocholine, phosphatidylcholine, and sphingomyelin correlated weakly with plasma free choline (ρ: 0.07, 0.05, 0.07, 0.07, and 0.05, respectively; P < 0.01). Dietary betaine correlated with plasma betaine (ρ: 0.23; P < 0.001).Conclusion: Dietary choline was positively associated with BMD in middle-aged and elderly participants.

Older hip fracture patients often have reduced muscle mass, which is associated with adverse outcomes. Dual energy X-ray absorptiometry (DXA) can determine muscle mass, but is not practical in the acute phase. We investigated bioelectrical impedance analysis (BIA) and anthropometry compared against DXA for detecting low muscle mass in hip fracture patients. This was a cross-sectional validation study at two Norwegian hospitals on 162 hip fracture patients aged ≥ 65 years. Appendicular lean mass (ALM) was determined by DXA, BIA and anthropometry 3 months after hip fracture. ALM by BIA was calculated by the Kyle, Janssen, Tengvall and Sergi equations, and ALM by anthropometry by the Heymsfield and Villani equations. The area under the receiver operating characteristic curve (AUC) was used to compare BIA and anthropometry for determining low ALM (≤5.67 kg/m2 for women and ≤7.25kg/m2 for men). Mean age was 79 years (SD 7.9), 74% were female. Mean ALM by DXA was 14.8 kg (SD 2.3) for women and 20.8 kg (SD 4.2) for men and 45% of women and 60% of men had low ALM. BIA (Kyle) in women (AUC 0.81, 95% confidence interval 0.72–0.89) and BIA (Sergi) in men (AUC 0.89, 95% CI 0.80–0.98) were best able to discriminate between low and normal ALM. Anthropometry (Heymsfield) was less accurate than BIA in women (AUC 0.64, 95% CI 0.54–0.75), and equal to BIA in men (AUC 0.72, 95% CI 0.72 0.56–0.87). BIA (Sergi, Kyle and Tengvall) and anthropometry (Heymsfield) can identify low muscle mass in hip fracture patients.

Declining incidences of hip fractures are reported from western countries. Norway has among the highest rates in the world. The aim of this study was to investigate trends in total hip fracture rates in Norway between 1999 and 2008 and risk of second hip fractures. All hospitalizations given a hip fracture diagnosis code (International Classification of Diseases (ICD) 9 or ICD 10) (cervical, trochanteric or subtrochanteric) in Norwegian hospitals were retrieved with accompanying surgical procedure codes and additional diagnoses. A total of 93,123 hip fractures were identified between 1999 and 2008 in persons ≥50 years. Annual incidences of hip fractures were calculated and tested for trends. Rates of first and second hip fractures (2006-2008) were compared. The age-standardized total incidence of hip fracture decreased by 13.4 % (95 % confidence interval (CI): 11.0-15.6) in women and 4.8 % (95 % CI: 0.7, 8.7) in men. Age-adjusted rates of second hip fractures did not change in the observation period. In those with a prior hip fracture, the age-standardized risk of a subsequent hip fracture was 2.5-fold (95 % CI: 2.5, 2.6) in women, and 4.6-fold (95 % CI: 4.5, 4.7) in men. Total hip fracture rates declined in both genders during 1999-2008, whereas rates of second hip fractures did not change.

Background Evidence of the effect of vitamin K on bone health is conflicting. The aim was to investigate the association between intake of vitamins K1 and K2 and subsequent risk of hip fracture in a general population sample, as well as potential effect modification by apolipoprotein E gene (APOE) status by presence of the E4 allele. Methods 1238 men and 1569 women 71–75 years of age were included in the community-based Hordaland Health Study 1997–1999 in Western Norway. Information on hip fracture was obtained from hospitalizations in the region from enrolment until 31 December 2009. Information on intake of vitamins K1 and K2 collected at baseline was used as potential predictors of hip fracture in Cox proportional hazards regression analyses. Results Participants in the lowest compared to the highest quartile of vitamin K1 intake had increased risk of suffering a hip fracture (hazard ratio (HR) = 1.57 [95% CI 1.09, 2.26]). Vitamin K2 intake was not associated with hip fracture. Presence of APOE4-allele did not increase the risk of hip fracture, nor was there any effect modification with vitamin K1 in relation to risk of hip fracture. Conclusions A low intake of vitamin K1, but not K2, was associated with an increased risk of hip fractures.

Data on associations between dietary intake of macronutrients and body composition in the general population are sparse. This population-based, cross-sectional study of 4478 middle-aged (47–49 y) and elderly (71–74 y) men and women from the Hordaland Health Study in western Norway was conducted using a validated FFQ and measurements by dual-energy X-ray absorptiometry. The relation between macronutrient intake [percentage of total energy intake (E%)] and percent body fat was investigated in the total population and in a subgroup with intermediate BMI and stable weight (BMI within the 25th–75th percentile and weight change ,5% during the last 6 y; n = 975). In the total population, protein intake (E%) was associated with higher percent body fat (partial r = 0.11; P , 0.001) in multivariate linear regression analysis. In the subgroup with intermediate BMI and stable weight, there was no association between protein intake (E%) and percent body fat. Fat intake (E%) was positively associated (partial r = 0.07) whereas carbohydrate intake (E%) was inversely associated (partial r = 20.07) with percent body fat (P = 0.042 for both) in the subgroup with intermediate BMI and stable weight. Both in the total population and in the stable weight group, physical activity was inversely related to adiposity (partial r = 20.15 and 20.12, respectively; P , 0.001). Our results may explain some of the conflicting data on the effects of macronutrients in different populations and suggest the potential importance of protein intake as a factor in obesity. J. Nutr. doi: 10.3945/jn.110.133710.

ObjectiveThe European League Against Rheumatism recommends implementing cardiovascular disease (CVD) risk assessments for patients with inflammatory joint diseases (IJDs) into clinical practice. Our goal was to design a structured programme for CVD risk assessments to be implemented into routine rheumatology outpatient clinic visits.MethodsThe NOrwegian Collaboration on Atherosclerosis in patients with Rheumatic joint diseases (NOCAR) started in April 2014 as a quality assurance project including 11 Norwegian rheumatology clinics. CVD risk factors were recorded by adding lipids to routine laboratory tests, self-reporting of CVD risk factors and blood pressure measurements along with the clinical joint examination. The patients’ CVD risks, calculated by the European CVD risk equation SCORE, were evaluated by the rheumatologist. Patients with high or very high CVD risk were referred to their primary care physician for initiation of CVD preventive measures.ResultsData collection (autumn 2015) showed that five of the NOCAR centres had implemented CVD risk assessments. There were 8789 patients eligible for CVD risk evaluation (rheumatoid arthritis (RA), 4483; ankylosing spondylitis (AS), 1663; psoriatic arthritis (PsA), 1928; unspecified and other forms of spondyloarthropathies (SpA), 715) of whom 41.4 % received a CVD risk assessment (RA, 44.7%; AS, 43.4%; PsA, 36.3%; SpA, 30.6%). Considerable differences existed in the proportions of patients receiving CVD risk evaluations across the NOCAR centres.ConclusionPatients with IJD represent a patient group with a high CVD burden that seldom undergoes CVD risk assessments. The NOCAR project lifted the offer of CVD risk evaluation to over 40% in this high-risk patient population.

Summary Associations between bone mineral density (BMD) and dietary vitamins K1 and K2 in 4,461 individuals were studied. For women, odds ratio of low BMD was 1.48 in lowest to highest quartile of K1. A weak positive association was found for K2. Our results do not support dietary vitamins K as being major determinants of BMD.

One third of 218 men and half of 1,576 women with low-energy distal radius fractures met the bone mineral density (BMD) criteria for osteoporosis treatment. A large proportion of patients with increased fracture risk did not have osteoporosis. Thus, all distal radius fracture patientsor=50 years should be referred to bone densitometry.Main objectives were to determine the prevalence of patients with a low-energy distal radius fracture in need of osteoporosis treatment according to existing guidelines using T-scoreor= -2.0 oror=-2.5 standard deviation (SD) and calculate their fracture risk.A total of 218 men and 1,576 womenor=50 years were included. BMD was assessed by dual energy X-ray absorptiometry (DXA) at femoral neck, total hip, and lumbar spine (L2-L4). The WHO fracture risk assessment tool (FRAX(R)) was applied to calculate the 10-year fracture risk.T-scoresor=-2.0 andor=-2.5 SD at femoral neck was found in 37.7% and 19.6% of men and 51.1% and 31.2% of women, respectively. The risk of hip fracture was 6.2% for men and 9.0% for women. The corresponding figures for patients with T-scoreor=-2.0 SD were 11.6% and 14.5% and for T-scoreor=-2.5 SD 16.3% and 18.2%, respectively. A large proportion of distal radius fracture patients with a high 10-year FRAX risk did not have osteoporosis.Every second to every third fracture patient met the present BMD criteria for osteoporosis treatment. Because a large proportion of distal radius fracture patients did not have osteoporosis, treatment decisions should not be based on fracture risk assessment without bone densitometry. Thus, all distal radius fracture patientsor=50 years should be referred to bone densitometry, and if indicated, offered medical treatment.

Weight loss is a risk factor for hip fractures, but few studies have evaluated the effect of weight loss on distal forearm fracture risk. In this longitudinal study including 7,871 postmenopausal women, weight loss of 5% or more was associated with an increased risk of distal forearm fractures. Weight loss is an established risk factor for hip fractures, but little is known about weight loss and distal forearm fractures risk. The study included 7,871 women aged 65 years or more in the Nord-Trondelag health study (HUNT) in 1994–1995 (HUNT II) who also had their height and weight measured in 1984–1986 (HUNT I). Forearm bone mineral density (BMD) by single energy x-ray absorptiometry was available for 5,688 women (HUNT II). Fractures sustained after HUNT II were registered during an average of 5.8 years. A total of 536 women sustained a distal forearm fracture. After adjustments for age and body mass index (BMI) at HUNT I, women who lost ≥5% of their weight between HUNT I and HUNT II had a relative risk of fractures of 1.33 (95% confidence interval: 1.09, 1.62) compared with the rest of the women. The higher risk of forearm fracture among women with weight loss was at least partially explained by their lower forearm BMD. Weight loss of 5% or more was associated with a 33% increased risk of distal forearm fractures.

BACKGROUND The lean phenotype of cystathionine beta-synthase-deficient homocystinuria and the positive association of plasma total cysteine (tCys) with body mass index (BMI) suggest that total homocysteine (tHcy) and tCys are associated with body composition. OBJECTIVES We aimed to study associations of tCys and tHcy with body composition in the general population. DESIGN Using data from 7038 Hordaland Homocysteine Study participants, we fitted regression models and dose-response curves of tCys and tHcy with BMI. In 5179 participants, we investigated associations of tCys and tHcy with fat mass and lean mass and examined whether changes in these aminothiols predicted body composition 6 y later. RESULTS tCys showed positive associations with BMI (partial r = 0.28, P < 0.001), and fat mass (partial r = 0.25, P < 0.001), independent of diet, exercise, and plasma lipids. Women in the highest tCys quintile had fat mass 9 kg (95% CI: 8, 10 kg; P < 0.001) greater than that of women in the lowest quintile. The corresponding values for men were 6 kg (95% CI: 5, 7 kg; P < 0.001; P < 0.001 in both sexes, ANOVA across quintiles). The rise in tCys over 6 y was associated with greater fat mass at follow-up (P < 0.001), but there was no effect on lean mass. tHcy was not associated with lean mass, and it became significantly inversely associated with BMI and fat mass only after adjustment for tCys. The association between tHcy and lean mass was not significant. CONCLUSIONS tCys concentrations show a strong positive association with BMI, mediated through fat mass. The link between cysteine and lipid metabolism deserves further investigation.

Large regional differences in hip fracture rates within Norway have previously been shown. However, regional differences in hip bone mineral density (BMD) have not yet been assessed. In this study including 10,504 hip scans, there were significant regional differences in BMD. Further studies to address reasons for the regional differences in hip fracture risk are warranted.Bone mineral density (BMD) at the hip is an important determinant of hip fracture. While regional differences in Norwegian hip fracture rates have previously been shown, no comparative studies of hip BMD have been conducted.Total hip BMD was measured by DXA in two population-based studies across Norway during 1997-2002. Valid hip scans with in vivo calibration were obtained from 5127 subjects in Tromsø (age 30-89 years) and 5377 subjects in Bergen (age 47-50 and 71-75 years).Womenor=60 years in Tromsø had 0.052 g/cm(2) higher age-adjusted BMD than women in Bergen, whereas BMD among women60 years was similar in Tromsø and Bergen. Age-adjusted total hip BMD was 0.035 g/cm(2) lower in menor=60 years in Bergen compared with Tromsø, and the corresponding figure for men60 years was 0.028 g/cm(2). While adjustment for body mass index explained some, but not all of the differences, smoking, physical activity, diabetes prevalence, self-perceived health, intake of alcohol and estrogen use did not.Regional differences in BMD at the hip were found in Norway. Reasons for this and potential impact on hip fracture rates should be explored in further studies.

The purpose of this study was to assess the agreement of in vivo hip scans on 3 densitometers (1 GE Lunar DPX-IQ and 2 GE Lunar Prodigy scanners) and to evaluate whether the European Spine Phantom (ESP) was able to reproduce the in vivo variability. Sixteen subjects had 3 repeated scans (with repositioning) on each densitometer, and the ESP was measured on each densitometer at least 40 times. Mean differences between hip scans on the Prodigy scanners were small and insignificant, and the in vivo results were not significantly different from the in vitro results. Bland and Altman plots showed no systematic differences between the Prodigy scanners over the range of bone mineral density (BMD). On the other hand, differences between Prodigy and DPX-IQ changed systematically over the range of BMD. The ESP did not fully reproduce the in vivo difference between Prodigy and DPX-IQ. In conclusion, the ESP is a valid substitute when assessing agreement between Prodigy scanners. However, when assessing agreement between different types of scanners, substitution of in vivo with in vitro measurements should be made with caution.

Homocysteine and related factors were evaluated as risk factors for subsequent hip fractures among 4766 elderly men and women. High levels of homocysteine and low levels of folate predicted fracture, whereas vitamin B12 and genotypes were not related to fracture risk. High homocysteine may be a modifiable risk factor for hip fracture. Introduction: Elevated plasma total homocysteine (tHcy) and deficiencies of folate and vitamin B12 are associated with risk of osteoporosis and fracture. We examined whether plasma levels of tHcy, folate, and vitamin B12 and the methylenetetrahydrofolate reductase (MTHFR) 677CT and 1298CT polymorphisms predicted hip fracture. Materials and Methods: This was a population-based prospective study of 2639 women and 2127 men who were 65–67 yr at enrollment in 1992–1993. Information on hip fracture was obtained from computerized records of discharge diagnoses from all hospitalizations in the region in the period between enrollment and November 30, 2005. Cox proportional hazard regression was used to estimate fracture risk according to levels of plasma tHcy, folate, and vitamin B12 and for different genotypes. Results: Over a median follow-up period of 12.6 yr, hip fracture was recorded in 184 (7.0%) women and 90 (4.2%) men. The adjusted hazard ratio (95% CI) for fracture in subjects with high (≥15 μM) compared with low levels (

Background Norway has the highest hip fracture rates worldwide and a relatively high vitamin A intake. Increased fracture risk at high intakes and serum concentrations of retinol (s-retinol) have been observed in epidemiologic studies. Objective We aimed to study the association between s-retinol and hip fracture and whether high s-retinol may counteract a preventive effect of vitamin D. Design We conducted the largest prospective analysis of serum retinol and hip fracture to date in 21,774 men and women aged 65-79 y (mean age: 72 y) who attended 4 community-based health studies during 1994-2001. Incident hip fractures occurring up to 10.7 y after baseline were retrieved from electronic hospital discharge registers. Retinol determined by high-pressure liquid chromatography with ultraviolet detection in stored serum was available in 1154 incident hip fracture cases with valid body mass index (BMI) data and in a subcohort defined as a sex-stratified random sample (n = 1418). Cox proportional hazards regression weighted according to the stratified case-cohort design was performed. Results There was a modest increased risk of hip fracture in the lowest compared with the middle quintile of s-retinol (HR: 1.41; 95% CI: 1.09, 1.82) adjusted for sex and study center. The association was attenuated after adjustment for BMI and serum concentrations of α-tocopherol (HR: 1.16; 95% CI: 0.88, 1.51). We found no increased risk in the upper compared with the middle quintile. No significant interaction between serum concentrations of 25-hydroxyvitamin D and s-retinol on hip fracture was observed (P = 0.68). Conclusions We found no evidence of an adverse effect of high serum retinol on hip fracture or any interaction between retinol and 25-hydroxyvitamin D. If anything, there tended to be an increased risk at low retinol concentrations, which was attenuated after control for confounders. We propose that cod liver oil, a commonly used food supplement in Norway, should not be discouraged as a natural source of vitamin D for fracture prevention.

Background: Jejunoileal (JI) bypass was a widely performed operation for morbid obesity in the 1970s.The aim of this study was to investigate the long-term status of bone mineral density (BMD) after weight loss induced by this technique. Subjects and Methods: 18 female patients (age 48-79 y, BMI 23-43 kg/m2) had BMD measurements performed 25 years after JI bypass. Dual energy x-ray absorptiometry was used, and measured sites were the lumbar spine L2-L4, left femoral neck and total hip. Vitamin and mineral supplementation had not routinely been prescribed. An assessment was made on age-adjusted BMD values, and as to whether present BMD was related to present demographic and biochemical variables. Results: No significant reduction of BMD was found beyond that which was expected for age. BMD was inversely and separately related to age and body weight. The serum level of vitamin D was low in 45% of the patients, and inversely correlated to body weight and BMI. Alk phosphatase and parathyroid hormone were the best markers for low BMD. Conclusion: These results suggest that JI bypass has not been detrimental to bone density in females. We recommend, however, vitamin D and calcium supplements after malabsorptive procedures for morbid obesity.

In the large community-based Hordaland Health Study, low plasma dimethylglycine was associated with low bone mineral density in both middle-aged and elderly subjects and to an increased risk of subsequent hip fracture among the elderly. These associations seemed to be particularly strong among subjects exposed to nicotine. Dimethylglycine (DMG) is a product of the choline oxidation pathway and formed from betaine during the folate-independent remethylation of homocysteine (Hcy) to methionine. Elevated plasma DMG levels are associated with atherosclerotic cardiovascular disease and inflammation, which in turn are related to osteoporosis. High plasma total Hcy and low plasma choline are associated with low bone mineral density (BMD) and hip fractures, but the role of plasma DMG in bone health is unknown. We studied the associations of plasma DMG with BMD among 5315 participants (46–49 and 71–74 years old) and with hip fracture among 3310 participants (71–74 years old) enrolled in the Hordaland Health Study. In age and sex-adjusted logistic regression models, subjects in the lowest versus highest DMG tertile were more likely to have low BMD (odds ratio [OR] 1.68, 95 % confidence interval [CI] 1.43–1.99). The association was stronger in participants exposed compared to those unexposed to nicotine (OR 2.31, 95 % CI 1.73–3.07 and OR 1.43, 95 % CI 1.16–1.75, respectively, p interaction = 0.008). In the older cohort, Cox regression analyses adjusted for sex showed that low plasma DMG was associated with an increased risk of hip fracture (hazard ratio [HR] 1.70, 95 % CI 1.28–2.26). A trend toward an even higher risk was found among women exposed to nicotine (HR 3.41, 95 % CI 1.40–8.28). Low plasma DMG was associated with low BMD and increased risk of hip fractures. A potential effect modification by nicotine exposure merits particular attention.

We investigated the risk of hip fracture according to circulating alpha-tocopherol, a plant-derived substance with antioxidant properties, in community-dwelling older Norwegians. We found a linear increasing risk of hip fracture with lower serum alpha-tocopherol concentrations, with a 51 % higher risk in the lowest compared to the highest quartile. Oxidative stress is a suggested contributing cause of osteoporosis and fractures. Vitamin E (α-tocopherol) has potent antioxidant properties in humans. The relationship between circulating α-tocopherol and fracture risk is not established. The aim of this study was to investigate the association between serum α-tocopherol concentrations and risk of hip fracture during up to 11 years of follow-up. We performed a case-cohort analysis among 21,774 men and women aged 65–79 years who participated in four community-based health studies in Norway 1994–2001. Serum α-tocopherol concentrations at baseline were determined in 1,168 men and women who subsequently suffered hip fractures (median follow-up 8.2 years) and in a random sample (n = 1,434) from the same cohort. Cox proportional hazard regression adapted for gender-stratified case-cohort data was performed. Median (25, 75 percentile) serum α-tocopherol was 30.0 (22.6, 38.3) μmol/L, and it showed a linear inverse association with hip fracture: hazard ratio (HR) 1.11 (95 % confidence interval (CI) 1.04–1.20) per 10-μmol/L decrease in serum α-tocopherol, adjusted for gender and study center. The lowest compared to the highest quartile conferred an HR of 1.51 (95 % CI 1.17–1.95), adjusted for gender and study center. Adjustment for smoking, month of blood sample, BMI, education, physical inactivity, self-rated health, and serum 25-hydroxyvitamin D (25(OH)D) yielded similar results. Taking serum total cholesterol concentration into account attenuated the association somewhat: HR of hip fracture was 1.37 (95 % CI 1.05–1.77) in first versus fourth quartile of serum α-tocopherol/total cholesterol ratio. Low serum concentrations of α-tocopherol were associated with increased risk of hip fracture in older Norwegians.

Lower bone mineral density (BMD) in smokers may be attributable to lower body weight or fat mass, rather than to a direct effect of smoking. We analyzed the effects of smoking exposure, assessed by plasma cotinine, and body fat on BMD and the risk of subsequent hip fracture. In the community-based Hordaland Health Study (HUSK), 3003 participants 46–49 years and 2091 subjects 71–74 years were included. Cotinine was measured in plasma and information on health behaviors was obtained from self-administered questionnaires. BMD and total body soft tissue composition were measured by dual X-ray absorptiometry. Information on hip fracture was obtained from computerized records containing discharge diagnoses for hospitalizations between baseline examinations 1997–2000 through December 31st, 2009. In the whole cohort, moderate and heavy smokers had stronger positive associations between fat mass and BMD compared to never smokers (differences in regression coefficient (95% CI) per % change in fat mass = 1.38 (0.24, 2.52) and 1.29 (0.17, 2.4), respectively). In moderate and heavy smokers there was a nonlinear association between BMD and fat mass with a stronger positive association at low compared to high levels of fat mass (Davies segmented test, p

Aims: This paper describes the history, purpose, data collection and contributions in the research collaboration Norwegian Osteoporosis Epidemiologic Studies (NOREPOS). Methods: NOREPOS encompasses almost 85,000 bone mineral density measurements within Cohort of Norway and data on almost 140,000 hip fractures in Norway 1994–2008. Included are anthropometric measurements, blood pressure, lipids and glucose, and 50 standard questions on sociodemographic factors, diseases and risk factors. Blood samples/DNA are stored. The main research question posed in NOREPOS is why hip fracture rates in Norway are the highest in the world. Data on hip fractures 2009–2013 will be added in 2014. Results: Main findings include: Every hour a Norwegian suffers a hip fracture; hip fracture incidence rates declined after 1999; only 16% of patients used anti-osteoporosis drugs 1 year after hip fracture; 25% of patients died within 1 year after the fracture; 12% suffered a new hip fracture within 10 years; rural dwellers had lower hip and forearm fracture incidence than city dwellers; magnesium in tap water may be protective whereas bacterial contamination, cadmium and lead may be harmful to bone health; low serum vitamin D and E levels were associated with higher hip fracture risk; vitamin A was not associated with fracture risk; and abdominal obesity increased the risk of hip fracture when BMI was accounted for. Conclusions: NOREPOS encompasses a unique source of information for aetiological research, genetic studies as well as for biomarkers of osteoporosis and fractures. Because of the increasing number of elderly people in Europe, hip fractures will continue to pose an international public health and health care challenge.

This is the accepted manuscript version. Published version is available at http://dx.doi.org/10.1007/s11657-014-0185-0 Summary: Bone mass achievement predicts later fracture risk. This population-based study describes bone mineral density levels (BMD) and associated factors in Norwegian adolescents. Compared with international reference ranges, BMD levels appear higher and physical activity levels are positively associated with BMD. Purpose: Norway has one of the highest reported incidences of osteoporotic fractures. Maximization of peak bone mass may prevent later fractures. This population-based study compared BMD levels of Norwegian adolescents with international reference ranges and explored associated factors. Methods: All first year upper secondary school students, aged 15-19 years in the Tromsø region were invited to the Fit Futures study in 2010-2011. Over 90% of the invited participants attended, 508 girls and 530 boys. BMD was measured at total hip, femoral neck and total body by dual x-ray absorptiometry. Lifestyle variables were collected by self-administered questionnaires and interviews. All analyses were performed sex stratified, using linear regression models. Results: In girls mean BMD (SD) was 1.060 (0.124), 1.066 (0.123) and 1.142 (0.077) g/cm² at the total hip, femoral neck and total body respectively. In boys corresponding values were 1.116 (0.147), 1.103 (0.150) and 1.182 (0.097), with significant higher values than the Lunar pediatric reference at 16 years of age In girls, height and self-reported intensive physical activity of more than four hours a week and early sexual maturation were positively associated with BMD at both femoral sites (pConclusions: Despite the heavy fracture burden, Norwegian adolescents´ BMD levels are higher than agematched Caucasians. Physical activity is associated with 1 SD increased BMD levels in those involved in competition or hard training.

OBJECTIVE—To further define clinical features associated with the syndrome of diabetes and pancreatic exocrine dysfunction due to mutations in the carboxyl-ester lipase (CEL) gene and to assess the effects of pancreatic enzyme substitution therapy. RESEARCH DESIGN AND METHODS—Nine patients with CEL gene mutation, exocrine deficiency, and diabetes were treated and followed for 30 months. RESULTS—Treatment improved symptoms in seven of nine patients. Exocrine and endocrine function assessed by fecal elastase and A1C were not affected, although fecal lipid excretion was reduced. Vitamin E was low in all patients but increased with treatment (P < 0.001 at 30 months) and improved in five subjects. A predominantly demyelinating neuropathy was seen in a majority of patients, and carpal tunnel syndrome was common. CONCLUSIONS—Pancreatic enzyme substitution alleviated symptoms and malabsorption and normalized vitamin E levels. Glycemic control was not significantly affected. The CEL syndrome seems associated with a demyelinating neuropathology.