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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

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.

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.

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 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.

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.

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.