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Correction to Lancet Gastroenterol Hepatol 2022; 7: 627-47. Lancet Gastroenterol Hepatol. 2022 Aug;7(8):704. doi: 10.1016/S2468-1253(22)00210-2. PMID: 35809605. Background: Colorectal cancer is the third leading cause of cancer deaths worldwide. Given the recent increasing trends in colorectal cancer incidence globally, up-to-date information on the colorectal cancer burden could guide screening, early detection, and treatment strategies, and help effectively allocate resources. We examined the temporal patterns of the global, regional, and national burden of colorectal cancer and its risk factors in 204 countries and territories across the past three decades. Methods: Estimates of incidence, mortality, and disability-adjusted life years (DALYs) for colorectal cancer were generated as a part of the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019 by age, sex, and geographical location for the period 1990-2019. Mortality estimates were produced using the cause of death ensemble model. We also calculated DALYs attributable to risk factors that had evidence of causation with colorectal cancer. Findings: Globally, between 1990 and 2019, colorectal cancer incident cases more than doubled, from 842 098 (95% uncertainty interval [UI] 810 408-868 574) to 2·17 million (2·00-2·34), and deaths increased from 518 126 (493 682-537 877) to 1·09 million (1·02-1·15). The global age-standardised incidence rate increased from 22·2 (95% UI 21·3-23·0) per 100 000 to 26·7 (24·6-28·9) per 100 000, whereas the age-standardised mortality rate decreased from 14·3 (13·5-14·9) per 100 000 to 13·7 (12·6-14·5) per 100 000 and the age-standardised DALY rate decreased from 308·5 (294·7-320·7) per 100 000 to 295·5 (275·2-313·0) per 100 000 from 1990 through 2019. Taiwan (province of China; 62·0 [48·9-80·0] per 100 000), Monaco (60·7 [48·5-73·6] per 100 000), and Andorra (56·6 [42·8-71·9] per 100 000) had the highest age-standardised incidence rates, while Greenland (31·4 [26·0-37·1] per 100 000), Brunei (30·3 [26·6-34·1] per 100 000), and Hungary (28·6 [23·6-34·0] per 100 000) had the highest age-standardised mortality rates. From 1990 through 2019, a substantial rise in incidence rates was observed in younger adults (age

Vertebral fracture is the most common type of osteoporotic fracture. However, the prevalence of osteoporosis and osteoporotic vertebral fractures were not explored previously in the United Arab Emirates (UAE). This study aims to describe for the first time the demographic and morphological characteristics of patients with fragility vertebral fractures in the UAE through a retrospective review of the medical records of patients with low-trauma vertebral fractures who visited two tertiary centers during 2011-2016. The sex, age at the time of fracture, nationality, body mass index (BMI), and anatomical fracture location were recorded for each patient. Overall, 143 subjects were diagnosed with low-trauma vertebral fractures in the Emirate of Abu Dhabi during 2011-2016. Of these, 98 were women (68.5%) and 45 were men (31.5%). The overall mean patient age at diagnosis was 62.5 years, and almost half were younger than 65 years. Approximately 60% of the patients were UAE nationals. Fifty-one patients (36.7%) were obese (mean BMI: 35.3 kg/m2), and women with vertebral fractures had a significantly higher mean BMI compared with men (p = 0.041). Nearly 40% of men had a normal BMI, compared with 20% of women. Most fractures were compression fractures (77.6%) in the thoracolumbar transition region. In conclusion, patients with fragility vertebral fractures were predominantly female and tended to be overweight or obese, although male patients tended to have a lower BMI than female patients.

BackgroundThe COVID-19 RT-PCR confirmed cases could be symptomatic or asymptomatic. In the United Arab Emirates (UAE), the identified COVID-19 RT-PCR confirmed cases are yet to be characterized. In this study, we characterized the first cohort of COVID-19 RT-PCR confirmed cases reported in the Abu Dhabi Emirate, UAE, according to symptomatic state, and identified factors associated with the symptomatic state. Also, the strength of association between the symptomatic state and testing positive in three subsequent RT-PCR testing rounds was examined and quantified.MethodWe analyzed data collected from the first cohort of the RT-PCR confirmed COVID-19 cases reported to the health authorities in the Abu Dhabi Emirate – UAE between February 28 and April 08, 2020. Self-reported sociodemographic, working status, travel history, and chronic comorbidities of 1,249 COVID-19 cases were analyzed according to symptomatic state (symptomatic and asymptomatic). After the first RT-PCR confirmatory test, the results of three subsequent testing rounds were also analyzed.ResultsA total of 791 confirmed cases with a mean age of 35.6 years±12.7 (range: 1-81 years) and information on symptomatic state were analyzed. Nearly, 56.0% were asymptomatic cases. The most frequent two symptoms were fever (58.0%) and cough (41.0%). The mean age of symptomatic (36.3 year ±12.6SD) was significantly higher than that of asymptomatic cases (34.5 year ±12.7SD). Compared to non-working populations, working in public places (aOR, 1.76, 95% CI: 1.11–2.80), healthcare settings (aOR, 2.09, 95% CI: 1.01–4.31), or in aviation and tourism sector (aOR, 2.24, 95% CI: 1.14–4.40), were independently associated with symptomatic state. Reporting at least one chronic comorbidity was also associated with symptomatic cases (aOR, 1.76, 5% CI: 1.03-3.01). Compared to asymptomatic, symptomatic COVID-19 cases had consistent odds of two or more of testing positive to COVID-19 in three subsequent testing rounds.ConclusionsA substantial proportion of the diagnosed COVID-19 cases in the Abu Dhabi Emirate was asymptomatic. Quarantine of asymptomatic cases along with prevention measures and raising awareness of populations working in high-risk settings is warranted. Further follow up research is needed to understand viral clearance and clinical outcomes according to the symptomatic state of the COVID-19 cases.

ObjectiveTo determine the global and regional burden of Epstein-Barr virus (EBV)-attributed malignancies.DesignAn international comparative study based on the Global Burden of Disease (GBD) Study estimates.SettingGlobal population by age, sex, region, demographic index and time.Methods and outcome measuresThe burden of EBV-attributed Burkitt lymphoma (BL), Hodgkin lymphoma (HL), nasopharyngeal carcinoma (NPC) and gastric carcinoma (GC) was estimated in a two-step process. In the first step, the fraction of each malignancy attributable to EBV was estimated based on published studies; this was then applied to the GBD estimates to determine the global and regional incidence, mortality and disability-adjusted life-years (DALYs) for each malignancy by age, sex, geographical region and social demographic index (SDI) from 1990 to 2017.ResultsThe combined global incidence of BL, HL, NPC and GC in 2017 was 1.442 million cases, with over 973 000 deaths. An estimated 265 000 (18%) incident cases and 164 000 (17%) deaths were due to the EBV-attributed fraction. This is an increase of 36% in incidence and 19% in mortality from 1990. In 2017, EBV-attributed malignancies caused 4.604 million DALYs, of which 82% was due to NPC and GC alone. The incidence of both of these malignancies was higher in high and middle-high SDI regions and peaked in adults aged between 50 and 70 years. All four malignancies were more common in males and the highest burden was observed in East Asia.ConclusionsThis study provides comprehensive estimates of the burden of EBV-attributed BL, HL, NPC and GC. The overall burden of EBV-related malignancies is likely to be higher since EBV is aetiologically linked to several other malignancies not included in this analysis. Increasing global population and life expectancy is expected to further raise this burden in the future. The urgency for developing an effective vaccine to prevent these malignancies cannot be overstated.

ObjectivesTo quantify SARS-CoV2 IgG antibody titers over time and assess the longevity of the immune response in a multi-ethnic population setting.SettingThis prospective study was conducted in a tertiary hospital in Abu Dhabi city, UAE, among COVID-19 confirmed patients. The virus-specific IgG were measured quantitatively in serum samples from the patients during three visits over a period of 6 months. Serum IgG levels ≥15 AU/ml was used to define a positive response.Participants113 patients were analyzed at first visit, with a mean (SD) age of participants of 45.9 (11.8) years 87.5% of the patients were men. 63 and 27 participants had data available for visits 2 and 3, respectively.Primary outcomeChange in SARS-CoV2 IgG antibody titers over the visits.ResultsNo mortality or re-infection were reported. 69% of the patients developed positive IgG response within the first month after the onset of symptoms. The levels of IgG showed a consistent increase during the first three months with a peak level during the third month. Increasing trend in the levels of IgG were observed in 82.5%, 55.6% and 70.4% of patients between visit 1 to visit 2, visit 2 to visit 3, and from visit 1 to visit 3, respectively. Furthermore, about 64.3% of the patients showed sustained increase in IgG response for more than 120 days.ConclusionsOur study indicates a sustained and prolonged positive immune response in COVID-19 recovered patients. The consistent rise in antibody and positive levels of IgG titers within the first 5 months suggest that immunization is possible, and the chances of reinfection minimal.

Background: Hip fractures are associated with diminished quality of life and survival especially amongst the elderly. Objective: All-cause mortality after hip fracture was investigated to assess its magnitude. Methods: A total of 122 808 participants from eight cohorts in Europe and the USA were followed up for a mean of 12.6 years, accumulating 4273 incident hip fractures and 27 999 deaths. Incident hip fractures were assessed through telephone interviews/questionnaires or national inpatient/fracture registries, and causes of death were verified with death certificates. Cox proportional hazards models and the time-dependent variable methodology were used to assess the association between hip fracture and mortality and its magnitude at different time intervals after the injury in each cohort. We obtained the effect estimates through a random-effects meta-analysis. Results: Hip fracture was positively associated with increased all-cause mortality; the hazard ratio (HR) in the fully adjusted model was 2.12, 95% confidence interval (CI) 1.76–2.57, after adjusting for potential confounders. This association was stronger amongst men [HR: 2.39, 95% CI: 1.72–3.31] than amongst women [HR: 1.92, 95% CI: 1.54–2.39], although this difference was not significant. Mortality was higher during the first year after the hip fracture [HR: 2.78, 95% CI: 2.12–3.64], but it remained elevated without major fluctuations after longer time since hip fracture [HR (95% CI): 1.89 (1.50–2.37) after 1–4 years; 2.15 (1.81–2.55) after 4–8 years; 1.79 (1.57–2.05) after 8 or more years]. Conclusion: In this large population-based sample of older persons across eight cohorts, hip fracture was associated with excess short- and long-term all-cause mortality in both sexes. © 2017 The Association for the Publication of the Journal of Internal Medicine

Background Data on breast cancer survival and its prognostic factors are lacking in the United Arab Emirates (UAE). Sociodemographic and pathologic factors have been studied widely in western populations but are very limited in this region. This study is the first to report breast cancer survival and investigate prognostic factors associated with its survival in the UAE. Methods This is a retrospective cohort study involving 988 patients who were diagnosed and histologically confirmed with breast cancer between January 2008 and December 2012 at Tawam hospital, Al Ain, UAE. Patient were followed from the date of initial diagnosis until the date of death from any cause, lost-to-follow up or the end of December 2018. The primary outcome is overall survival (OS). The Kaplan-Meier method was used to estimate the survival curve along with the 2- and 5-year survivals. Different group of patients categorized according to prognostic factors were compared using the log-rank test. Multiple Cox proportional hazards models was used to examine the impact of several prognostic factors on the overall survival. Results The median study follow-up was 35 months. Of the 988 patients, 62 had died during their follow-up, 56 were lost to follow-up and 870 were still alive at the end of the study. The average age of patients was 48 years. The majority of patients presented to the hospital with grade II or III, 24% with at least stage 3 and 9.2% had metastasis. The 2-year and 5-year survivals were estimated to 97% and 89% respectively. Results of the multiple Cox proportional hazard model show that tumor grade, and stage of cancer at presentation are jointly significantly associated with survival. Conclusion The 2- and 5-year survival are within the norms compared to other countries. Significant clinical and pathological prognostic factors associated with survival were tumor grade, and the stage of cancer at presentation.

article i nfo Bone turnover markers (BTM) predict bone loss and fragility fracture. Although cortical porosity and cortical thinning are important determinants of bone strength, the relationship between BTM and cortical porosity has, however, remained elusive. We therefore wanted to examine the relationship of BTM with cortical porosity and risk of non-vertebral fracture. In 211 postmenopausal women aged 54-94 years with non-vertebral fractures and 232 age-matched fracture- free controls from the Tromso Study, Norway, we quantified femoral neck areal bone mineral density (FN aBMD), femoral subtrochanteric bone architecture, and assessed serum levels of procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX). Fracture cases exhibited higher PINP and CTX levels, lower FN aBMD, larger total and medullary cross-sectional area (CSA), thinner cortices, and higher cortical porosity of the femoral subtrochanter than controls (p ≤ 0.01). Each SD increment in PINP and CTX was associated with 0.21-0.26 SD lower total volumetric BMD, 0.10-0.14 SD larger total CSA, 0.14-0.18 SD larger medullary CSA, 0.13-0.18 SD thinner cortices, and 0.27-0.33 SD higher porosity of the total cortex, compact cortex, and transitional zone (all p ≤ 0.01). Moreover, each SD of higher PINP and CTX was associated with increased odds for fracture after adjustment for age, height, and weight (ORs 1.49; 95% CI, 1.20-1.85 and OR 1.22; 95% CI, 1.00-1.49, both p b 0.05). PINP, but not CTX, remained associ- ated with fracture after accounting for FN aBMD, cortical porosity or cortical thickness (OR ranging from 1.31 to 1.39, p ranging from 0.005 to 0.028). In summary, increased BTM levels are associated with higher cortical porosity, thinner cortices, larger bone size and higher odds for fracture. We infer that this is produced by increased periosteal apposition, intracortical and endocortical remodeling; and that these changes in bone architecture are predisposing to fracture.

Summary: The role of socioeconomic status in hip fracture incidence is unclear. In a diverse population of elderly, higher education was found to be associated with lower, whereas living alone, compared to being married/cohabiting, with higher hip fracture risk. Educational level and marital status may contribute to hip fracture risk. Introduction: The evidence on the association between socioeconomic status and hip fracture incidence is limited and inconsistent. We investigated the potential association of education and marital status with hip fracture incidence in older individuals from Europe and USA. Methods: A total of 155,940 participants (79 % women) aged 60 years and older from seven cohorts were followed up accumulating 6456 incident hip fractures. Information on education and marital status was harmonized across cohorts. Hip fractures were ascertained through telephone interviews/questionnaires or through record linkage with registries. Associations were assessed through Cox proportional hazard regression adjusting for several factors. Summary estimates were derived using random effects models. Results: Individuals with higher education, compared to those with low education, had lower hip fracture risk [hazard ratio (HR) = 0.84, 95 % confidence interval (CI) 0.72–0.95]. Respective HRs were 0.97 (95 % CI 0.82–1.13) for men and 0.75 (95 % CI 0.65–0.85) for women. Overall, individuals living alone, especially those aged 60–69 years, compared to those being married/cohabiting, tended to have a higher hip fracture risk (HR = 1.12, 95 % CI 1.02–1.22). There was no suggestion for heterogeneity across cohorts (Pheterogeneity > 0.05). Conclusions: The combined data from >150,000 individuals 60 years and older suggest that higher education may contribute to lower hip fracture risk. Furthermore, this risk may be higher among individuals living alone, especially among the age group 60–69 years, when compared to those being married/cohabiting. © 2015, International Osteoporosis Foundation and National Osteoporosis Foundation.

Source at https://doi.org/10.1371/journal.pone.0181417 Background: Female gender has been associated with musculoskeletal complaints (MSCs), but there are limited studies on how other factors may influence women and men differently. The aim of this prospective cohort study was to explore possible predictors of MSCs in women and men free of MSCs at baseline. Methods: The present study included participants from the population-based Tromsø study, with baseline data from 1994–1995 and follow-up data from 2007–2008. MSCs were defined as having pain and/or stiffness in muscles and joints for 3 consecutive months during the past year. Predictors of MSCs were examined through binary logistic regression analyses and presented as odds ratios with 95% confidence intervals. Results: At baseline 4,496 participants reported no MSCs and among these 2,015 (44.8%) and 441 (9.8%) participants reported mild or severe MSCs, respectively, at follow-up. Female gender predicted MSCs in multivariable logistic regression analyses (odds ratio [OR] 1.46, 95% confidence interval [CI]: 1.29–1.66). Educational level of primary/secondary school (OR 1.73, 95% CI: 1.46–2.05) was the strongest predictor of MSCs, followed by poor self-perceived health (OR 1.62, 95% CI: 1.30–2.02). Other predictors were BMI 30 kg/m 2 (OR 1.39, 95% CI: 1.10–1.77) and smoking (OR 1.33, 95% CI: 1.16–1.52). Age and physical activity level were not significantly associated with MSCs. Gender-stratified analyses revealed that mental health complaints (i.e., depression and/or anxiety) predicted MSCs in men (OR 2.03, 95% CI: 1.18–3.50), but not in women. Current smoking (OR 1.43, 95%CI: 1.16–1.76) and poor self-perceived health (OR 1.90, 95% CI: 1.34–2.71) showed slightly higher odds ratios among women than men, but the gender differences were not significant. Conclusion: The present study demonstrate s that several negative health determinants are predicting subsequent MSCs. However, the examined risk factors could not explain the higher prevalence of MSCs in women.

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.

Published version. Source at http://doi.org/10.1371/journal.pone.0164341. License CC BY 4.0. Background The long-term consequences of chronic pain and/or stiffness from the musculoskeletal system (musculoskeletal complaints: MSCs) have not been well explored. The aims of this study were to investigate whether MSCs reported at baseline influence all-cause and cause-specific mortality during 21 years follow-up of a general Northern Norwegian adult population. Methods A total of 26,977 men and women aged 25–97 years who participated in the 1994–1995 survey of the Tromsø study (response rate 77%) were included in the present prospective cohort study. Baseline data were collected from the 1994–1995 survey and information on death and emigration was taken from the National Register of Norway. Cox regression analyses were performed to examine if MSCs predicted risk of mortality. Results 5693 (21.1%) participants died during follow-up. Mean time between entry into the survey and death or emigration was 18.6 years (standard deviation 4.87) for all-cause mortality. There was an increased risk of death among those with MSCs at baseline in the crude Cox regression model. However, the multivariable model revealed no significant association between MSCs at baseline and all-cause mortality by sex (women: hazard ratio [HR] = 0.93, 95% confidence interval [CI]: 0.85–1.01; men: HR = 0.93, 95%CI: 0.85–1.01). Furthermore, no significant associations were found between widespread MSCs at baseline and all-cause mortality in multivariable models (women: HR = 0.90, 95%CI: 0.80–1.01; men HR = 0.87, 95%CI: 0.76–1.00). Analyses on cause-specific mortality did not reveal any significant results. Conclusion MSCs are not independently associated with increased risk of death from cardiovascular disease, cancer, or death from all causes.

Purpose: The adoption of electronic medical record (EMR) system is gradually increasing. However, various time-motion studies reveal conflicting data regarding time effectiveness on workflow due to computerization. One of the major issues for physicians is their uncertainty with EMRs' potential impact of time on workflow. A tertiary eye hospital in south India was in the process of implementing an EMR system in their ambulatory care unit. Many of the staff did not have previous computing experience and there were conflicting views on the time effectiveness of the computerized system after implementation. The management was thus interested to know the real time effectiveness of EMR in their hospital. The study compliments existing studies of this type by comparing the time efficiency of documentation time using EMR system with paper documentation in a hospital in a developing country where a transition between paper and EMR documentation was currently in progress. Methods: Ten randomly selected optometrists documented the time they spent during consultation with both paper and EMR documentation. The time spent was documented for a total of 200 records (100 EMR and 100 paper records). The independent-samples t-test and analysis of variance were used to compare the means of the consultation time and calculated documentation time spent between the electronic and paper records. Results: There was no statistically significant difference in the time spent for documentation between electronic and paper records. The mean time spent in documenting electronic records was 0.92min (95% CI -3.06 to 1.14) longer than in paper records. Conclusion: EMR systems can be adopted in eye hospitals without having significant negative impact on duration of consultation and documentation for optometrists. More time-motion studies that include ophthalmologists are however needed in order to get a more complete picture of time impact of the EMR system on clinical workflow in eye hospitals.

In this longitudinal study of 5,286 persons, men with anemia had a 2.15 higher risk of non-vertebral fractures than men with high hemoglobin levels. Women with anemia had no increased fracture risk.Low hemoglobin levels are associated with several risk factors for fractures such as low physical function, impaired cognition, and low bone mass. The aim of this population-based, prospective study was to examine whether anemia predicts non-vertebral fractures.A total of 5,286 inhabitants from the municipality of Tromsø, Norway (2,511 men and 2,775 women), 55-74 years old at baseline, were followed for mean 8.3 years. Measurements of hemoglobin, mean corpuscular volume, height, weight, blood pressure, blood lipids, serum creatinine, and bone mineral density and questionnaire information concerning smoking and drinking habits, physical activity, prevalent diseases, and use of medication was collected before start of follow-up. Non-vertebral fractures were registered during follow-up.A total of 235 men and 641 women sustained a new non-vertebral fracture. One SD lower value of hemoglobin was associated with a 1.27 higher risk of fracture in men (p0.001, after multiple adjustments) and 1.08 (p = 0.07) in women. Men with anemia (hemoglobin levels13 g/dL) had a 2.15 higher risk of non-vertebral fractures than men with high levels (15.2-18.8, g/dL) whereas women with anemia (hemoglobin levels12 g/dL) had no increased fracture risk.Anemia is associated with non-vertebral fractures in men but not in women.

We assessed the association between the rate of forearm bone loss and non-vertebral fracture. Bone loss at the distal forearm predicted fractures, independently of baseline BMD, but not independently of follow-up BMD in women. The BMD level where an individual ends up is the significant predictor of fracture risk. Bone loss may predict fracture risk independently of baseline BMD. The influence of follow-up BMD on this prediction is unknown. The aim of this study was to assess the association between bone loss and fracture risk in both sexes in a prospective population-based study. We included 1,208 postmenopausal women (50 to 74 years), and 1,336 men (55 to 74 years) from the Tromso Study, who had repeated distal and ultra-distal forearm BMD measurements. Non-vertebral fractures were registered from 2001 to 2005. A total of 100 women and 46 men sustained fractures during the follow-up time. Independent of baseline BMD, the RR associated with distal site bone loss of 1 SD %/year was 1.23 (1.01-1.50) for low-trauma fractures (excluding hand, foot, skull & high-trauma) and 1.32 (1.07-1.62) for osteoporotic fractures (hip, wrist and shoulder). However, bone loss did not predict fracture after adjusting for follow-up BMD. The BMD level where an individual ends up became the significant predictor of fracture risk and not the rate of bone loss. Follow-up BMD at ultra-distal site was associated with low-trauma fractures in both sexes. While ultra-distal site BMD changes were not associated with fracture risk in both sexes. Bone loss at the distal forearm predicted non-vertebral fractures, independently of baseline BMD, but not independently of follow-up BMD, in women. The BMD level where an individual ends up is the significant predictor of fracture risk and not the rate of bone loss.

This study describes bone mineral density (BMD) and the prevalence of osteoporosis in women and men between 30-89 years in an unselected population. BMD was measured in g/cm(2) at total hip and femoral neck by dual-energy-X-ray absorptiometry in 3,094 women and 2,132 men in the 2001 Tromsø Study. BMD levels were significantly explained by age and declined progressively in both sexes from middle into old age, with highest decline in women. With osteoporosis defined as a T-score of two and a half standard deviation below the young adult mean BMD, the prevalence at the total hip in subjects above 70 years was 6.9% in men and 15.3% in women, respectively, using the Lunar reference material for T-score calculations. The prevalence increased significantly to 7.3% in men and 19.5% in women, when T-scores were calculated on basis of the young adult mean BMD (age group 30-39 years) in the study population. At the femoral neck, prevalence of osteoporosis increased from 13.5 to 18.5% in men, and from 20.4 to 35.2% in women above 70 years, respectively, depending on how T-scores were calculated. The study highlights the challenges with fixed diagnostic levels when measuring normally distributed physiologic parameters. Although BMD only partly explains fracture risk, future studies should evaluate which calculations give optimal fracture prediction.

Bone architecture as well as size and shape is important for bone strength and risk of fracture. Most bone loss is cortical and occurs by trabecularization of the inner part of the cortex. We therefore wanted to identify determinants of the bone architecture, especially the area and porosity of the transitional zone, an inner cortical region with a large surface/matrix volume available for intracortical remodeling. In 211 postmenopausal women aged 54 to 94 years with nonvertebral fractures and 232 controls from the Tromsø Study, Norway, we quantified femoral subtrochanteric architecture in CT images using StrAx1.0 software, and serum levels of bone turnover markers (BTM, procollagen type I N-terminal propeptide and C-terminal cross-linking telopeptide of type I collagen). Multivariable linear and logistic regression analyses were used to quantify associations of age, weight, height, and bone size with bone architecture and BTM, and odds ratio (OR) for fracture. Increasing age, height, and larger total cross-sectional area (TCSA) were associated with larger transitional zone CSA and transitional zone CSA/TCSA (standardized coefficients [STB] = 0.11 to 0.80, p ≤ 0.05). Increasing weight was associated with larger TCSA, but smaller transitional zone CSA/TCSA and thicker cortices (STB = 0.15 to 0.22, p0.01). Increasing height and TCSA were associated with higher porosity of the transitional zone (STB = 0.12 to 0.46, p0.05). Increasing BTM were associated with larger TCSA, larger transitional zone CSA/TCSA, and higher porosity of each of the cortical compartments (p0.01). Fracture cases exhibited larger transitional zone CSA and higher porosity than controls (p0.001). Per SD increasing CSA and porosity of the transitional zone, OR for fracture was 1.71 (95% CI, 1.37 to 2.14) and 1.51 (95% CI, 1.23 to 1.85), respectively. Cortical bone architecture is determined mainly by bone size as built during growth and is modified by lifestyle factors throughout life through bone turnover. Fracture cases exhibited larger transitional zone area and porosity, highlighting the importance of cortical bone architecture for fracture propensity.

We wanted to examine whether the features of the metabolic syndrome carried an increased risk of non-vertebral fracture. This is a population-based, 6-year follow-up of 27,159 subjects from the municipality of Tromso, followed from 1994 until 2001. Age range was 25–98 years. Non-fasting serum levels of high-density lipoprotein (HDL), triglycerides and glucose, blood pressure (BP), weight and height were measured at baseline. All non-vertebral fractures were registered by computerised search in radiographic archives. A total of 1,249 non-vertebral fractures were registered. Increasing number of metabolic syndrome features was associated with significantly reduced fracture risk in both men and women, p= 0.004 and p

We wanted to estimate the independent fracture risk associated with chronic diseases for men and women separately, adjusting for other known risk factors. This is a population-based study of all those who attended the fourth survey (1994-1995) in the Tromso Study (n=27,159) who were followed until 31 December 2000 with respect to non-vertebral fractures. At baseline the age range was 25-98 years. Chronic disease cases were defined by self-report in questionnaires. All non-vertebral fractures were registered by computerized search in radiographic archives in the sole provider of radiographic service in the area. A total of 446 and 803 non-vertebral fractures were registered among men and women, respectively. Self-reported diabetes mellitus, stroke, asthma, hypo- and hyperthyroidism and psychiatric disorders were associated with increased fracture risk. Multivariate analyses showed an independent risk of fractures associated with self-reported diabetes mellitus, hypothyroidism and psychiatric disorders among men. Among women the independent risk was associated with self-reported asthma, hypo- and hyperthyroidism and psychiatric disorders. Self-reported heart disease had a protective effect on wrist fracture, especially in women. Increased burden of chronic diseases increase the risk of all non-vertebral (P

Background The aims of this study were to estimate the prevalence and severity of MSCs in the adult general population of Northern Norway, and to study associations between MSCs and various demographic and lifestyle variables. Methods Data from the Tromsø 6 survey (2007–2008) of the population-based Tromsø Study were used (12,984 participants, 65.7% participation rate). We included 8,439 participants aged 30–79 years in the analyses. Associations between demographic and lifestyle variables and chronic MSCs (i.e., those lasting for at least 3 consecutive months, hereafter referred to as simply MSCs) was examined using logistic regression analysis. Results The total age-adjusted prevalence of both mild and severe MSCs was 63.4% and 52.9% in women and men, respectively. In women, the age-adjusted prevalence was 44.0% and 19.4% for mild and severe MSCs, respectively; the corresponding values in men were 40.8% and 12.1%. The highest prevalence was found in the neck/shoulder region (34.2% and 8.9% for mild and severe MSCs, respectively). The prevalence of MSCs in ≥5 body regions was three times higher in women than in men (14.9% vs 5.6%). Current smoking was significantly associated with MSCs (odds ratio [OR]: 1.41, 95% confidence interval [CI]: 1.22-1.62), but showed a stronger effect in women (OR: 1.60, 95% CI: 1.30-1.96) than in men (OR: 1.25, 95% CI: 1.02-1.52). Self-perceived poor health was strongly associated with MSC (OR: 3.73, 95% CI: 3.27-4.24). Moderate vs low level of physical activity was associated with MSCs only in women (OR: 1.37, 95% CI: 1.12-1.67). Other demographic and lifestyle variables associated with MSCs were age (OR: 1.04, 95% CI: 1.01-1.06), body mass index (BMI) >30 kg/m2 (OR: 1.42, 95% CI: 1.23-1.66), low education level (OR: 1.78, 95% CI: 1.53-2.08) and former smoking (OR: 1.21, 95% CI: 1.09-1.35). Marital status, BMI

Low-grade inflammation is associated with fractures, while the relationship between inflammation and bone mineral density (BMD) is less clear. Moreover, any gender differences in the sensitivity to inflammation are still poorly elucidated. We therefore tested the hypothesis that high-sensitivity C-reactive protein (CRP) is an independent risk factor for low BMD and non-vertebral fractures, in both genders, and whether there are gender differences in these associations. CRP levels and BMD at the total hip and femoral neck were measured in 1902 women and 1648 men between 55 and 74 years of age, at baseline in the Tromso Study, Norway, in 2001–2002. Non-vertebral fractures were registered from hospital X-ray archives during an average of 7.2 years follow-up. Linear regression analyses were used for CRP association with BMD and Cox proportional hazards model for fracture prediction by CRP. During 25 595 person-years follow-up, 366 (19%) women and 126 (8%) men suffered a non-vertebral fracture. There was no association between CRP and BMD in women, but an inverse association in men ( p = 0.001) after adjustment for age and body mass index. Each standard deviation (SD) increase in log-CRP was associated with an increased risk for non-vertebral fracture by 13% in women and 22% in men (hazard ratios (HRs) 1.13, 95% confidence interval (CI) 1.02–1.26, p = 0.026 and 1.22, 95% CI = 1.00–1.48, p = 0.046, respectively). After adjustment for BMD and other risk factors, women with CRP in the upper tertile exhibited 39% higher risk for fracture than those in the lowest tertile of CRP (HR = 1.39, 95% CI = 1.06–1.83, p = 0.017), while men in the upper tertile exhibited 80% higher risk (HR = 1.80, 95% CI = 1.10–2.94, p = 0.019). In summary, CRP was not associated with BMD in women but inversely associated in men, and predicted fractures in both genders. We infer that inflammation influence fracture risk in both women and men, although the biological mechanisms may differ between the genders.

Background Absolute risk estimation is a preferred approach for assessing fracture risk and treatment decision making. This study aimed to evaluate and validate the predictive performance of the Garvan Fracture Risk Calculator in a Norwegian cohort. Methods The analysis included 1637 women and 1355 aged 60+ years from the Tromsø study. All incident fragility fractures between 2001 and 2009 were registered. The predicted probabilities of non-vertebral osteoporotic and hip fractures were determined using models with and without BMD. The discrimination and calibration of the models were assessed. Reclassification analysis was used to compare the models performance. Results The incidence of osteoporotic and hip fracture was 31.5 and 8.6 per 1000 population in women, respectively; in men the corresponding incidence was 12.2 and 5.1. The predicted 5-year and 10-year probability of fractures was consistently higher in the fracture group than the non-fracture group for all models. The 10-year predicted probabilities of hip fracture in those with fracture was 2.8 (women) to 3.1 times (men) higher than those without fracture. There was a close agreement between predicted and observed risk in both sexes and up to the fifth quintile. Among those in the highest quintile of risk, the models over-estimated the risk of fracture. Models with BMD performed better than models with body weight in correct classification of risk in individuals with and without fracture. The overall net decrease in reclassification of the model with weight compared to the model with BMD was 10.6% (p = 0.008) in women and 17.2% (p = 0.001) in men for osteoporotic fractures, and 13.3% (p = 0.07) in women and 17.5% (p = 0.09) in men for hip fracture. Conclusions The Garvan Fracture Risk Calculator is valid and clinically useful in identifying individuals at high risk of fracture. The models with BMD performed better than those with body weight in fracture risk prediction.

Bone mineral density (BMD) is a reflection of bone strength and lifestyles that preserve bone mass and may reduce fracture risk in old age. This study examined the effect of combined profiles of smoking, physical activity, and body mass index (BMI) on lifetime bone loss. Data were collected from the population-based Tromsø Study. BMD was measured as g/cm(2) by dual-energy X-ray absorptiometry (DXA) at the total hip and femoral neck in 2580 women and 2084 men aged 30 to 80 years in the 2001-02 survey, and repeated in 1401 women and 1113 men in the 2007-08 survey. Height and weight were measured and lifestyle information was collected through questionnaires. Data were analyzed using linear mixed models with second-degree fractional polynomials. From the peak at the age around 40 years to 80 years of age, loss rates varied between 4% at the total hip and 14% at femoral neck in nonsmoking, physically active men with a BMI of 30 kg/m(2) to approximately 30% at both femoral sites in heavy smoking, physically inactive men with a BMI value of 18 kg/m(2) . In women also, loss rates of more than 30% were estimated in the lifestyle groups with a BMI value of 18 kg/m(2) . BMI had the strongest effect on BMD, especially in the oldest age groups, but a BMI above 30 kg/m(2) did not exert any additional effect compared with the population average BMI of 27 kg/m(2) . At the age of 80 years, a lifestyle of moderate BMI to light overweight, smoking avoidance, and physical activity of 4 hours of vigorous activity per week through adult life may result in 1 to 2 standard deviations higher BMD levels compared with a lifestyle marked by heavy smoking, inactivity, and low weight. In the prevention of osteoporosis and fracture risk, the effect of combined lifestyles through adult life should be highlighted. © 2014 American Society for Bone and Mineral Research.

This article is part of Svanhild Waterloo's doctoral thesis, available in Munin at http://hdl.handle.net/10037/5557 Health-related quality of life (HRQL) may be associated with increased mortality in the elderly. The effect of prevalent vertebral fractures on HRQL in elderly women and men is not well described. The purpose of this study was to examine the association between prevalent vertebral fractures and back pain, neck pain, and HRQL in elderly women and men, and to study possible gender differences in the reported pain and HRQL. Information on prevalent vertebral fractures was ascertained by a vertebral fracture assessment (VFA) method (dual-energy X-ray absorptiometry (DXA), GE Lunar Prodigy) in 2887 women and men, mean age 65.4 (SD 9.4) who participated in the population-based Tromsø Study which was conducted in 2007–08. Bone mineral density (BMD; g/cm2) was measured by DXA at the femoral sites. Self-reported HRQL was assessed using the standardized measures EQ-5D-3 L and EQ VAS from the EuroQol Group. Lifestyle information was collected by questionnaires. The association between vertebral fractures and pain was analyzed using logistic regression, between vertebral fractures and EQ-5D-3 L and EQ VAS scores by multiple regression analyses. In women, presence of vertebral fractures was associated with an increased risk of back pain with an OR of 1.76 (95% CI: 1.24 – 2.50) after adjustments for age, height, weight, and BMD. Women with vertebral fractures had lower EQ-5D-3 L scores (p

The risk of subsequent fracture is increased after initial fractures; however, proper understanding of its magnitude is lacking. This population-based study examines the subsequent fracture risk in women and men by age and type of initial incident fracture. All incident nonvertebral fractures between 1994 and 2009 were registered in 27,158 participants in the Tromsø Study, Norway. The analysis included 3108 subjects with an initial incident fracture after the age of 49 years. Subsequent fracture (n = 664) risk was expressed as rate ratios (RR) and absolute proportions irrespective of death. The rates of both initial and subsequent fractures increased with age, the latter with the steepest curve. Compared with initial incident fracture rate of 30.8 per 1000 in women and 12.9 per 1000 in men, the overall age-adjusted RR of subsequent fracture was 1.3 (95% CI, 1.2-1.5) in women, and 2.0 (95% CI, 1.6-2.4) in men. Although the RRs decreased with age, the absolute proportions of those with initial fracture who suffered a subsequent fracture increased with age; from 9% to 30% in women and from 10% to 26% in men, between the age groups 50-59 to 80+ years. The type of subsequent fracture varied by age from mostly minor fractures in the youngest to hip or other major fractures in the oldest age groups, irrespective of type and severity of initial fracture. In women and men, 45% and 38% of the subsequent hip or other major fractures, respectively, were preceded by initial minor fractures. The risk of subsequent fracture is high in all age groups. At older age, severe subsequent fracture types follow both clinically severe and minor initial incident fractures. Any fragility fracture in the elderly reflects the need for specific osteoporosis management to reduce further fracture risk.

Background: Though financial and policy level efforts are made to expand antiretroviral treatment (ART) service free of cost, survival outcome of ART program has not been systematically evaluated in Nepal. This study assesses the mortality rates and determinants among adult HIV-infected patients on ART in Far-western region of Nepal. Methods: This retrospective cohort study included 1024 (51.2% men) HIV-infected patients aged ≥15 years, who started ART between May 15th 2006 and May 15th 2011 in five ART sites in the Far-western region, Nepal. Follow-up time was calculated from the date of ART initiation to date of death or censoring (loss to follow-up, transferred out, or 15 November 2011). Mortality rates (per 100 person-years) were calculated. Kaplan-Meier and Cox-regression models were used to estimate survival and explore determinants of mortality. Results: The median follow-up time was 19.1 months. The crude mortality rate was 6.3 (95% confidence interval (CI) 5.3-7.6) but more than three-times higher in first 3 months after ART initiation (21.9 (95% CI 16.6- 28.8)). About 12% (83% men) of those newly initiated on ART died during follow-up. The independent determinants of mortality were male sex (hazard ratio (HR) 4.55, 95% CI 2.43-8.51), poor baseline performance scale (bedridden 50% of the day during the past month, HR 3.41, 95% CI 1.67-6.98 compared to normal activity), one standard deviation decrease in baseline bodyweight (HR 1.04, 95% CI 1.01-1.07), and poor WHO clinical stage (stage III, HR 2.96, 95% CI 1.31-6.69; stage IV, HR 3.28, 95% CI 1.30-8.29 compared to WHO clinical stage I or II). Conclusions: High mortality was observed within the first 3 months of ART initiation. Patients with poor baseline clinical characteristics had higher mortality, especially men. Earlier initiation of ART through expanded testing and counselling should be encouraged in HIV-infected patients. publishedVersion

This article is part of Svanhild H. Waterloo's doctoral thesis, available in Munin at http://hdl.handle.net/10037/5557 Vertebral fractures, the most common type of osteoporotic fractures, are associated with increased risk of subsequent fracture, morbidity, and mortality. The aim of this study was to examine the contribution of important risk factors to the variability in vertebral fracture risk. Vertebral fracture was ascertained by VFA method (DXA, GE Lunar Prodigy) in 2887 men and women, aged between 38 and 87 years, in the population-based Tromsø Study 2007/2008. Bone mineral density (BMD; g/cm2) at the hip was measured by DXA. Lifestyle information was collected by questionnaires. Multivariable logistic regression model, with anthropometric and lifestyle factors included, was used to assess the association between each or combined risk factors and vertebral fracture risk. Population attributable risk was estimated for combined risk factors in the final multivariable model. In both sexes, age (odds ratio [OR] per 5 year increase: 1.32; 95% CI 1.19-1.45 in women and 1.21; 95% CI 1.10-1.33 in men) and BMD (OR per SD decrease: 1.60; 95% CI 1.34-1.90 in women and1.40; 95% CI 1.18-1.67 in men) were independent risk factors for vertebral fracture. At BMD levels higher than 0.85 g/cm2, men had a greater risk of fracture than women (OR 1.52; 95% CI 1.14-2.04), after adjusting for age. In women and men, respectively, approximately 46% and 33% of vertebral fracture risk was attributable to advancing age (more than 70 years) and low BMD (less than 0.85 g/cm2), with the latter having a greater effect than the former. These data confirm that age and BMD are major risk factors for vertebral fracture risk. However, in both sexes the two factors accounted for less than half of fracture risk. The identification of individuals with vertebral fracture is still a challenge.

This article is part of Svanhild H. Waterloo's doctoral thesis, available in Munin at http://hdl.handle.net/10037/5557 Osteoporotic vertebral fractures are, as the hip fractures, associated with increased morbidity and mortality. Norway has one of the highest reported incidences of hip fractures in the world. Because of methodological challenges, vertebral fractures are not extensively studied. The aim of this population based study was to describe, for the first time, the age- and sex specific occurrence of osteoporotic vertebral fractures in Norway. Data was collected in the Tromso Study, 2007/8 survey. By the use of dual x-ray absorptiometry (GE Lunar Prodigy) vertebral fracture assessments were performed in 2887 women and men aged from 38 to 87 years, in addition to measurements of bone mineral density at the femoral sites. Information on lifestyle was collected through questionnaires. Comparisons between fractures and non-fractures were done sex stratified, by univariate analyses, adjusting for age when relevant. The prevalence of vertebral fractures varied from about 3% in the age group below 60 to about 19% in the 70+ group in women, and from 7.5% to about 20% in men, with an overall prevalence of 11.8% in women and 13.8% in men (p = 0.07). Among those with fractures, only one fracture was the most common; two and more fractures were present in approximately 30% of the cases. Fractures were seen from the fourth lumbar to the fifth thoracic vertebrae, most common between first lumbar and sixth thoracic vertebrae. The most common type of fracture was the wedge type in both sexes. Bone mineral density at the hip differed significantly according to type of fracture, being highest in those with wedge fractures and lowest in those with compression fractures. The prevalence of vertebral fractures increased by age in women and men, but the overall prevalence was lower than expected, considering the high prevalence of hip and forearm fractures in Norway. In both sexes, the wedge type was the fracture type most frequently observed and most common in the thoracic region.

Despite reported bone loss during pregnancy and lactation, no study has shown deleterious long-term effects of parity or breastfeeding. Studies have shown higher bone mineral density and reduced risk for fracture in parous than in nulliparous women or no effect of parity and breastfeeding, so long-term effects are uncertain. We studied the effect of parity and breastfeeding on risk for hip, wrist and non-vertebral fragility fractures (hip, wrist, or proximal humerus) in 4681 postmenopausal women aged 50 to 94 years in the Tromso Study from 1994-95 to 2010, using Cox's proportional hazard models. During 51 906 person-years, and a median of 14.5 years follow-up, 442, 621, and 1105 of 4681 women suffered incident hip, wrist, and fragility fractures, and the fracture rates were 7.8, 11.4, and 21.3 per 1000 person-years, respectively. The risk for hip, wrist, and fragility fracture did not differ between parous (n = 4230, 90.4%) and nulliparous women (n = 451, 9.6%). Compared with women who did not breast-feed after birth (n = 184, 4.9%), those who breastfed (n = 3564, 95.1%) had 50% lower risk for hip fracture (HR 0.50; 95% CI 0.32 to 0.78), and 27% lower risk for fragility fracture (HR 0.73; 95% CI 0.54 to 0.99), but similar risk for wrist fracture, after adjustment for age, BMI, height, physical activity, smoking, a history of diabetes, previous fracture of hip or wrist, use of hormone replacement therapy, and length of education. Each 10 months longer total duration of breastfeeding reduced the age-adjusted risk for hip fracture by 12% (HR 0.88; 95% CI 0.78 to 0.99, p for trend = 0.03) before, and marginally after, adjustment for BMI and other covariates (HR 0.91; 95% CI 0.80 to 1.04). In conclusion, this data indicates that pregnancy and breastfeeding has no long-term deleterious effect on bone fragility and fractures, and that breastfeeding may contribute to a reduced risk for hip fracture after menopause.

Our aim was to examine associations between leisure time physical activity and risk of non-vertebral fractures in men and women aged ≥55 years, with focus on the anatomical fracture location. Self-reported physical activity was registered in 3,450 men and 4,072 women aged 55–97 years at baseline in the Tromso Study, Norway, in 1994–1995. Non-vertebral fractures were registered through December 31, 2009. During 75,546 person-years at risk, 1,693 non-vertebral fractures were identified. Risk of any non-vertebral fracture decreased with increasing physical activity level in men (P trend = 0.006) and non-significantly in women (P trend = 0.15), after adjustment for age, body mass index, height, smoking, and previous fracture. The reduced fracture risk was due to a reduced risk in the weight-bearing skeleton, particular at the hip, whereas risk of fracture in the non-weight-bearing skeleton was not related to physical activity. At weight-bearing sites, an inverse relationship between physical activity and fracture risk was present in both sexes (P trend ≤ 0.013). Compared with sedentary subjects, the most active men and women had respectively 37% (HR = 0.63, 95% CI: 0.45, 0.88) and 23% (HR = 0.77, 95% CI: 0.62, 0.95) reduced fracture risk in the weight-bearing skeleton. Physical activity is associated with reduced fracture risk at weight-bearing sites, with no associations at non-weight-bearing sites, in both sexes. Habitual physical activity is an important amendable approach to prevent hip fracture.

Summary In this open population-based study from Northern Norway, there was no increase in hip fracture incidence in women and men from 1994 to 2008. Age-adjusted hip fracture rates was lower compared to reported rates from the Norwegian capital Oslo, indicating regional differences within the country. Introduction The aim of the present population-based study was to describe age- and sex-specific incidence of hip fractures in a Northern Norwegian city, compare rates with the Norwegian capital Oslo, describe time trends in hip fracture incidence, place of injury, seasonal variation and compare mortality after hip fracture between women and men. Methods Data on hip fractures from 1994 to 2008 in women and men aged 50 years and above were obtained from the Harstad Injury Registry. Results There were altogether 603 hip fractures in Harstad between 1994 and 2008. The annual incidenc rose exponentially from 5.8 to 349.2 per 10,000 in men, and from 8.7 to 582.2 per 10,000 in women from the age group 50–54 to 90+ years. The age-adjusted incidence rates were 101.0 and 37.4 in women and men, respectively, compared to 118.0 in women (p = 0.005) and 44.0 in men (p = 0.09) in Oslo. The age-adjusted incidence rates did not increase between 1994–1996 and 2006–2008. The majority of hip fractures occurred indoors and seasonal variation was significant in fractures occurring outdoors only. After adjusting for age at hip fracture, mortality after fracture was higher in men than in women 3, 6 and 12 months (p ≤ 0.002) after fracture. Conclusions There are regional differences in hip fracture incidence that cannot be explained by a north–south gradient in Norway. Preventive strategies must be targeted to indoor areas throughout the year and to outdoor areas in winter.

In this longitudinal study of 4,160 postmenopausal women (3,947 without and 213 with self-reported diabetes), smoking was strongly related to fracture risk in those with diabetes. Smoking is related to low bone mass and increased risk of fracture risk in postmenopausal women of the general population. The aim of the present longitudinal population-based study was to examine the effect of smoking on the risk of non-vertebral fractures in women ≥55 years of age, with specific focus on its relationship with diabetes. A total of 4,160 women (3,947 without and 213 with self-reported diabetes) from the municipality of Tromso, Norway, were followed for a mean of 7.6 years. Measurements of height and weight and questionnaire information concerning smoking and alcohol consumption habits, physical activity, prevalent diseases, and use of medication were collected before the start of follow-up. Non-vertebral fractures were registered during follow-up. A total of 1,015 without and 66 with diabetes sustained a new non-vertebral fracture. Smoking status (never, past, and current) was significantly associated with an increased risk of fracture both in women with and without diabetes (p values for trend 0.02 and

Few studies have examined the association between body mass index (BMI) change and fracture in a general population. We observed that BMI loss was associated with increased fracture risk in non-smoking men and women, but not in smokers. BMI gain was associated with decreased fracture risk in women. Weight loss has been associated with increased fracture risk, but few studies have included men. The aim of this study was to examine the association between BMI change and fracture risk in both genders. A population-based cohort study in Tromso, Norway, of adults, aged 20 to 54 years in 1979, who participated in two or three health surveys in 1979–1980, 1986–1987, and 1994–1995. Weight and height were measured at each survey. Information about lifestyle was obtained by questionnaires. Poisson regression was used to estimate incidence rates and Cox proportional hazards regression model to assess the association between fracture risk and BMI change. Fractional polynomials were used to accommodate non-linear associations. A total of 5,549 men and 5,428 women participated. There were 1,135 fractures during 10 years of follow-up. Reduction in BMI was associated with increased non-vertebral fracture risk in non-smokers, but not in smokers. The hazard ratio in male and female non-smokers per 10-year BMI decrease of 2 kg/m2 versus a BMI increase of 1 kg/m2 was 1.79 (95% confidence interval (CI), 1.17–2.75) and 1.60 (95% CI, 1.28–1.99), respectively. The association was not significantly modified by initial BMI or age or by exclusion of subjects with cardiovascular diseases, diabetes, or cancer. In female non-smokers, weight gain was inversely associated with fracture risk. In a general Norwegian population, reduction in BMI was significantly associated with increased fracture risk in male and female non-smokers, but not in smokers. These findings could not be explained by preexisting disease.

Aim of this study is to estimate the gender- and age-specific 10-year and lifetime absolute risks of non-vertebral and osteoporotic (included hip, distal forearm and proximal humerus) fractures in a large cohort of men and women. This is a population-based 10 years follow-up study of 26,891 subjects aged 25 years and older in Tromso, Norway. All non-vertebral fractures were registered from 1995 throughout 2004 by computerized search in radiographic archives. Absolute risks were estimated by life-table method taking into account the competing risk of death. The absolute fracture risk at each year of age was estimated for the next 10 years (10-year risk) or up to the age of 90 years (lifetime risk). The estimated 10-year absolute risk of all non-vertebral fracture was higher in men than women before but not after the age of 45 years. The 10-year absolute risk for non-vertebral and osteoporotic fractures was over 10%, respectively, in men over 65 and 70 years and in women over 45 and 50 years of age. The 10-year absolute risks of hip fractures at the age of 65 and 80 years were 4.2 and 18.6% in men, and 9.0 and 24.0% in women, respectively. The risk estimates for distal forearm and proximal humerus fractures were under 5% in men and 13% in women. The estimated lifetime risks for all fracture locations were higher in women than men at all ages. At the age of 50 years, the risks were 38.1 and 24.8% in men and 67.4 and 55.0% in women for all non-vertebral and osteoporotic fractures, respectively. The estimated gender- and age-specific 10-year and lifetime absolute fracture risk were higher in Tromso than in other populations. The high lifetime fracture risk reflects the increased burden of fractures in this cohort.

A physically active, nonsmoking lifestyle with weight maintenance positively influences bone health. The authors estimated the effect of lifestyles on peak bone mass and lifetime bone loss in the Tromso Study, Norway. Bone mineral density (BMD) was measured at distal and ultradistal forearm sites with single x-ray absorptiometric devices in 7,948 men and women aged 24-84 years in 1994-1995 and repeated in 2001 in 6,182 subjects. BMD was significantly higher at peak than at old age. However, the difference, estimated as lifetime loss, varied between lifestyle groups. Lifetime loss in nonsmoking, physically active men with a body mass index of 25 kg/m(2) compared with smoking, inactive, and lean men was 15.9% and 25.9% at the distal site and 17.5% and 29.7% at the ultradistal site, respectively. In women, the corresponding loss estimates were 34.4% and 45.7% and 35.6% and 55.7%, respectively. The differences in BMD at the age of 80 years correspond to an increased forearm fracture risk of 69% in men and 85% in women with greatest bone loss. A lifestyle including nonsmoking, a high physical activity level, and a high body weight reduces bone loss and fracture risk in both sexes, with increasing effect from peak bone mass to old age.

Background Individuals with end-stage renal disease are at higher risk of fractures compared with subjects in the general population. We examined whether elevated albumin-creatinine ratios (ACRs) were associated with nonvertebral fractures in subjects without diabetes or macroalbuminuria. Methods A total of 4497 subjects (2267 men and 2230 women) 55 to 74 years old at baseline were followed for a mean of 8.4 years. Measurements of ACR, height, weight, blood pressure, lipids, serum creatinine, and bone mineral density were performed, and information about smoking and drinking habits, physical activity, prevalent diseases, and use of medication was collected before the start of follow-up. Nonvertebral fractures were registered during follow-up. Results A total of 135 men and 382 women sustained a new nonvertebral fracture. For a 1-SD higher value for the log-transformed ACR, the relative risk for a fracture was 1.01 in men ( P = .94, after multiple adjustments) and 1.15 in women ( P = .005). Women with ACRs in the highest quartile had a 71% higher risk of nonvertebral fractures compared with women with ACRs in the lowest quartile ( P value for linear trend over the quartiles, .001). Bone mineral density tended to be lower with higher ACRs in both sexes, but this did not explain the increased fracture risk in women. Conclusion Albumin-creatinine ratio was associated with nonvertebral fractures in women without diabetes or macroalbuminuria but not in men.

Objectives: As bone fragility is partly the result of sex hormone deficiency, we sought to determine whether circulating sex steroids or sex hormone-binding globulin (SHBG) predicts non-vertebral fractures. Methods: Forearm bone mineral density (BMD), total estradiol and testosterone, calculated free levels, and SHBG were measured in 1386 postmenopausal women and 1364 men aged 50–84 years at baseline in the Tromsø Study (1994–1995). Non-vertebral fractures were documented between 1994 and 2005. Results: During 8.4 years (range 0.01–10.4) of follow-up, 281 women and 105 men suffered non-vertebral fractures. For both sexes, fracture cases had lower BMD and higher SHBG, but sex steroids were not lower. Each standard deviation (s.d.) increase in SHBG increased non-vertebral fracture risk in women (hazards ratio (HR) 1.17; 95% confidence interval (CI) 1.03–1.33) and men (HR 1.26; 95% CI 1.03–1.54). After further adjustment for BMD, the risk was not statistically significant in women (HR 1.09; 95% CI 0.95–1.24) or men (HR 1.22; 95% CI 0.99–1.49). Each s.d. decrease in BMD increased fracture risk in women (HR 1.36; 95% CI 1.19–1.56) and men (HR 1.41; 95% CI 1.15–1.73). Fracture rates were highest in participants with SHBG in the highest tertile and BMD in the lowest tertile and were 37.9 and 17.0 per 1000 person-years in women and men respectively. However, in both sexes the combination of BMD and SHBG was no better predictor of fracture risk than BMD alone. Sex steroids were not associated with fracture risk. Conclusions: Measurements of sex steroids or SHBG are unlikely to assist in decision making regarding fracture risk susceptibility.

Atherosclerosis and osteoporosis appear to be related, but prospective studies on the relationship are sparse. In order to examine whether carotid artery plaques with different morphology predict nonvertebral fractures, we followed 2,733 women, aged 55-74 years (75% of the eligible population in Tromsø, Norway), for 6 years. At baseline, plaque morphology in terms of ultrasound echogenicity was categorized into three groups, ranging from low echogenicity (echolucent plaques with a high content of soft tissue) to strong echogenicity (echogenic plaques with a high content of dense fibrous tissue and calcified material). We found that the age-adjusted relative risk (RR) of fracture was significantly higher among women with echogenic plaques than among women without plaques: 1.7 (95% confidence interval [CI] 1.0-2.7). After adjustment for bone mineral density at baseline in addition to age, the RR was 1.6 (95% CI 1.0-2.6), and further adjustments for body mass index, body height, high-density lipoprotein cholesterol, smoking status, and muscle strength did not influence the association. Subjects with other plaque types were not at an increased risk compared to subjects without plaques: RRor = 1.1, after multiple adjustments. We conclude that in the general population elderly women with echogenic carotid plaques are at higher risk of nonvertebral fractures than women without plaques.

We wanted to determine the risk of non-vertebral fracture associated with type and duration of diabetes mellitus, adjusting for other known risk factors. This is a population-based 6-year follow-up of 27,159 subjects from the municipality of Tromso, followed from 1994 until 2001. The age range was 25-98 years. Self-reported diabetes cases were validated by review of the medical records. All non-vertebral fractures were registered by computerized search in radiographic archives. A total of 1,249 non-vertebral fractures was registered, and 455 validated cases of diabetes were identified. Men with type I diabetes had an increased risk of all non-vertebral [relative risk (RR) 3.1 (95% CI 1.3-7.4)] and hip fractures [RR 17.8 (95% CI 5.6-56.8)]. Diabetic women, regardless of type of diabetes, had significantly increased hip fracture risk [RR 8.9 (95% CI 1.2-64.4) and RR 2.0 (95% CI 1.2-3.6)] for type I and type II diabetes, respectively. Diabetic men and women using insulin had increased hip fracture risk. Duration of disease did not alter hip fracture risk. An increased risk of all non-vertebral fractures and, especially, hip fractures was associated with diabetes mellitus, especially type I. Type II diabetes was associated with increased hip fracture risk in women only.

Published version. Source at http://doi.org/10.1007/s00198-015-3118-x. Summary We tested whether cortical porosity of the proximal femur measured using StrAx1.0 software provides additional information to areal bone mineral density (aBMD) or Fracture Risk Assessment Tool (FRAX) in differentiating women with and without fracture. Porosity was associated with fracture independent of aBMD and FRAX and identified additional women with fractures than by osteoporosis or FRAX thresholds. Introduction Neither aBMD nor the FRAX captures cortical porosity, a major determinant of bone strength. We therefore tested whether combining porosity with aBMD or FRAX improves identification of women with fractures. Methods We quantified femoral neck (FN) aBMD using dual-energy X-ray absorptiometry, FRAX score, and femoral subtrochanteric cortical porosity using StrAx1.0 software in 211 postmenopausal women aged 54–94 years with nonvertebral fractures and 232 controls in Tromsø, Norway. Odds ratios (ORs) were calculated using logistic regression analysis. Results Women with fractures had lower FN aBMD, higher FRAX score, and higher cortical porosity than controls (all p 20 %, whereas porosity >80th percentile identified 61 women (29 %). Porosity identified 26 % additional women with fractures than identified by the osteoporosis threshold and 21 % additional women with fractures than by this FRAX threshold. Conclusions Cortical porosity is a risk factor for fracture independent of aBMD and FRAX and improves identification of women with fracture.