Risk of hip and forearm fracture in subjects with type 2 diabetes mellitus and latent autoimmune diabetes of adults. The HUNT Study, Norway.

Type 1 and type 2 diabetes mellitus incur an increased risk of fracture, with a generally higher risk among individuals with type 1 diabetes. The fracture risk among individuals with latent autoimmune diabetes of adulthood (LADA) is not known. The present cohort study aimed to estimate the risk of hip and forearm fracture among individuals with LADA, alongside type 1 and type 2 diabetes, using data from the second survey of the Trøndelag Health Study (HUNT2) in 1995-97. All inhabitants aged 20 years or older (N = 92,936) were invited to attend, of whom 65,234 (70%) participated. A total of 1972 (3%) reported to have diabetes; 1399 were found to have type 2 diabetes, 144 to have LADA, and 138 to have type 1 diabetes. All participants were followed prospectively with respect to hip- and forearm fractures by linkage to the local fracture registry. During a median follow-up of 16.2 years, 2695 persons with hip fractures and 3533 persons with forearm fractures were identified. There was an increased risk of hip fracture in women with type 2 diabetes (HR = 1.51, 95% CI 1.24-1.85) and LADA (HR = 2.15, 95% CI 1.25-3.72), whereas women with type 1 diabetes did not have a significantly increased risk (HR = 2.13, 95% CI 0.89-5.14). Among men, only LADA was associated with an increased risk of hip fracture (HR = 2.69, 95% CI 1.34-5.41). There was no statistically significant association between any of the diabetes types and forearm fracture. In women with type 2 diabetes, the highest risks of hip fracture were observed among those with highest HbA1c level at baseline, longest time since diagnosis, and most visual and movement impairment. We found that individuals with LADA had an increased risk of hip fracture similar to that previously reported for individuals with type 1 diabetes, and no increased risk of forearm fracture.

MEPE loss-of-function variant associates with decreased bone mineral density and increased fracture risk.

A major challenge in genetic association studies is that most associated variants fall in the non-coding part of the human genome. We searched for variants associated with bone mineral density (BMD) after enriching the discovery cohort for loss-of-function (LoF) mutations by sequencing a subset of the Nord-Trøndelag Health Study, followed by imputation in the remaining sample (N = 19,705), and identified ten known BMD loci. However, one previously unreported variant, LoF mutation in MEPE, p.(Lys70IlefsTer26, minor allele frequency [MAF] = 0.8%), was associated with decreased ultradistal forearm BMD (P-value = 2.1 × 10-18), and increased osteoporosis (P-value = 4.2 × 10-5) and fracture risk (P-value = 1.6 × 10-5). The MEPE LoF association with BMD and fractures was further evaluated in 279,435 UK (MAF = 0.05%, heel bone estimated BMD P-value = 1.2 × 10-16, any fracture P-value = 0.05) and 375,984 Icelandic samples (MAF = 0.03%, arm BMD P-value = 0.12, forearm fracture P-value = 0.005). Screening for the MEPE LoF mutations before adulthood could potentially prevent osteoporosis and fractures due to the lifelong effect on BMD observed in the study. A key implication for precision medicine is that high-impact functional variants missing from the publicly available cosmopolitan panels could be clinically more relevant than polygenic risk scores.

Urban-Rural Differences in Hip Fracture Mortality: A Nationwide NOREPOS Study.

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: <1/3, semirural: 1/3 to 2/3, and urban: >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.

Psychosocial consequences among women with false-positive results after mammography screening in Norway.

BACKGROUND: Mammography screening may cause psychosocial harm for women experiencing a false-positive screening result. Previous studies suggest long-term consequences. The aim of the present study was to assess psychosocial consequences of false-positive findings on screening mammography within a six month follow-up. METHODS: A prospective matched cohort survey study using the questionnaire 'Consequences of Screening for Breast Cancer' (COS-BC), which was translated from Danish to Norwegian. Psychometric analyses investigated the measurement properties of the Norwegian version. Two screening clinics in Norway distributed the survey to 299 women with an abnormal mammogram and 541 women with a normal screen. Women received the questionnaire when receiving the screening result, and one and six months after screening. RESULTS: At six months, statistically significant differences appeared in two scales: existential values and breast examination. At six-month follow-up, women with false-positive results showed no statistically significant differences from women diagnosed with breast cancer in three outcomes: sense of dejection, anxiety, and keeping my mind off things. CONCLUSION: Our results indicate that the psychosocial consequences from having false-positive screening mammography results diminish after six months. The results support previous research describing breast-specific outcomes. However, our results indicate that Norwegian women are less frightened than other Scandinavian mammography screening participants.

Mortality in persons with undetected and diagnosed hypertension, type 2 diabetes, and hypothyroidism, compared with persons without corresponding disease - a prospective cohort study; The HUNT Study, Norway.

BACKGROUND: Suggested strategies in reducing the impact of non-communicable diseases (NCD) are early diagnosing and screening. We have limited proof of benefit of population screening for NCD. Increased mortality in persons with diagnosed NCD has been shown for decades. However, mortality in undetected NCD has barely been studied. This paper explores whether all-cause mortality differed between persons with diagnosed hypothyroidism, type 2 diabetes (T2DM), and hypertension, compared with persons with undetected-, and with persons without the corresponding disease. METHODS: A prospective cohort study of the general population in Nord-Trøndelag, Norway. Persons ≥20 years at baseline 1995-97 were followed until death or June 15, 2016. Cox proportional hazards models were used to compute age and multiple adjusted hazard ratios (HR) with 95% confidence intervals (CI) for the association between disease status and all-cause mortality. The number of participants in the hypothyroidism study was 31,960, in the T2DM study 37,957, and in the hypertension study 63,371. RESULTS: Mortality was increased in persons with diagnosed type 2 diabetes and hypertension, compared to persons without corresponding disease; HR 1.69 (95% CI 1.55-1.84) and HR 1.23 (95% CI 1.09-1.39), respectively. Among persons with undetected T2DM, the HR was 1.21 (95% CI 1.08-1.37), whilst among undetected hypothyroidism and hypertension, mortality was not increased compared with persons without the diseases. Further, the association with mortality was stronger in persons with long duration of T2DM (HR 1.96 (95% CI 1.57-2.44)) and hypertension (HR 1.32 (95% CI 1.17-1.49)), compared with persons with short duration (HR 1.29 (1.09-1.53) and HR 1.16 (1.03-1-30) respectively). CONCLUSIONS: Mortality was increased in persons with diagnosed T2DM and hypertension, and in undetected T2DM, compared with persons without the diseases. The strength of the association with mortality in undetected T2DM was however lower compared with persons with diagnosed T2DM, and mortality was not increased in persons with undetected hypothyroidism and hypertension, compared with persons without the diseases. Thus, future research needs to test more thoroughly if early diagnosing of these diseases, such as general population screening, is beneficial for health.

No increase in risk of hip fracture at high serum retinol concentrations in community-dwelling older Norwegians: the Norwegian Epidemiologic Osteoporosis Studies.

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.

Diagnostic labelling influences self-rated health. A prospective cohort study: the HUNT Study, Norway.

BACKGROUND: Studies have shown an independent association between poor self-rated health (SRH) and increased mortality. Few studies, however, have investigated any possible impact on SRH of diagnostic labelling. OBJECTIVE: To test whether SRH differed in persons with known and unknown hypothyroidism, diabetes mellitus (DM) or hypertension, opposed to persons without these conditions, after 11-year follow-up. METHODS: Prospective population-based cohort study in North-Trøndelag County, Norway, HUNT2 (1995-97) to HUNT3 (2006-08). All inhabitants aged 20 years and older were invited. The response rate was 69.5% in HUNT2 and 54.1% in HUNT3. In total, 34144 persons aged 20-70 years were included in the study population. The outcome was poor SRH. RESULTS: Persons with known disease had an increased odds ratio (OR) to report poor SRH at follow-up; figures ranging from 1.11 (0.68-1.79) to 2.52 (1.46-4.34) (men with hypothyroidism kept out owing to too few numbers). However, in persons not reporting, but having laboratory results indicating these diseases (unknown disease), no corresponding associations with SRH were found. Contrary, the OR for poor SRH in women with unknown hypothyroidism and unknown hypertension was 0.64 (0.38-1.06) and 0.89 (0.79-1.01), respectively. CONCLUSIONS: Awareness opposed to ignorance of hypothyroidism, DM and hypertension seemed to be associated with poor perceived health, suggesting that diagnostic labelling could have a negative effect on SRH. This relationship needs to be tested more thoroughly in future research but should be kept in mind regarding the benefits of early diagnosing of diseases.

Ovulation Prevalence in Women with Spontaneous Normal-Length Menstrual Cycles - A Population-Based Cohort from HUNT3, Norway.

BACKGROUND: Ovulatory menstrual cycles are essential for women's fertility and needed to prevent bone loss. There is a medical/cultural expectation that clinically normal menstrual cycles are inevitably ovulatory. Currently within the general population it is unknown the proportion of regular, normal-length menstrual cycles that are ovulatory. Thus, the objective of this study was to determine the population point prevalence of ovulation in premenopausal, normally menstruating women. The null hypothesis was that such cycles are ovulatory. METHODS: This is a single-cycle, cross-sectional, population-based study-a sub-study of the HUNT3 health study in the semi-rural county (Nord Trøndelag) in mid-Norway. Participants included >3,700 spontaneously (no hormonal contraception) menstruating women, primarily Caucasian, ages 20-49.9 from that county. Participation rate was 51.9%. All reported the date previous flow started. A single, random serum progesterone level was considered ovulatory if ≥9.54 nmol/L on cycle days 14 to -3 days before usual cycle length (CL). RESULTS: Ovulation was assessed in 3,168 women mean age 41.7 (interquartile range, [IQR] 36.8 to 45.5), cycle length 28 days (d) (IQR 28 to 28) and body mass index (BMI) 26.3 kg/m2 (95% CI 26.1 to 26.4). Parity was 95.6%, 30% smoked, 61.3% exercised regularly and 18% were obese. 1,545 women with a serum progesterone level on cycle days 14 to -3 were presumed to be in the luteal phase. Of these, 63.3% of women had an ovulatory cycle (n = 978) and 37% (n = 567) were anovulatory. Women with/ without ovulation did not differ in age, BMI, cycle day, menarche age, cigarette use, physical activity, % obesity or self-reported health. There were minimal differences in parity (96.7% vs. 94.5%, P = 0.04) and major differences in progesterone level (24.5 vs. 3.8 nmol/L, P = 0.001). CONCLUSION: Anovulation in a random population occurs in over a third of clinically normal menstrual cycles.

Educational Inequalities in Post-Hip Fracture Mortality: A NOREPOS Study.

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.

Women's Experiences With Mammography Screening Through 6 Years of Participation--A Longitudinal Qualitative Study.

In this article we explore women's experiences with 6 years of mammography screening. Regular and repeated mammography screening is promoted as an important tool for disease prevention among women worldwide. The purpose of the present study was to explore how continued participation in screening influences how women perceive screening and breast cancer. We carried out focus groups with 24 screening participants in 2003 and 2009. Our analysis highlights that while women were excited about the examination in 2003, it was perceived as routine in 2009. Waiting for the results became easier over the years, while stress related to receiving the results letter did not diminish. Knowledge of risk factors for breast cancer did not change. Personal risk assessment remained low, though high incidence of cancer among acquaintances suggested high risk for breast cancer among women in general. Analysis of participant experiences suggests that continuous participation in screening has led surveillance medicine to become a part of ordinary life.

Cohort profile: Norwegian Epidemiologic Osteoporosis Studies (NOREPOS).

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.

Impact of comorbidity, age, and gender on seasonal variation in hip fracture incidence. A NOREPOS study.

UNLABELLED: Based on a total of 136,140 hip fractures, we found a distinct seasonal variation in hip fracture incidence present in subgroups defined by age, gender, and comorbidity. The seasonal variation was most pronounced in the youngest and the healthiest patients. PURPOSE: The purpose of this study was to examine the possible seasonal variation in hip fracture incidence in Norway by comorbidity, age, and gender. METHODS: Data were retrieved from the NOREPOS Hip Fracture Database containing all hip fractures in Norway during the time period 1994-2008. Hip fractures were identified by computerized hospital discharge diagnoses. Charlson comorbidity index was calculated based on additional diagnoses and categorized (0, 1, and ≥2). Summer was defined as June, July, and August and winter as December, January, and February. Incidence rate ratios for hip fracture according to season were calculated by negative binomial models. RESULTS: In patients aged 50-103 years, 136,140 eligible fractures were identified (72.5 % women). The relative risk of hip fracture in winter versus summer was 1.40 (95 % confidence interval (CI) 1.36-1.45) in men and 1.26 (95 % CI 1.23-1.28) in women. June had the lowest number of fractures in both genders. We found seasonal variation in all subgroups by age and gender, although least pronounced in patients >79 years. There was a significant interaction between season and comorbidity (p = 0.022). When comparing winter to summer, we found relative risks of 1.40 (95 % CI 1.31-1.50) in patients with Charlson index = 0, 1.29 (95 % CI 1.19-1.40) in patients with Charlson index = 1, and 1.18 (95 % CI 1.08-1.28) in patients with Charlson index ≥2. CONCLUSIONS: There was a distinct seasonal variation in hip fracture incidence, present in all subgroups of gender, age, or comorbidity. This variation should be accounted for when planning health-care services.

Is there an association between disease ignorance and self-rated health? The HUNT Study, a cross-sectional survey.

OBJECTIVE: To explore whether awareness versus unawareness of thyroid dysfunction, diabetes mellitus or hypertension is associated with self-rated health. DESIGN: Large-scale, cross-sectional population-based study. The association between thyroid function, diabetes mellitus and blood pressure and self-rated health was explored by multiple logistic regression analysis. SETTING: The second survey of the Nord-Trøndelag Health Study, HUNT2, 1995-1997. PARTICIPANTS: 33 734 persons aged 40-70 years. PRIMARY OUTCOME MEASURES: Logistic regression was used to estimate ORs for good self-rated health as a function of thyroid status, diabetes mellitus status and blood pressure status. RESULTS: Persons aware of their hypothyroidism, diabetes mellitus or hypertension reported poorer self-rated health than individuals without such conditions. Women with unknown and subclinical hypothyroidism reported better self-rated health than women with normal thyroid status. In women and men, unknown and probable diabetes as well as unknown mild/moderate hypertension was not associated with poorer health. Furthermore, persons with unknown severe hypertension reported better health than normotensive persons. CONCLUSIONS: People with undiagnosed but prevalent hypothyroidism, diabetes mellitus and hypertension often have good self-rated health, while when aware of their diagnoses, they report reduced self-rated health. Use of screening, more sensitive tests and widened diagnostic criteria might have a negative effect on perceived health in the population.

Mortality following the first hip fracture in Norwegian women and men (1999-2008). A NOREPOS study.

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.

A prospective population-based cohort study of lactation and cardiovascular disease mortality: the HUNT study.

BACKGROUND: Recent studies suggest that lactation has long-term effects on risk for cardiovascular disease in women, but the effects on cardiovascular mortality are less well known. METHOD: In a Norwegian population-based prospective cohort study, we studied the association of lifetime duration of lactation with cardiovascular mortality in 21,889 women aged 30 to 85 years who attended the second Nord-Trøndelag Health Survey (HUNT2) in 1995-1997. The cohort was followed for mortality through 2010 by a linkage with the Cause of Death Registry. Adjusted hazard ratios (HR) for death from all causes and cardiovascular disease were calculated using Cox regression. RESULTS: During follow-up, 1,246 women died from cardiovascular disease. Parous women younger than 65 years who had never lactated had a higher cardiovascular mortality than the reference group of women who had lactated 24 months or more (HR 2.77, 95% confidence interval [CI]: 1.28, 5.99). There was some evidence of a U-shaped association, where women who reported lactating 7-12 months had a HR of 0.55 (95% CI: 0.27, 1.09). No clear associations were observed among women 65 years or older. CONCLUSIONS: Excess cardiovascular mortality rates were observed among parous women younger than 65 years who had never lactated. These findings support the hypothesis that lactation may have long-term influences on maternal cardiovascular health.

Changing patterns of cytomegalovirus seroprevalence among pregnant women in Norway between 1995 and 2009 examined in the Norwegian Mother and Child Cohort Study and two cohorts from Sor-Trondelag County: a cross-sectional study.

OBJECTIVES: To examine cytomegalovirus (CMV) seroprevalence and associated risk factors for CMV seropositivity in pregnant Norwegian women. DESIGN: Cross-sectional study. SETTING: The Norwegian Mother and Child Cohort Study (MoBa) in addition to two random samples of pregnant women from Sør-Trøndelag County in Norway. PARTICIPANTS: Study group 1 were 1000 pregnant women, randomly selected among 46 127 pregnancies in the MoBa (1999-2006) at 17/18 week of gestation. Non-ethnic Norwegian women were excluded. Study groups 2 (n=1013 from 1995) and 3 (n=979 from 2009) were pregnant women at 12 weeks of gestation from Sør-Trøndelag County. OUTCOME MEASURES: CMV seropositivity in blood samples from pregnant Norwegian women. RESULTS: CMV-IgG antibodies were detected in 59.9% and CMV-IgM antibodies in 1.3% of pregnant Norwegian women in study group 1. Women from North Norway demonstrated a higher CMV-IgG seroprevalence (72.1%) than women from South Norway (58.5%) (OR 1.83, 95% CI 1.17 to 2.88). The CMV-IgG seroprevalence was higher among women with low education (70.5%) compared to women with higher education (OR 2.20, 95% CI 1.24 to 3.90). Between 1995 and 2009 the CMV-IgG seroprevalence increased from 63.1% to 71.4% in pregnant women from Sør-Trøndelag County (study groups 2 and 3; p<0.001). The highest CMV-IgG seroprevalence (79.0%) was observed among the youngest pregnant women (<25 years) from Sør-Trøndelag County in 2009 (study group 3). CONCLUSIONS: The CMV-IgG seroprevalence of pregnant Norwegian women varies with geographic location and educational level. Additionally, the CMV-IgG seroprevalence appears to have increased over the last years, particularly among young pregnant women.

Does thyroid function influence fracture risk? Prospective data from the HUNT2 study, Norway.

OBJECTIVE: To prospectively study the relation between TSH and risk of hip and forearm fractures. DESIGN: A population-based cohort study. METHODS: In a substudy of the second survey of the Nord Trøndelag Health Study, Norway (HUNT2, 1995-97), linked with a hospital-based fracture registry, we investigated the relation between baseline TSH and risk of hip and/or forearm fractures. POPULATION: A total of 16 610 women and 8595 men aged 40 years or more, without previous self-reported thyroid disease and hip or forearm fractures. RESULTS: During 12.5 years follow-up, a total of 1870 women and 342 men experienced hip or forearm fractures. Overall, there was no relation between baseline TSH and fracture risk. However, there was weak evidence that women with TSH <0.5 and >3.5 mU/l had a slightly increased risk of hip fractures (hazard ratio (HR) 1.30, 95% CI 0.97-1.94 and HR 1.19, 95% CI 0.93-1.52) compared with the reference group with TSH of 1.5-2.4 mU/l. Supplementary analyses showed higher hip fracture risk in women with TSH >4.0 mU/l and negative thyroid peroxidase antibodies (TPOAb) compared with the reference group (HR 1.75, 95% CI 1.24-2.46). CONCLUSION: We found no statistically significant relation between baseline TSH and subsequent fracture risk, but the data suggest a weak positive association with hip fracture risk among women with both low and high TSH. The latter association was confined to women with negative TPOAb status.

Low serum levels of 25-hydroxyvitamin D predict hip fracture in the elderly: a NOREPOS study.

BACKGROUND: Despite considerable interest, the relationship between circulating 25-hydroxyvitamin D and the risk of hip fracture is not fully established. OBJECTIVE: The objective of the study was to study the association between serum 25-hydroxyvitamin D concentrations [s-25(OH)D] and the risk of hip fracture in Norway, a high-latitude country that has some of the highest hip fracture rates worldwide. METHODS: A total of 21 774 men and women aged 65-79 years attended 4 community-based health studies during 1994-2001. Information on subsequent hip fractures was retrieved from electronic hospital discharge registers, with a maximum follow-up of 10.7 years. Using a stratified case-cohort design, s-25(OH)D was determined by HPLC-atmospheric pressure chemical ionization-mass spectrometry in stored serum samples in hip fracture cases (n = 1175; 307 men, 868 women) and in gender-stratified random samples (n = 1438). Cox proportional hazards regression adapted for the case-cohort design was performed. RESULTS: We observed an inverse association between s-25(OH)D and hip fracture; those with s-25(OH)D in the lowest quartile (<42.2 nmol/L) had a 38% [95% confidence interval (CI) 9-74%] increased risk of hip fracture compared with the highest quartile (≥67.9 nmol/L) in a model accounting for age, gender, study center, and body mass index. The association was stronger in men than in women: hazard ratio 1.65 (95% CI 1.04-2.61) vs hazard ratio 1.25 (95% CI 0.95-1.65). CONCLUSION: In this prospective case-cohort study of hip fractures, the largest ever reported, we found an increased risk of hip fracture in subjects in the lowest compared with the highest quartile of serum 25-hydroxyvitamin D. In accordance with the findings of previous community-based studies, low vitamin D status was a modest risk factor for hip fracture.

Bone mass density, fracture history, self-reported osteoporosis as proxy variables for estrogen and the risk of non-small-cell lung cancer--a population based cohort study, the HUNT study: are proxy variables friends or faults?

Lung cancer has the highest mortality of all cancers. Patients with early stage disease have the best cure rates and that emphasizes the importance of early detection. About half of all non-small cell lung cancers (NSCLC) are estrogen receptor positive. The impact of estrogen and its receptors for NSCLC carcinogenesis has been studied but is still unclear. Low estrogen levels are associated with osteoporosis. We hypothesize that low bone mineral density (BMD), a positive history of fracture or self-reported osteoporosis, used as a proxy variable for life time estrogen exposure, are associated with a low incidence of NSCLC. We analyzed data from a cohort study, the Nord-Trøndelag Health Study 2 (1995-1997) linked to the Norwegian Cancer Registry. Using the logistic regression model we calculated the odds ratio (OR) with a 95% confidence interval (CI) for the risk of NSCLC for the three proxy variables, stratified by sex. Participants older than 50 years of age, having measured bone density (N = 18,156), having answered the questions on self-reported fracture (N = 37,883) and osteoporosis (N = 25,701) and known body mass index (BMI) (N = 29,291), were evaluated for inclusion. In 6996 participants all these information was available in addition to tobacco use, and in women also hormonal replacement therapy (HRT). Lung function (FEV1 percent of predicted) was included in a sensitivity analysis. We identified 132 (1.9%) cases of NSCLC, 59 (1.2%) and 73 (3.3%) cases in women and men, respectively. Low BMD was associated with a higher risk of NSCLC, OR: 2.38, 95% CI: 1.09-5.18 and OR: 2.67, 95% CI: 1.39-5.16 in women and men, respectively. No association was found between the two other proxy variables and the risk of NSCLC. Inclusion of lung function in the model did not change the results. Contrary to our hypothesis, women and men with low BMD had a higher risk for NSCLC. In addition the study demonstrates that the risk depends on which proxy variable was chosen, and we may ask: are proxy variables reliable?