Proton pump inhibitors and fracture risk. The HUNT study, Norway.

Proton pump inhibitors (PPIs) have been linked to increased risk of fracture; the data have, however, been diverging. We did not find any increased risk of fractures among users of PPIs in a Norwegian population of 15,017 women and 13,241 men aged 50-85 years with detailed information about lifestyle and comorbidity. INTRODUCTION: Proton pump inhibitors (PPIs) are widely prescribed and have been linked to increased risk of fracture. METHODS: We used data from the Nord-Trøndelag Health Study (HUNT3), The Fracture registry in Nord-Trøndelag, and the Norwegian Prescription Database, including 15,017 women and 13,241 men aged 50-85 years. The study population was followed from the date of participating in HUNT3 (2006-2008) until the date of first fracture (forearm or hip), death, or end of study (31 December 2012). The Cox proportional hazards model with time-dependent exposure to PPIs was applied, and each individual was considered as unexposed until the first prescriptions was filled. To be included, the prescription of PPIs should minimum be equivalent to 90 defined daily doses (DDD) in the period. Individuals were defined as exposed until 6 months after end of drug supply. RESULTS: The proportion of women and men using PPIs was 17.9% and 15.5%, respectively. During a median of 5.2 years follow-up, 266 women and 134 men had a first hip fracture and 662 women and 127 men, a first forearm fracture. The combined rate/1000 patient-years for forearm and hip fractures in women was 49.2 for users of PPIs compared with 64.1 among non-users; for men 18.6 and 19.8, respectively. The hazard ratios with 95% confidence interval for the first forearm or hip fracture among users of PPIs in the age-adjusted analysis were 0.82 (0.67-1.01) for women and 1.05 (0.72-1.52) for men. Adjusting for age, use of anti-osteoporotic drugs, and FRAX, the HR declined to 0.80 (0.65-0.98) in women and 1.00 (0.69-1.45) in men. CONCLUSIONS: Use of PPIs was not associated with an increased risk of fractures.

Anti-osteoporosis drug use: too little, too much, or just right? The HUNT study, Norway.

Use of anti-osteoporotic drugs (AODs) was examined in a Norwegian population 50-85 years. Among them with Fracture Risk Assessment Tool (FRAX) score for major osteoporotic fracture ≥ 20, 25% of the women and 17% of the men received AODs. The strongest predictors for AODs were high age in women and use of glucocorticoids among men. INTRODUCTION: To examine the use of anti-osteoporotic drugs (AODs) and to identify predictors for prescriptions. METHODS: Data were obtained from the Nord-Trøndelag Health Study (HUNT3) performed in 2006-2008 and the Norwegian Prescription Database, including 15,075 women and 13,386 men aged 50-85 years. Bone mineral density (BMD) in the femoral neck was measured in a subgroup of 4538 women and 2322 men. High fracture risk was defined as a FRAX score for major osteoporotic fracture (MOF) ≥ 20%; in the subgroup with BMD, high risk was in addition defined as FRAXMOF ≥ 20% or T-score ≤ - 2.5. Hazard ratios (HRs) for predictors of incident use of AODs within 2 years after HUNT3 were estimated by Cox' proportional hazards model. RESULTS: Among individuals with FRAX MOF ≥ 20%, 25% of the women and 17% of the men were treated with AODs. Among those with FRAX MOF < 20%, 3% and 1% were treated, respectively. In the subgroup with BMD measurement, 24% of the women and 16% of the men at high risk of fractures were treated, compared to 3 and 1% in women and men not fulfilling the criteria. In women, high age was the strongest predictor for treatment (HR 3.84: 95% confidence interval 2.81-5.24), followed by use of glucocorticoids (GCs) (2.68:1.84-3.89). In men, predictors were use of GCs (5.28: 2.70-10.35) followed by multimorbidity (3.16:1.31-7.63). In the subgroup with BMD, T-score ≤ - 2.5 was the strongest predictor (women 3.98:2.67-5.89; men 13.31:6.17-28.74). CONCLUSIONS: This study suggests an undertreatment of AODs in individuals at high risk of fracture.

Psoriasis, fracture risk and bone mineral density: the HUNT Study, Norway.

BACKGROUND: An association between psoriasis and osteoporosis has been reported. OBJECTIVES: To investigate, in a large prospective population-based Norwegian study, whether psoriasis is associated with increased risk of forearm or hip fracture; to investigate the cross-sectional association between psoriasis and bone mineral density (BMD) T-score in a subpopulation. METHODS: Hospital-derived fracture data from Nord-Trøndelag County (1995-2013) were linked to psoriasis information, BMD measurements and lifestyle factors from the third survey of the Nord-Trøndelag Health Study 2006-08 (HUNT3); socioeconomic data from the National Education Database; and use of medication from the Norwegian Prescription Database. RESULTS: Among 48 194 participants in HUNT3, we found no increased risk of forearm or hip fracture in 2804 patients with self-reported psoriasis [overall age- and sex-adjusted hazard ratio 1·03, 95% confidence interval (CI) 0·82-1·31]. No clear association was found between psoriasis and mean BMD T-score; overall age- and sex-adjusted differences in total hip, femoral neck and lumbar spine BMD T-scores were 0·02 (95% CI -0·11 to 0·14), 0·05 (95% CI -0·06 to 0·17) and 0·07 (95% CI -0·09 to 0·24), respectively. No clear association was found between psoriasis and prevalent osteoporosis in either total hip, femoral neck or lumbar spine; overall age- and sex-adjusted odds ratio was 0·77 (95% CI 0·54-1·10). Associations did not change substantially after adjustment for education, smoking, systemic steroid use and body mass index. CONCLUSIONS: We found no association between psoriasis and risk of fracture. The study did not indicate reduced BMD T-score or higher prevalence of osteoporosis among patients with psoriasis.

Continued decline in hip fracture incidence in Norway: a NOREPOS study.

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

Excess mortality after hip fracture among elderly women in Norway. The HUNT study.

UNLABELLED: We wanted to study mortality after hip fractures among elderly women in Norway. We found that excess mortality was highest short time after hip fracture, but persisted for several years after the fracture. The excess mortality was not explained by pre-fracture medical conditions. INTRODUCTION: The purpose of the present study was to investigate short and long term mortality after hip fracture, and to evaluate how comorbidity, bone mineral density, and lifestyle factors affect the survival after hip fractures. METHODS: The study cohort emerges from a population-based health survey in the county of Nord-Trøndelag, Norway. Women aged 65 or more at participation at the health survey who sustained a hip fracture after attending the health survey are cases in this study (n = 781). A comparison cohort was constructed based on participants at HUNT 2 with no history of hip fractures (n = 3, 142). Kaplan-Meier survival curves were used to evaluate crude survival, and Cox regression analyses were used to study age-adjusted hazard ratios for mortality and for multivariable analyses involving relevant covariates. RESULTS: Mean length of follow-up after fracture was 2.8 years. Within the first 3 months of follow-up, 78 (10.0%) of the hip fracture patients died, compared to only 39 (1.7%) in the control group. HR for mortality 3 months after hip fracture was 6.5 (95% CI 4.2-9.6). For the entire follow-up period women who sustained a hip fracture had an HR for mortality of 1.9 (95% CI 1.6-2.3), compared with women without a hip fracture. CONCLUSIONS: We found that elderly women who sustained a hip fracture had increased mortality risk. The excess mortality was highest short time after the fracture, but persisted for several years after the fracture, and was not explained by pre-fracture medical conditions.

Physical activity, body mass index and bone mineral density-associations in a prospective population-based cohort of women and men: the Canadian Multicentre Osteoporosis Study (CaMos).

BACKGROUND: Physical activity (PA) is an important modifiable risk factor for both bone mineral density (BMD) and body mass index (BMI). However, BMI is itself strongly predictive of BMD. Our aim was to determine the association between PA and BMD, with consideration of BMI as a potential mediating factor. METHODS: The Canadian Multicentre Osteoporosis Study (CaMos) is a population-based prospective cohort study of Canadian women and men. PA was determined from interviewer-administered questionnaires at baseline and Year 5 and summarized as daily energy expenditure in total metabolic equivalents of the task multiplied by minutes/day (MET*m/d). Height, weight, and total hip and lumbar spine BMD were measured at baseline and Year 5. General linear models assessed relationships between PA and BMD, both cross-sectionally (baseline PA with baseline BMD) and longitudinally (average PA and change in PA with change in BMD). BMI was considered as a mediating factor. Potential confounders included age, center, education, caffeine intake, alcohol exposure, smoking history, history of weight-cycling, age at menarche, past use of oral contraceptives, history of >3 months missed menstruation, menopausal status, and antiresorptive use, as relevant. RESULTS: The study included 2855 men and 6442 women. PA was inversely associated with BMI at baseline, and an increase in PA between baseline and Year 5 was associated with a decrease in BMI, with 0.41 (95% CI: 0.22, 0.60) kg/m(2) loss per 1000 MET*m/d increase (in men) and 0.40 (95% CI: 0.23, 0.57) kg/m(2) loss per 1000 MET*m/d increase (in women). BMI was strongly associated with BMD, both cross-sectionally and longitudinally. However, increased PA was associated with a small increase in total hip BMD, 0.004 (95% CI: 0.000-0.008) g/cm(2) per 1000 MET*m/d (in men) and 0.003 (95% CI: 0.000-0.007) g/cm(2) per 1000 MET*m/d (in women). Average PA was associated with an increase in lumbar spine BMD in women, but not in men; it was not associated with change in total hip BMD in either sex. CONCLUSION: Increased PA is associated with an increase in BMD and a concomitant decrease in BMI. These findings suggest that population-level interventions to increase PA would favorably impact bone and other health outcomes.

A low COMT activity haplotype is associated with recurrent preeclampsia in a Norwegian population cohort (HUNT2).

The etiology of preeclampsia is complex, with susceptibility being attributable to multiple environmental factors and a large genetic component. Although many candidate genes for preeclampsia have been suggested and studied, the specific causative genes still remain to be identified. Catechol-O-methyltransferase (COMT) is an enzyme involved in catecholamine and estrogen degradation and has recently been ascribed a role in development of preeclampsia. In the present study, we have examined the COMT gene by genotyping the functional Val108/158Met polymorphism (rs4680) and an additional single-nucleotide polymorphism, rs6269, predicting COMT activity haplotypes in a large Norwegian case/control cohort (n(cases)= 1135, n(controls)= 2262). A low COMT activity haplotype is associated with recurrent preeclampsia in our cohort. This may support the role of redox-regulated signaling and oxidative stress in preeclampsia pathogenesis as suggested by recent studies in a genetic mouse model. The COMT gene might be a genetic risk factor shared between preeclampsia and cardiovascular diseases.

Cryo-SEM method for the observation of entrapped bubbles and degree of water filling in large wet powder compacts.

There are generally two problems associated with cryogenic scanning electron microscopy (cryo-SEM) observations of large wet powder compacts. First, because water cannot be vitrified in such samples, formation of artefacts is unavoidable. Second, large frozen samples are difficult to fracture but also to machine into regular pieces which fit in standard holders, especially if made of hard materials like ceramics. In this article, we first describe a simple method for planning hard cryo-samples and a low-cost technique for cryo-fracture and transfer of large specimens. Subsequently, after applying the entire procedure to green pellets of iron ore produced by balling, we compare the influence of plunge- and unidirectional freezing on large entrapped bubbles throughout the samples as well as the degree of water filling at the outer surface of the pellets. By carefully investigating the presence of artefacts in large areas of the samples and by controlling the orientation of the sample during freezing and preparation, we demonstrate that unidirectional freezing enables the observation of large entrapped bubbles with minimum formation of artefacts, whereas plunge freezing is preferable for the characterization of the degree of water filling at the outer surface of wet powder compacts. The minimum formation of artefacts was due to the high packing density of the iron ore particles in the matrix.

STOX2 but not STOX1 is differentially expressed in decidua from pre-eclamptic women: data from the Second Nord-Trondelag Health Study.

Variation in the Storkhead box-1 (STOX1) gene has previously been associated with pre-eclampsia. In this study, we assess candidate single nucleotide polymorphisms (SNPs) in STOX1 in an independent population cohort of pre-eclamptic (n = 1.139) and non-pre-eclamptic (n = 2.269) women (the HUNT2 study). We also compare gene expression levels of STOX1 and its paralogue, Storkhead box-2 (STOX2) in decidual tissue from pregnancies complicated by pre-eclampsia and/or fetal growth restriction (FGR) (n = 40) to expression levels in decidual tissue from uncomplicated pregnancies (n = 59). We cannot confirm association of the candidate SNPs to pre-eclampsia (P > 0.05). For STOX1, no differential gene expression was observed in any of the case groups, whereas STOX2 showed significantly lower expression in deciduas from pregnancies complicated by both pre-eclampsia and FGR as compared with controls (P = 0.01). We further report a strong correlation between transcriptional alterations reported previously in choriocarcinoma cells over expressing STOX1A and alterations observed in decidual tissue of pre-eclamptic women with FGR.

Challenges of informed choice in organised screening.

CONTEXT: Despite much research on informed choice and the individuals' autonomy in organised medical screening, little is known about the individuals' decision-making process as expressed in their own words. OBJECTIVES: To explore the decision-making process among women invited to a mammography screening programme. SETTING: Women living in the counties of Sør- and Nord-Trøndelag, Norway, invited to the first round of the Norwegian Breast Cancer Screening Program (NBCSP) in 2003. METHODS: Qualitative methods based on eight semistructured focus-group interviews with a total of 69 women aged 50-69 years. RESULTS: The decision to attend mammography screening was not based on the information in the invitation letter and leaflet provided by the NBCSP. They perceived the invitation letter with a prescheduled appointment as if a decision for mammography had already been made. This was experienced as an aid in overcoming the postponements that easily occur in daily lives. The invitation to mammography screening was embraced as an indication of a responsible welfare state, "like a mother taking care." CONCLUSION: In a welfare state where governmental institutions are trusted, mass screening for disease is acknowledged by screening participants as a valued expression of paternalism. Trust, gratitude, and convenience were more important factors than information about benefits, harms, and risks when the women made their decisions to attend screening. These elements should be included in the ethical debates on informed choice in preventive medicine.

Height loss, forearm bone density and bone loss in menopausal women: a 15-year prospective study. The Nord-Trøndelag Health Study, Norway.

UNLABELLED: In a population-based cohort of 1,421 women 45-60 years old followed for 15.5 years, 71% of the women had lost height. Height loss was associated with low forearm bone density and increased bone loss, but high body weight and oestrogen therapy were protective factors. Increased height loss indicates a generalized state of bone loss. INTRODUCTION: The degree of height loss and its association to forearm bone mineral density (BMD) and bone loss was investigated in a population-based cohort of middle-aged women followed for more than 15 years. METHODS: Among 8,856 women aged 45-60 years attending the first HUNT Study, Norway (1984-86), a 35% random sample was invited to forearm densitometry 11.3 years later (HUNT 2, 1995-97), and 2,188 attended (78.3%). In 2001, 15.5 years since baseline, all were invited to follow-up densitometry and height measurement. RESULTS: A total of 71.2% and 17.4% of the 1,421 women attending had lost >1 cm and >3 cm of height since baseline, respectively. Women aged >or= 64 years at HUNT 2 had a relative risk (RR) for height loss >3 cm of 3.1 (95% CI 2.2, 4.3) compared to women <64 years. A strong and negative association was found between height loss and forearm BMD, adjusted for time since menopause. A high rate of height loss was associated to increased forearm bone loss. High body weight, oestrogen treatment and good self-rated health were protective against height loss. CONCLUSION: Height loss is frequent in middle-aged women, and increased height loss indicates a generalized state of bone loss.

Higher bone mineral density in rural compared with urban dwellers: the NOREPOS study.

Norway has a very high incidence of osteoporotic fractures, with substantial regional differences in fracture incidence. The present study evaluated whether there are differences in bone mineral density (BMD) between regions in Norway with differences in fracture incidence. The authors used data collected in four large, population-based, multipurpose studies performed in four regions of Norway during 1994-2001. Distal forearm BMD was measured by single energy x-ray absorptiometry in 10,667 participants aged 40-75 years. Cross-calibration was performed by using the European Forearm Phantom. Mean distal forearm BMD was lower in the urban populations of Tromso, Oslo, and Bergen compared with the rural county of Nord-Trondelag, whereas there was no difference between the rural part of Tromso and Nord-Trondelag. For women, body mass index explained some of these differences. The prevalence of low BMD (z score < or = -1) in Oslo, Bergen, and urban Tromso, compared with Nord-Trondelag, was 1.6-1.7 times higher in men and 1.5-2.0 times higher in women, whereas no significant difference was found between rural Tromso and Nord-Trondelag. In this study, higher BMD was found in rural compared with urban areas of Norway, which might help explain the differences in fracture incidence. There was no apparent north-south gradient in BMD.

How do reproductive and lifestyle factors influence bone density in distal and ultradistal radius of early postmenopausal women? The Nord-Trøndelag Health Survey, Norway.

In a population-based health survey, densitometry was performed at the distal and ultradistal radius with single-energy X-ray absorptiometry. Bone mineral density (BMD) data and self-reported reproductive and lifestyle data from 1652 randomly selected peri- and postmenopausal women aged 50-59 years were analyzed. A total of 893 (54.1%) postmenopausal women reported no prior use of hormone replacement therapy (HRT) and constituted the principal group of study. These women were more frequently smokers, consumed less alcohol, more coffee and had made less use of oral contraceptives (OC) than women in the HRT group. The strongest association with both distal and ultradistal radius bone densities was found for age, weight, time since menopause and a history of bilateral oophorectomy. Among reproductive factors, nulliparous women had lower BMD than parous women; however, no linear relationship was found between parity and bone density. A weak, positive relationship was found for OC and BMD in bivariate, but not in multivariate analyses. A history of hysterectomy was positively associated with BMD, stronger at the ultradistal than distal radius. A positive relationship between alcohol consumption and BMD was found at the ultradistal radius. Present or prior smokers had lower BMD than never smokers. In the multivariate model, interaction between pack-years of smoking and daily coffee intake was observed at the distal radius, and both factors had a stronger negative influence on distal than ultradistal radius bone density. In perimenopausal women, most reproductive and lifestyle risk factors found to be associated with BMD of the radius may be explained by different levels of estrogen.

[The murder at Grünerløkken--a centenary]. / Drabet paa Grünerløkken--et hundreårsminne.

In December 1898, a five year old boy was found murdered and sexually abused at Grünerløkka in Oslo. The crime was reported to the police by a 19 year old boy, who soon after was detained and charged with the misdeed. In spring 1899 he was found guilty and sentenced to life imprisonment with hard labour. This article is based on a long and detailed forensic medical and psychiatric report from the investigation and trial, published in this Journal in 1899, and on the Oslo press coverage of the crime. It shows that much has changed during these 100 years regarding both the privacy of the victim, the accused and their families, and factors paid attention to in the psychiatric assessment of the accused.

Treatment of pre-invasive conditions during opportunistic screening and its effectiveness on cervical cancer incidence in one Norwegian county.

Norway had until recently no organized screening programme for cervical cancer, but opportunistic screening was common. This study focuses on the effectiveness of treatment of pre-malignant cervical conditions (CIN III) on cervical-cancer incidence in the county of Sør-Trøndelag in Norway, prior to the introduction of organized mass screening. The study is based on cervical-cancer incidence rates during the years 1965-92 and treatment data for CIN III. The expected number of cervical-cancer cases prevented due to early intervention was expressed in a regression model with 2 unknown parameters: the probability, p, of cancer development in case of CIN III, and the time lag, t, between treatment and when clinical cancer would otherwise have been diagnosed. The estimated probability that a patient treated for CIN III would have developed cervical cancer if not treated was found to be approximately 20%, and the mean time delay was around 16 years. In the last period of study (1988-92), the incidence was reduced by nearly 40% of what would have been expected without early intervention. Based on equal treatment rates as in 1990, parameter estimates were used to predict future incidence reduction. Maximum effectiveness will be achieved around the year 2005, with a nearly 70% reduction. Opportunistic screening and treatment of CIN III seems to have had considerable influence on cervical-cancer incidence. The costs, however, are substantial over-treatment, since our results indicate that 4 of 5 women treated for CIN III would not progress into the invasive state.

Pregnancy outcome after laser surgery for cervical intraepithelial neoplasia.

BACKGROUND: Little is published about obstetrical problems after treatment of cervical intraepithelial neoplasia with the C02-laser. The aim of this study was to determine the risk of low birth weight in the subsequent pregnancy after laser conization or vaporization in a follow-up study of women treated for cervical intraepithelial neoplasia (CIN). Methods. Of 319 women treated for CIN with the C02-laser in the Department of Obstetrics and Gynecology, University Hospital of Tromsø, Norway and followed for pregnancy outcome, 87 women had given birth (after 24th week) four to nine years after treatment. Sixty-five women had undergone conization and 22 women had been treated with vaporization. For each delivery, two controls matched for parity, age (+/- 3 years) and place of delivery were identified. The material was analyzed as a matched cohort study. RESULTS: A strong relationship was found between conization and low birth weight. Mean birth weight after conization was 3185 g vs 3473 g,in the control women (p=0.03). Thirteen (20%) infants from women subject to conization had birth weight less than 2500 g. Relative risk of birth weight<2500 g was 2.2 (1.04-4.5) after conization, for<2000 g and< 1500 g the risk was 3.5 (1.02-12.0) and 10.0 (1.2-85.6), respectively. Four women (6.2%) with normal deliveries prior to conization experienced one or several stillbirths after treatment. No difference in birth weight was observed for women after vaporization compared to their controls. CONCLUSION: Excisional surgery on the cervix increases the risk for low birth weight in subsequent pregnancies. Pregnant women with prior conization need careful antenatal care.