The hip fracture incidence in the high-risk area Oslo continues to decline.

Oslo in Norway has had the highest incidence of hip fractures in the world. The incidence in Oslo has been thoroughly described every decade since the late 1970s. The incidence in Oslo has previously been higher compared to the rest of Norway but has now decreased to a level below the country average. PURPOSE: The purpose of this study was to report the incidence of hip fractures in Oslo in 2019 and compare it with the incidence rates from the previous four decades. METHODS: Patients residing in Oslo in 2019 with a new hip fracture identified by searching the Oslo hospital's patient administrative systems and protocols from the operating theaters. The diagnosis was verified through medical records and/or radiographs. To compare with previous studies, the direct standardization method was used with the population of Oslo in 2019 as the standard. RESULTS: A total of 758 hip fractures, 70% women, were identified in 2019. The age-standardized incidence rates per 10,000 person-years in 2019 (95% CI) were 45 (41.1-48.8) for women and 30 (25.8-33.8) for men. In women, there has been a continuous decline in age-standardized rates the last three decades and in men the last two decades. The most pronounced decline was seen in the oldest age groups over 70 years. There has been a secular decline in both cervical and trochanteric fractures; however, the decrease in trochanteric fractures was most distinct for males, with more than two times higher risk in 1996/1997 compared to 2019. CONCLUSION: Incidence rates for hip fractures in Oslo in 2019 were the lowest rate reported since 1978. The decrease was significant for both men and women. For the first time, the incidence rates are below the national rates of Norway. However, the rates are still among the highest worldwide.

Elevated blood pressure, antihypertensive medications and bone health in the population: revisiting old hypotheses and exploring future research directions.

Blood pressure and bone metabolism appear to share commonalities in their physiologic regulation. Specific antihypertensive drug classes may also influence bone mineral density. However, current evidence from existing observational studies and randomised trials is insufficient to establish causal associations for blood pressure and use of blood pressure-lowering drugs with bone health outcomes, particularly with the risks of osteoporosis and fractures. The availability and access to relevant large-scale biomedical data sources as well as developments in study designs and analytical approaches provide opportunities to examine the nature of the association between blood pressure and bone health more reliably and in greater detail than has ever been possible. It is unlikely that a single source of data or study design can provide a definitive answer. However, with appropriate considerations of the strengths and limitations of the different data sources and analytical techniques, we should be able to advance our understanding of the role of raised blood pressure and its drug treatment on the risks of low bone mineral density and fractures. As elevated blood pressure is highly prevalent and blood pressure-lowering drugs are widely prescribed, even small effects of these exposures on bone health outcomes could be important at a population level.

Does treatment with bisphosphonates protect against fractures in real life? The HUNT study, Norway.

Bisphosphonates reduce fractures in randomized controlled trials (RCT); however, there is less information from real life. In our population including 14,990 women and 13,239 men, use of bisphosphonates reduced risk of fractures in hip and forearm in women. The magnitude of the effect was comparable to results from RCT. INTRODUCTION: The objective was to examine if treatment with bisphosphonates (BPs) was associated with reduced risk of fractures in the hip and forearm in women and men in the general population. METHODS: In a cohort study based on data from the third wave of the population-based HUNT Study (HUNT3), the fracture registry in Nord-Trøndelag, and the Norwegian Prescription Database, 14,990 women and 13,239 men 50-85 years were followed from the date of participating in HUNT3 (2006-2008) until the date of first fracture in the hip or forearm, death, or end of study (31 December 2012). Hazard ratios with 95% confidence intervals for hip and forearm fracture according to use of BPs were estimated using Cox proportional hazards models with time-dependent exposure. Adjustment for individual FRAX® fracture risk assessment scores was included. RESULTS: BPs, predominantly alendronate, were used by 9.4% of the women and 1.5% of the men. During a median of 5.2 years of follow-up, 265 women and 133 men had a hip fracture, and 662 women and 127 men had a forearm fracture. Compared with non-users of BPs, the hazard ratios with 95% confidence interval for a fracture among users of BPs adjusted for age and FRAX® were 0.67 (0.52-0.86) for women and 1.13 (0.50-2.57) for men. Among users of glucocorticoids, the corresponding figures were 0.35 (0.19-0.66) and 1.16 (0.33-4.09), respectively. CONCLUSIONS: Use of BPs was associated with reduced risk of fractures in hip and forearm in women, and the magnitude of effect is comparable to results from RCTs.

Contribution of elevation and residential proximity to the coast in explaining geographic variations in hip fracture incidence. A Norwegian Epidemiologic Osteoporosis Studies (NOREPOS) study.

A higher risk of hip fracture was found in areas of Norway at higher elevation and farther from the coast. However, the previously seen county variations could not be explained by these geographical factors. INTRODUCTION: Norway is an elongated country extending north of the Arctic Circle with substantial coast-inland variation in topography and climate. Differences in hip fracture incidence between counties and a distinct seasonal variation have previously been shown. The aim of the current study was to explore these variations further by considering associations of height above sea level (elevation) and distance to the coast with hip fracture incidence. METHODS: All patients with hip fractures admitted to Norwegian hospitals in the period 2009-2018 were included. Individual residential elevation and distance to the coast was calculated in Geographic Information Systems and combined with individual-level population data on all Norwegians 50 years of age or older during the observation period, including hospital information on fractures. Age-standardized incidences rate and incidence rate ratios with 95% confidence intervals (IRR, 95% CI) according to elevation and coastal proximity were estimated. The associations were tested using Poisson models adjusting for sex, urban/rural location of residency, country of birth, and season of hip fracture occurrence. RESULTS: From 2009 to 2018, there were 85,776 first hip fractures. There was an increasing risk with higher residential elevation (above versus below mean) for women: IRR = 1.04, 95% CI: 1.02, 1.05), but not for men (IRR = 1.00, 95% CI: 0.97, 1.02). Incidence of hip fracture increased with distance from the coast. Women residing the farthest away from the coast (above versus below mean distance) had a higher age-adjusted incidence of hip fracture compared to those living closer to the coast (IRR = 1.04 (95% CI: 1.02, 1.06), whereas no association was found in men (IRR = 1.00 (95% CI: 1.00, 1.01). Combining elevation and distance to coast showed a higher incidence in women living at high elevation far from the coast compared with women living at low elevation near the coast (IRR = 1.07, 95% CI: 1.04, 1.10). A similar result was found in men but only for hip fractures occurring during March-May (IRR = 1.07, 95% CI: 1.00, 1.15). The previously shown patterns of county differences and seasonal variations were unchanged when considering geography. CONCLUSION: We found a somewhat higher incidence of hip fracture in inland residents living in areas of high elevation, as compared to those living in more coastal proximity; however, the geographic variation did not explain county and seasonal differences in fracture incidence in Norway. More in-depth analyses on temperature and climate factors may give further clues.

Ethnic differences in risk of hip fracture in Norway: a NOREPOS study.

Hip fracture is a major public health problem, and the incidence rates vary considerably between countries. Ethnic differences in bone mineral density have been identified as a factor to explain some of the geographical differences in rates of hip fracture. In this Norwegian register-based study, we found that all immigrant groups experienced lower risk of hip fracture than individuals born in Norway. INTRODUCTION: Norway is among the countries with the highest incidence rates. The aim of this study was to investigate differences in risk of hip fracture between ethnic groups living in Norway. METHODS: We linked individuals in the Norwegian Population and Housing Census conducted in 2001 and a database consisting of all hip fractures in Norway in the period 2001-2013. Residents (n = 1,392,949) between 50 and 89 years and born in nine different geographical regions of the world were examined, and we computed age-standardized incidence rates for the different geographic regions-denoted ethnic groups in the paper. Gender-stratified Cox regression analysis, adjusted for age, was used to model risk of hip fracture as a function of region of birth. RESULTS: Age-standardized incidence rates of hip fracture varied considerably between regions of birth living in Norway, in both genders. All immigrant groups had lower risk of hip fracture compared to the Norwegian-born population. Immigrants from Central and Southeast Asia had the lowest risk of hip fracture when compared to individuals born in Norway (HR = 0.2, 95% CI 0.1-0.3 and HR =0.2, 95% CI 0.2-0.4 in men and women, respectively). CONCLUSION: Lower risk of hip fracture was found in all immigrant groups compared to the Norwegian-born majority population.

Grip strength in men and women aged 50-79 years is associated with non-vertebral osteoporotic fracture during 15 years follow-up: The Tromsø Study 1994-1995.

In 50-79-year-olds who participated in the Tromsø Study (1994-1995), the risk of non-vertebral osteoporotic fractures during 15 years follow-up increased by 22% in men and 9% in women per 1 SD lower grip strength. The strongest association was observed in men aged 50-64 years. INTRODUCTION: We aimed to explore whether low grip strength was associated with increased risk of non-vertebral osteoporotic fracture in the population-based Tromsø Study 1994-1995. METHODS: Grip strength (bar) was measured by a Martin Vigorimeter and fractures were retrieved from the X-ray archives at the University Hospital of North Norway between 1994 and 2010. At baseline, weight and height were measured, whereas information on the other covariates were obtained through self-reported questionnaires. Cox regression was used to estimate the hazard ratio (HR) of fracture in age- and gender-specific quintiles of grip-strength, and per 1 SD lower grip strength. Similar analyses were done solely for hip fractures. Adjustments were made for age, height, body mass index (BMI), marital status, education, smoking, physical activity, use of alcohol, self-perceived health, and self-reported diseases. RESULTS: In 2891 men and 4002 women aged 50-79 years, 1099 non-vertebral osteoporotic fractures-including 393 hip fractures-were sustained during the median 15 years follow-up. Risk of non-vertebral osteoporotic fracture increased with declining grip strength: hazard ratios per SD decline was 1.22 (95% CI 1.05-1.43) in men and 1.09 (95% CI 1.01-1.18) in women. HR for fracture in lower vs. upper quintile was 1.58 (95% CI 1.02-2.45) in men and 1.28 (95% CI 1.03-1.59) in women. The association was most pronounced in men aged 50-64 years with HR = 3.39 (95% CI 1.76-6.53) in the lower compared to the upper quintile. CONCLUSIONS: The risk of non-vertebral osteoporotic fracture increased with declining grip-strength in both genders, particularly in men aged 50-64 years.

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.

Geographic variations in hip fracture incidence in a high-risk country stretching into the Arctic: a NOREPOS study.

There are geographic variations in hip fracture incidence rates across Norway, with a lower incidence in the coastal areas of the southwest and in the Arctic north, contrary to what may be expected with regard to vitamin D exposure from sunlight. The regional differences have become smaller in recent years. INTRODUCTION: To investigate geographic variation in hip fracture incidence within Norway and regional differences in time trends. METHODS: All hip fractures treated in Norwegian hospitals 2002-2013 were included, and demographic information was obtained from Statistics Norway. Age-standardized incidence rates were calculated separately for 19 counties. Incidence rate ratios with 95% confidence intervals for county differences and time trends were estimated using Poisson regression. RESULTS: Age-standardized number of hip fractures per 10,000 person-years varied between counties from 69 to 84 in women and from 34 to 41 in men. The highest rates were observed in the southeastern capital city of Oslo, while rates were low in the four northernmost counties. There was an east-west gradient, with lower incidence in the coastal southwest compared with the southeast. Women showed a statistically significant decline during 2002-2013 in almost all counties (up to 31%). In men, only a few counties showed a decline. In both genders, hip fracture rates at age 80 in the combined five counties with the highest rates were significantly higher than in the combined five counties with the lowest rates across the period, although the trends converged over time. CONCLUSIONS: In Norway, the hip fracture incidence was lower in the north compared with the south. In addition, we observed an east-west gradient with the highest incidence in the southeast and lower incidence in the coastal southwest. While there has been an overall declining trend in hip fracture incidence over time, regional differences are still apparent.

Milk and other dairy foods and risk of hip fracture in men and women.

The role of dairy foods for hip fracture prevention remains controversial. In this study, among US men and women, a glass of milk per day was associated with an 8% lower risk of hip fracture. This contrasts with a reported increased risk with higher milk intake in Swedish women. INTRODUCTION: The purpose of this study was to examine whether higher milk and dairy food consumption are associated with risk of hip fracture in older adults following a report of an increased risk for milk in Swedish women. METHODS: In two US cohorts, 80,600 postmenopausal women and 43,306 men over 50 years of age were followed for up to 32 years. Cox proportional hazards models were used to calculate the relative risks (RR) of hip fracture per daily serving of milk (240 mL) and other dairy foods that were assessed every 4 years, controlling for other dietary intakes, BMI, height, smoking, activity, medications, and disease diagnoses. RESULTS: Two thousand one hundred thirty-eight incident hip fractures were identified in women and 694 in men. Each serving of milk per day was associated with a significant 8% lower risk of hip fracture in men and women combined (RR = 0.92, 95% confidence interval (CI) 0.87 to 0.97). A suggestive inverse association was found for cheese in women only (RR = 0.91, CI 0.81 to 1.02). Yogurt consumption was low and not associated with risk. Total dairy food intake, of which milk contributed about half, was associated with a significant 6% lower risk of hip fracture per daily serving in men and women (RR = 0.94, CI 0.90 to 0.98). Calcium, vitamin D, and protein from non-dairy sources did not modify the association between milk and hip fracture, nor was it explained by contributions of these nutrients from milk. CONCLUSIONS: In this group of older US adults, higher milk consumption was associated with a lower risk of hip fracture.

The association between alcohol consumption and risk of hip fracture differs by age and gender in Cohort of Norway: a NOREPOS study.

The association between alcohol consumption and hip fracture differed by gender: Men aged 30-59 years drinking frequently or 14+ gl/week had higher risk than moderate drinkers. No significant association was seen in older men. Women not drinking alcohol had higher risk than those drinking moderately both regarding frequency and amount. INTRODUCTION: We aimed to examine alcohol consumption and risk of hip fracture according to age and gender in the population-based Cohort of Norway (1994-2003). METHODS: Socio-demographics, lifestyle, and health were self-reported and weight and height were measured in 70,568 men and 71,357 women ≥ 30 years. Information on subsequent hip fractures was retrieved from hospitals' electronic patient registries during 1994-2013. Frequency of alcohol consumption was categorized: never/seldom, moderate (≤ 2-3 times/week), or frequent (≥ 4 times/week), and amount as number of glasses per week: 0, 1-6, 7-13, 14-27, and 28+. Type of alcohol (wine vs. beer/hard liquor) was also examined. Cox's proportional hazards regression was used to estimate hazard ratios (HRs) stratified on gender and baseline age < 60 and ≥ 60 years. RESULTS: During median 15-year follow-up, 1558 men and 2511 women suffered a hip fracture. Using moderate drinkers as reference, men < 60 years drinking frequently had multivariable adjusted HR = 1.73 (CI 1.02-2.96) for hip fracture and more than 2.5 times higher risk if they consumed 14+ glasses compared to 1-6 glasses per week. In other groups of age and gender, no statistically significant increased risk was found in those consuming the highest levels of alcohol. Compared to women with moderate or frequent alcohol use, never/seldom-drinking women had the highest fracture risk. In women, use of wine was associated with lower fracture risk than other types of alcohol. CONCLUSIONS: Risk of hip fracture was highest in men < 60 years with the highest frequency and amount of alcohol consumption and in non-drinking women.

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.

Protein intake and risk of hip fractures in postmenopausal women and men age 50 and older.

In this study, we followed postmenopausal women and men aged 50 and above for up to 32 years and found no evidence that higher protein intake increased the risk of hip fracture. Protein intake from specific sources was inversely associated with risk, but these associations appeared to differ by gender. INTRODUCTION: We examined the association between intakes of total and specific sources of protein and hip fracture risk in postmenopausal women and men over 50 years of age. Our hypothesis was that a higher protein intake would not be associated with a higher risk of hip fractures. METHODS: In this analysis, we followed 74,443 women in the Nurses' Health Study between 1980 and 2012 and 35,439 men from the Health Professionals Follow-up Study between 1986 and 2012. Health and lifestyle information and hip fractures were self-reported on biennial questionnaires. Protein was assessed approximately every 4 years with a food frequency questionnaire. Relative risks (RR) were computed for hip fracture by quintiles of total, animal, dairy, and plant protein intakes using Cox proportional hazard models, adjusting for potential confounders. RESULTS: During follow-up, we ascertained 2156 incident hip fractures in women and 595 fractures in men. Among men, we observed significant inverse associations for each 10 g increase of total protein (RR = 0.92, 95% CI = 0.85-0.99) and animal protein (RR = 0.91, 95% CI = 0.85-0.98) intakes. Total and animal proteins were not significantly associated with hip fractures in women. Both plant (RR = 0.88, 95% CI 0.79-0.99 per 10 g) and dairy protein (RR = 0.92, 95% CI 0.86-0.97) were associated with significantly lower risks of hip fracture when results for men and women were combined. None of these associations were modified by BMI, smoking, physical activity, age, or calcium intake. CONCLUSION: We found no evidence that higher protein intake increases risk of hip fracture in these Caucasian men and women. Protein intake from specific sources was inversely associated with risk, but these associations appeared to differ by gender.

Excess mortality following hip fracture: impact of self-perceived health, smoking, and body mass index. A NOREPOS study.

Self-perceived health, smoking, and body mass index measured years before the hip fracture predicted excess post-hip fracture mortality, and even hip fracture patients with the most favorable levels of these risk factors had higher mortality than subjects who did not fracture. INTRODUCTION: This study aimed to investigate the impact of pre-fracture self-perceived health, smoking, and body mass index (BMI) on excess post-hip fracture mortality using matched peers without hip fracture as reference. METHODS: The study was based on the Cohort of Norway (CONOR) consisting of 10 regional health studies (1994-2003) and the NOREPOS hip fracture database (1994-2008). A matched cohort design was used to compare survival between hip fracture patients and subjects without fracture (matched on gender, age at participation in CONOR, and study site). Subjects aged ≥60 years were included. Hazard ratios were estimated using stratified Cox regression. Age-standardized mortality was also calculated. RESULTS: Overall, hip fracture patients (N = 3177) had a 2.26-fold (95 % CI 2.13, 2.40) increased mortality compared to matched subjects (N = 20,282). The highest excess mortality was found in hip fracture patients reporting poor health (HR 4.08, 95 % CI 3.17, 5.26) and daily smoking (HR 3.25, 95 % CI 2.89, 3.66) and in patients with BMI <18.5 (HR 3.07, 95 % CI 2.11, 4.47) prior to the fracture. However, excess mortality was also observed in hip fracture patients in all other categories of BMI, self-perceived health, and smoking. CONCLUSIONS: Information on self-perceived health, smoking, and BMI collected years before hip fracture predicted excess post-hip fracture mortality, and even hip fracture patients with the most favorable levels of these risk factors had higher mortality than the matched subjects who did not fracture. This suggests that both pre-fracture health status and factors related to the hip fracture itself might affect post-hip fracture mortality.

Validation of FRAX and the impact of self-reported falls among elderly in a general population: the HUNT study, Norway.

Fracture Risk Assessment Tool (FRAX) without bone mineral density (BMD) for hip fracture prediction was validated in a Norwegian population 50-90 years. Fracture risk increased with higher FRAX score, and the observed number of hip fractures agreed well with the predicted number, except for the youngest and oldest men. Self-reported fall was an independent risk factor for fracture in women. INTRODUCTION: The primary aim was to validate FRAX without BMD for hip fracture prediction in a Norwegian population of men and women 50-90 years. Secondary, to study whether information of falls could improve prediction of fractures in the subgroup aged 70-90 years. METHODS: Data were obtained from the third survey of the Nord-Trøndelag Health Study (HUNT3), the fracture registry in Nord-Trøndelag, and the Norwegian Prescription Database (NorPD), including 15,432 women and 13,585 men. FRAX hip without BMD was calculated, and hip fractures were registered for a median follow-up of 5.2 years. The number of estimated and observed fractures was assessed, ROC curves with area under the curve (AUC), and Cox regression analyses. For the group aged 70-90 years, self-reported falls the last year before HUNT3 were included in the Cox regression model. RESULTS: The risk of fracture increased with higher FRAX score. When FRAX groups were categorized in a 10-year percentage risk for hip fracture as follows, <4, 4-7.9, 8-11.9, and ≥12%, the hazard ratio (HR) for hip fracture between the lowest and the highest group was 17.80 (95% CI: 12.86-24.65) among women and 23.40 (13.93-39.30) in men. Observed number of hip fractures agreed quite well with the predicted number, except for the youngest and oldest men. AUC was 0.81 (0.78-0.83) for women and 0.79 (0.76-0.83) for men. Self-reported fall was an independent risk factor for fracture in women (HR 1.64, 1.20-2.24), and among men, this was not significant (1.09, 0.65-1.83). CONCLUSIONS: FRAX without BMD predicted hip fracture reasonably well. In the age group 70-90 years, falls seemed to imply an additional risk among women.

Hepatic expression of proteasome subunit alpha type-6 is upregulated during viral hepatitis and putatively regulates the expression of ISG15 ubiquitin-like modifier, a proviral host gene in hepatitis C virus infection.

The interferon-stimulated gene 15 (ISG15) plays an important role in the pathogenesis of hepatitis C virus (HCV) infection. ISG15-regulated proteins have previously been identified that putatively affect this proviral interaction. The present observational study aimed to elucidate the relation between ISG15 and these host factors during HCV infection. Transcriptomic and proteomic analyses were performed using liver samples of HCV-infected (n = 54) and uninfected (n = 10) or HBV-infected controls (n = 23). Primary human hepatocytes (PHH) were treated with Toll-like receptor ligands, interferons and kinase inhibitors. Expression of ISG15 and proteasome subunit alpha type-6 (PSMA6) was suppressed in subgenomic HCV replicon cell lines using specific siRNAs. Comparison of hepatic expression patterns revealed significantly increased signals for ISG15, IFIT1, HNRNPK and PSMA6 on the protein level as well as ISG15, IFIT1 and PSMA6 on the mRNA level in HCV-infected patients. In contrast to interferon-stimulated genes, PSMA6 expression occurred independent of HCV load and genotype. In PHH, the expression of ISG15 and PSMA6 was distinctly induced by poly(I:C), depending on IRF3 activation or PI3K/AKT signalling, respectively. Suppression of PSMA6 in HCV replicon cells led to significant induction of ISG15 expression, thus combined knock-down of both genes abrogated the antiviral effect induced by the separate suppression of ISG15. These data indicate that hepatic expression of PSMA6, which is upregulated during viral hepatitis, likely depends on TLR3 activation. PSMA6 affects the expression of immunoregulatory ISG15, a proviral factor in the pathogenesis of HCV infection. Therefore, the proteasome might be involved in the enigmatic interaction between ISG15 and HCV.

Abdominal obesity and hip fracture: results from the Nurses' Health Study and the Health Professionals Follow-up Study.

UNLABELLED: Abdominal obesity might increase fracture risk. We studied the prospective associations between waist circumference, waist-to-hip ratio, and hip fracture. The indicators of abdominal obesity were associated with increased hip fracture risk in women, but not in men. The increased risk was restricted to women with low physical activity. INTRODUCTION: Low weight is an established risk factor for osteoporosis and hip fracture. However, the association between fat tissue, muscle, and bone is complex, and abdominal obesity might increase fracture risk. We studied the prospective associations between indicators of abdominal obesity and hip fracture in two large US cohorts. METHODS: At baseline in 1986 and through biennial follow-up, information on hip fracture and potential risk factors was collected in 61,677 postmenopausal women and 35,488 men above age 50. Waist and hip circumferences were reported at baseline and updated twice. RESULTS: During follow-up, 1168 women and 483 men sustained a hip fracture. After controlling for known risk factors, there was a significant association in women between increasing waist circumference and hip fracture (RR per 10-cm increase 1.13 (95 % CI 1.04-1.23) and between increasing waist-to-hip ratio and hip fracture (RR per 0.1 unit increase 1.14 (95 % CI 1.04-1.23), but these associations were not seen in men. In women, both measures interacted with physical activity. Those in the highest (≥0.90) versus lowest (<0.75) category of waist-to-hip ratio had increased risk of hip fracture if their activity was less than the population median (RR = 1.61, 95 % CI 1.18-2.19) but not if their activity was higher (RR = 1.00, 95 % CI 0.72-1.40). A similar pattern was found for waist circumference. CONCLUSION: Indicators of abdominal obesity were associated with increased hip fracture risk after controlling for BMI in women. The increased risk was restricted to women with low physical activity. In men, no significant associations were found.

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.

A combination of low serum concentrations of vitamins K1 and D is associated with increased risk of hip fractures in elderly Norwegians: a NOREPOS study.

UNLABELLED: The present study investigated the risk of incident hip fractures according to serum concentrations of vitamin K1 and 25-hydroxyvitamin D in elderly Norwegians during long-term follow-up. The results showed that the combination of low concentrations of both vitamin D and K1 provides a significant risk factor for hip fractures. INTRODUCTION: This case-cohort study aims to investigate the associations between serum vitamin K1 and hip fracture and the possible effect of 25-hydroxyvitamin D (25(OH)D) on this association. METHODS: The source cohort was 21,774 men and women aged 65 to 79 years who attended Norwegian community-based health studies during 1994-2001. Hip fractures were identified through hospital registers during median follow-up of 8.2 years. Vitamins were determined in serum obtained at baseline in all hip fracture cases (n = 1090) and in a randomly selected subcohort (n = 1318). Cox proportional hazards regression with quartiles of serum vitamin K1 as explanatory variable was performed. Analyses were further performed with the following four groups as explanatory variable: I: vitamin K1 ≥ 0.76 and 25(OH)D ≥ 50 nmol/l, II: vitamin K1 ≥ 0.76 and 25(OH)D < 50 nmol/l, III: vitamin K1 < 0.76 and 25(OH)D ≥ 50 nmol/l, and IV: vitamin K1 < 0.76 and 25(OH)D < 50 nmol/l. RESULTS: Age- and sex-adjusted analyses revealed an inverse association between quartiles of vitamin K1 and the risk of hip fracture. Further, a 50 % higher risk of hip fracture was observed in subjects with both low vitamin K1 and 25(OH)D compared with subjects with high vitamin K1 and 25(OH)D (HR 1.50, 95 % CI 1.18-1.90). The association remained statistically significant after adjusting for body mass index, smoking, triglycerides, and serum α-tocopherol. No increased risk was observed in the groups low in one vitamin only. CONCLUSION: Combination of low concentrations of vitamin K1 and 25(OH)D is associated with increased risk of hip fractures.

Abdominal obesity increases the risk of hip fracture. A population-based study of 43,000 women and men aged 60-79 years followed for 8 years. Cohort of Norway.

BACKGROUND: The question as to whether abdominal obesity has an adverse effect on hip fracture remains unanswered. The purpose of this study was to investigate the associations of waist circumference, hip circumference, waist-hip ratio, and body mass index with incident hip fracture. METHODS: The data in this prospective study is based on Cohort of Norway, a population-based cohort established during 1994-2003. Altogether 19,918 women and 23,061 men aged 60-79 years were followed for a median of 8.1 years. Height, weight, waist and hip circumference were measured at baseline using standard procedures. Information on covariates was collected by questionnaires. Hip fractures (n = 1,498 in women, n = 889 in men) were identified from electronic discharge registers from all general hospitals in Norway between 1994 and 2008. RESULTS: The risk of hip fracture decreased with increasing body mass index, plateauing in obese men. However, higher waist circumference and higher waist-hip ratio were associated with an increased risk of hip fracture after adjustment for body mass index and other potential confounders. Women in the highest tertile of waist circumference had an 86% (95% CI: 51-129%) higher risk of hip fracture compared to the lowest, with a corresponding increased risk in men of 100% (95% CI 53-161%). Lower body mass index combined with abdominal obesity increased the risk of hip fracture considerably, particularly in men. CONCLUSION: Abdominal obesity was associated with an increased risk of hip fracture when body mass index was taken into account. In view of the increasing prevalence of obesity and the number of older people suffering osteoporotic fractures in Western societies, our findings have important clinical and public health implications.