Educational gradient in hip fracture incidence in Norway. The Norwegian Epidemiologic Osteoporosis Studies (NOREPOS).

Examining fracture dynamics by socioeconomic status may inform healthcare and prevention. We found a higher risk of hip fracture in men and women with lower educational level in Norway. However, by age 90 + years, the cumulative incidence was higher in those with higher education, due to their higher life expectancy. PURPOSE: Socioeconomic gradients are seen for several health outcomes in high-income countries. We aimed to examine possible educational gradients in risk of hip fracture in Norway and to describe the cumulative incidence of hip fracture by educational level. METHODS: In a population-wide cohort of Norwegians aged ≥ 50 years, information on attained education from Statistics Norway was linked to hospital-treated hip fractures and deaths during 2002-2019. We estimated relative fracture risk by educational level (primary, secondary or tertiary) in Cox proportional hazards regression. We also examined the cumulative incidence over attained age by gender and educational level in competing risk regression. RESULTS: The population included N = 1,389,858 individuals with 135,938 incident hip fractures. Compared with men who had attained tertiary education, hazard ratios (95% confidence intervals) for hip fracture were 1.44 (1.40, 1.49) in men with primary education only and 1.26 (1.22, 1.29) in men with secondary education. In women, the corresponding estimates were 1.28 (1.25, 1.31) and 1.16 (1.13, 1.19). In the age range 50 to 90 years, the highest cumulative incidence of hip fracture was seen in those with primary education. The gradient gradually diminished with advancing age and was reversed in the oldest (> 90 years) in both genders. CONCLUSIONS: There was a clear educational gradient in hip fracture incidence in both men and women in Norway, with a higher risk in people with lower education. Despite this, the cumulative incidence of hip fracture in old age was highest among people with higher education, due to their higher life expectancy.

The medication-based Rx-Risk Comorbidity Index and risk of hip fracture - a nationwide NOREPOS cohort study.

BACKGROUND: Few previous studies have assessed overall morbidity at the individual level with respect to future risk of hip fracture. The aim of this register-based cohort study was to examine the association between morbidity measured by the medication-based Rx-Risk Comorbidity Index (Rx-Risk) and the risk of first hip fracture. METHODS: Individual-level data on medications dispensed from pharmacies (2005-2016) was retrieved from the Norwegian Prescription Database and used to calculate Rx-Risk for each calendar year. Information on first hip fractures (2006-2017) was obtained from a nationwide hip fracture database. Individuals ≥ 51 years who filled at least one prescription during the study period comprised the population at risk. Using Rx-Risk as a time-varying exposure variable, relative risk estimates were obtained by a negative binomial model. RESULTS: During 2006-2017, 94,104 individuals sustained a first hip fracture. A higher Rx-Risk was associated with increased risk of hip fracture within all categories of age and sex. Women with the highest Rx-Risk (> 25) had a relative risk of 6.1 (95% confidence interval (CI): 5.4, 6.8) compared to women with Rx-Risk ≤ 0, whereas the corresponding relative risk in women with Rx-Risk 1-5 was 1.4 (95% CI: 1.3, 1.4). Similar results were found in men. Women > 80 years with Rx-Risk 21-25 had the highest incidence rate (514 (95% CI: 462, 566) per 10, 000 person years). The relative increase in hip fracture risk with higher Rx-Risk was most pronounced in the youngest patients aged 51-65 years. CONCLUSIONS: Rx-Risk is a strong predictor of hip fracture in the general outpatient population and may be useful to identify individuals at risk in a clinical setting and in future studies.

Validation of forearm fracture diagnoses in administrative patient registers.

The validity of forearm fracture diagnoses recorded in five Norwegian hospitals was investigated using image reports and medical records as gold standard. A relatively high completeness and correctness of the diagnoses was found. Algorithms used to define forearm fractures in administrative data should depend on study purpose. PURPOSE: In Norway, forearm fractures are routinely recorded in the Norwegian Patient Registry (NPR). However, these data have not been validated. Data from patient administrative systems (PAS) at hospitals are sent unabridged to NPR. By using data from PAS, we aimed to examine (1) the validity of the forearm fracture diagnoses and (2) the usefulness of washout periods, follow-up codes, and procedure codes to define incident forearm fracture cases. METHODS: This hospital-based validation study included women and men aged ≥ 19 years referred to five hospitals for treatment of a forearm fracture during selected periods in 2015. Administrative data for the ICD-10 forearm fracture code S52 (with all subgroups) in PAS and the medical records were reviewed. X-ray and computed tomography (CT) reports from examinations of forearms were reviewed independently and linked to the data from PAS. Sensitivity and positive predictive values (PPVs) were calculated using image reports and/or review of medical records as gold standard. RESULTS: Among the 8482 reviewed image reports and medical records, 624 patients were identified with an incident forearm fracture during the study period. The sensitivity of PAS registrations was 90.4% (95% CI: 87.8-92.6). The PPV increased from 73.9% (95% CI: 70.6-77.0) in crude data to 90.5% (95% CI: 88.0-92.7) when using a washout period of 6 months. Using procedure codes and follow-up codes in addition to 6-months washout increased the PPV to 94.0%, but the sensitivity fell to 69.0%. CONCLUSION: A relatively high sensitivity of forearm fracture diagnoses was found in PAS. PPV varied depending on the algorithms used to define cases. Choice of algorithm should therefore depend on study purposes. The results give useful measures of forearm fracture diagnoses from administrative patient registers. Depending on local coding practices and treatment pathways, we infer that the findings are relevant to other fracture diagnoses and registers.

Forearm fractures - are we counting them all? An attempt to identify and include the missing fractures treated in primary care.

OBJECTIVE: Norway has a high incidence of forearm fractures, however, the incidence rates based on secondary care registers can be underestimated, as some fractures are treated exclusively in primary care. We estimated the proportion of forearm fracture diagnoses registered exclusively in primary care and assessed the agreement between diagnosis for forearm fractures in primary and secondary care. DESIGN: Quality assurance study combining nationwide data from 2008 to 2019 on forearm fractures registered in primary care (Norwegian Control and Payment of Health Reimbursement) and secondary care (the Norwegian Patient Registry). SETTING AND PATIENTS: Forearm fracture diagnoses in patients aged ≥20 treated in primary care (n = 83,357) were combined with injury diagnoses for in- and outpatients in secondary care (n = 3,294,336). MAIN OUTCOME MEASURES: Proportion of forearm fractures registered exclusively in primary care, and corresponding injury diagnoses for those registered in both primary and secondary care. RESULTS: Of 189,105 forearm fracture registrations in primary and secondary care, 13,948 (7.4%) were registered exclusively in primary care. The proportion ranged from 4.9% to 13.5% on average between counties, but was higher in some municipalities (>30%). Of 66,747 primary care forearm fractures registered with a diagnosis in secondary care, 62% were incident forearm fractures, 28% follow-up controls, and 10% other fractures or non-fracture injuries. CONCLUSION: An overall small proportion of forearm fractures were registered only in primary care, but it was larger in some areas of Norway. Failing to include fractures exclusively treated in primary care could underestimate the incidence rates in these areas.

Norwegian forearm fracture incidence based on secondary care may be underestimated by not including fractures treated exclusively in primary care.The mean proportion of forearm fractures exclusively handled in primary care is 7% and varies from 5% to 14% between counties.Fractures treated in primary care can be considered for more accurate national incidence rates. Correct fracture diagnosis needs further investigation.

Provider-initiated HIV testing uptake and socio-economic status among women in a conflict zone in the Central African Republic: a mixed-methods cross-sectional study.

INTRODUCTION: In the Central African Republic (CAR), HIV/AIDS is the main cause of death in women aged 15-49 years. Increased testing coverage is essential in prevention of HIV/AIDS, especially in areas where conflict hinders access to health care. Socio-economic status (SES) has been shown to be associated with HIV testing uptake. We investigated whether "Provider-initiated HIV testing and counselling" (PITC) could be implemented in a family planning clinic in an active conflict zone in the Central African Republic to reach women of reproductive age and assessed whether socioeconomic status was associated with testing uptake. METHODS: Women aged 15-49 years were recruited from a free family planning clinic run by Médecins Sans Frontières in the capital Bangui. An asset-based measurement tool was created based on analysis of qualitative in-depth interviews. Measures of socioeconomic status were constructed from the tool, also by using factor analysis. Logistic regression was used to quantify the association between SES and HIV testing uptake (yes/no), while controlling for potential confounders: age, marital status, number of children, education level and head of household. RESULTS: A total of 1419 women were recruited during the study period, where 87.7% consented to HIV testing, and 95.5% consented to contraception use. A total of 11.9% had never been tested for HIV previously. Factors negatively associated with HIV testing uptake were: being married (OR = 0.4, 95% CI 0.3-0.5); living in a household headed by the husband as opposed to by another person (OR = 0.4, 95% CI 0.3-0.6), and lower age (OR = 0.96, 95% CI 0.93-0.99). Higher level of education (OR = 1.0, 95% CI 0.97-1.1) and having more children aged under 15 (OR = 0.92, 95% CI 0.81-1.1) was not associated with testing uptake. In multivariable regression, testing uptake was lower in the higher SES groups, but the differences were not significant (OR = 0.80, 95% CI 0.55-1.18). CONCLUSIONS: The findings show that PITC can be successfully implemented in the patient flow in a family planning clinic, without compromising contraception uptake. Within the PITC framework in a conflict setting, socioeconomic status was not found to be associated with testing uptake in women of reproductive age.

The Association of Cold Ambient Temperature With Fracture Risk and Mortality: National Data From Norway-A Norwegian Epidemiologic Osteoporosis Studies (NOREPOS) Study.

Norway is an elongated country with large variations in climate and duration of winter season. It is also a high-risk country for osteoporotic fractures, in particular hip fractures, which cause high mortality. Although most hip fractures occur indoors, there is a higher incidence of both forearm and hip fractures during wintertime, compared with summertime. In a nationwide longitudinal cohort study, we investigated whether cold ambient (outdoor) temperatures could be an underlying cause of this high incidence and mortality. Hospitalized/outpatient forearm fractures (International Classification of Diseases and Related Health Problems, 10th Revision [ICD-10] code S52) and hospitalized hip fractures (ICD-10 codes S72.0-S72.2) from 2008 to 2018 were retrieved from the Norwegian Patient Registry. Average monthly ambient temperatures (degrees Celsius, °C) from the years 2008 to 2018 were provided by the Norwegian Meteorological Institute and linked to the residential area of each inhabitant. Poisson models were fitted to estimate the association (incidence rate ratios [IRRs], 95% confidence intervals [CIs]) between temperature and monthly incidence of total number of forearm and hip fractures. Flexible parametric survival models (hazard ratios [HR], 95% CI) were used to estimate the association between temperature and post-hip fracture mortality, taking the population mortality into account. Monthly temperature ranged from -20.2°C to 22.0°C, with a median of -2.0°C in winter and 14.4°C in summer. At low temperatures (<0°C) compared to ≥0°C, there was a 53% higher risk of forearm fracture (95% CI, 51%-55%) and 21% higher risk of hip fracture (95% CI, 19%-22%), adjusting for age, gender, calendar year, urbanization, residential region, elevation, and coastal proximity. When taking the population mortality into account, the post-hip fracture mortality in both men (HR 1.08; 95% CI, 1.02-1.13) and women (HR 1.09; 95% CI, 1.04-1.14) was still higher at cold temperatures. There was a higher risk of forearm and hip fractures, and an excess post-hip fracture mortality at cold ambient temperatures. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Increased Mortality in Hip Fracture Patients Living Alone: A NOREPOS Study.

Hip fracture is associated with excess mortality, persisting for many years after the fracture. Several factors may affect survival; however, the role of social support has been less studied. Living situation could be an indicator of a person's social support, which predicts mortality in the general population. In this longitudinal cohort study, we considered whether living alone was a risk factor for post-hip fracture mortality compared with living with a partner. Information on hip fractures from all hospitals in Norway from 2002 to 2013 was combined with the 2001 National Population and Housing Census. The association between living situation and mortality during 12.8 years of follow-up in 12,770 men and 22,067 women aged 50 to 79 years at fracture was investigated using flexible parametric survival analysis. We also estimated relative survival of hip fracture patients compared with that of the non-fractured background population in the same living situation (alone or with a partner). Higher mortality after hip fracture was found in both men and women living alone versus with a partner (hazard ratio [HR] men = 1.37, 95% confidence interval [CI] 1.29-1.44; HR women = 1.23, 95% CI 1.18-1.28, adjusting for age, education level, urbanization degree, and number of children). We demonstrated the strongest association in male hip fracture patients aged <60 years (long-term mortality HR = 3.29, 95% CI 2.25-6.49). Compared with the general population, relative survival 8 years after a hip fracture was 43% in men and 61% in women living alone, whereas relative survival in those living with a partner was 51% in men and 67% in women. In conclusion, hip fracture patients who lived alone had higher mortality than those living with a partner and lower survival relative to the general population. © 2021 American Society for Bone and Mineral Research (ASBMR).

Serum Lipid Profile and Its Association with Diabetes and Prediabetes in a Rural Bangladeshi Population.

Dyslipidemia is commonly associated with diabetes (T2DM). This has been demonstrated for the Caucasian population, but few data are available for Asian Indians. The paper aims to investigate serum lipids (separately or in combination) and their association with glucose intolerance status (T2DM and prediabetes) in a rural Bangladeshi population. A sample of 2293 adults (≥20 years) were included in a community based cross-sectional survey in 2009. Anthropometric measures, blood pressure, blood glucose (fasting and 2-h oral glucose tolerance test) and fasting serum lipids (total cholesterol, T-Chol; triglycerides, Tg; low density lipoprotein cholesterol, LDL-C and high density lipoprotein cholesterol, HDL-C) were registered. Analysis of covariance (ANCOVA) and regression analysis were performed. High Tg levels were seen in 26% to 64% of the participants, depending on glucose tolerance status. Low HDL-C levels were seen in all groups (>90%). Significant linear trends were observed for high T-Chol, high Tg and low HDL-C with increasing glucose intolerance (p for trend <0.001). T2DM was significantly associated with high T-Chol (Odds ratio (OR): 2.43, p < 0.001), high Tg (OR: 3.91, p < 0.001) and low HDL-C (OR: 2.17, p = 0.044). Prediabetes showed a significant association with high Tg (OR: 1.96, p < 0.001) and low HDL-C (OR: 2.93, p = 0.011). Participants with combined high Tg and low HDL-C levels had a 12.75-fold higher OR for T2DM and 4.89 OR for prediabetes. In Asian Indian populations an assessment of serum lipids is warranted not only for T2DM patients, but also for those with prediabetes.

Population data on calcium in drinking water and hip fracture: An association may depend on other minerals in water. A NOREPOS study.

BACKGROUND: The Norwegian population has among the highest hip fracture rates in the world. The incidence varies geographically, also within Norway. Calcium in drinking water has been found to be beneficially associated with bone health in some studies, but not in all. In most previous studies, other minerals in water have not been taken into account. Trace minerals, for which drinking water can be an important source and even fulfill the daily nutritional requirement, could act as effect-modifiers in the association between calcium and hip fracture risk. The aim of the present study was to investigate the association between calcium in drinking water and hip fracture, and whether other water minerals modified this association. MATERIALS AND METHODS: A survey of trace metals in 429 waterworks, supplying 64% of the population in Norway, was linked geographically to the home addresses of patients with incident hip fractures (1994-2000). Drinking water mineral concentrations were divided into "low" (below and equal waterworks average) and "high" (above waterworks average). Poisson regression models were fitted, and all incidence rate ratios (IRRs) were adjusted for age, geographic region, urbanization degree, type of water source, and pH of the water. Effect modifications were examined by stratification, and interactions between calcium and magnesium, copper, zinc, iron and manganese were tested both on the multiplicative and the additive scale. Analyses were stratified on gender. RESULTS: Among those supplied from the 429 waterworks (2,110,916 person-years in men and 2,397,217 person-years in women), 5433 men and 13,493 women aged 50-85 years suffered a hip fracture during 1994-2000. Compared to low calcium in drinking water, a high level was associated with a 15% lower hip fracture risk in men (IRR=0.85, 95% CI: 0.78, 0.91) but no significant difference was found in women (IRR=0.98, 95%CI: 0.93-1.02). There was interaction between calcium and copper on hip fracture risk in men (p=0.051); the association between calcium and hip fracture risk was stronger when the copper concentration in water was high (IRR=0.52, 95% CI: 0.35, 0.78) as opposed to when it was low (IRR=0.88, 95% CI: 0.81, 0.94). This pattern persisted also after including potential confounding factors and other minerals in the model. No similar variation in risk was found in women. CONCLUSION: In this large, prospective population study covering two thirds of the Norwegian population and comprising 19,000 hip fractures, we found an inverse association between calcium in drinking water and hip fracture risk in men. The association was stronger when the copper concentration in the water was high.

Do cadmium, lead, and aluminum in drinking water increase the risk of hip fractures? A NOREPOS study.

The aim of this study was to investigate relations between cadmium, lead, and aluminum in municipality drinking water and the incidence of hip fractures in the Norwegian population. A trace metals survey in 566 waterworks was linked geographically to hip fractures from hospitals throughout the country (1994-2000). In all those supplied from these waterworks, 5,438 men and 13,629 women aged 50-85 years suffered a hip fracture. Poisson regression models were fitted, adjusting for age, region of residence, urbanization, and type of water source as well as other possibly bone-related water quality factors. Effect modification by background variables and interactions between water quality factors were examined (correcting for false discovery rate). Men exposed to a relatively high concentration of cadmium (IRR = 1.10; 95 % CI 1.01, 1.20) had an increased risk of fracture. The association between relatively high lead and hip fracture risk was significant in the oldest age group (66-85 years) for both men (IRR = 1.11; 95 % CI 1.02, 1.21) and women (IRR = 1.10; 95 % CI 1.04, 1.16). Effect modification by degree of urbanization on hip fracture risk in men was also found for all three metals: cadmium, lead, and aluminum. In summary, a relatively high concentration of cadmium, lead, and aluminum measured in drinking water increased the risk of hip fractures, but the associations depended on gender, age, and urbanization degree. This study could help in elucidating the complex effects on bone health by risk factors found in the environment.

Nationwide data on municipal drinking water and hip fracture: could calcium and magnesium be protective? A NOREPOS study.

Norway has a high incidence of hip fractures, and the incidence varies by degree of urbanization. This variation may reflect a difference in underlying environmental factors, perhaps variations in the concentration of calcium and magnesium in municipal drinking water. A trace metal survey (1986-1991) in 556 waterworks (supplying 64% of the Norwegian population) was linked geographically to hip fractures from hospitals throughout the country (1994-2000). In all, 5472 men and 13,604 women aged 50-85years suffered a hip fracture. Poisson regression models were fitted, adjusting for age, urbanization degree, region of residence, type of water source, and pH. The concentrations of calcium and magnesium in drinking water were generally low. An inverse association was found between concentration of magnesium and risk of hip fracture in both genders (IRR men highest vs. lowest tertile=0.80, 95% CI: 0.74, 0.87; IRR women highest vs. lowest tertile=0.90, 95% CI: 0.85, 0.95), but no consistent association between calcium and hip fracture risk was observed. The highest tertile of urbanization degree (city), compared to the lowest (rural), was related to a 23 and 24% increase in hip fracture risk in men and women, respectively. The association between magnesium and hip fracture did not explain the variation in hip fracture risk between city and rural areas. Magnesium in drinking water may have a protective role against hip fractures; however this association should be further investigated.

Lifestyle impact on lifetime bone loss in women and men: the Tromsø Study.

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

Effect of hyperglycemic condition on proteoglycan secretion in cultured human endothelial cells.

BACKGROUND: Proteoglycans (PGs) are important constituents of the plasma membrane and of the basement membrane supporting the endothelial cell layer. Changes in the amounts or the structures of PGs in the endothelium may affect important functions such as turnover of lipoproteins, filtration properties, and regulation of chemokines during inflammation, which are all relevant in diabetes. AIM OF THE STUDY: The purpose of this study was to investigate if hyperglycemic conditions would affect the biosynthesis and secretion of PGs in cultured primary human endothelial cells. METHODS: Primary human umbilical cord vein endothelial cells were established and cultured in vitro. The cells were cultured either in medium with low glucose (LG) (1 g/l) or high glucose (HG) (4.5 g/l). From day 3-4 cells were labeled with (35)S-sulfate for 24 h. (35)S-Labeled macromolecules (medium) were purified by gel chromatography, and isolated macromolecules were analyzed by gel chromatography after different types of treatment, electrophoresis, and immunoprecipitation. RESULTS: Lower levels of secreted PGs were found in human endothelial cells exposed to HG. The major part of the PGs released was of the heparan sulfate (HS) type, and immunoprecipitation experiments showed that one such PG was syndecan-1. However, there was no difference in the ratio between HS and chondroitin sulfate (CS) under the different experimental conditions. Further, the PGs expressed neither differ with regard to molecular size of the glycosaminoglycan (GAG) chains, nor were their polyanionic properties affected by the different experimental conditions. CONCLUSION: The results obtained suggest that treatment of primary human endothelial cells with hyperglycemia leads to a decrease in PG secretion in primary cultures of human endothelial cells.

[Advanced glycation end products and hyperglycaemia]. / Avanserte glykerte endeprodukter og hyperglykemi.

Hyperglycaemia leads to increased formation and accumulation of advanced glycation end products, and these molecules play an important role in the development of micro- and macrovascular complications in diabetes. The formation of advanced glycation end products are complex reactions that take place both intra- and extracellularly. Advanced glycation end products affect gene regulation by binding to receptors, but can also modify proteins, DNA and lipids directly. The amount in serum and tissues depends upon several factors. The extent of hyperglycaemia is the main determining factor for levels of glycation products in the body, but the ability to break down and excrete these products in the urine is also important. The most effective way of preventing late complications in diabetes caused by glycation products is strict regulation of blood sugar levels. Drugs that inhibit advanced glycation end products could potentially be important in the prevention of late complications in diabetes, but this needs further investigation.