Early intervention with probiotics and metformin alleviates liver injury in NAFLD rats via targeting gut microbiota dysbiosis and p-AKT/mTOR/LC-3II pathways.

Non-alcoholic fatty liver disease (NAFLD) constitutes a major health problem worldwide and intimately links with obesity and diabetes. This study aimed to explore the therapeutic impact of early treatment with metformin (MTF) alone or in combination with Lactobacillus reuteri DSM 17938 (L. reuteri) + metronidazole (MTZ) in male Sprague Dawley rats with high-fat diet (HFD)-induced NAFLD. Hepatic steatosis was induced by feeding rats HFD for 6 weeks. MTF (150 mg/kg/day) or L. reuteri (2 × 109 colony forming unit/day) were given orally for 4 weeks; meanwhile, MTZ (15 mg/kg/day, p.o.) was administered for 1 week. Administration of L. reuteri + MTZ in combination with MTF produced a superior effect concerning insulin resistance (IR), lipid profile, liver function, oxidative stress, inflammatory and autophagic markers than using each treatment alone. Besides, this combination resulted in disappearance of steatosis, inflammation and vacuolation within hepatic architecture. Moreover, it normalized short chain fatty acids (SCFAs) as well as Firmicutes and Bacteroidetes faecal contents. In conclusion, early treatment with L. reuteri + MTZ in combination with MTF could prevent NAFLD progression and liver injury through targeting gut dysbiosis, inflammation and autophagic pathways.

Delayed-onset paraparesis in Lassa fever: A case report.

Lassa fever (LF) is an endemic viral hemorrhagic fever in West Africa. Among the serious complications of the disease are neurological manifestations whose spectrum is incompletely known. Here we report the case of a 61-year-old man who developed a delayed-onset paraparesis a few weeks after getting infected with Lassa virus, thereby suggesting a possible association between LF and spinal cord disorders.

Impact of osteoporotic fracture type and subsequent fracture on mortality: the Tromsø Study.

Less is known about the impact of non-hip non-vertebral fractures (NHNV) on early death. This study demonstrated increased risk of dying following hip and NHNV fractures which was further increased by a subsequent fracture. This highlights the importance of early intervention to prevent both initial and subsequent fractures and improve survival. INTRODUCTION: Osteoporotic fractures are a major health concern. Limited evidence exists on their impact on mortality in ageing populations. This study examined the contribution of initial fracture type and subsequent fracture on mortality in a Norwegian population that has one of the highest rates of fractures. METHODS: The Tromsø Study is a prospective population-based cohort in Norway. Women and men aged 50+ years were followed from 1994 to 2010. All incident hip and non-hip non-vertebral (NHNV) fractures were registered. NHNV fractures were classified as either proximal or distal. Information on self-reported co-morbidities, lifestyle factors, general health and education level was collected. Multivariable Cox models were used to quantify mortality risk with incident and subsequent fractures analysed as time-dependent variables. RESULTS: Of 5214 women and 4620 men, 1549 (30%) and 504 (11%) sustained a fracture, followed by 589 (38%) and 254 (51%) deaths over 10,523 and 2821 person-years, respectively. There were 403 (26%) subsequent fractures in women and 68 (13%) in men. Hip fracture was associated with a two-fold increase in mortality risk (HR 2.05, 95% CI 1.73-2.42 in women and 2.49, 95% CI 2.00-3.11 in men). Proximal NHNV fractures were associated with 49% and 81% increased mortality risk in women and men (HR 1.49, 95% CI 1.21-1.84 and 1.81, 95% CI 1.37-2.41), respectively. Distal NHNV fractures were not associated with mortality. Subsequent fracture was associated with 89% and 77% increased mortality risk in women and men (HR 1.89, 95% CI 1.52-2.35 and 1.77, 95% CI 1.16-2.71), respectively. CONCLUSION: Hip, proximal NHNV and subsequent fractures were significantly associated with increased mortality risk in the elderly, highlighting the importance of early intervention.

The association between childhood fractures and adolescence bone outcomes: a population-based study, the Tromsø Study, Fit Futures.

Childhood fracture may predict persistent skeletal fragility, but it may also reflect high physical activity which is beneficial to bone development. We observe a difference in the relationship between previous fracture and bone outcome across physical activity level and sex. Further elaboration on this variation is needed. PURPOSE: Childhood fracture may be an early marker of skeletal fragility, or increased levels of physical activity (PA), which are beneficial for bone mineral accrual. This study investigated the association between a previous history of childhood fracture and adolescent bone mineral outcomes by various PA levels. METHODS: We recruited 469 girls and 492 boys aged 15-18 years to this study. We assessed PA levels by questionnaire and measured areal bone mineral density (aBMD) and bone mineral content (BMC) using dual-energy X-ray absorptiometry (DXA) at arm, femoral neck (FN), total hip (TH), and total body (TB) and calculated bone mineral apparent density (BMAD, g/cm3). Fractures from birth to time of DXA measurements were retrospectively recorded. We analyzed differences among participants with and without fractures using independent sample t test. Multiple linear regression was used to examine the association between fractures and aBMD and BMC measurements according to adolescent PA. RESULTS: Girls with and without a previous history of fracture had similar BMC, aBMD, and BMAD at all sites. In multiple regression analyses stratified by physical activity intensity (PAi), there was a significant negative association between fracture and aBMD-TH and BMC-FN yet only in girls reporting low PAi. There was a significant negative association between forearm fractures, BMAD-FN, and BMAD-arm among vigorously active boys. CONCLUSION: Our findings indicate a negative association between childhood fractures and aBMD/BMC in adolescent girls reporting low PAi. In boys, such an association appears only in vigorously active participants with a history of forearm fractures.

Excess mortality after hip fracture in elderly persons from Europe and the USA: the CHANCES project.

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

Measurement of cortical porosity of the proximal femur improves identification of women with nonvertebral fragility fractures.

UNLABELLED: We tested whether cortical porosity of the proximal femur measured using StrAx1.0 software provides additional information to areal bone mineral density (aBMD) or Fracture Risk Assessment Tool (FRAX) in differentiating women with and without fracture. Porosity was associated with fracture independent of aBMD and FRAX and identified additional women with fractures than by osteoporosis or FRAX thresholds. INTRODUCTION: Neither aBMD nor the FRAX captures cortical porosity, a major determinant of bone strength. We therefore tested whether combining porosity with aBMD or FRAX improves identification of women with fractures. METHODS: We quantified femoral neck (FN) aBMD using dual-energy X-ray absorptiometry, FRAX score, and femoral subtrochanteric cortical porosity using StrAx1.0 software in 211 postmenopausal women aged 54-94 years with nonvertebral fractures and 232 controls in Tromsø, Norway. Odds ratios (ORs) were calculated using logistic regression analysis. RESULTS: Women with fractures had lower FN aBMD, higher FRAX score, and higher cortical porosity than controls (all p < 0.001). Each standard deviation higher porosity was associated with fracture independent of FN aBMD (OR 1.39; 95% confidence interval 1.11-1.74) and FRAX score (OR 1.58; 1.27-1.97) in all women combined. Porosity was also associated with fracture independent of FRAX score in subgroups with normal FN aBMD (OR 1.88; 1.21-2.94), osteopenia (OR 1.40; 1.06-1.85), but not significantly in those with osteoporosis (OR 1.48; 0.68-3.23). Of the 211 fracture cases, only 18 women (9%) were identified using FN aBMD T-score < -2.5, 45 women (21%) using FRAX threshold >20%, whereas porosity >80th percentile identified 61 women (29%). Porosity identified 26% additional women with fractures than identified by the osteoporosis threshold and 21% additional women with fractures than by this FRAX threshold. CONCLUSIONS: Cortical porosity is a risk factor for fracture independent of aBMD and FRAX and improves identification of women with fracture.

Education, marital status, and risk of hip fractures in older men and women: the CHANCES project.

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

Does recalled dieting increase the risk of non-vertebral osteoporotic fractures? The Tromsø Study.

UNLABELLED: The risk of non-vertebral osteoporotic fractures increased by increasing recalled amount of weight loss when dieting in women aged ≥ 46 years and in those with BMI < 25 kg/m(2) participating in the Tromsø Study (1994/1995-2009). The increased risk was present both in women with few and several episodes of recalled dieting. INTRODUCTION: The influence of repeated dieting on bone health is uncertain. This study aims to investigate whether recalled dieting is a risk factor for non-vertebral osteoporotic fractures. METHODS: In 1994/1995 weight and height were measured in all participants aged 25-69 years in the population-based Tromsø Study. Information about socioeconomic background, diseases and lifestyle factors was collected by questionnaires-including number of recalled dieting episodes and largest amount of weight loss when dieting. The participating 20,745 women and men were followed for 15 years, fractures were registered from X-ray archives and analysed by Cox's proportional hazards models. RESULTS: Among those who recalled dieting, 975 women and 364 men suffered a non-vertebral osteoporotic fracture during follow-up. Compared to women without recalled weight loss when dieting, women who reported their largest weight loss of 11 kg or more had a hazard ratio (HR) = 1.48 (95% CI 1.13-1.94) for osteoporotic fracture, adjusted for age, marital status, body mass index, height, education, physical activity, smoking, alcohol intake, history of cardiovascular disease and psychological distress. The increased risk was statistically significant only in women aged ≥ 46 years and in those with BMI < 25 kg/m(2). Women who recalled ≥ 11 dieting episodes had HR = 1.73 (CI 1.11-2.68) for osteoporotic fracture compared to those with no recalled episodes. Dieting was not associated with risk of fractures in men, but the number of fractures was low. CONCLUSIONS: The increased risk of non-vertebral osteoporotic fractures by recalled dieting in women indicates that maintenance of a stable weight may have beneficial effects on fracture risk.

Hip fractures in a city in Northern Norway over 15 years: time trends, seasonal variation and mortality : the Harstad Injury Prevention Study.

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

BMI change is associated with fracture incidence, but only in non-smokers. The Tromsø Study.

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

Bone loss and the risk of non-vertebral fractures in women and men: the Tromsø study.

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

Features of the metabolic syndrome and the risk of non-vertebral fractures: the Tromsø study.

INTRODUCTION: We wanted to examine whether the features of the metabolic syndrome carried an increased risk of non-vertebral fracture. METHODS: This is a population-based, 6-year follow-up of 27,159 subjects from the municipality of Tromsø, followed from 1994 until 2001. Age range was 25-98 years. Non-fasting serum levels of high-density lipoprotein (HDL), triglycerides and glucose, blood pressure (BP), weight and height were measured at baseline. All non-vertebral fractures were registered by computerised search in radiographic archives. RESULTS: A total of 1,249 non-vertebral fractures were registered. Increasing number of metabolic syndrome features was associated with significantly reduced fracture risk in both men and women, p= 0.004 and p<0.0001, respectively. High BP was protective against fracture in men [relative risk (RR) 0.89; 95% confidence interval (CI) 0.8-0.99)] while increased body mass index (BMI) was protective in women (RR 0.91; 95% CI 0.84-0.98). Increasing non-fasting serum levels of HDL increased fracture risk in women (RR 1.12; 95% CI 1.05-1.21). BMI modified the effect of HDL in men. Accordingly, high HDL increased fracture risk in men with high BMI (RR 1.51; 95% CI 1.2-1.9). CONCLUSIONS: Increasing burden of metabolic syndrome features protects against non-vertebral fractures. Reduced non-vertebral fracture risk was associated with high BP in men and increased body mass in women. Lower non-fasting serum levels of HDL protect against fractures in women and obese men.