Evaluation of a Population-Based Targeted Screening Approach for Skin Cancer with Long-Time Follow-Up in Austria including Potential Effects on Melanoma Mortality.

BACKGROUND: whether screening for skin cancer affects melanoma-specific mortality in a population-based setting remains unclear. METHODS: in this population-based cohort study, we characterized and evaluated a skin cancer prevention program following a targeted screening approach conducted in 1989-1994 in the Austrian province Vorarlberg, with follow-up until 2019. The general population and attendees of a health examination program served for comparison. RESULTS: in the screening program including full follow-up until 2019, 207 invasive and 187 in situ melanomas were identified in 8997 individuals. Incidences of invasive and in situ melanomas were elevated compared to the general population (IRR 2.92, 95%-CI 2.49-3.41, and IRR 4.13, 95%-CI 3.53-4.83, respectively) and the health examination program (HR 3.02, 95%-CI 2.59-3.52, and HR 3.90, 95%-CI 3.30-4.61, respectively). Breslow thickness and Clark's level at time of invasive diagnosis were significantly lower in 1989-2019, but the tumor characteristics of the melanomas diagnosed during 1989-1994 did not differ from the comparison groups. Moreover, melanoma mortality was significantly elevated in the screening program (IRR 1.66, 95%-CI 1.00-2.75 vs. the general population, HR 2.12, 95%-CI 1.25-3.61 vs. the health examination cohort). Melanoma mortality in Vorarlberg declined until 2004, though statistically non-significantly. CONCLUSIONS: given the uncertain effectiveness and high public expenditures of population-wide mass screening programs, primary prevention and targeted risk-based skin cancer screening might be promising alternatives.

The value of earlier-in-life systolic and diastolic blood pressure for cardiovascular risk prediction.

Blood pressure (BP) varies over a lifetime. This cardiovascular observation study (OS) compared the predictive value of earlier- and later-in-life blood pressure (BP) in 1,497 cardiovascular disease patients utilizing readings taken during a health survey (HS) and 15 years later from the same subjects at the baseline of this OS. Prediction of the cardiovascular risk during the OS follow-up (21 years) was significantly more effective if the earlier BP readings at HS were used instead of recent OS readings (NRI = 0.30, p < 0.001). For HS readings, each 10 mm Hg increase of systolic and diastolic BP was associated with a 17% and 20% higher risk, respectively. At OS, systolic BP lost significance and diastolic BP reversed its association. Noteworthy, different BP categorizations (European vs. US guidelines) yielded similar results. This study highlights the poor predictive power of BP readings in elderly cardiovascular disease patients but emphasizes the significant prognostic value of earlier-in-life BP.

The Association of Excess Body Weight with Risk of ESKD Is Mediated Through Insulin Resistance, Hypertension, and Hyperuricemia.

BACKGROUND: Insulin resistance, hypertension, hyperuricemia, and hypercholesterolemia are hypothesized to be important intermediates in the relationship between excess body weight and CKD risk. However, the magnitude of the total effect of excess body weight on ESKD mediated through these four pathways remains to be quantified. METHODS: We applied a model for analysis of correlated mediators to population-based data from 100,269 Austrian individuals (mean age 46.4 years). Association of body mass index (BMI) was coalesced with ESKD risk into direct association. Indirect associations were mediated through the triglyceride-glucose (TyG) index (as an indicator of insulin resistance), mean arterial pressure (MAP), uric acid (UA), and total cholesterol (TC). RESULTS: Mean follow-up was 23.1 years with 463 (0.5%) incident ESKD cases. An unhealthy metabolic profile (prevalence 32.4%) was associated with a markedly increased ESKD risk (multivariably adjusted hazard ratio (aHR), 3.57; 95% CI, 2.89 to 4.40), independent of BMI. A 5-kg/m2 higher BMI was associated with a 57% increased ESKD risk (aHRtotal association, 1.57; 1.38 to 1.77). Of this association, 99% (76% to 140%) arose from all mediators jointly; 33% (22% to 49%) through TyG index; 34% (24% to 50%) through MAP; 30% (21% to 45%) through UA; and 2% (-1% to 4%) through TC. The remaining direct association was nonsignificant (aHRdirect association, 1.01; 0.88 to 1.14). CONCLUSIONS: TyG index, MAP, and UA, but not TC, mediate the association of BMI with ESKD in middle-aged adults. Our findings highlight that in addition to weight reduction, the control of metabolic risk factors might be essential in mitigating the adverse effects of BMI on kidney function.

Thirty years of hip fracture incidence in Austria: is the worst over?

Nationwide hip fracture incidence in the Austrian population was assessed over a period of 30 years (1989-2018), including 20 years data from a previous study and a recent 10 years follow-up. While absolute numbers in men continued to increase, absolute numbers in women and age-standardized incidences in both men and women decreased. PURPOSE: In the Austrian population ≥ 50 years, nationwide hip fracture incidences over a period of 20 years (1989-2008) have shown an initial steep increase, followed by a leveling-off during the last few years of observation. The purpose of the present study was to follow up on hip fracture incidences for another 10 years (2009-2018) and to analyze trends over the entire period of 30 years. METHODS: ICD-10 code classes S72.0, S72.1, and S72.2 were applied. All data were retrieved from the Statistics Austria database and its hospital discharge register. Annual absolute numbers, crude and age-standardized incidences, and incidence rate ratios (IRR) were stratified by sex and 5-year age intervals, and calculated by using a correction factor for multiple registrations. RESULTS: Total number of hip fracture cases increased from 13,984 (2009) to 14,640 (2015), and decreased thereafter to 14,457 (2018), despite a persistent increase in men. Age-standardized incidences peaked at 476/100,000 (2010), followed by a decrease to 408/100,000 (2018). The observed overall decrease was mainly driven by the female population. Incidence rate ratios (IRRs) yielded a statistically significant average annual decrease of age-standardized incidences in both women and men (∆IRR 0.984; 0.981-0.987). CONCLUSION: While absolute numbers of hip fracture in women showed a slight decrease during the last 10 years of observation, numbers in men continued to increase. Age-standardized incidences nevertheless decreased in both men and women, which may be interpreted as a trend in the right direction. However, due to the rapid aging of the population, it cannot be precluded that this trend will be compromised during the next few decades.

Value of total cholesterol readings earlier versus later in life to predict cardiovascular risk.

BACKGROUND: Prognostic implications of blood cholesterol may differ at different stages of life. This cohort study compares the value of total cholesterol (TC) readings earlier versus later in life for the prediction of coronary atherosclerosis, cardiovascular events, and cardiovascular death. METHODS: In a cardiovascular observation study (CVOS) we performed coronary angiography and prospectively recorded cardiovascular events in 1090 patients over up to 19 years. These patients had participated in a health survey (HS) 15 years prior to the CVOS baseline. TC was measured twice, first at the earlier HS and then later at CVOS recruiting. FINDINGS: Patients in the highest versus the lowest TC-category of the HS had an OR of 4.30 [2.41-7.65] for significant CAD at angiography, a HR of 1.74 [1.10-2.76] for cardiovascular events, and a HR of 7.55 [1.05-54.49] for cardiovascular death after multivariate adjustment. In contrast, TC as measured at the baseline of the CVOS was neither significantly associated with significant CAD (OR= 0.75 [0.49-1.13]) nor with cardiovascular events or death during follow-up (HR= 0.86 [0.62-1.18] and 0.79 [0.41-1.53], respectively). Moreover, the ESC/EAS-SCORE was found to be more powerful in predicting cardiovascular mortality when using earlier instead of later TC, with a continuous net reclassification improvement of 0.301 (p<0.001). INTERPRETATION: Early measurement not only enables early intervention in keeping with the concept of lifelong exposure to atherogenic lipoproteins. These data also suggest that cardiovascular risk prediction is more accurate if using earlier in life TC readings. FUNDING: The present study did not receive any particular funding.

Serum uric acid is associated with incident hip fractures in women and men - Results from a large Austrian population-based cohort study.

OBJECTIVES: Serum markers that can be used to estimate the risk of bone fractures are rare, and findings for one candidate marker, uric acid, are heterogeneous. Our aim was to investigate the potential of serum uric acid (SUA) to predict hip fractures occurring in people aged 50 years and over. STUDY DESIGN: During a medical prevention program over the period 1985-2005 in Vorarlberg, baseline data were collected on SUA levels and covariates (age, BMI, blood pressure, smoking status, diabetes, triglycerides and cholesterol) from 185,397 individuals, of whom 42,488 women and 35,908 men met the inclusion criteria of this population-based cohort study. Information on incident cancer and end-stage kidney disease was acquired from registries. MAIN OUTCOME MEASURE: Incident hip fracture occurring in participants aged 50 years and over during the observation period 2003-2013. RESULTS: SUA was associated with a rise in female hip fracture risk by 6% per unit increase (HR 1.06, 95 %-CI 1.01-1.10), and risk in the highest vs. lowest SUA quartile was significantly increased (HR 1.17, 95 %-CI 1.01-1.35), but not at hyperuricemic (>5.7 mg/dl) vs. normouricemic (≤5.7 mg/dl) levels. In men, hip fracture risk rose by 15 % per unit increase (HR 1.15, 95 %-CI 1.08-1.22), and risk was significantly higher in the highest vs. lowest SUA quartile (HR 1.50, 95 %-CI 1.17-1.91) as well as at hyperuricemic (>7.0 mg/dl) vs. normouricemic (≤7.0 mg/dl) levels (HR 1.48, 95 %-CI 1.19-1.84). CONCLUSIONS: Our results link SUA with increased risk of hip fractures, particularly in men.

The Triglyceride-Glucose Index and Obesity-Related Risk of End-Stage Kidney Disease in Austrian Adults.

Importance: It is unknown whether the triglyceride-glucose (TyG) index as a measure of insulin resistance is associated with the risk of developing end-stage kidney disease (ESKD). Because individuals who are overweight or obese often develop insulin resistance, mediation of the association between body mass index (BMI) and ESKD risk through the TyG index seems plausible but has not been investigated. Objective: To evaluate whether the TyG index is associated with ESKD risk and, if so, to what extent the TyG index mediates the association between BMI and ESKD. Design, Setting, and Participants: A total of 176 420 individuals were recruited during routine health examinations to participate in the Austrian Vorarlberg Health Monitoring and Promotion Program (VHM&PP), a prospective, population-based cohort study with participant enrollment between January 1, 1988, and June 30, 2005, and a mean follow-up of 22.7 years. Data analysis was conducted from March 1, 2020, to September 30, 2020. Exposures: Body mass index and the logarithmized product of fasting triglyceride and glucose concentrations (TyG index), as determined during the baseline health examination. Main Outcomes and Measures: End-stage kidney disease, as indicated by initiation of kidney replacement therapy, either dialysis or kidney transplantation. Results: Of the 176 420 participants, 94 885 were women (53.8%); mean (SD) age was 42.5 (15.4) years. During a mean (SD) follow-up of 22.7 (6.9) years, 454 (0.3%) participants developed ESKD and 35 234 (20.0%) died. In multivariable-adjusted Cox proportional hazards models, the TyG index was significantly associated with the risk of ESKD, both with (hazard ratio [HR] per 1-SD increase, 1.68; 95% CI, 1.56-1.82) and without (HR per 1-SD increase, 1.79; 95% CI, 1.66-1.93) the inclusion of BMI as a covariate. Mediation analysis using a newly proposed 2-stage regression method for survival data showed that a 5-point increase in BMI increased the risk of ESKD by 58% (HR [total association], 1.58; 95% CI, 1.43-1.75), and that 41.7% of the total association (95% CI, 31.6%-51.8%) was mediated through the TyG index (HR [indirect association], 1.21; 95% CI, 1.18-1.25). Conclusions and Relevance: This study found that the TyG index appeared to be associated with ESKD risk and mediates nearly half of the total association between BMI and ESKD in the general population. Public health efforts aiming at the reduction of body weight might decrease the kidney sequelae of insulin resistance and the burden of ESKD.

Mineral and organic matrix composition at bone forming surfaces in postmenopausal women with osteoporosis treated with either teriparatide or zoledronic acid.

The ability of bone to resist fracture is dependent on the composite nature of its mineral and organic matrix content. Teriparatide (TPTD) and zoledronic acid (ZOL) are approved anabolic and antiresorptive therapies, respectively, to reduce fracture risk in women with postmenopausal osteoporosis. In the SHOTZ study, postmenopausal women with osteoporosis were treated with TPTD (20 µg daily, subcutaneous) or ZOL (5 mg/year, intravenous infusion) for 24 months. Iliac crest biopsies were obtained at 6 months and again at 24 months from approximately one third of the original study cohort. To investigate the early effects of these two drugs on the quality of newly formed bone, we used vibrational spectroscopic techniques to analyze tetracycline-labelled transiliac biopsies obtained from participants at the 6-month time point. Raman spectra were acquired at forming trabecular and intra-cortical surfaces (identified by fluorescent double labels), to determine mineral, organic matrix, glycosaminoglycan, and tissue water content, as well as mineral maturity/crystallinity at three specific tissue ages (1-5, 15, and ≥25 days). Fourier transformed infrared microspectroscopy was used to determine pyridinoline/divalent collagen cross-link ratios. At 6 months, treatment with TPTD versus ZOL resulted in lower mineral and higher organic matrix content, increased tissue water content, and lower mineral/matrix, mineral maturity/crystallinity, glycosaminoglycan content, and pyridinoline/divalent enzymatic collagen cross-link ratio. Our results suggest that TPTD and ZOL have differential effects on material properties of newly formed bone at individual remodeling sites, highlighting their different mechanisms of action.

Metabolic factors and hip fracture risk in a large Austrian cohort study.

To explore the association of incident hip fractures with metabolic syndrome (MetS) and its single components, we designed a prospective cohort study of hip fracture incidence among 117,053 participants of a population-based health surveillance program in Vorarlberg, the westernmost Austrian province. Incident hip fractures were recorded between 5 and 10 years after inclusion at baseline from 2003 to 2009. Applying Cox proportional hazard models for each MetS component and for a composite z-score for MetS, hazards for fracture were estimated in quintiles, as continuous z-score variables, and as pathological cut off values. Mean age was 50.1 ± 15.6 years at baseline, 5-10 years after which 947 incident hip fractures occurred. An association of a higher composite MetS score with decreased hip fracture risk was observed in women (HR 0.80, 95%-CI 0.88-0.96, p < 0.01) which disappeared upon adjustment for BMI. BMI was inversely associated with hip fracture risk in women and men (HR for the highest compared with the lowest quintile: 0.83 (95%-CI: 0.63-1.10, p trend < 0.05) and 0.55 (95%-CI: 0.38-0.79, p trend < 0.001), respectively). Only in women, hip fracture risk was reduced at high cholesterol levels (HR for the highest relative to the lowest quintile: 0.64, 95%-CI: 0.48-0.84, p trend < 0.05) and in hypercholesterolemic patients (HR 0.82, 95%-CI: 0.67-0.99, p < 0.05), but elevated in hyperglycemic patients (HR 1.33, 95%-CI: 1.05-1.70, p < 0.05). Hypertriglyceridemia was associated with increased male hip fracture risk (HR 1.33, 95%-CI: 1.03-1.72, p < 0.05). The inverse association between the MetS and hip fracture risk is mainly driven by one single component, namely BMI.

Vascular cell adhesion molecule 1 in patients with severe osteoarthritis of the hip : A prospective cross-sectional study.

BACKGROUND: Osteoarthritis (OA) of the hip is a frequent and debilitating joint disease. Only few clinical risk factors for hip OA are established and clinically applicable biomarkers to identify patients at risk are still lacking. The glycoprotein vascular cell adhesion molecule 1 (VCAM-1) is expressed by chondrocytes and synovial tissue and was a predictive marker for development of severe large joint OA in a previous study. OBJECTIVE: It was tested whether increased serum levels of VCAM-1 are prevalent in patients with severe OA of the hips. METHODS: In this prospective, multicenter, cross-sectional study, risk factors of severe hip OA were investigated in patients scheduled for hip joint arthroplasty and 100 patients were randomly selected for validation of VCAM-1 as a potential biomarker for hip OA. Serum samples were analyzed by an enzyme-linked immunosorbent assay and compared with a sex and age-matched control cohort. RESULTS: The groups were similar in age, gender ratio and prevalence of diabetes. Serum concentrations of VCAM-1 were 8% higher in OA patients compared to controls, without reaching statistical significance (818 ng ml-1, 95% confidence interval, CI 746-891 ng ml-1 versus 759 ng m-1, 95% CI 711-807 ng ml-1; P = 0.4839). CONCLUSION: The results of this study show that serum concentrations of VCAM-1 cannot distinguish patients with severe hip OA from age and sex-matched controls.

Higher dose but not low dose proton pump inhibitors are associated with increased risk of subsequent hip fractures after first hip fracture: A nationwide observational cohort study.

AIM: To examine the association of proton pump inhibitor (PPI) use with subsequent hip fracture incidence in hip fracture patients, accounting for gender, age, PPI doses, PPI initiation before or after first fracture, and year from first fracture in which the first subsequent fracture occurred. METHODS: Data from 31,668 Austrian patients ≥50 years with the first hip fracture between July 2008 and December 2010 were analyzed retrospectively. After exclusion of patients on anti-osteoporotic medication, incidence of subsequent hip fractures was compared between users and non-users of PPIs using regression models. RESULTS: In general, use of PPIs among hip fracture patients was associated with increased risk for subsequent hip fracture (OR 1.58, 95%-CI 1.25-2.00), in particular in men, in the age group of 70-84 years, and when PPIs were initiated before the first fracture. Low PPI doses of ≤90 cumulative DDDs and ≤0.25 DDDs/day, however, were not linked to elevated subsequent fracture risk, especially among female patients. Subsequent hip fracture incidence was elevated within the first year after first fracture in female and male PPI users (OR 1.75, 95%-CI 1.28-2.38) and dropped in women but not in men in the second year. CONCLUSIONS: Low-dose PPI use is not associated with increased risk of subsequent hip fractures, especially in women. Patients thus get most benefit of short-term PPI use after a hip fracture that has previously been linked to lowered mortality if low doses are not exceeded. Varying risk profiles for the time of subsequent hip fracture could have implications for risk group-specific follow-up care.

Bone Mineral Density and Breast Cancer Incidence and Mortality in Postmenopausal Women: A Long-Term Follow-Up Study.

Purpose: To examine whether bone mineral density (BMD) is predictive of breast cancer risk and mortality in a population of early postmenopausal women participating in a medical prevention program in western Austria. Patients and Methods: Between May 1991 and February 1999, lumbar spine BMD was measured by dual-energy X-ray absorptiometry (N = 1163, mean age 56.9 ± 5.7 years) or quantitative computed tomography (N = 2283, mean age 56.8 ± 5.4 years) in 3446 women aged ≥50 years. Data on medication and lifestyle factors were collected by questionnaire. Participants were prospectively followed up for breast cancer incidence, and breast cancer patients were followed up for mortality. To calculate risk of breast cancer and mortality, Cox proportional hazards models were applied. Results: During median follow-up of 20.7 years, 185 invasive breast cancer cases and 22 deaths due to breast cancer occurred. Risk of breast cancer in the highest versus the lowest BMD quartile was nonsignificantly reduced, in particular when follow-up was restricted to 10 years (hazard ratio 0.53, 95% confidence interval 0.25-1.12). There was no risk reduction when follow-up began 10 years after BMD measurement. There was no association between BMD and all-cause or breast cancer-specific mortality among breast cancer patients, but a trend toward reduced mortality risk in the highest BMD quartile. Conclusions: We hypothesize that BMD is not reflective of estrogen exposure and not predictive of breast cancer risk, at least in young postmenopausal women. Confounders such as vitamin D might underlie low breast cancer risk at high BMD, thus mirroring better health status.

HFE hemochromatosis screening in patients with severe hip osteoarthritis: A prospective cross-sectional study.

OBJECTIVE: Despite the high frequency of HFE gene mutations in Western Europe, widespread screening for HFE hemochromatosis is not recommended due to its variable phenotype. Joint pain and a premature osteoarthritis-like disease including the hip joints are the most frequent manifestation in patients with HFE hemochromatosis and iron overload. Therefore, screening of patients with severe osteoarthritis of the hip could identify patients with HFE hemochromatosis. METHODS: In this prospective cross-sectional study, 940 patients aged <70 years with end-stage osteoarthritis of the hip undergoing elective joint replacement surgery were screened for HFE hemochromatosis and compared to age- and sex-matched controls. RESULTS: No greater prevalence of C282Y homozygosity mutation or elevated serum ferritin or transferrin saturation levels was found in the study cohort with severe osteoarthritis of the hip than in controls from the general population. CONCLUSION: Our screening approach could not identify an increased prevalence of HFE gene mutations and iron overload in younger patients with severe osteoarthritis of the hip.

A randomized controlled trial-based algorithm for insulin-pump therapy in hyperglycemic patients early after kidney transplantation.

Treating hyperglycemia in previously non-diabetic individuals with exogenous insulin immediately after kidney transplantation reduced the odds of developing Posttransplantation Diabetes Mellitus (PTDM) in our previous proof-of-concept clinical trial. We hypothesized that insulin-pump therapy with maximal insulin dosage during the afternoon would improve glycemic control compared to basal insulin and standard-of-care. In a multi-center, randomized, controlled trial testing insulin isophane for PTDM prevention, we added a third study arm applying continuous subcutaneous insulin lispro infusion (CSII) treatment. CSII was initiated in 24 patients aged 55±12 years, without diabetes history, receiving tacrolimus. The mean daily insulin lispro dose was 9.2±5.2 IU. 2.3±1.1% of the total insulin dose were administered between 00:00 and 6:00, 19.5±11.6% between 6:00 and 12:00, 62.3±15.6% between 12:00 and 18:00 and 15.9±9.1% between 18:00 and 24:00. Additional bolus injections were necessary in five patients. Mild hypoglycemia (52-60 mg/dL) occurred in two patients. During the first post-operative week glucose control in CSII patients was overall superior compared to standard-of-care as well as once-daily insulin isophane for fasting and post-supper glucose. We present an algorithm for CSII treatment in kidney transplant recipients, demonstrating similar safety and superior short-term efficacy compared to standard-of-care and once-daily insulin isophane.

Hip fracture incidence 2003-2013 and projected cases until 2050 in Austria: a population-based study.

OBJECTIVES: Elevated hip fracture incidence is a major public health problem looming to aggravate in industrialized countries due to demographic developments. We report hip fracture incidence and expected future cases from Vorarlberg, the westernmost province of Austria, results potentially representative of Central European populations. METHODS: Crude and standardized hip fracture incidence rates in Vorarlberg 2003-2013 are reported. Based on the age-specific incidence in 2013 or trends 2003-2013, we predict hip fractures till 2050. RESULTS: Female age-standardized hip fracture incidence decreased 2005-2013, whereas for men, the trend was rather unclear. Uncorrected forecasts indicate that by 2050, female and male cases will each have more than doubled from 2015 in all demographic core scenarios. Corrected by incidence trends before 2013, cases are expected to drop among women but rise among men. CONCLUSIONS: We anticipate rising hip fracture numbers in Vorarlberg within the next decades, unless prevention programs that presumably account for decreasing incidence rates, particularly among women since 2005, take further effect to counteract the predicted steady increase due to demographic changes. Concomitantly, augmented endeavors to target the male population by these programs are needed.

Evidence for a Role for Nanoporosity and Pyridinoline Content in Human Mild Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous connective tissue disorder characterized by bone fragility that arises from decreased bone mass and abnormalities in bone material quality. OI type I represents the milder form of the disease and according to the original Sillence classification is characterized by minimal skeletal deformities and near-normal stature. Raman microspectroscopy is a vibrational spectroscopic technique that allows the determination of bone material properties in bone biopsy blocks with a spatial resolution of ∼1 µm, as a function of tissue age. In the present study, we used Raman microspectroscopy to evaluate bone material quality in transiliac bone biopsies from children with a mild form of OI, either attributable to collagen haploinsufficiency OI type I (OI-Quant; n = 11) or aberrant collagen structure (OI-Qual; n = 5), as a function of tissue age, and compared it against the previously published values established in a cohort of biopsies from healthy children (n = 54, ages 1 to 23 years). The results indicated significant differences in bone material compositional characteristics between OI-Quant patients and healthy controls, whereas fewer were evident in the OI-Qual patients. Differences in both subgroups of OI compared with healthy children were evident for nanoporosity, mineral maturity/crystallinity as determined by maxima of the v1 PO4 Raman band, and pyridinoline (albeit in different direction) content. These alterations in bone material compositional properties most likely contribute to the bone fragility characterizing this disease. © 2016 American Society for Bone and Mineral Research.

Aging Versus Postmenopausal Osteoporosis: Bone Composition and Maturation Kinetics at Actively-Forming Trabecular Surfaces of Female Subjects Aged 1 to 84 Years.

Bone strength depends on the amount of bone, typically expressed as bone mineral density (BMD), determined by dual-energy X-ray absorptiometry (DXA), and on bone quality. Bone quality is a multifactorial entity including bone structural and material compositional properties. The purpose of the present study was to examine whether bone material composition properties at actively-forming trabecular bone surfaces in health are dependent on subject age, and to contrast them with postmenopausal osteoporosis patients. To achieve this, we analyzed by Raman microspectroscopy iliac crest biopsy samples from healthy subjects aged 1.5 to 45.7 years, paired biopsy samples from females before and immediately after menopause aged 46.7 to 53.6 years, and biopsy samples from placebo-treated postmenopausal osteoporotic patients aged 66 to 84 years. The monitored parameters were as follows: the mineral/matrix ratio; the mineral maturity/crystallinity (MMC); nanoporosity; the glycosaminoglycan (GAG) content; the lipid content; and the pyridinoline (Pyd) content. The results indicate that these bone quality parameters in healthy, actively-forming trabecular bone surfaces are dependent on subject age at constant tissue age, suggesting that with advancing age the kinetics of maturation (either accumulation, or posttranslational modifications, or both) change. For most parameters, the extrapolation of models fitted to the individual age dependence of bone in healthy individuals was in rough agreement with their values in postmenopausal osteoporotic patients, except for MMC, lipid, and Pyd content. Among these three, Pyd content showed the greatest deviation between healthy aging and disease, highlighting its potential to be used as a discriminating factor.

Mortality after hip fracture in Austria 2008-2011.

Osteoporosis-related hip fractures represent a substantial cause of mortality and morbidity in industrialized countries like Austria. Identification of groups at high risk for mortality after hip fracture is crucial for health policy decisions. To determine in-hospital, long-term, and excess mortality after osteoporosis-related hip fracture in Austrian patients, we conducted a retrospective cohort analysis of pseudonymized invoice data from Austrian social insurance authorities covering roughly 98 % of the entire population. The data set included 31,668 subjects aged 50 years and above sustaining a hip fracture between July 2008 and December 2010 with follow-up until June 2011, and an age-, gender-, and regionally matched control population without hip fractures (56,320 subjects). Kaplan-Meier and Cox hazard regression analyses served to determine unadjusted and adjusted mortality rates: Unadjusted all-cause 1-year mortality amounted to 20.2 % (95 % CI: 19.7-20.7 %). Males had significantly higher long-term, in-hospital, and excess mortality rates than females, but younger males exhibited lower excess mortality than their female counterparts. Advanced age correlated with increased long-term and in-hospital mortality, but lower excess mortality. Excess mortality, particularly in males, was highest in the first 6 months after hip fracture, but remained statistically significantly elevated throughout the observation period of 3 years. Longer hospital stay per fracture was correlated with mortality reduction in older patients and in patients with more subsequent fractures. In conclusion, more efforts are needed to identify causes and effectively prevent excess mortality especially in male osteoporosis patients.