Serum Beta-Defensin-2 is a biomarker for psoriasis but not subclinical atherosclerosis: Role of IL17a, PI-3 kinase and Rac1.

Background: Beta-defensins (BDs) are antimicrobial peptides secreted upon epithelial injury. Both chemotactic and antimicrobial properties of BDs function as initial steps in host defense and prime the adaptive immune system in the body. Psoriasis, a chronic immune-mediated inflammatory disease, has both visible cutaneous manifestations as well as known associations with higher incidence of cardiometabolic complications and vascular inflammation. Objectives: We aimed to investigate the circulating expression of beta-defensin-2 (BD2) in psoriasis at baseline compared to control subjects, along with changes in BD2 levels following biologic treatment at one-year. The contribution of BD2 to subclinical atherosclerosis is also assessed. In addition, we have sought to unravel signaling mechanisms linking inflammation with BD2 expression. Methods: Multimodality imaging as well inflammatory biomarker assays were performed in biologic naïve psoriasis (n=71) and non-psoriasis (n=53) subjects. A subset of psoriasis patients were followed for one-year after biological intervention (anti-Tumor Necrosis Factor-α (TNFα), n=30; anti-Interleukin17A (IL17A), n=21). Measurements of circulating BD2 were completed by Enzyme-Linked Immunosorbent Assay (ELISA). Using HaCaT transformed keratinocytes, expression of BD2 upon cytokine treatment was assessed by quantitative polymerase chain reaction (qPCR) and ELISA. Results: Herein, we confirm that human circulating BD2 levels associate with psoriasis, which attenuate upon biologic interventions (anti-TNFα, anti-IL-17A). A link between circulating BD2 and sub-clinical atherosclerosis markers was not observed. Furthermore, we demonstrate that IL-17A-driven BD2 expression occurs in a Phosphatidylinositol 3-kinase (PI3-kinase) and Rac1 GTPase-dependent manner. Conclusions: Our findings expand on the potential role of BD2 as a tractable biomarker in psoriasis patients and describes the role of an IL-17A-PI3-kinase/Rac signaling axis in regulating BD2 levels in keratinocytes.

The psoriasis area and severity index is an independent risk factor for cardiovascular events: A prospective register study.

BACKGROUND: Patients treated with systemics for moderate-to-severe psoriasis have increased risk of cardiovascular disease (CVD). However, to the best of our knowledge, there are no data on the association between clinical disease activity and future cardiovascular events in this population. Such data could help identify patients at increased CVD risk and inform the potential for CVD prevention with effective psoriasis treatment. OBJECTIVE: To estimate the association between the Psoriasis Area and Severity Index (PASI) and cardiovascular events defined as hospitalization for CVD and cardiovascular death. METHODS: We linked prospectively collected data on PASI and CVD risk factors to population-based administrative data on hospitalizations and causes of death. We estimated the association between PASI and cardiovascular events using Cox proportional hazard models with PASI and Framingham 10-year cardiovascular risk as time-varying covariates. RESULTS: A total of 767 patients with 6264 PASI scores were included. After adjusting for 10-year cardiovascular risk and prior CVD, a one-point increase in PASI was associated with a hazard ratio of 1.04 (95% CI: 1.01-1.07) for cardiovascular events. The findings were robust in sensitivity analyses. CONCLUSION: PASI is an independent marker for future cardiovascular events in patients with moderate-to-severe psoriasis.

A micro-costing analysis of post-fracture care pathways: results from the International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS).

This study identified the costs and health-related quality of life impacts of several post-fracture multidisciplinary care pathways specific to individual skeletal site (hip, distal forearm, vertebrae, humerus). These care pathways may assist healthcare providers in allocating resources for osteoporotic fractures in more effective and cost-efficient ways. INTRODUCTION: This micro-costing study was undertaken to provide the estimated healthcare costs of several fracture site-specific health service use pathways associated with different trajectories of health-related quality of life (HRQoL) 12-months post-fracture. METHODS: The study included 4126 adults aged ≥ 50 years with a fragility fracture (1657 hip, 681 vertebrae, 1354 distal forearm, 434 humerus) from the International Costs & Utilities Related to Osteoporotic fractures Study (ICUROS). ICUROS participants were asked to recall the frequency and duration (where applicable) of their health and community care service use at 4- and 12-month follow-up visits. Patient-level costs were identified and aggregated to determine the average cost of healthcare use related to the fracture in each care pathway (presented in Australian 2021 dollars). Mean cost differences were calculated and analysed using a one-way analysis of variance (ANOVA) and post hoc Bonferroni correction to determine any statistically significant differences. RESULTS: The total direct cost of fractures was estimated at $89564, $38926, $18333, and $38461AUD per patient for hip, vertebral, wrist, and humeral participants, respectively. A Kruskal-Wallis test yielded a statistically significant difference in cost values between most care pathways (p < 0.001). Of the 20 care pathways, those associated with recovery of HRQoL had lower mean costs per patient across each fracture site. CONCLUSIONS: This study identified the costs and HRQoL impacts of several multidisciplinary care pathways for individual fracture sites based on the health service utilization of an international cohort of older adults. These care pathways may assist healthcare providers in allocating resources for fragility fractures in more effective and cost-efficient ways.

Mind the gap: Incidence of osteoporosis treatment after an osteoporotic fracture - results of the Austrian branch of the International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS).

INTRODUCTION: Despite availability of effective treatment options proven to prevent osteoporotic fractures, a huge gap in osteoporosis treatment exists. The aim of the present study was to evaluate the treatment rate after a major osteoporotic fracture (MOF) in Austria, one of the 25 wealthiest countries worldwide. METHODS: This analysis is based on the data of the International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS), a prospective observational study assessing data from patients who suffered a MOF. We stratified these patients by treatment status at time of fracture and compared treatment use following MOF by sex as well as by fracture sites at the time of the index fracture, and 4, 12, and 18 months thereafter. Descriptive statistics, t-tests for continuous variables and chi-squared tests for nominal variables, were performed to compare treatment groups. RESULTS: A total of 915 patients (78 % female) were recruited at 8 different trauma centers throughout Austria. At the time of fracture, 731 patients (80 %) did not receive osteoporosis treatment. In this group, follow-up analysis after 4, 12 and 18 months revealed a treatment rate of 18 %, 16 %, 15 % in women, and 8 %, 12 %, 10 % in men, respectively. In those who received osteoporosis medication at the time of fracture the treatment rate was 65 %, 54 % and 60 % in women, and comparable results in men. CONCLUSIONS: Only 1 in 10 men, and less than 2 in 10 women of those who did not receive osteoporosis treatment at the time of fracture were prescribed an adequate osteoporosis treatment. Thus, the vast majority of patients who sustained an osteoporotic fracture and thus were at imminent risk of receiving subsequent fractures did not receive an adequate treatment. There is a clear need for the implementation of coordinated, multi-disciplinary models of care for secondary fracture prevention.

Circulating microRNAs in extracellular vesicles as potential biomarkers for psoriatic arthritis in patients with psoriasis.

BACKGROUND: Psoriatic arthritis (PsA) develops in ~30% of patients with psoriasis. The diagnosis of PsA is challenging, and there are no reliable molecular markers in clinical use. MicroRNAs are short non-coding regulatory RNAs, which can be actively packaged into extracellular vesicles (EVs) and secreted to the circulation. OBJECTIVES: To explore whether plasma-derived EV microRNAs may serve as biomarkers for PsA in patients with psoriasis. METHODS: Plasma samples were obtained from patients with cutaneous-only psoriasis (PsC) and patients with psoriasis and PsA. Plasma EVs were isolated using miRCURY™ Exosome Isolation Kit. RNA sequencing was used to identify differentially expressed EV miRNAs in the discovery phase (PsC, n = 15; PsA, n = 14). In the validation phase (PsC, n = 29; PsA, n = 28), 41 selected miRNAs were analysed in plasma EVs by qPCR. The association of the identified miRNAs with PsA was assessed by logistic regression analysis. RESULTS: RNA sequencing identified 19 plasma EV miRNAs with significantly different levels between PsA and PsC in the discovery cohort. Significantly lower levels of plasma EV let-7b-5p and miR-30e-5p in PsA vs. PsC were confirmed in the validation cohort, and their decreased levels were found to be associated with the presence of PsA. ROC analysis revealed an AUC of 0.68 (95% CI 0.53-0.83) for let-7b-5p and 0.69 (95% CI 0.55-0.84) for miR-30e-5p. CONCLUSIONS: Circulating EV microRNA levels are altered in patients with PsA as compared with PsC. Findings of this exploratory study suggest that circulating EV microRNAs may serve as biomarkers for arthritis in psoriasis patients.

Real-world comparative effectiveness of adalimumab, etanercept and methotrexate: a Swedish register analysis.

BACKGROUND: The advent of biosimilars may render etanercept (ETN) and adalimumab (ADA) viable alternatives to methotrexate (MTX) as first-line systemics in psoriasis. However, real-world relative effectiveness data comparing ADA and ETN to MTX are limited. OBJECTIVE: To estimate the relative effectiveness of ADA and ETN compared to MTX. METHODS: We analysed data from DermaReg, a regional register in Stockholm, Sweden, to estimate drug survival and mean Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) during maintenance treatment. RESULTS: A total of 524 patients initiated 727 treatment episodes with ADA, ETN or MTX. After adjusting for confounders, patients treated with ADA had better drug survival (HR: 0.67; P = 0.003), lower mean PASI (-2.0; P < 0.001) and lower mean DLQI (-0.9; P < 0.001) during maintenance treatment compared to patients treated with MTX. The results for ETN compared to MTX were mixed. After adjusting for confounding, there was no significant difference in drug survival (HR 1.23; P = 0.082), but patients on ETN had lower mean PASI (-0.7; P = 0.006) during maintenance treatment. CONCLUSION: Adalimumab is superior to MTX in clinical practice whereas the relative effectiveness between ETN and MTX is less clear. This study also highlights the importance of appropriate confounding control in effectiveness analysis.

Cost-effectiveness of pharmacological fracture prevention for osteoporosis as prescribed in clinical practice in France, Germany, Italy, Spain, and the United Kingdom.

This study estimated the cost-effectiveness of pharmacological fracture prevention as prescribed in the five largest European countries (EU5) using the IOF reference cost-effectiveness model. Pharmacological fracture prevention as prescribed in clinical practice was cost-saving (provided more QALYs at lower costs) compared to no treatment in each of the EU5. PURPOSE: To estimate the real-world cost-effectiveness of pharmacological fracture prevention as prescribed in the five largest European countries by population size: France, Germany, Italy, Spain, and the United Kingdom (UK) (collectively EU5). MATERIALS AND METHODS: We analyzed sales data on osteoporosis drugs in each of the EU5 to derive a hypothetical intervention that corresponds to the mix of osteoporosis medication prescribed in clinical practice. The costs for this treatment mix were obtained directly from the sales data, and the efficacy of the treatment mix was estimated by weighing the treatment-specific fracture risk reductions from a published meta-analysis. Subsequently, we estimated the cost-effectiveness using costs per quality adjusted life year (QALY) of the intervention compared to no treatment in each of the EU5 using the International Osteoporosis Foundation (IOF) reference cost-effectiveness model. The model population comprised postmenopausal women, mean age 72 years with established osteoporosis (T-score ≤ - 2.5) among whom 23.6% had a prevalent vertebral fracture. The model was populated with country-specific data from the literature. RESULTS: Pharmacological fracture prevention as prescribed in clinical practice was cost-saving (provided more QALYs at lower costs) compared to no treatment in each country. The findings were robust in scenario analyses. CONCLUSIONS: Pharmacological fracture prevention as prescribed in clinical practice is cost-saving in each of the EU5. Because of the under-diagnosis and under-treatment of post-menopausal osteoporosis, from a health economic perspective, further cost-savings may be reached by expanding treatment to those at increased risk of fracture currently not receiving any treatment.

Clinical course of multiple sclerosis and labour-force absenteeism: a longitudinal population-based study.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a chronic neurological disease associated with substantial disability and morbidity. The objective of our study was to assess the long-term consequences of MS clinical course on sick leave and disability pension. METHODS: Patients with relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS) were identified through the Swedish Multiple Sclerosis Registry. We calculated the mean annual prevalence and number of sick leave and disability pension days by clinical course, age and year pre- and post-diagnosis, and compared outcomes using Welch's t-tests and ANOVA models, mixed-effects regression and survival analysis. RESULTS: The sample included 5371 patients (4568 with RRMS, 390 with SPMS and 413 with PPMS). The mean annual number of days with sick leave and disability pension ranged from 101 at 1 year after diagnosis to 164 after 11 years for patients with RRMS. Corresponding estimates for PPMS were 188 and 311 days. Higher levels of absenteeism were observed in patients with PPMS versus RRMS 7 years before diagnosis for sick leave (P < 0.025) and 10 years before diagnosis for disability pension (P < 0.034). Differences between SPMS and PPMS were minor. CONCLUSIONS: Patients with RRMS had substantially lower levels of sick leave and disability pension over time compared with their counterparts with SPMS and PPMS, whereas labour-force absenteeism was similar for patients with SPMS and PPMS. These findings contribute to the understanding of the impact of MS on socioeconomic outcomes and help inform the discussion on the clinical classification of different courses of the disease.

Health-related quality of life during the first year after a hip fracture: results of the Mexican arm of the International Cost and Utility Related to Osteoporotic Fractures Study (MexICUROS).

We investigated changes in health-related quality of life (HRQoL) due to hip fracture in Mexican adults aged ≥ 50 years during the first year post-fracture. Mean accumulated loss was 0.27 quality-adjusted life years (QALYs). HRQoL before fracture was the main contributor to explain the loss of QALYs. INTRODUCTION: We aimed to estimate the health-related quality of life (HRQoL) loss over 1 year in patients sustaining a hip fracture in Mexico. METHODS: Individuals aged ≥ 50 years old with diagnosis of a low-energy-induced hip fracture enrolled in the International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS) composed the study population. After a recall of their own pre-fracture status, HRQoL was prospectively collected in three phases over 12 months of follow-up using EQ-5D-3L. The UK preference weight set was applied to calculate the utility values. The accumulated quality-adjusted life years (QALYs) loss in the first year post-fracture was estimated using the trapezoid method. Multivariate regression analysis allowed identifying determinants of QALYs loss. RESULTS: One hundred ninety-three patients (mean ± SD age 77.2 ± 9.9 years; 80% women; 15.5% with prior fracture in the last 5 years; 78% in low-income category) were evaluated. Mean (95% CI) utility value before fracture was 0.64 (0.59-0.68). It dropped to 0.01 (0.01-0.02) immediately after fracture and then improved to 0.46 (0.42-0.51) and 0.60 (0.55-0.64) at 4 and 12 months post-fracture, respectively. Disregarding fracture-related mortality, accumulated QALYs loss over the first year was 0.27 (0.24-0.30) QALYs. Mobility, self-care, and usual activities were the most affected domains throughout the whole year. HRQoL before fracture was the main contributor to explain the loss of QALYs. CONCLUSIONS: Hip fractures reduce dramatically the HRQoL, with the loss sustained at least over the first year post-fracture in Mexico. The utility values derived from this study can be used in future economic evaluations.

Quality of life for up to 18 months after low-energy hip, vertebral, and distal forearm fractures-results from the ICUROS.

This study used data from the International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS) to estimate the quality of life (QoL) impact of fracture. Hip, vertebral, and distal forearm fractures incur substantial QoL losses. Hip and vertebral fracture results in markedly impaired QoL for at least 18 months. INTRODUCTION: The International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS) is a multinational observational study that aims to describe costs and quality of life (QoL) consequences of osteoporotic fractures. To date, 11 countries have participated in the study: Australia, Austria, Estonia, France, Italy, Lithuania, Mexico, Russia, Spain, the UK, and the USA. The objective of this paper is to describe the QoL impact of hip, vertebral, and distal forearm fracture. METHODS: Data were collected at four time-points for five QoL point estimates: within 2 weeks after fracture (including pre-fracture recall) and at 4, 12, and 18 months after fracture. Quality of life was measured as health state utility values (HSUVs) derived from the EQ-5D-3L. Complete case analysis was conducted as the base case with available case and multiple imputation performed as sensitivity analyses. Multivariate analysis was performed to explore predictors of QoL impact of fracture. RESULTS: Among 5456 patients enrolled using convenience sampling, 3021 patients were eligible for the base case analysis (1415 hip, 1047 distal forearm, and 559 vertebral fractures). The mean (SD) difference between HSUV before and after fracture for hip, vertebral, and distal forearm fracture was estimated at 0.89 (0.40), 0.67 (0.45), and 0.48 (0.34), respectively (p < 0.001 for all fracture types). Eighteen months after fracture, mean HSUVs were lower than before the fracture in patients with hip fracture (0.66 vs. 0.77 p < 0.001) and vertebral fracture (0.70 vs. 0.83 p < 0.001). Hospitalization and higher recalled pre-fracture QoL were associated with increased QoL impact for all fracture types. CONCLUSIONS: Hip, vertebral, and distal forearm fractures incur substantial loss in QoL and for patients with hip or vertebral fracture, QoL is markedly impaired for at least 18 months.

Quality of life, resource use, and costs related to hip fracture in Estonia.

UNLABELLED: We assessed the impact of hip fracture on health-related quality of life (HRQoL) and costs in Estonia. The mean 18-month HRQoL loss in quality adjusted life years (QALY) was estimated at 0.31, and the average cumulative cost from a societal perspective was 8146 euros per hip fracture patient. INTRODUCTION: The aim of this study is to estimate the impact of hip fracture on HRQoL, resource consumption, and cost over 18 months after the fracture among individuals aged over 50 in Estonia. METHODS: A cohort of 205 hip fracture patients ≥50 years was followed up for 18 months. HRQoL was estimated before fracture (recall), after fracture, and at 4, 12, and 18 months using the EQ-5D instrument. Health care utilization and costs were obtained from a public health insurance fund database; social, informal, and indirect costs were estimated using patient-reported data. RESULTS: Hip fracture resulted in the mean 18-month HRQoL loss of 0.31 QALYs. The mean 18-months cumulative cost of hip fracture from a societal perspective was estimated at 8146 (95 % CI 6236-10717) euros per patient. Most of the cost was related to health care (56 %) and informal care (33 %), while social care contributed only 5 %. Utilization of outpatient rehabilitation and nursing care was low (8 % of patients). CONCLUSIONS: The impact of hip fracture on HRQoL and cost was substantial. Despite appropriate inpatient care, utilization of rehabilitation, nursing care, and social care were low and potentially insufficient to meet the needs of patients with low HRQoL. The shortfall may partially explain a remarkably high use of informal care.

Treatment patterns with topicals, traditional systemics and biologics in psoriasis - a Swedish database analysis.

BACKGROUND: Little data exist on real-world treatment patterns in psoriasis, especially from European settings. OBJECTIVE: To estimate, for topicals, systemics and biologics, the time to non-persistency, switching, augmentation and insufficient treatment result (only for biologics), as well as to estimate the time to restart, in patients treated with each treatment class in Sweden based on registry data. METHODS: This database analysis utilized data from patients with psoriasis from several Swedish administrative registers. Patients were identified through combinations of diagnoses from two regional registers and filled prescriptions for relevant treatments from the Swedish Prescribed Drug Register. Kaplan-Meier time-to-event ('survival') functions were estimated with relevant treatment events as failure and the proportions of patients having experienced an event at specific time-points were derived from the failure rates. RESULTS: For topicals, systemics and biologics the number of indexed treatment episodes were 25,396, 2963, and 628 respectively. One year after treatment initiation, the proportion of patients who were classed as non-persistent with topicals, systemics and biologics were estimated at 88.3%, 47.9% and 43.2% respectively. Among patients who remained persistent, within 1 year of treatment start the proportions of treatment episodes in which patients were augmented were estimated at 56.0% for topicals, 45.3% for systemics and 58.9% for biologics. In addition, within 1 year of non-persistence, 49.0% of topicals, 60.8% of systemics and 80.2% of biologics treatment episodes were re-initiated, with 35.4-52.5% re-initiated on the non-persistent treatment depending on treatment class. In addition, among patients on biologics, 29.2% of treatment episodes had an insufficient treatment result within 1 year of treatment start. CONCLUSION: Persistency to psoriasis treatments may be sub-optimal and patients who remain persistent relatively frequently receive augmentation therapy or switch to another therapy. Therefore, current treatment options in psoriasis may be insufficient.

Epidemiology and economic burden of osteoporosis in Switzerland.

UNLABELLED: This report describes the epidemiology, economic burden and treatment of osteoporosis in Switzerland. INTRODUCTION: Osteoporosis is characterized by reduced bone mass and disruption of bone architecture, resulting in increased risks of fragility fractures which represent the main clinical consequence of the disease. Fragility fractures are associated with substantial pain and suffering, disability and even death for the affected patients and substantial costs to society. The aim of this report is to describe the epidemiology and economic burden of fragility fractures as a consequence of osteoporosis in Switzerland, as a detailed addition to the report for the European Union (EU27): "Osteoporosis in the European Union: Medical Management, Epidemiology and Economic Burden". METHODS: The literature on fracture incidence and costs of fractures in Switzerland was reviewed and incorporated into a model estimating the clinical and economic burden of osteoporotic fractures in 2010. Furthermore, data on sales of osteoporosis treatments and the population at high risk of fracture were used to estimate treatment uptake and treatment gap. RESULTS: It was estimated that approximately 74,000 new fragility fractures were sustained in Switzerland in 2010, comprising 14,000 hip fractures, 11,000 vertebral fractures, 13,000 forearm fractures and 36,000 other fractures (i.e. fractures of the pelvis, rib, humerus, tibia, fibula, clavicle, scapula, sternum and other femoral fractures). The economic burden of incident and previous fragility fractures was estimated at CHF 2,050 million for the same year. Incident fractures represented 76 % of this cost, long-term fracture care 21 % and pharmacological prevention 3 %. Previous and incident fractures also accounted for 24,000 quality-adjusted life years (QALYs) lost during 2010. When accounting for the demographic projections for 2025, the number of incident fractures was estimated at 98,786 in 2025, representing an increase of 25,000 fractures. Hip, clinical vertebral (spine), forearm and other fractures were estimated to increase by 4,900, 3,200, 3,500 and 13,000, respectively. The burden of fractures in terms of costs (excluding value of QALYs lost) in Switzerland in 2025 was estimated to increase by 29 % to CHF 2,642 million. Though the uptake of osteoporosis treatments increased from 2001, the proportion of patients aged 50 or above who received treatment remained at low levels in the past few years. The majority of women at high fracture risk do not receive active treatment. CONCLUSIONS: In spite of the high cost of osteoporosis, a substantial treatment gap and projected increase of the economic burden driven by an aging population, the use of pharmacological prevention of osteoporosis is significantly less than optimal, suggesting that a change in health care policy concerning the disease is warranted.

Epidemiology of distal forearm fractures in Austria between 1989 and 2010.

UNLABELLED: Only few studies have been published hitherto on country-specific incidence of distal forearm fracture. In the prevailing study, incidences were estimated, and trend analyses were performed for the entire Austrian population aged ≥50á. Incidence decreased significantly in women, but not in men, over the past 12 years of observation. INTRODUCTION: To estimate incidence of distal forearm fracture and assess incidence trends in the entire Austrian population aged ≥50á from 1989-2010 for inpatient fractures and from 1999 to 2010 for all fractures. METHODS: The number of inpatient forearm fractures was obtained from the Austrian Hospital Discharge Register (AHDR) for the entire population aged ≥50á from 1989 to 2010. Total number of distal forearm fractures was modeled using patient-level data on 36,327 patients with distal forearm fractures. Crude and age-standardized incidence rates (cases per 100,000) were estimated in 5-year age intervals. To analyze the change in incidence over time, average annual changes expressed as incidence rate ratios (IRR) were calculated. RESULTS: For all distal forearm fractures, age-standardized incidence in women in 1999 and 2009 were estimated at 709 (95 % CI 675-743) and 607 (578-637), respectively. The age-standardized incidences in men the same years were estimated at 171 (156-185) and 162 (151-174), respectively. IRR analyses showed a significant decrease in women (-1.1 %, p < 0.01) but not in men (-0.8 %, p > 0.05) over the last 12 years (1999-2010). CONCLUSION: Incidence of distal forearm fracture in the entire Austrian population is comparable to hip fracture incidence which is known to be among the highest worldwide. However, trend analyses reveal a significant decrease for all distal forearm fractures in women, but not in men, over the last 12 years.

Comparative cost-effectiveness of bazedoxifene and raloxifene in the treatment of postmenopausal osteoporosis in Europe, using the FRAX algorithm.

UNLABELLED: Bazedoxifene and raloxifene were evaluated in the treatment of postmenopausal osteoporosis from health economic perspective in Europe. Based on a computer-based algorithm calculating efficacy of the treatments, bazedoxifene appears to be a cost-effective strategy compared to raloxifene, particularly in patients at high fracture risk. INTRODUCTION: The purpose of this study was to compare cost-effectiveness of bazedoxifene and raloxifene in eight European countries: Belgium, France, Germany, Ireland, Italy, Spain, Sweden, and the UK. METHODS: The Fracture Risk Assessment Tool, which is a computer-based algorithm to calculate fracture probability using clinical risk factors alone or with bone mineral density, was incorporated in a Markov Tunnel model to evaluate cost-effectiveness of bazedoxifene 20 or 40 mg vs. raloxifene 60 mg in postmenopausal osteoporotic women. The efficacy of bazedoxifene and raloxifene for vertebral and non-vertebral fractures was measured as a function of the 10-year probability of a major osteoporotic fracture. The model estimated the incremental cost-effectiveness ratio and net monetary benefit (NMB) from a healthcare perspective, given the willingness to pay 30,000. RESULTS: In postmenopausal osteoporotic women, bazedoxifene was a cost saving strategy compared to raloxifene in the countries studied. The median NMB of bazedoxifene compared to raloxifene increased monotonically with the 10-year fracture probability. In general, the median NMB became greater than 0 in women with 10-year probabilities of a major osteoporotic fracture between 5 and 10% or above. The impact on results by varying the assumptions in the model was examined in sensitivity analysis. CONCLUSION: Bazedoxifene appears to be a cost-effective strategy compared to raloxifene for the treatment of postmenopausal osteoporotic women in Europe, particularly in patients at high fracture risk.

Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA).

UNLABELLED: This report describes the epidemiology, burden, and treatment of osteoporosis in the 27 countries of the European Union (EU27). INTRODUCTION: Osteoporosis is characterized by reduced bone mass and disruption of bone architecture, resulting in increased risk of fragility fractures which represent the main clinical consequence of the disease. Fragility fractures are associated with substantial pain and suffering, disability and even death for affected patients and substantial costs to society. The aim of this report was to characterize the burden of osteoporosis in the EU27 in 2010 and beyond. METHODS: The literature on fracture incidence and costs of fractures in the EU27 was reviewed and incorporated into a model estimating the clinical and economic burden of osteoporotic fractures in 2010. RESULTS: Twenty-two million women and 5.5 million men were estimated to have osteoporosis; and 3.5 million new fragility fractures were sustained, comprising 610,000 hip fractures, 520,000 vertebral fractures, 560,000 forearm fractures and 1,800,000 other fractures (i.e. fractures of the pelvis, rib, humerus, tibia, fibula, clavicle, scapula, sternum and other femoral fractures). The economic burden of incident and prior fragility fractures was estimated at 37 billion. Incident fractures represented 66 % of this cost, long-term fracture care 29 % and pharmacological prevention 5 %. Previous and incident fractures also accounted for 1,180,000 quality-adjusted life years lost during 2010. The costs are expected to increase by 25 % in 2025. The majority of individuals who have sustained an osteoporosis-related fracture or who are at high risk of fracture are untreated and the number of patients on treatment is declining. CONCLUSIONS: In spite of the high social and economic cost of osteoporosis, a substantial treatment gap and projected increase of the economic burden driven by the aging populations, the use of pharmacological interventions to prevent fractures has decreased in recent years, suggesting that a change in healthcare policy is warranted.

Osteoporosis in the European Union: a compendium of country-specific reports.

UNLABELLED: This report describes epidemiology, burden, and treatment of osteoporosis in each of the 27 countries of the European Union (EU27). INTRODUCTION: In 2010, 22 million women and 5.5 million men were estimated to have osteoporosis in the EU; and 3.5 million new fragility fractures were sustained, comprising 620,000 hip fractures, 520,000 vertebral fractures, 560,000 forearm fractures and 1,800,000 other fractures. The economic burden of incident and prior fragility fractures was estimated at € 37 billion. Previous and incident fractures also accounted for 1,180,000 quality-adjusted life years lost during 2010. The costs are expected to increase by 25 % in 2025. The majority of individuals who have sustained an osteoporosis-related fracture or who are at high risk of fracture are untreated and the number of patients on treatment is declining. The aim of this report was to characterize the burden of osteoporosis in each of the EU27 countries in 2010 and beyond. METHODS: The data on fracture incidence and costs of fractures in the EU27 were taken from a concurrent publication in this journal (Osteoporosis in the European Union: Medical Management, Epidemiology and Economic Burden) and country specific information extracted. RESULTS: The clinical and economic burden of osteoporotic fractures in 2010 is given for each of the 27 countries of the EU. The costs are expected to increase on average by 25 % in 2025. The majority of individuals who have sustained an osteoporosis-related fracture or who are at high risk of fracture are untreated and the number of patients on treatment is declining. CONCLUSIONS: In spite of the high cost of osteoporosis, a substantial treatment gap and projected increase of the economic burden driven by aging populations, the use of pharmacological prevention of osteoporosis has decreased in recent years, suggesting that a change in healthcare policy concerning the disease is warranted.

Epidemiology of proximal humeral fractures in Austria between 1989 and 2008.

UNLABELLED: Incidence rates of proximal humeral fractures in Austria over a period of twenty years (1989-2008) were estimated. Age standardized incidence rates increased until 2008, primarily driven by an increase in incidence rates in women. INTRODUCTION: The aim of the prevailing study was to estimate incidence rates of proximal humeral fractures and to assess changes in trend in the Austrian population aged 50 years and above, over a period of 20 years (1989-2008). METHODS: Number of proximal humeral fractures were obtained from the Austrian Hospital Discharge Register for the entire population >50 years of age. Adjustment factors were determined for multiple registrations of the same diagnosis, and for the fact that not all patients with proximal humeral fractures are treated in an inpatient setting. To analyze the overall change in this type of fracture for the period, average annual changes expressed as incidence rate ratios were calculated. RESULTS: The estimated age-standardized incidence (fractures per 100,000 individuals) of proximal humeral fractures among Austrians >50 years of age increased in men from 112 (95% CI, 99-124) to 141 (129-153) and in women from 222 (202-241) to 383 (360-406). The increase appeared to be linear with no leveling off towards the end of the study period. CONCLUSION: While some caution is necessary when interpreting the results given the use of adjustment factors, there appears to have been a rise in the incidence of proximal humeral fractures in Austria in both men and women, with no leveling off in recent years. The reasons for this are not clear, but in the light of previously reported leveling off in the increase in the incidence of hip fractures, a change in the patterns of falls cannot be ruled out.

The International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS)--quality of life during the first 4 months after fracture.

UNLABELLED: The quality of life during the first 4 months after fracture was estimated in 2,808 fractured patients from 11 countries. Analysis showed that there were significant differences in the quality of life (QoL) loss between countries. Other factors such as QoL prior fracture and hospitalisation also had a significant impact on the QoL loss. INTRODUCTION: The International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS) was initiated in 2007 with the objective of estimating costs and quality of life related to fractures in several countries worldwide. The ICUROS is ongoing and enrols patients in 11 countries (Australia, Austria, Estonia, France, Italy, Lithuania, Mexico, Russia, Spain, UK and the USA). The objective of this paper is to outline the study design of ICUROS and present results regarding the QoL (measured using the EQ-5D) during the first 4 months after fracture based on the patients that have been thus far enrolled ICUROS. METHODS: ICUROS uses a prospective study design where data (costs and quality of life) are collected in four phases over 18 months after fracture. All countries use the same core case report forms. Quality of life was collected using the EQ-5D instrument and a time trade-off questionnaire. RESULTS: The total sample for the analysis was 2,808 patients (1,273 hip, 987 distal forearm and 548 vertebral fracture). For all fracture types and countries, the QoL was reduced significantly after fracture compared to pre-fracture QoL. A regression analysis showed that there were significant differences in the QoL loss between countries. Also, a higher level of QoL prior to the fracture significantly increased the QoL loss and patients who were hospitalised for their fracture also had a significantly higher loss compared to those who were not. CONCLUSIONS: The findings in this study indicate that there appear to be important variations in the QoL decrements related to fracture between countries.

Balloon kyphoplasty compared to vertebroplasty and nonsurgical management in patients hospitalised with acute osteoporotic vertebral compression fracture: a UK cost-effectiveness analysis.

UNLABELLED: The purpose of the study was to estimate the cost-effectiveness of balloon kyphoplasty compared to nonsurgical management and vertebroplasty for the treatment of hospitalised osteoporotic vertebral compression fractures in the UK. A cost-effectiveness model was constructed and used for analysis. Balloon kyphoplasty may be cost-effective compared to relevant alternatives. INTRODUCTION: The objective of this study was to estimate the cost-effectiveness of balloon kyphoplasty (BKP) for the treatment of patients hospitalised with acute osteoporotic vertebral compression fracture (OVCF) compared to percutaneous vertebroplasty (PVP) and nonsurgical management (NSM) in the UK. METHODS: A Markov simulation model was developed to evaluate treatment with BKP, NSM and PVP in patients with symptomatic OVCF. Data on health-related quality of life (HRQoL) with acute OVCF were derived from the FREE and VERTOS II randomised clinical trials (RCTs) and normalised to the NSM arm in the FREE trial. Estimated differences in mortality among the treatments and costs for NSM were obtained from the literature whereas procedure costs for BKP and PVP were obtained from three National Health Service hospitals. It was assumed that BKP and PVP reduced hospital length of stay by 6 days compared to NSM. RESULTS: The incremental cost-effectiveness ratio was estimated at Great Britain Pound Sterling (GBP) 2,706 per quality-adjusted life year (QALY) and GBP 15,982 per QALY compared to NSM and PVP, respectively. Sensitivity analysis showed that the cost-effectiveness of BKP vs. NSM was robust when mortality and HRQoL benefits with BKP were varied. The cost-effectiveness of BKP compared to PVP was particularly sensitive to changes in the mortality benefit. CONCLUSION: BKP may be a cost-effective strategy for the treatment of patients hospitalised with acute OVCF in the UK compared to NSM and PVP. Additional RCT data on the benefits of BKP and PVP compared to simulated sham surgery and further data on the mortality benefits with BKP compared to NSM and PVP would reduce uncertainty.