[Geriatric traumatological management of osteoporosis : "Let the first fracture be the last"]. / Alterstraumatologisches Management der Osteoporose : "Lass die erste Fraktur die Letzte sein".

In Germany more than 800,000 osteoporotic fractures occur every year, with severe medical, social and health economic consequences. Nevertheless, as in many other countries there is a large gap in care. Fractures frequently occur in older geriatric patients, who are increasingly being (or should be) treated in geriatric trauma centers. This multidisciplinary approach offers the opportunity not only to restore the patient's mobility and independence but also to set the course for preventing further fractures. Diagnosing osteoporosis and initiating treatment early after a fracture is particularly important as there is an imminently high risk of further fractures in the months and years following a fracture. This review article describes a pragmatic, guideline-based approach to osteoporosis management for geriatric trauma patients. It discusses fracture risk assessment, current treatment thresholds and treatment strategies as well as the individual osteoporosis drugs, the indications and contraindications. This review aims to show that the treatment of osteoporosis within the framework of a geriatric traumatology team is feasible in the majority of cases. It is suggested that a treatment decision can be systematically made based on a few questions or a flow chart.

The Fracture Phenotypes in Women and Men of 50 Years and Older with a Recent Clinical Fracture.

PURPOSE OF REVIEW: We review the literature about patients 50 years and older with a recent clinical fracture for the presence of skeletal and extra-skeletal risks, their perspectives of imminent subsequent fracture, falls, mortality, and other risks, and on the role of the fracture liaison service (FLS) for timely secondary fracture prevention. RECENT FINDINGS: Patients with a recent clinical fracture present with heterogeneous patterns of bone-, fall-, and comorbidity-related risks. Short-term perspectives include bone loss, increased risk of fractures, falls, and mortality, and a decrease in physical performance and quality of life. Combined evaluation of bone, fall risk, and the presence of associated comorbidities contributes to treatment strategies. Since fractures are related to interactions of bone-, fall-, and comorbidity-related risks, there is no one-single-discipline-fits-all approach but a need for a multidisciplinary approach at the FLS to consider all phenotypes for evaluation and treatment in an individual patient.

Is orthotic treatment beneficial for fresh osteoporotic vertebral fractures? A propensity score matching study.

BACKGROUND CONTEXT: Orthotic treatment is a common option for the conservative treatment of osteoporotic vertebral fractures (OVF). However, there is insufficient evidence of its clinical benefit. PURPOSE: To investigate the effectiveness of orthotic treatment for OVF. STUDY DESIGN/SETTING: Retrospective cohort study with data from two prospective studies. PATIENT SAMPLE: This study included 160 patients with fresh OVF enrolled in 2012 and 2020 prospective cohort studies. OUTCOME MEASURES: The visual analog scale (VAS) score for low back pain was used for clinical outcomes, and radiographic parameters included the percent height of the vertebra and angular change of the vertebral body. Moreover, the occurrence of secondary vertebral fractures was followed-up over time. METHODS: The patients were divided into brace and no-brace groups and were matched according to propensity score for age, sex, anterior percent height at the initial examination, and presence of old OVFs. Hazard ratio for the cumulative incidence of secondary vertebral fractures with and without bracing were calculated and analyzed using the generalized Wilcoxon test. In addition, the brace group was divided into soft and rigid brace groups and compared with the no-brace group. RESULTS: Each group had 61 cases after propensity score matching. There were no significant differences in the VAS improvement for low back pain and the change in percent height of the anterior and posterior walls from initial examination to 6 months after injury (p=.87, p=.39 and p=.14, respectively, mixed-effect models). Meanwhile, the mean angular change of fractured vertebrae was 4.3° / 3.2° initially and 1.2° / 2.5° at 6 months (the brace group / no-brace group, respectively; p=.007, mixed-effect models). A significant difference was also observed between the rigid brace group and the no-brace group (p=.008, mixed effect models). The incidence of secondary vertebral fractures was 1.6% / 11.4% at 1 month, indicating a significant difference (the brace group / no-brace group, respectively; p = .028). The hazard ratio for the cumulative incidence of secondary fractures due to orthotic treatment was 0.47 (95% confidence interval 0.20-1.09, p=.054). CONCLUSIONS: Although orthotic treatment for fresh OVF did not relieve pain, it might contribute to the stabilization of the fractured vertebra, especially using a rigid brace. Moreover, it might influence a reduction of the imminent vertebral fracture risk immediately after the onset of OVF. CLASSIFICATIONS: Clinical study.

The development and validation of a prediction model for imminent vertebral osteoporotic fracture in postmenopausal women.

PURPOSE: This study aimed to develop and validate a new model that focused on the risk of imminent vertebral fractures in women with osteoporosis. METHODS: Data from 2,048 patients were extracted from three hospitals, of which 1,720 patients passed the inclusion and exclusion screen. The patients from Nanfang Hospital (NFH) were randomized at a 2:1 ratio to create a training cohort (n = 709) and an internal validation cohort (n = 355), with the patients from the other two hospitals (n = 656) used for external validation. The risk factors included in the imminent osteoporotic vertebral compression fractures (OVCFs) prediction model (labelled TVF) were sorted by the least absolute shrinkage and selection operator and constructed by logistic regression. The area under the receiver operating characteristic curve (AUC), the decision curve, and the clinical impact curves of the optimal model were analyzed to verify the model. RESULTS: There were 138 and 161 fresh fractures in NFH and the other two hospitals, respectively. The lowest BMD T value and the history of vertebral fracture were integrated into the TVF model. The prediction power of TVF was demonstrated by the AUCs of 0.788 (95% confidence interval [CI], 0.728-0.849) in the training cohort and 0.774 (95% CI, 0.705-0.842) in the internal validation cohort, and 0.790 (95% CI, 0.742-0.839) and 0.741 (95% CI, 0.668-0.813) in the external validation cohorts. CONCLUSION: The TVF model demonstrated good discrimination to stratify the imminent risk of OVCFs. We therefore consider the model as a pertinent commencement in the search for more accurate imminent OVCFs prediction.

Refracture and mortality risk in the elderly with osteoporotic fractures: the AGES-Reykjavik study.

There is imminent refracture risk in elderly individuals for up to six years, with a decline thereafter except in women below 75 who face a constant elevated risk. Elderly men with fractures face the highest mortality risk, particularly those with hip and vertebral fractures. Targeted monitoring and treatment strategies are recommended. PURPOSE: Current management and interventions for osteoporotic fractures typically focus on bone mineral density loss, resulting in suboptimal evaluation of fracture risk. The aim of the study is to understand the progression of fractures to refractures and mortality in the elderly using multi-state models to better target those at risk. METHODS: This prospective, observational study analysed data from the AGES-Reykjavik cohort of Icelandic elderly, using multi-state models to analyse the evolution of fractures into refractures and mortality, and to estimate the probability of future events in subjects based on prognostic factors. RESULTS: At baseline, 4778 older individuals aged 65 years and older were included. Elderly men, and elderly women above 80 years of age, had a distinct imminent refracture risk that lasted between 2-6 years, followed by a sharp decline. However, elderly women below 75 continued to maintain a nearly constant refracture risk profile for ten years. Hip (30-63%) and vertebral (24-55%) fractures carried the highest 5-year mortality burden for elderly men and women, regardless of age, and for elderly men over 80, lower leg fractures also posed a significant mortality risk. CONCLUSION: The risk of refracture significantly increases in the first six years following the initial fracture. Elderly women, who experience fractures at a younger age, should be closely monitored to address their long-term elevated refracture risk. Elderly men, especially those with hip and vertebral fractures, face substantial mortality risk and require prioritized monitoring and treatment.

Evaluative research of a mental health urgences protocol for the primary care level / Investigación evaluativa de un protocolo para urgencias de salud mental en el primer nivel de atención.

Introducción: Materiales y métodos: Resultados: Introduction: This research stems from certain obstacles in the implementation of the National Mental Health Law, especially at the primary care level and regarding emergency management, with or without certain and imminent risk. The scarcity of mental health intervention protocols and the perception that they could limit the clinical understanding of each critical situation are challenges identified in practice. However, protocols can be valuable organizational tools in complex circumstances. The literature emphasizes the need to accompany their implementation with training to prevent exclusively bureaucratic and dehumanized approaches. Materials and methods: The purpose of this work was to address this gap, by developing an emergency mental health action protocol and training for first-level healthcare personnel in a territory of the metropolitan area of Buenos Aires. The research aimed to evaluate its effectiveness. Qualitative and quantitative methods were used to characterize interventions before the protocol's implementation, comparing them with those after training and protocol application. Results: It was found that this device facilitated more appropriate responses in critical contexts and improved knowledge about resolution strategies that can be implemented within the framework of the National Mental Health Law. Additionally, it strengthened protective factors for the mental health of healthcare workers, such as the possibility to access to a strategy that aids in task organization, and teamwork.

Introducción: Esta investigación parte de algunos obstáculos en la implementación de la Ley Nacional de Salud Mental, especialmente en el primer nivel de atención y en lo relativo al manejo de urgencias, con o sin riesgo cierto e inminente. La escasez de protocolos de intervención en salud mental y la percepción de que podrían limitar la lectura singular de cada situación crítica son desafíos identificados en la práctica. No obstante, los protocolos pueden ser herramientas organizativas valoradas en circunstancias complejas. En la bibliografía se destaca la necesidad de acompañar su implementación con capacitación para evitar enfoques exclusivamente burocráticos y deshumanizados. Materiales y métodos: Para abordar esta brecha, se realizó esta investigación,en la que se diseñó un protocolo de actuación en urgencias de salud mental y una capacitación acorde para el personal de salud del primer nivel de atención de un  territorio del área metropolitana de Buenos Aires. Objetivo: El objetivo de la investigación fue evaluar su efectividad. Se utilizaron métodos cuali-cuantitativos con el fin de caracterizar las intervenciones previas a la implementación del protocolo, comparándolas con las posteriores a la capacitación y aplicación del protocolo. Resultados: Se halló que su implementación favoreció respuestas más adecuadas en contextos críticos y mejoró el conocimiento acerca de las estrategias de resolución que pueden efectuarse en el marco de la Ley Nacional de Salud Mental, reforzando asimismo factores protectores de la salud mental de los trabajadores de la salud, tales como el acceso a una estrategia que colabore en la organización de la tarea y el trabajo en equipo.

Cost-effectiveness of romosozumab for the treatment of postmenopausal women with osteoporosis at high risk of fracture in Belgium.

This study evaluated the cost-effectiveness of sequential treatment with romosozumab-to-alendronate compared to alendronate monotherapy and teriparatide-to-alendronate, in postmenopausal osteoporotic women from a Belgian healthcare perspective. Romosozumab-to-alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide-to-alendronate for osteoporotic women at high risk of fracture in Belgium. PURPOSE: This study aimed to evaluate the cost-effectiveness of sequential treatment with romosozumab followed by alendronate compared to alendronate monotherapy and teriparatide followed by alendronate, in postmenopausal osteoporotic women at high risk of fracture, from a Belgian healthcare perspective. Romosozumab is reimbursed in Belgium since December 2021. METHODS: A Markov microsimulation model was used to evaluate the cost-effectiveness of romosozumab-to-alendronate compared to alendronate monotherapy and to teriparatide-to-alendronate over a lifetime horizon. Patients transition between five different health states every 6 months based on fracture risks or death. The model was populated with Belgium-specific epidemiological and cost data, where available. The fracture risk reduction of romosozumab treatment was collated from the ARCH study, and from a published network meta-analysis. Costs were included from a healthcare perspective (NIHDI). Cost-effectiveness was reported in terms of costs per quality-adjusted life year (QALY), reported in Euro (€) 2022. Deterministic (DSA) and probabilistic sensitivity analyses (PSA) were performed. RESULTS: Romosozumab-to-alendronate was associated with 0.12 additional QALYs at an additional cost of €2314 compared to alendronate monotherapy, resulting in an ICER of €19,978. Compared to teriparatide-to-alendronate, romosozumab-to-alendronate was found to be dominant, with higher QALYs and lower costs. The base-case results were robust to uncertainty in the input parameters when conducting the sensitivity analysis. CONCLUSION: Sequential treatment with romosozumab followed by alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide followed by alendronate for postmenopausal women with osteoporosis at high risk of fracture in Belgium.

Pre-job loss grief reactions and work attachment among sick-listed employees: Introduction of the imminent Job Loss Scale.

BACKGROUND: With this study, we aimed to explore the emotional experiences of sick-listed employees facing imminent job loss, as this emotional distress may hinder successful job search outcomes. The study had two objectives: (1) to develop and validate the Imminent Job Loss Scale (IJLS) for assessing pre-job loss grief reactions and (2) to examine its relationship to work attachment. METHODS: Development of the 9-item IJLS was carried out using feedback from an expert panel, consisting of five academic experts in grief and labour, five re-integration specialists, and five sick-listed employees facing imminent job loss. The psychometric properties of the IJLS were evaluated, and its association with work attachment was examined using data from 200 sick-listed employees facing imminent job loss. RESULTS: The IJLS demonstrated strong internal consistency and temporal stability, distinctiveness from depression and anxiety symptoms, and solid convergent validity. Work-centrality and organizational commitment were positively related to pre-job loss grief reactions, while work engagement and calling showed no significant associations. CONCLUSION: This study provides valuable insights into pre-job loss grief reactions and shows the potential utility of the IJLS for screening and monitoring purposes. Understanding pre-job loss grief reactions can improve the re-integration and job prospects of sick-listed employees. In future research, explorations of these dynamics should continue to provide better support to sick-listed employees during this challenging period.

[Do All Very Old Patients Benefit from Osteoporosis Drug Treatment?]

INTRODUCTION: Osteoanabolic osteoporosis drugs have become better available. The osteoanabolic therapeutic principle has a stronger, faster-onset fracture-reducing effect than the antiresorptive preparations. It has also been newly recognized that the significance of a first fragility fracture as a risk factor is time-dependent: the less time that has elapsed since the first fracture, the higher the resulting re-fracture risk. Patients older than 65 years whose index fragility fracture occurred less than two years before are therefore grouped in a separate "Imminent Fracture Risk" category. These innovations were implemented by updating the osteoporosis therapy guideline. According to this guideline, patients in the "Imminent Fracture Risk" category should be offered osteoporosis therapy as soon as possible, in order to avoid as many fractures as possible. We are critical of an overly strict implementation of this algorithm in very old fracture patients. Our own data indicate that more than 30 % of this subpopulation do not experience the effect of a newly started osteoporosis therapy. We advocate a clinically based indication for osteoporosis therapy. For this, we propose a "Question Surprise" modified for osteological purposes. "Would I be surprised if I had to treat the same patient for a fracture again in a year?" If the question is answered with "No," then that patient could be a candidate for specific osteoporosis treatment.

Imminent fall risk after fracture.

RATIONALE: Adults with a recent fracture have a high imminent risk of a subsequent fracture. We hypothesise that, like subsequent fracture risk, fall risk is also highest immediately after a fracture. This study aims to assess if fall risk is time-dependent in subjects with a recent fracture compared to subjects without a fracture. METHODS: This retrospective matched cohort study used data from the UK Clinical Practice Research Datalink GOLD. All subjects ≥50 years with a fracture between 1993 and 2015 were identified and matched one-to-one to fracture-free controls based on year of birth, sex and practice. The cumulative incidence and relative risk (RR) of a first fall was calculated at various time intervals, with mortality as competing risk. Subsequently, analyses were stratified according to age, sex and type of index fracture. RESULTS: A total of 624,460 subjects were included; 312,230 subjects with an index fracture, matched to 312,230 fracture-free controls (71% females, mean age 70 ± 12, mean follow-up 6.5 ± 5 years). The RR of falls was highest in the first year after fracture compared to fracture-free controls; males had a 3-fold and females a 2-fold higher risk. This imminent fall risk was present in all age and fracture types and declined over time. A concurrent imminent fracture and mortality risk were confirmed. CONCLUSION/DISCUSSION: This study demonstrates an imminent fall risk in the first years after a fracture in all age and fracture types. This underlines the need for early fall risk assessment and prevention strategies in 50+ adults with a recent fracture.

Prediction using serum glycosylated fibronectin and angiogenic factors of superimposed pre-eclampsia in women with chronic hypertension.

OBJECTIVE: To compare the predictive performance for delivery with pre-eclampsia (PE) within 2 weeks of assessment in women with chronic hypertension at 24-41 weeks' gestation between serum glycosylated fibronectin (GlyFn) concentration, serum placental growth factor (PlGF) concentration and soluble fms-like tyrosine kinase-1 (sFlt-1) to PlGF concentration ratio. METHODS: This was a prospective study of 104 women with a singleton pregnancy and chronic hypertension presenting at 24-41 weeks' gestation. Twenty-six (25.0%) cases developed superimposed PE within 2 weeks of sampling. We compared the predictive performance for superimposed PE between GlyFn, PlGF and the sFlt-1/PlGF ratio at a fixed screen-positive rate of approximately 10%. RESULTS: The median gestational age at sampling was 34.1 (interquartile range, 31.5-35.6) weeks and 84.6% (88/104) of cases were sampled at < 36 weeks. The predictive performance for superimposed PE of the three methods of screening was similar, with detection rates of about 23-27%, at a screen-positive rate of 11% and a false-positive rate of about 5%. CONCLUSIONS: Measurement of GlyFn is a simple point-of-care test that can be carried out without need for a laboratory and provide results within 10 min of testing. In this respect, it could potentially replace the angiogenic markers that are used currently in the prediction of imminent PE in high-risk women. However, neither GlyFn nor angiogenic factors are likely to improve the management of women with chronic hypertension because their predictive performance for superimposed PE is poor. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Clinical and biological parameters associated with fracture recurrence according to fracture liaison service dataset.

This study describes the characteristics of 337 patients seen by the fracture liaison service of the Amiens University Hospital for at least two osteoporotic fractures between 2009 and 2019. Results showed that recurrent fracture occurs rapidly after the index fracture. Rheumatological and therapeutic managements are not sufficient, mainly because of cognitive disorders or patients' refusal. PURPOSE: The aim of this study was to describe the characteristics of patients taken in charge by a fracture liaison service and sustaining a recurrent osteoporotic fracture. METHODS: This was a retrospective and monocentric study based on the dataset of patients included in the FLS of the Department of Rheumatology of the Amiens University Hospital. To be included in the study cohort, patients must have had at least two consecutive osteoporotic fractures between January 2009 and December 2019. RESULTS: Three hundred thirty-seven patients were included. The mean age at index fracture was 77.3 ± 12.5 years. Eighty-four percent of the patients were women. 89.3% of the patients had a Charlson comorbidity index between 1 and 4. Nearly half of the patients had cognitive disorders. Femoral neck was the most frequent site for both index and recurrent fractures. Thirty-seven percent of patients benefited from a consultation in Rheumatology after their index fracture. The main reasons for the lack of follow-up were cognitive disorders and patient rejection. CONCLUSION: Our study showed that recurrent fracture occurs rapidly after the index fracture and that rheumatological and therapeutic managements are not sufficient, mainly because of cognitive disorders or patients' refusal impairing the patients to benefit from specialized management.

MRI-based radiomics assessment of the imminent new vertebral fracture after vertebral augmentation.

BACKGROUND: Imminent new vertebral fracture (NVF) is highly prevalent after vertebral augmentation (VA). An accurate assessment of the imminent risk of NVF could help to develop prompt treatment strategies. PURPOSE: To develop and validate predictive models that integrated the radiomic features and clinical risk factors based on machine learning algorithms to evaluate the imminent risk of NVF. MATERIALS AND METHODS: In this retrospective study, a total of 168 patients with painful osteoporotic vertebral compression fractures treated with VA were evaluated. Radiomic features of L1 vertebrae based on lumbar T2-weighted images were obtained. Univariate and LASSO-regression analyses were applied to select the optimal features and construct radiomic signature. The radiomic signature and clinical signature were integrated to develop a predictive model by using machine learning algorithms including LR, RF, SVM, and XGBoost. Receiver operating characteristic curve and calibration curve analyses were used to evaluate the predictive performance of the models. RESULTS: The radiomic-XGBoost model with the highest AUC of 0.93 of the training cohort and 0.9 of the test cohort among the machine learning algorithms. The combined-XGBoost model with the best performance with an AUC of 0.9 in the training cohort and 0.9 in the test cohort. The radiomic-XGBoost model and combined-XGBoost model achieved better performance to assess the imminent risk of NVF than that of the clinical risk factors alone (p < 0.05). CONCLUSION: Radiomic and machine learning modeling based on T2W images of preoperative lumbar MRI had an excellent ability to evaluate the imminent risk of NVF after VA.

Prediction using serum glycosylated fibronectin of imminent pre-eclampsia in women with new-onset hypertension.

OBJECTIVE: To compare the predictive performance for delivery with pre-eclampsia (PE) within 2 weeks after assessment in women with new-onset hypertension at 24-41 weeks' gestation between serum glycosylated fibronectin (GlyFn) concentration, serum placental growth factor (PlGF) concentration and soluble fms-like tyrosine kinase-1 (sFlt-1) to PlGF concentration ratio. METHODS: This was a prospective observational study of 409 women with a singleton pregnancy presenting at 24-41 weeks' gestation with new-onset hypertension. The recommended cut-off for sFlt-1/PlGF ratio for the prediction of PE in the platform used in this study is 85; the appropriate cut-offs for GlyFn and PlGF were determined to achieve the same screen-positive rate as that of sFlt-1/PlGF ratio > 85. We then compared the predictive performance for delivery with PE within 2 weeks after presentation between GlyFn, PlGF and sFlt-1/PlGF, both overall and in subgroups according to gestational age at presentation. RESULTS: Delivery with PE within 2 weeks occurred in 93 (22.7%) cases. The screen-positive rate for sFlt-1/PlGF ratio > 85 was 46.2%. The cut-off corresponding to a screen-positive rate of 46.2% was 75 pg/mL for PlGF and 510 µg/mL for GlyFn. The overall detection rate for delivery with PE within 2 weeks after presentation was 62.4% (95% CI, 51.7-72.2%) for GlyFn and sFlt-1/PlGF and 60.2% (95% CI, 49.5-70.2%) for PlGF. In all women who delivered with PE within 2 weeks after presentation at < 34 weeks' gestation and in about 60-70% of those presenting at < 38 weeks, GlyFn and sFlt-1/PlGF were increased and PlGF was reduced. However, the screen-positive rate for these tests was very high at about 45%. The predictive performance for delivery with PE within 2 weeks after presentation at ≥ 38 weeks' gestation was poorer for all three methods of screening, with detection rates of 47-63% at screen-positive rates of 40-50%. CONCLUSIONS: In women with new-onset hypertension, the predictive performance for delivery with PE within 2 weeks after presentation for serum GlyFn is similar to that of PlGF and the sFlt-1/PlGF ratio, but GlyFn may be the preferred option because it is a rapid point-of-care test. However, the predictive performance for all tests is relatively poor. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Risk factors predicting the 'time to first fracture' and its association with imminent fractures: a substudy of the FRISBEE cohort.

Only previous glucocorticoid use and rheumatoid arthritis were predictors of an early fracture (< 2 years after inclusion). A shorter 'time to first fracture' was not an independent clinical risk factor for imminent fractures. PURPOSE: Risk factors for fragility fractures independent of BMD were assessed in several prediction models. However, predictors of a shorter 'time to first fracture' and its impact on imminent fractures are unknown. METHODS: We studied the concept of 'time to first fracture' in the FRISBEE ("Fracture RIsk Brussels Epidemiological Enquiry") cohort (3560 postmenopausal women). Validated fractures were divided into 3 groups: first fracture < 2 years, 2-5 years, and > 5 years after inclusion. Factors associated with first fracture risk were evaluated with uni- and multivariate analyses using Cox modeling. We examined 'time to first fracture' as a risk factor for imminent fractures in untreated subjects and in those receiving pharmacological treatment. RESULTS: Classical risk factors (age, prior fracture, fall history and low BMD) were associated with first fracture in all groups. Previous glucocorticoids and rheumatoid arthritis (RA) were predictors for fracture < 2 years. Imminent fractures were similar in subjects with or without osteoporosis treatment, despite a higher estimated 10-year risk of fragility fracture in those treated, suggesting that treatment is efficient. 'Time to first fracture' was not an independent risk factor for imminent fractures. CONCLUSION: Among the risk factors considered, previous glucocorticoid use and RA were predictors for early fracture, consistent with the concept of very high risk. The 'time to first validated fracture' was not an independent risk factor for imminent fractures. Patients with a first osteoporotic fracture should thus be considered at very high risk for re-fracture, independent of the 'time to first fracture'.

Osteoporosis treatment gap in patients at risk of fracture in Egypt: a multi-center, cross-sectional observational study.

Despite the wide availability of a wide variety of approved osteoporosis medications and DXA scan centers in Egypt, only a minority of patients at high risk of sustaining a fragility fracture receive treatment, even after their first fracture. Such big "treatment gap" leaves the most high-risk individuals unprotected against fragility fractures. This study provides a benchmark to monitor national trends in osteoporosis management and service uptake. PURPOSE: To assess the treatment gap among men and postmenopausal women presenting with a fragility fracture, and to analyze the characteristics and fracture risks of the patients presenting with an index fragility fracture. METHODS: This was a multi-center, cross-sectional, observational study. Both men and postmenopausal women, admitted with an osteoporotic fracture (whether major osteoporosis or hip fracture), were consecutively recruited for this work. The fracture risk was assessed based on their FRAX calculation prior to the index fracture. All the patients were assessed for their falls and sarcopenia risks. Blood tests for bone profile as well as DXA scan were offered to all the patients. RESULTS: Two hundred and thirty-six patients presenting with fragility fractures were included in this work. 70.8% were women and 29.2% were men. Mean age was 70.1 (SD = 9.2) years. Ten-year probability of fracture (without BMD) was high in 65.9% of the postmenopausal women and 40.3% of the men. 82.1% of the postmenopausal women and 100% in men identified to be eligible for osteoporosis therapy did not receive any form of osteoporosis therapy. FRAX score correlated significantly with bone mineral density assessment at both hip and spine. Falls, sarcopenia, and functional disability showed significant relation to the fracture risk. CONCLUSIONS: There is a large treatment gap in Egyptian older adults. The recent guidelines for osteoporosis management in Egypt endorsed fracture centric approach to identify people at risk. The gap appears to be related to a low rate of osteoporosis diagnosis and lack of patient education.

Selection for treatment of patients at high risk of fracture by the short versus long term prediction models - data from the Belgian FRISBEE cohort.

Our imminent model was less sensitive but more selective than FRAX® in the choice of treatment to prevent imminent fractures. This new model decreased NNT by 30%, which could reduce the treatment costs. In the Belgian FRISBEE cohort, the effect of recency further decreased the selectivity of FRAX®. PURPOSE: We analyzed the selection for treatment of patients at high risk of fracture by the Belgian FRISBEE imminent model and the FRAX® tool. METHODS: We identified in the FRISBEE cohort subjects who sustained an incident MOF (mean age 76.5 ± 6.8 years). We calculated their estimated 10-year risk of fracture using FRAX® before and after adjustment for recency and the 2-year probability of fracture using the FRISBEE model. RESULTS: After 6.8 years of follow-up, we validated 480 incident and 54 imminent MOFs. Of the subjects who had an imminent fracture, 94.0% had a fracture risk estimated above 20% by the FRAX® before correction for recency and 98.1% after adjustment, with a specificity of 20.2% and 5.9%, respectively. The sensitivity and specificity of the FRISBEE model at 2 years were 72.2% and 55.4%, respectively, for a threshold of 10%. For these thresholds, 47.3% of the patients were identified at high risk in both models before the correction, and 17.2% of them had an imminent MOF. The adjustment for recency did not change this selection. Before the correction, 34.2% of patients were selected for treatment by FRAX® only, and 18.8% would have had an imminent MOF. This percentage increased to 47% after the adjustment for recency, but only 6% of those would suffer a MOF within 2 years. CONCLUSION: In our Belgian FRISBEE cohort, the imminent model was less sensitive but more selective in the selection of subjects in whom an imminent fracture should be prevented, resulting in a lower NNT. The correction for recency in this elderly population further decreased the selectivity of FRAX®. These data should be validated in additional cohorts before using them in everyday practice.

How are rheumatologists from Argentina managing patients with arthralgias suspicious for progressing to rheumatoid arthritis?

Patients with arthralgias who could be at risk of progressing to rheumatoid arthritis (RA) represent a clinical challenge. Recommendations for their management and treatment are lacking. The purpose of the present study was to determine how Argentinean rheumatologists deal with these patients. We developed an anonymous ad hoc survey which was sent to 522 Argentinean rheumatologists. The RA study group of our Argentinean Rheumatology National Society assisted in forwarding the surveys to its members via the internet (e-mail or WhatsApp). The findings of the collected data are presented as descriptive statistics. The questionnaires were completed by 255 rheumatologists (overall response rate of 48.9%), and 97.6% confirmed that their practices had received medical consultations to rule out RA in patients with arthralgias. Ultrasound (US) was the method of first choice (93.7%) as part of the evaluation of these patients. For those in whom US power Doppler signal was present in at least one joint, 93.7% of the participants would start treatment and methotrexate was the first choice (58.1%). In patients with tenosynovitis but no synovitis on US, most rheumatologists would start treatment (89.4%), being NSAIDs the drug of first choice (52.3%). Argentinean rheumatologists evaluate patients with imminent RA and treat them based on their clinical judgment and findings from the US evaluation of affected joints; the drug of first choice for these patients among these rheumatologists was methotrexate. Despite published data of recent clinical trials, recommendations for the management and treatment of these patients are necessary.

Risk of osteoporotic fracture and refracture: the importance of index fracture site.

The current study shows that patients aged 50 or more who have sustained an osteoporotic fracture have a significant risk of suffering a new fracture. Refracture risk is also increased when anatomic site of both index and subsequent fracture are the same. PURPOSE: The purpose of this study is to describe the profile of a patient sustaining a fragility fracture, the influence of the initial or index fracture on subsequent fracture risk and the role that anatomic site of index and subsequent fracture play on fracture risk. METHODS: In this retrospective observational cohort study, individuals aged ≥ 50 years who sustained at least one clinical fragility fracture were identified from the public health service register between January 1, 2014, and December 31, 2015. Two separate analysis cohorts were identified. Group 1 (index FF) included patients that sustained at least one clinical fragility fracture during the study period. Group 2 (subsequent FF) included those patients from group 1 who sustained at least one clinical subsequent fracture during the following 2 years after index fracture. RESULTS: A total of 11,986 fractures constituted group 1 (index FF), and 792 constituted group 2 (subsequent FF). The incidence of subsequent fractures was 6.61%, with a major percentage of them (36.99%) identified within the first 6 months following index FF. Hip was the most frequent site for index (30.09%) and subsequent fracture (34.85%). We found an increased risk mainly when anatomic site of index and subsequent FF are the same. CONCLUSIONS: Sustaining a subsequent fracture after an index fracture is a common event in the population over age 50, more commonly occurring within 6 months of index fracture. Analysis of fracture site correlation shows that refracture risk is increased mainly when index and subsequent fracture site are the same.

Resistance-proof antimicrobial drug discovery to combat global antimicrobial resistance threat.

Drug resistance is well-defined as a serious problem in our living world. To survive, microbes develop defense strategies against antimicrobial drugs. Drugs exhibit less or no effective results against microbes after the emergence of resistance because they are unable to cross the microbial membrane, in order to alter enzymatic systems, and/or upregulate efflux pumps, etc. Drug resistance issues can be addressed effectively if a "Resistance-Proof" or "Resistance-Resistant" antimicrobial agent is developed. This article discusses first the need for resistance-proof drugs, the imminent properties of resistance-proof drugs, current and future research progress in the discovery of resistance-proof antimicrobials, the inherent challenges, and opportunities. A molecule having imminent resistance-proof properties could target microbes efficiently, increase potency, and rule out the possibility of early resistance. This review triggers the scientific community to think about how an upsurge in drug resistance can be averted and emphasizes the discussion on the development of next-generation antimicrobials that will provide a novel effective solution to combat the global problem of drug resistance. Hence, resistance-proof drug development is not just a requirement but rather a compulsion in the drug discovery field so that resistance can be battled effectively. We discuss several properties of resistance-proof drugs which could initiate new ways of thinking about next-generation antimicrobials to resolve the drug resistance problem. This article sheds light on the issues of drug resistance and discusses solutions in terms of the resistance-proof properties of a molecule. In summary, the article is a foundation to break new ground in the development of resistance-proof therapeutics in the field of infection biology.