Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX.

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX. INTRODUCTION: The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD). METHODS: We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted ß-coefficients. RESULTS: A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination. CONCLUSION: A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.

Transplantation to save the life, TSH screening to save the brain: A report and brief literature review of autoimmune thyroid disease after HSCT for severe combined immunodeficiency.

Autoimmune thyroid disease has been described as a complication of HSCT for different indications and as a manifestation of inborn errors of immunity, like SCID. A 1-month female was diagnosed with RAG1-mutated SCID and received allogenic HSCT. She developed autoimmune hypothyroidism 5 months after transplantation and was treated with levo-thyroxine with a good response. Autoimmune thyroid disease can develop after HSCT during the immune reconstitution phase, leading to potentially severe neurological and growth impairment, particularly in SCID patients, often transplanted during the first year of life. Recommendations regarding early and frequent vigilance for thyroid function are needed in these patients.

Reference microarchitectural values measured by HR-pQCT in a Franco-Swiss cohort of young adult women.

Bone microarchitecture assessed by high-resolution peripheral quantitative computed tomography varies across populations of different origin. The study presents a reference dataset of microarchitectural parameters in a homogeneous group of participants aged within 22-27 range determined by a discriminant analysis of a larger cross-sectional cohort of 339 women. INTRODUCTION: High-resolution peripheral quantitative computed tomography (HR-pQCT) non-invasively measures three-dimensional bone microarchitectural parameters and volumetric bone mineral density. Previous studies established normative reference HR-pQCT datasets for several populations, but there were few data assessed in a reference group of young women with Caucasian ethnicity living in Western Europe. It is important to obtain different specific reference dataset for a valid interpretation of cortical and trabecular microarchitecture data. The aim of our study was to find the population with the most optimal bone status in order to establish a descriptive reference HR-pQCT dataset in a young and healthy normal-weight female cohort living in a European area including Geneva, Switzerland, Lyon and Saint-Etienne, France. METHODS: We constituted a cross-sectional cohort of 339 women aged 19-41 years with a BMI > 18 and < 30 kg/m2. All participants had HR-pQCT measurements at both non-dominant distal radius and tibia sites. RESULTS: We observed that microarchitectural parameters begin to decline before the age of 30 years. Based on a discriminant analysis, the optimal bone profile in this population was observed between the age range of 22 to 27 years. Consequently, we considered 43 participants aged 22-27 years to establish a reference dataset with median values and percentiles. CONCLUSION: This is the first study providing reference values of HR-pQCT measurements considering specific age bounds in a Franco-Swiss female cohort at the distal radius and tibia sites.

Update of the fracture risk prediction tool FRAX: a systematic review of potential cohorts and analysis plan.

We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. INTRODUCTION: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. METHODS: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. RESULTS: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. CONCLUSIONS: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).

Ventilation strategies to reduce airborne transmission of viruses in classrooms: A systematic review of scientific literature.

The recent pandemic due to SARS-CoV-2 has brought to light the need for strategies to mitigate contagion between human beings. Apart from hygiene measures and social distancing, air ventilation highly prevents airborne transmission within enclosed spaces. Among others, educational environments become critical in strategic planning to control the spread of pathogens and viruses amongst the population, mainly in cold conditions. In the event of a virus outbreak - such as COVID or influenza - many school classrooms still lack the means to guarantee secure and healthy environments. The present review examines school contexts that implement air ventilation strategies to reduce the risk of contagion between students. The analysed articles present past experiences that use either natural or mechanical systems assessed through mathematical models, numerical models, or full-scale experiments. For naturally ventilated classrooms, the studies highlight the importance of the architectural design of educational spaces and propose strategies for aeration control such as CO2-based control and risk-infection control. When it comes to implementing mechanical ventilation in classrooms, different systems with different airflow patterns are assessed based on their ability to remove airborne pathogens considering parameters like the age of air and the generation of airflow streamlines. Moreover, studies report that programmed mechanical ventilation systems can reduce risk-infection during pandemic events. In addition to providing a systematic picture of scientific studies in the field, the findings of this review can be a valuable reference for school administrators and policymakers to implement the best strategies in their classroom settings towards reducing infection risks.

Vertebral fracture: epidemiology, impact and use of DXA vertebral fracture assessment in fracture liaison services.

Vertebral fractures are independent risk factors for vertebral and nonvertebral fractures. Since vertebral fractures are often missed, the relatively new introduction of vertebral fracture assessment (VFA) for imaging of the lateral spine during DXA-measurement of the spine and hips may contribute to detect vertebral fractures. We advocate performing a VFA in all patients with a recent fracture visiting a fracture liaison service (FLS). Fracture liaison services (FLS) are important service models for delivering secondary fracture prevention for older adults presenting with a fragility fracture. While commonly age, clinical risk factors (including fracture site and number of prior fracture) and BMD play a crucial role in determining fracture risk and indications for treatment with antiosteoporosis medications, prevalent vertebral fractures usually remain undetected. However, vertebral fractures are important independent risk factors for future vertebral and nonvertebral fractures. A development of the DXA technology, vertebral fracture assessment (VFA), allows for assessment of the lateral spine during the regular DXA bone mineral density measurement of the lumbar spine and hips. Recent approaches to the stratification of antiosteoporosis medication type according to baseline fracture risk, and differences by age in the indication for treatment by prior fracture mean that additional information from VFA may influence initiation and type of treatment. Furthermore, knowledge of baseline vertebral fractures allows reliable definition of incident vertebral fracture events during treatment, which may modify the approach to therapy. In this manuscript, we will discuss the epidemiology and clinical significance of vertebral fractures, the different methods of detecting vertebral fractures, and the rationale for, and implications of, use of VFA routinely in FLS. • Vertebral fracture assessment is a tool available on modern DXA instruments and has proven ability to detect vertebral fractures, the majority of which occur without a fall and without the signs and symptoms of an acute fracture. • Most osteoporosis guidelines internationally suggest that treatment with antiosteoporosis medications should be considered for older individuals (e.g., 65 years +) with a recent low trauma fracture without the need for DXA. • Younger individuals postfracture may be risk-assessed on the basis of FRAX® probability including DXA and associated treatment thresholds. • Future fracture risk is markedly influenced by both site, number, severity, and recency of prior fracture; awareness of baseline vertebral fractures facilitates definition of true incident vertebral fracture events occurring during antiosteoporosis treatment. • Detection of previously clinically silent vertebral fractures, defining site of prior fracture, might alter treatment decisions in younger or older FLS patients, consistent with recent IOF-ESCEO guidance on baseline-risk-stratified therapy, and provides a reliable baseline from which to define new, potentially therapy-altering, vertebral fracture events.

Diagnosis and management of osteoporosis in chronic kidney disease stages 4 to 5D: a call for a shift from nihilism to pragmatism.

The European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) CKD-MBD working group, in collaboration with the Committee of Scientific Advisors of the International Osteoporosis Foundation, published a position paper for the diagnosis and management of osteoporosis in patients with CKD stages 4-5D (eGFR < 30 ml/min 1.73 m2). The present article reports and summarizes the main recommendations included in this 2021 document. The following areas are reviewed: diagnosis of osteoporosis; risk factors for fragility fractures; fracture risk assessment; intervention thresholds for pharmacological intervention; general and pharmacological management of osteoporosis; monitoring of treatment, and systems of care, all in patients with CKD stages 4-5D. Guidance is provided for clinicians caring for CKD stages 4-5D patients with osteoporosis, allowing for a pragmatic individualized diagnostic and therapeutic approach as an alternative to current variations in care and treatment nihilism.

Higher serum levels of a cathepsin K-generated periostin fragment are associated with fractures in postmenopausal women with primary hyperparathyroidism: a pilot study.

The only difference between fractured and non-fractured postmenopausal women with PHPT of same sex, age, and BMI was a significantly mean higher serum k-periostin level. K-periostin value was associated with fracture at any site (odds ratio 1.044, 95% CI 1.005-1.091, p = 0.03). INTRODUCTION: To assess serum k-periostin fragment levels in patients with primary hyperparathyroidism (PHPT), fractured and non-fractured matched for sex, age, and body mass index. METHODS: Twenty-five Caucasian fractured postmenopausal women with PHPT (group Fx) and 25 PHPT non-fractured (group NFx) were enrolled. Each patient underwent DXA scan at lumbar, hip, and forearm, spine X-ray, and biochemical evaluation of calcium metabolism. For k-periostin analyses, we utilized a specific ELISA test that detects CatK-generated fragment levels in the bloodstream. RESULTS: We found no difference in mean BMD and bone turnover marker values between Fx and NFx groups. Prevalence of osteoporosis was not significantly different in Fx vs NFx (72% vs 60%, p = 0.55). Among Fx, 16% reported multiple fractures, 28% morphometric vertebral fractures, 4% femoral fractures, 28% non-vertebral non-femoral fractures, and 8% wrist fractures. The only detectable difference between Fx and NFx group was a significantly mean higher k-periostin serum level (46.2 ± 21.4 vs 34.7 ± 13.5 ng/ml, p = 0.02). K-periostin was associated with fracture at any site (odds ratio 1.044, 95% CI 1.005-1.091, p = 0.03). No difference in mean k-periostin values was found between patients with vertebral fracture vs those with non-vertebral fracture, and between those with multiple fractures vs those with single fracture. CONCLUSION: Serum k-periostin is significantly associated with fracture in PHPT. If confirmed by further studies, k-periostin could be considered a new marker of bone fragility in PHPT, independently of BMD.

Is orthorexia nervosa a feature of obsessive-compulsive disorder? A multicentric, controlled study.

PURPOSE: The term orthorexia nervosa (ON) was coined to describe altered thoughts and behaviours related to healthy eating. The prevalence of ON was found to scale up to almost 90% among high-risk populations (ballet dancers, athletes, and health workers). ON seem to share psychopathological aspects with both Eating Disorders (ED) and Obsessive-Compulsive Disorder (OCD). The aim of the study was to analyse the frequency and intensity of ON symptoms among subjects diagnosed with OCD, hypothesising that they would be higher than in two control groups (subjects with anxiety-depressive disorders and general population). METHODS: We conducted a multi-centre, observational, controlled study. Subjects filled in a socio-demographic questionnaire including questions related to life-style and two psychometric instruments: ORTO-15, for ON symptoms, and OCI-R, for OCD symptoms. Post hoc analysis of the dataset was performed using the revised version of ORTO-15, the ORTO-R. RESULTS: In the final sample of 328 subjects, the overall prevalence of ORTO-15-ON was 59.5%, mean score 37.9 ± 4.2. The mean score at the ORTO-R was 16.6 ± 4.6. No statistically significant differences were found in the prevalence of ON or in the mean ORTO-15 score among OCD patients and the two control groups, and this was confirmed by the multiple regression analysis. At the ORTO-R re-scoring, OCD patients scored significantly lower than the two clinical subgroups (p = .0005) and a lower ORTO-R score was associated to positivity at the OCI-R, confirming the initial hypothesis of the study. CONCLUSIONS: ON symptoms do seem to be more prevalent among subjects suffering from OCD. The psychometric properties of tools available to calculate ON symptoms, namely ORTO-15 vs. ORTO-R, play a relevant role in explaining such finding. ORTO-R seems to be a valid alternative able to overcome such difficulties, though further studies are needed to confirm this.

The underestimated burden of aspiration event and pneumonia within hospitals: what happens after dysphagia.

Study design: Prospective observational study. Background: Despite dysphagia large prevalence and the growing ageing phenomenon occurring in European countries, aspiration events among inpatients are often underestimated, given their frequent spontaneous resolution or silent contribution to aspiration syndromes. Our main objective was to evaluate the incidence of aspiration events among medical inpatients and to identify risk factors influencing the outcome of the event. Methods: Data about aspiration events - day, hour, type and outcome of the event occurred - along with underlying patient clinical conditions at the admission were collected. Between May 2015 and September 2016, data about aspiration event occurred among medical inpatients were collected in three large Italian hospitals. Results: Patients affected by aspiration events were 135 on 102,619 cumulative days of hospitalization; they were mostly females (53%) with an average age of 82. The total incidence of aspiration events was of 1.4 every 1,000 days of hospitalization (C.I. 95%: 1.2-1.7) and the most frequent manifestation was cough (61.6%). The addition of drugs or an infection diagnosis during the 24 hours preceding the event acted as risk factors for those events that needed additional interventions during the hospitalization (OR 3.1 e OR 1.9 respectively), while the elimination of one or more prescribed drugs seemed to lead to aspiration events without impact on the hospitalization. Conclusions: Results showed a large incidence of aspiration events within medical wards, many of them influencing patient outcomes. Healthcare professionals' attention concerning aspiration events should be fostered during the first hours and days of hospitalization.

Perspectives on the non-invasive evaluation of femoral strength in the assessment of hip fracture risk.

We reviewed the experimental and clinical evidence that hip bone strength estimated by BMD and/or finite element analysis (FEA) reflects the actual strength of the proximal femur and is associated with hip fracture risk and its changes upon treatment. INTRODUCTION: The risk of hip fractures increases exponentially with age due to a progressive loss of bone mass, deterioration of bone structure, and increased incidence of falls. Areal bone mineral density (aBMD), measured by dual-energy X-ray absorptiometry (DXA), is the most used surrogate marker of bone strength. However, age-related declines in bone strength exceed those of aBMD, and the majority of fractures occur in those who are not identified as osteoporotic by BMD testing. With hip fracture incidence increasing worldwide, the development of accurate methods to estimate bone strength in vivo would be very useful to predict the risk of hip fracture and to monitor the effects of osteoporosis therapies. METHODS: We reviewed experimental and clinical evidence regarding the association between aBMD and/orCT-finite element analysis (FEA) estimated femoral strength and hip fracture risk as well as their changes with treatment. RESULTS: Femoral aBMD and bone strength estimates by CT-FEA explain a large proportion of femoral strength ex vivo and predict hip fracture risk in vivo. Changes in femoral aBMD are strongly associated with anti-fracture efficacy of osteoporosis treatments, though comparable data for FEA are currently not available. CONCLUSIONS: Hip aBMD and estimated femoral strength are good predictors of fracture risk and could potentially be used as surrogate endpoints for fracture in clinical trials. Further improvements of FEA may be achieved by incorporating trabecular orientations, enhanced cortical modeling, effects of aging on bone tissue ductility, and multiple sideway fall loading conditions.

A patient-level key performance indicator set to measure the effectiveness of fracture liaison services and guide quality improvement: a position paper of the IOF Capture the Fracture Working Group, National Osteoporosis Foundation and Fragility Fracture Network.

The International Osteoporosis Foundation (IOF) Capture the Fracture® Campaign with the Fragility Fracture Network (FFN) and National Osteoporosis Foundation (NOF) has developed eleven patient-level key performance indicators (KPIs) for fracture liaison services (FLSs) to guide quality improvement. INTRODUCTION: Fracture Liaison Services (FLSs) are recommended worldwide to reduce fracture risk after a sentinel fracture. Given not every FLS is automatically effective, the IOF Capture the Fracture working group has developed and implemented the Best Practice Framework to assess the organisational components of an FLS. We have now developed a complimentary KPI set that extends this assessment of performance to the patient level. METHODS: The Capture the Fracture working group in collaboration with the Fragility Fracture Network Secondary Fragility Fracture Special Interest Group and National Osteoporosis Foundation adapted existing metrics from the UK-based Fracture Liaison Service Database Audit to develop a patient-level KPI set for FLSs. RESULTS: Eleven KPIs were selected. The proportion of patients: with non-spinal fractures; with spine fractures (detected clinically and radiologically); assessed for fracture risk within 12 weeks of sentinel fracture; having DXA assessment within 12 weeks of sentinel fracture; having falls risk assessment; recommended anti-osteoporosis medication; commenced of strength and balance exercise intervention within 16 weeks of sentinel fracture; monitored within 16 weeks of sentinel fracture; started anti-osteoporosis medication within 16 weeks of sentinel fracture; prescribed anti-osteoporosis medication 52 weeks after sentinel fracture. The final KPI measures data completeness for each of the other KPIs. For these indicators, levels of achievement were set at the < 50%, 50-80% and > 80% levels except for treatment recommendation where a level of 50% was used. CONCLUSION: This KPI set compliments the existing Best Practice Framework to support FLSs to examine their own performance using patient-level data. By using this KPI set for local quality improvement cycles, FLSs will be able to efficiently realise the full potential of secondary fracture prevention and improved clinical outcomes for their local populations.

Subgroup comparison according to clinical phenotype and serostatus in autoimmune encephalitis: a multicenter retrospective study.

BACKGROUND AND PURPOSE: Autoimmune encephalitides (AE) include a spectrum of neurological disorders whose diagnosis revolves around the detection of neuronal antibodies (Abs). Consensus-based diagnostic criteria (AE-DC) allow clinic-serological subgrouping of AE, with unclear prognostic implications. The impact of AE-DC on patients' management was studied, focusing on the subgroup of Ab-negative-AE. METHODS: This was a retrospective multicenter study on patients fulfilling AE-DC. All patients underwent Ab testing with commercial cell-based assays (CBAs) and, when available, in-house assays (immunohistochemistry, live/fixed CBAs, neuronal cultures) that contributed to defining final categories. Patients were classified as Ab-positive-AE [N-methyl-d-aspartate-receptor encephalitis (NMDAR-E), Ab-positive limbic encephalitis (LE), definite-AE] or Ab-negative-AE (Ab-negative-LE, probable-AE, possible-AE). RESULTS: Commercial CBAs detected neuronal Abs in 70/118 (59.3%) patients. Testing 37/48 Ab-negative cases, in-house assays identified Abs in 11 patients (29.7%). A hundred and eighteen patients fulfilled the AE-DC, 81 (68.6%) with Ab-positive-AE (Ab-positive-LE, 40; NMDAR-E, 32; definite-AE, nine) and 37 (31.4%) with Ab-negative-AE (Ab-negative-LE, 17; probable/possible-AE, 20). Clinical phenotypes were similar in Ab-positive-LE versus Ab-negative-LE. Twenty-four/118 (20.3%) patients had tumors, and 19/118 (16.1%) relapsed, regardless of being Ab-positive or Ab-negative. Ab-positive-AE patients were treated earlier than Ab-negative-AE patients (P = 0.045), responded more frequently to treatments (92.3% vs. 65.6%, P < 0.001) and received second-line therapies more often (33.3% vs. 10.8%, P = 0.01). Delays in first-line therapy initiation were associated with poor response (P = 0.022; odds ratio 1.02; confidence interval 1.00-1.04). CONCLUSIONS: In-house diagnostics improved Ab detection allowing better patient management but was available in a patient subgroup only, implying possible Ab-positive-AE underestimation. Notwithstanding this limitation, our findings suggest that Ab-negative-AE and Ab-positive-AE patients share similar oncological profiles, warranting appropriate tumor screening. Ab-negative-AE patients risk worse responses due to delayed and less aggressive treatments.

Clinical and Socio-demographic Variables Associated with the Outcome of Vocational Rehabilitation Programs: A Community-Based Italian Study.

This study aims to identify clinical and socio-demographic variables associated with the outcome of vocational rehabilitation programs (VRPs). All users of an Italian Community Mental Health Centre (CMHC) included in VRPs delivered according to the model of Supported Employment in years 2011-2016 were retrospectively enrolled. Fifty users who ended the program with employment were compared with fifty users who dropped out, with respect to clinical and socio-demographic variables. VRPs lasting less than 6 months and oriented toward the competitive labor market had a higher probability of employment. Among users who successfully ended the VRP, the median of health interventions significantly decreased after employment. In the same group of users, less non-health interventions strictly linked to the VRP were required, when compared with users who dropped out. We conclude that employment is associated with improvement of users' clinical conditions and reduced workload for the CMHC.

Associations between radius low-frequency axial ultrasound velocity and bone fragility in elderly men and women.

An exploratory study in elderly women and men from the Geneva Retirees Cohort indicates that low-frequency quantitative ultrasound measurement at the radius captures aBMD, bone size, and cortical tissue mineral density and might be used for screening purposes prior to DXA to evaluate fracture risk. INTRODUCTION: The contribution of distal radius bone mineral density (BMD) and cortical microstructure to fracture risk has recently been demonstrated. In this exploratory study, we investigated whether low-frequency quantitative ultrasound measurement at the distal radius may capture the peripheral determinants of bone fragility assessed with dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Low-frequency velocity (VLF) was measured at the radius using OsCare Sono®, a portable axial transmission ultrasonometer, in 271 community-dwelling postmenopausal women and men (age 71.5 ± 1.4 years) from the Geneva Retirees Cohort. Cortical (Ct) and trabecular (Tb) volumetric (v) BMD and microstructure at the distal radius were assessed by HR-pQCT, in addition to areal (a) BMD by DXA, at the same time point. RESULTS: VLF was highly correlated with aBMD at the distal third radius (r = 0.72, p < 0.001). For microstructure parameters, the highest correlation was observed with cortical area (r = 0.59, p < 0.001). VLF also captured bone geometry (total area) and cortical tissue mineral density independently of aBMD. In models adjusted for age and sex, VLF was significantly associated with prevalent low-trauma fractures [OR 95%CI for one SD decrease of VLF 1.50 (1.05, 2.14), p = 0.024], with discrimination performance comparable to femoral neck or distal radius aBMD. CONCLUSION: Measurement of VLF at the radius captures aBMD, bone size, and cortical tissue mineral density and might be used for screening purposes prior to DXA to evaluate fracture risk.

Higher rates of osteoporosis treatment initiation and persistence in patients with newly diagnosed vertebral fracture when introduced in inpatients than later in outpatients.

Whether in-hospital management of patients with newly identified vertebral fractures leads to a higher rate of osteoporosis medication than delayed outpatient management remains unknown. Our study showed that early osteoporosis therapy initiation in a fracture liaison service during hospital stay was a more efficacious strategy for secondary fracture prevention. INTRODUCTION: Fracture liaison services are standard care for secondary fracture prevention. A higher rate of osteoporosis treatment initiation may be considered when introduced in the hospital rather than an outpatient recommendation to a primary care physician (PCP). Whether this applies to patients with newly detected vertebral fractures in a general internal medicine ward remains unknown. We prospectively investigated whether in-hospital management of newly identified vertebral fractures led to a higher rate of osteoporosis medication initiation and persistence at 3 and 6 months than delayed outpatient management by a PCP. METHODS: We conducted a prospective study including hospitalized patients > 60 years systematically searched for asymptomatic vertebral fractures on lateral chest and/or abdominal radiographs. Patients were included either in phase 1 (outpatient care recommendations on osteoporosis management to a PCP) or in phase 2 (inpatient care management initiated during hospitalization). The percentage of patients under osteoporosis treatment was evaluated by telephone interview at 3 and 6 months. RESULTS: Outpatients' (84 with fracture/407 assessed (21%); 75.7 ± 7.7 years) and inpatients' (100/524 (19%); 77.8 ± 9.4 years) characteristics were similar. Osteoporosis medication was more often prescribed in inpatients at 3 (67% vs. 19%, respectively; p < 0.001) and 6 months (69 vs. 27%, respectively; p < 0.001). The percentage under treatment was also higher in inpatients than in outpatients at 3 (52 vs. 19%, p < 0.001) and 6 months (54 vs. 22%, p < 0.001). Length of stay and destination post-discharge were not different between groups. CONCLUSIONS: Early patient management after a newly detected vertebral fracture during hospitalization was a more efficacious strategy of secondary fracture prevention than delayed outpatient management following discharge.

Fracture risk following intermission of osteoporosis therapy.

Given the widespread practice of recommending drug holidays, we reviewed the impact of medication discontinuation of two common anti-osteoporosis therapies (bisphosphonates and denosumab). Trial evidence suggests the risk of new clinical fractures, and vertebral fracture increases when osteoporosis treatment with bisphosphonates or denosumab is stopped. INTRODUCTION: The aim of this paper was to review the available literature to assess what evidence exists to inform clinical decision-making with regard to drug holidays following treatment with bisphosphonates (BiP) or denosumab. METHODS: Systematic review. RESULTS: Differing pharmacokinetics lead to varying outcomes on stopping therapy. Prospective and retrospective analyses report that the risk of new clinical fractures was 20-40% higher in subjects who stopped BiP treatment, and vertebral fracture risk was approximately doubled. Rapid bone loss has been well described following denosumab discontinuation with an incidence of multiple vertebral fractures around 5%. Studies have not identified risk factors for fracture after stopping treatment other than those that provide an indication for treatment (e.g. prior fracture and low BMD). Studies that considered long-term continuation did not identify increased fracture risk, and reported only very low rates of adverse skeletal events such as atypical femoral fracture. CONCLUSIONS: The view that patients on long-term treatment with bisphosphonates or denosumab should always be offered a drug holiday is not supported by the existing evidence. Different pharmacokinetic properties for different therapies require different strategies to manage drug intermission. In contrast, long-term treatment with anti-resorptives is not associated with increased risk of fragility fractures and skeletal adverse events remain rare.

Diagnosis, prevention, and treatment of bone fragility in people living with HIV: a position statement from the Swiss Association against Osteoporosis.

Life expectancy of people living with HIV (PLWH) is reaching similar length as in the general population. Accordingly, age-related comorbidities, including osteoporosis, are increasing. Fracture risk is higher and increases approximately 10 years earlier in PLWH. Classical risk factors of bone fragility are highly prevalent in PLWH but factors specific for HIV infection itself and the type of antiretroviral therapy (ART) (triple combination antiretroviral therapy) regimen (especially tenofovir and protease inhibitors) also contribute to bone loss. The majority of bone loss occurs during virus activity and at initiation of ART (immune reconstitution) and is associated with an increase of bone resorption (upregulation RANKL). Recent data indicate that calcium and vitamin D supplements as ART initiation lower BMD loss. The reduction of tenofovir plasma concentrations with tenofovir alafenamide attenuates BMD loss but it remains unknown whether it will contribute to reduce fracture risk. Hence, special considerations for the management of bone fragility in PLWH are warranted. Based on the current state of epidemiology and pathophysiology of osteoporosis in PLWH, we provide the consensus of the Swiss Association against Osteoporosis on best practice for diagnosis, prevention, and management of osteoporosis in this population. Periodic assessment of fracture risk is indicated in all HIV patients and general preventive measures should be implemented. All postmenopausal women, men above 50 years of age, and patients with other clinical risk for fragility fractures qualify for BMD measurement. An algorithm clarifies when treatment with bisphosphonates and review of ART regimen in favour of more bone-friendly options are indicated.

Genotoxicity Evaluation of the Soybean Isoflavone Genistein in Human Papillary Thyroid Cancer Cells. Study of Its Potential Use in Thyroid Cancer Therapy.

Genistein is one of the several known isoflavonic phytoestrogens found in a number of plants, with soybeans and soy products being the primary food source. The aim of the study is to evaluate if genistein is able to exert antineoplastic action in primary human papillary thyroid cancer (PTC) cells. Thyroid tissues were treated with genistein (1-10-50-100 µM). Cell viability, proliferation, DNA primary damage and chromosomal damage were evaluated. An antiproliferative effect was induced by the highest doses of genistein, and such an effect was synergistically enhanced by the cotreatment with the antineoplastic drug sorafenib. Comet assay did not show any genotoxic effect in terms of primary DNA damage at all the times (4 and 24 h) and tested doses. A reduction of hydrogen peroxide-induced DNA primary damage in primary thyrocytes from PTC cells pretreated with genistein was observed. Data suggest that genistein exerts antineoplastic action, does not induce genotoxic effects while reduces oxidative-induced DNA damage in primary thyrocytes from PTC cells, supporting its possible use in therapeutic intervention.

Detection of Campylobacter spp. in water by dead-end ultrafiltration and application at farm level.

AIMS: The purposes were to evaluate the detection of low levels of Campylobacter in water by dead-end ultrafiltration (DEUF) to determine the sensitivity and suitability for use under field condition. METHODS AND RESULTS: The DEUF technique followed by detection according to ISO 10272 was tested on artificially and naturally contaminated water. Campylobacter were detected in all samples spiked with more than 10 CFU 60 l-1 and in four of nine samples with a concentration below 10 CFU 60 l-1 water. Naturally contaminated water from five different broiler producers was analysed. Campylobacter were detected in four of 12 samples from ponds near the houses and in three of 24 samples from water pipes inside the broiler houses, but not in tap water sampled at the entrance of the broiler houses. CONCLUSIONS: The results indicate that DEUF is useful for detection of low numbers of Campylobacter in large volumes of water. SIGNIFICANCE AND IMPACT OF THE STUDY: Contaminated water is an important source for transmission of Campylobacter to broilers and humans. The concentration of Campylobacter is usually low with a high level of background microbiota. This study shows the advantages of DEUF both in the laboratory and under field conditions.