PPI use is not associated with bone microarchitecture and strength assessed with HR-pQCT after three-years follow-up in patients visiting the Fracture Liaison Service.

BACKGROUND: The use of proton pump inhibitors (PPIs) has been associated with an increased fracture risk in observational studies. However, the reported association between PPI use and bone mineral density (BMD), bone microarchitecture, and bone strength is inconsistent. This study aims to assess the association between PPI use and bone microarchitecture and strength using high-resolution peripheral quantitative CT (HR-pQCT) in a three-year follow-up study in patients with a recent fracture visiting the Fracture Liaison Service (FLS). METHODS: This three-year prospective cohort study included FLS patients aged ≥ 50 years with a recent fracture (median age 62 [IQR 56-69] years, 68.7 % females) and without anti-osteoporosis treatment indication. HR-pQCT scans (distal radius and tibia) were obtained at baseline (T0) and three-year follow-up (T3). Volumetric bone mineral density and bone area, microarchitecture, and strength (micro-finite element analysis) were determined. The association between three-year continuous PPI use and the percentage change in HR-pQCT parameters between T0 and T3 was assessed using sex-stratified multivariate linear regression analyses. Covariates included age, BMI, vitamin-D deficiency (< 50 nmol/l), glucocorticoid use, and cardiovascular co-morbidity (males and females) fracture type (major/hip vs. all others, only males) and probable sarcopenia (only females). RESULTS: In total, 282 participants had available medication data throughout follow-up, of whom 20.6 % were continuous PPI users. In both males and females with complete HR-pQCT follow-up data (males: N = 69 radius, N = 84 tibia; females: N = 147 radius, N = 168 tibia), PPI use was not associated with the percentage change of any of the bone microarchitecture or strength parameters between T0 and T3 at the radius and tibia as compared to non-use. CONCLUSION: Compared to non-use, PPI use was not associated with the change of bone microarchitecture and strength in FLS patients at three years of follow-up. These results do not support that an altered bone microarchitecture or strength may contribute to the increased fracture risk associated with PPI use, as reported in observational studies.

Physical performance and sarcopenia assessment in patients with a recent fracture visiting the Fracture Liaison Service.

Impaired physical performance is associated with increased fracture risk. Performance on four physical functioning tests and prevalence of sarcopenia were assessed for 1789 fracture patients and compared to reference data. Performance was low on all tests, especially for patients with a hip, major or ≥ 1 prevalent vertebral fracture. PURPOSE INTRODUCTION: Impaired physical performance and sarcopenia are associated with increased fracture risk. This study aims to assess physical performance and the prevalence of sarcopenia in patients with a recent clinical fracture attending the Fracture Liaison Service (FLS) compared to population means. METHODS: In this cross-sectional study, chair stand test (CST), handgrip strength (HGS), timed-up-and-go (TUG), 6-min walking-test (6MWT), and sarcopenia (following EWGSOP2) were assessed. The proportion of patients with impaired/poor performance compared to reference data was calculated (Z-score: ≥ - 2SD to < - 1 (impaired) and < - 2 SD (poor)). Associations of fracture type, sex, age, and time since fracture with Z-scores were assessed using linear regression analyses. RESULTS: A total of 1789 consecutive FLS patients were included (median age (IQR): 66 (59-74), 70.7% females, 3.9 (± 1.6) months after fracture). The prevalence of impaired/poor performance for CST, HGS, TUG, and 6MWT was 39.2%, 30.4%, 21.9%, and 71.5%, respectively (expected proportion of 16%) and 2.8% had sarcopenia. Lower Z-scores (P < 0.001) were found for hip, major, and ≥ 1 prevalent vertebral fracture (VF) in CST (major: regression coefficient (B) (95%CI) = - 0.25 [- 0.34, - 0.16]; hip: B = - 0.32 [- 0.47, - 0.17], VF: B = - 0.22 [- 0.34, - 0.11]), TUG; (major: B = - 0.54 [- 0.75, - 0.33]; hip: B = - 1.72 [- 2.08, -1.35], VF: B = - 0.61 [- 0.88, - 0.57]), 6MWT (major: B = - 0.34 [- 0.47, - 0.21]; hip: B = - 0.99 [- 1,22, - 0.77], VF: B = - 0.36 [- 0.53, - 0.19]). CONCLUSIONS: Physical performance is significantly lower in FLS patients compared to healthy peers, especially in patients with hip, major or prevalent VF. These findings underline the need to assess and improve the physical performance of FLS patients, despite a low prevalence of sarcopenia.

Physical Functioning in Patients with a Recent Fracture: The "Can Do, Do Do" Framework Applied to Explore Physical Capacity, Physical Activity and Fall Risk Factors.

Physical capacity (PC) and physical activity (PA) are associated physical performance measures, and combined, PC and PA are used to categorize physical performance in the "can do, do do" framework. We aimed to explore physical performance of patients attending the fracture liaison service (FLS). In this cross-sectional study, PC was measured by 6-min-walking-test (can't do/can do) and PA by accelerometer (don't do/do do). Following quadrants were defined based on predefined cut-off scores for poor performance: (1) "can't do, don't do"; (2) "can do, don't do"; (3) "can't do, do do"; (4) "can do, do do". Odds ratios (OR) were calculated and fall and fracture risk factors were assessed between quadrants. Physical performance of 400 fracture patients was assessed (mean age 64; female 70.8%). Patients performed as follows: 8.3% "can't do, don't do"; 3.0% "can do, don't do"; 19.3% "can't do, do do"; 69.5% "can do, do do". For the "can't do" group the OR for low PA was 9.76 (95% CI: 4.82-19.80). Both the "can't do, don't do" and "can't do, do do" group differed significantly compared to the "can do, do do" group on several fall and fracture risk factors and had lower physical performance. The "can do, do do" framework is able to identify fracture patients with an impaired physical performance. Of all FLS patients 20% "can't do, but "do do" while having a high prevalence of fall risk factors compared to persons that "can do, do do", which may indicate this group is prone to fall.

Health-related quality of life of patients with a recent fracture attending a fracture liaison service: a 3-year follow-up study.

This study explored the course of health state utility value over 3 years in patients with a recent fracture attending a Fracture Liaison Service and suggested that the overall change in health-related quality of life was not significant, although significant improvements were observed at 6 and 12 months compared to baseline. INTRODUCTION: To estimate the 3-year health-related quality of life (HRQoL) of patients with a recent fracture presenting at a Fracture Liaison Service (FLS) and to explore factors associated with health state utility value (HSUV). METHODS: Patients' HSUVs were derived from the EQ-5D-5L and SF-6D and calculated at six time points. Multiple imputation was applied for missing data. Linear mixed-effects regression analysis with random intercept and slope was applied to explore the course of HSUV over 3 years. The impact of subsequent fracture and the length of time between FLS visit and patients' index fracture on HSUV were also investigated. A backward stepwise elimination was applied to identify factors associated with HSUV. RESULTS: A total of 499 patients were included. The change of EQ-5D HSUV was not significant over 3-year follow-up (P = 0.52), although slightly but significantly higher HSUV was captured at 6 months (mean difference (MD): 0.015, P = 0.02) and 12 months (MD: 0.018, P = 0.01). There was no significant difference in the course of EQ-5D HSUV between fracture locations (P = 0.86). A significant increase in HSUV was only captured for patients had shorter time period (< 107 days) between FLS visit and their index fracture. Suffering a subsequent fracture was associated with significant QoL loss (MD: - 0.078, P < 0.001). Subsequent fracture, previous treatment with anti-osteoporosis medication, a prevalent vertebral fracture (grade 2 or 3), use of a walking aid, previous falls, and higher BMI were negatively associated with mean EQ-5D HSUV over 3 years. Comparable results were found using SF-6D HSUV. The lack of HRQoL data immediately after fracture and selection bias were two main limitations. CONCLUSION: The 3-year change in HSUV was not statistically significant, although significant improvements were observed at 6 and 12 months in comparison with baseline. Six factors were negatively associated with EQ-5D HSUV.

Association of secondary displacement of distal radius fractures with cortical bone quality at the distal radius.

INTRODUCTION: The aim of this study was to investigate the associations of patient characteristics, bone mineral density (BMD), bone microarchitecture and calculated bone strength with secondary displacement of a DRF based on radiographic alignment parameters. MATERIALS AND METHODS: Dorsal angulation, radial inclination and ulnar variance were assessed on conventional radiographs of a cohort of 251 patients, 38 men and 213 women, to determine the anatomic position of the DRF at presentation (primary position) and during follow-up. Secondary fracture displacement was assessed in the non-operatively treated patients (N = 154) with an acceptable position, preceded (N = 97) or not preceded (N = 57) by primary reduction (baseline position). Additionally, bone microarchitecture and calculated bone strength at the contralateral distal radius and tibia were assessed by HR-pQCT in a subset of, respectively, 63 and 71 patients. OUTCOME: Characteristics of patients with and without secondary fracture displacement did not differ. In the model with adjustment for primary reduction [OR 22.00 (2.27-212.86), p = 0.008], total [OR 0.16 (95% CI 0.04-0.68), p = 0.013] and cortical [OR 0.19 (95% CI 0.05-0.80], p = 0.024] volumetric BMD (vBMD) and cortical thickness [OR 0.13 (95% CI 0.02-0.74), p = 0.021] at the distal radius were associated with secondary DRF displacement. No associations were found for other patient characteristics, such as age gender, BMD or prevalent vertebral fractures. CONCLUSIONS: In conclusion, our study indicates that besides primary reduction, cortical bone quality may be important for the risk of secondary displacement of DRFs.

The association between prevalent vertebral fractures and bone quality of the distal radius and distal tibia as measured with HR-pQCT in postmenopausal women with a recent non-vertebral fracture at the Fracture Liaison Service.

We evaluated the association between prevalent vertebral fractures and bone micro-architecture and strength measured using HR-pQCT in postmenopausal women with a recent non-vertebral fracture visiting the Fracture Liaison Service. The presence and severity of prevalent vertebral fracture reflect generalized bone deterioration. INTRODUCTION: We evaluated the association between prevalent vertebral fractures (VFs) and bone micro-architecture and strength measured using HR-pQCT in postmenopausal women visiting the Fracture Liaison Service. METHODS: In this cross-sectional study in women aged 50-90 with a recent non-vertebral fracture (NVF), VFs were identified on lateral spine images by dual-energy X-ray absorptiometry. Bone micro-architecture and strength were measured at the non-dominant distal radius and distal tibia using HR-pQCT. Linear regression analyses were used to estimate the association between prevalent VFs and HR-pQCT parameters. RESULTS: We included 338 women of whom 74 (21.9%) women had at least one prevalent VF. After adjustment for femoral neck aBMD (FN aBMD) and other parameters, women with at least one prevalent vertebral fracture had significantly lower total and trabecular vBMD and trabecular number (ß - 16.7, - 11.8, and - 7.8 in the radius and - 21.4, - 16.6, and - 7.2 in the tibia, respectively), higher trabecular separation at the radius and tibia (ß 9.0 and 9.3, respectively), and lower cortical thickness and calculated ultimate failure load and compressive bone strength at the tibia (ß - 5.9, - 0.6, and - 10.9, respectively) as compared with those without prevalent VFs. Furthermore, more severe prevalent VFs were associated with even lower total and trabecular vBMD and lower ultimate failure load and compressive stiffness at the radius and tibia, and lower trabecular number and higher trabecular separation at the radius. CONCLUSION: This study indicates that the presence and severity of prevalent VFs reflect generalized bone deterioration in women with a recent NVF, independently of FN aBMD.

Biomarkers of neonatal stress assessment: A prospective study.

INTRODUCTION: Early diagnosis of perinatal asphyxia, the major cause of neonatal mortality and morbidity, might be improved by the detection of neonatal stress biomarkers such as cardiac troponin (CTn)T, CTnI, NT-Terminal-pro-Brain Natriuretic Peptide (NT-pro-BNP), copeptin, and high sensitivity C-reactive protein (hs-CRP). However, reference values in neonates are lacking. The objective of our study was therefore to establish a reference range of these biomarkers in healthy full term newborns and to analyze the influence of delivery mode on their cord blood concentrations. PATIENTS AND METHODS: CTnT, CTnI, NT-pro-BNP, Copeptin and hs-CRP levels were determined in 201 neonates enrolled in this prospective study and correlated to the delivery mode and post-natal outcome. RESULTS: Using the 99th percentile, the upper reference limit in healthy newborns was established for all biomarkers. Neonates born after complicated delivery had significantly higher values of CTnT, CTnI and Copeptin than those born after uncomplicated delivery. In the multiple regression models with CTnT as dependent variable, the delivery mode was the statistically significant independent variable. CONCLUSION: In this study, we established reference values of cord blood concentrations of cardiac stress biomarkers in healthy newborns. We showed that cardiac-related birth stress is dependent on delivery mode.

[Vitamin D deficiency during pregnancy : what's the local situation ?] / Prévalence de l'hypovitaminose D chez la femme enceinte : quelle est la situation en région liégeoise ?

Vitamin D deficiency is a worldwide health problem, also during pregnancy. Inadequate maternal vitamin D status in pregnancy is associated with poor fetal growth, impaired bone development and rickets in infants after birth. Furthermore, higher rates of preeclampsia and gestational diabetes are associated with low maternal vitamin D status during pregnancy. Toxicity of vitamin D is rare. Most countries recommend vitamin D supplementation during pregnancy but guidelines are controversial and inadequate compared to real mother's and child's needs. Wath's the best strategy to follow and supplement mother during pregnancy? In a study carried out at the maternity clinic Notre-Dame des Bruyères (CHU Liège), we studied for a year the vitamin D concentrations of young women at start of pregnancy and of others after delivery to evaluate the local situation and management of vitamin D status during pregnancy. We did not collect the cord blood samples in this study. However, this is a project we would like to achieve soon. This would allow us to compare the vitamin D results of the mother at the time of delivery, to those of the cord blood of their respective child.

Les déficiences en vitamine D sont très répandues dans la population générale liégeoise, mais aussi chez la femme enceinte. Les ressources en vitamine D du nouveau-né sont complètement dépendantes de celles de sa mère. Les déficiences maternelles sont associées à un risque accru de rachitisme, de faible minéralisation osseuse, de naissance avant terme et de faible poids à la naissance chez l'enfant et de pré-éclampsie, de diabète gestationnel et d'accouchement par césarienne chez la mère. Les recommandations de supplémentation en vitamine D durant la grossesse sont très variées et semblent insuffisantes pour couvrir les besoins réels de la mère et de l'enfant. Quelle stratégie adopter pour un suivi correct et une supplémentation suffisante pendant la grossesse ? Dans une étude réalisée à la maternité de la clinique Notre-Dame des Bruyères (CHU Liège), nous avons étudié, pendant une année, les concentrations en vitamine D chez des jeunes femmes en début de grossesse et chez d'autres en fin de grossesse afin d'évaluer la situation locale et la prise en charge du statut en vitamine D pendant la grossesse. Nous n'avons pas récolté les échantillons de sang de cordon dans cette étude. Il s'agit cependant d'un projet que nous souhaiterions réaliser prochainement, ce qui nous permettrait de comparer les résultats en Vitamine D de la mère au moment de l'accouchement, à ceux du sang du cordon de leur enfant respectif.

Comorbidities and medication use in patients with a recent clinical fracture at the Fracture Liaison Service.

In this cross-sectional study, two-thirds of Fracture Liaison Service (FLS) patients had comorbidities and medications associated with increased bone- or fall-related fracture risk. Bone-related and fall-related fracture risk (BRR and FRR) were associated with age and fracture type, but not with gender or BMD. Systematic evaluation of these factors leads to a more profound assessment in FLS care. INTRODUCTION: This study is a systematic evaluation of comorbidities and medications associated with increased fracture risk in patients aged 50-90 years with a recent fracture visiting the FLS. METHODS: In this cross-sectional cohort study, comorbidities were classified according to ICD-10 and medications according to the Anatomic Therapeutic Chemical (ATC) classification and further categorized into those associated BRR and FRR. RESULTS: Of 1282 patients (72% women; 65 ± 9 years), 53% had at least one BRR, 46% had at least one FRR, and 66% at least one BRR and/or FRR. At least one BRR, as well as at least one FRR were associated with age, BMI, and fracture type, but not with gender or BMD. The proportion of patients with only BRR (± 20%) or only FRR (± 10%) was similar among ages, gender, BMI, fracture type, and BMD. The combination of at least one BRR and at least one FRR was significantly associated with age, BMI, and major fractures, but not with gender or BMD. CONCLUSION: Comorbidities and medications associated with increased fracture risk are present in two-thirds of patients visiting the FLS. In addition, the proportion of patients having a combination of BRR and FRR increased significantly with age, BMI, and fracture severity. This indicates that systematic evaluation of these factors is important for a more profound assessment of subsequent fracture risk in FLS care.

[Hypophosphatasia]. / L'hypophosphatasie.

Hypophosphatasia (HPP) is a rare genetic disorder characterized by the diminution of the enzymatic activity of the alkaline phosphatase (ALP). The disease mainly involves multiple defects of the mineralization of the skeleton including bone fragilities. It will be expressed to varying degrees of severity and will allow to characterize different forms of HPP. Unfortunately, the prevalence of this pathology remains probably underestimated and its diagnosis must be multidisciplinary by taking into account the biochemical assays, the clinical history as well as the radiological imaging. So, in the approach of this diagnosis, a retrospective screening was carried out by the clinical chemistry department of the CHU of Liège. The aim of this study is to potentially identify the affected patients on the basis of their biochemical assays and their anamnesis in order to propose a genetic screening. Unfortunately, no case could be formally identified, which testifies the difficulty to establish a diagnosis of the slight forms encountered mainly in the adults.

L'hypophosphatasie (HPP) est une pathologie héréditaire rare caractérisée par une diminution de l'activité enzymatique de la phosphatase alcaline (PAL). La maladie entraîne, principalement, de multiples défauts de minéralisation du squelette conduisant à des fragilités osseuses, qui s'exprimeront à des degrés plus ou moins sévères et permettront de caractériser différentes formes d'HPP. Malheureusement, la prévalence de cette pathologie reste probablement sous-estimée et son diagnostic doit être pluridisciplinaire, en prenant en compte les dosages biochimiques, l'histoire clinique du patient ainsi que des iconographies radiologiques. C'est donc dans une optique de diagnostic que nous avons réalisé un screening rétrospectif au sein du laboratoire de chimie clinique du CHU de Liège. Le but de cette étude était d'identifier des patients potentiellement atteints par cette pathologie sur base de leurs dosages biochimiques et d'une clinique évocatrice afin de proposer un dépistage génétique. Malheureusement, aucun cas n'a pu être formellement identifié, ce qui témoigne de la difficulté d'établir un diagnostic des formes légères rencontrées et ce, principalement chez l'adulte.

[Pediatric reference intervals : retrospective study on thyroid hormone levels]. / Etude rétrospective du bilan thyroïdien : définition de valeurs de référence pédiatriques.

Defining reference range is an essential tool for diagnostic. Age and sexe influences on thyroid hormone levels have been already discussed. In this study, we are defining a new pediatric reference range for TSH, FT3 and FT4 for Cobas C6000 analyzer. To do so, we have taken in account 0 to 18 year old outclinic patients. During the first year of life, thyroid hormone levels change dramatically before getting stabilized around 3 years old. We also compared our results to those obtained in a Canadian large-scale prospective study (the CALIPER initiative).

L'établissement de valeurs de référence thyroïdiennes pédiatriques est un élément essentiel dans l'aide au diagnostic des dysfonctionnements thyroïdiens chez l'enfant et l'adolescent. L'influence de l'âge et du sexe sur les concentrations des hormones thyroïdiennes a de nombreuses fois été évoquée. Dans cette étude, nous définissons un nouvel intervalle de référence pédiatrique pour la TSH, la FT3 et la FT4 sur l'analyseur Cobas C6000 (Roche). Pour ce faire, nous avons collecté les données des patients ambulants de 0 à 18 ans de notre institution. Au cours de la première année, les valeurs d'hormones thyroïdiennes fluctuent fortement avant de se stabiliser vers l'âge de 3 ans. Nous comparons également nos résultats à ceux d'une étude prospective de grande ampleur menée au Canada (étude CALIPER). e.

The direct impact of landslides on household income in tropical regions: A case study from the Rwenzori Mountains in Uganda.

Landslides affect millions of people worldwide, but theoretical and empirical studies on the impact of landslides remain scarce, especially in Sub-Saharan Africa. This study proposes and applies a method to estimate the direct impact of landslides on household income and to investigate the presence of specific risk sharing and mitigation strategies towards landslides in a tropical and rural environment. An original cross-sectional household survey is used in combination with geographical data to acquire detailed information on livelihoods and on hazards in the Rwenzori mountains, Uganda. Ordinary least square regressions and probit estimations with village fixed effects are used to estimate the impact of landslides and the presence of mitigation strategies. Geographical information at household level allows to disentangle the direct impact from the indirect effects of landslides. We show that the income of affected households is substantially reduced during the first years after a landslide has occurred. We find that members of recently affected households participate more in wage-employment or in self-employed activities, presumably to address income losses following a landslide. Yet, we see that these jobs do not provide sufficient revenue to compensate for the loss of income from agriculture. Given that landslides cause localized shocks, finding a significant direct impact in our study indicates that no adequate risk sharing mechanisms are in place in the Rwenzori sub-region. These insights are used to derive policy recommendations for alleviating the impact of landslides in the region. By quantifying the direct impact of landslides on household income in an agricultural context in Africa this study draws the attention towards a problem that has been broadly underestimated so far and provides a sound scientific base for disaster risk reduction in the region. Both the methodology and the findings of this research are applicable to other tropical regions with high landslide densities.

A methodological framework to assess the socio-economic impact of underground quarries: A case study from Belgian Limburg.

This study developed a methodology to assess the socio-economic impact of the presence and collapse of underground limestone quarries. For this we rely on case study evidence from Riemst, a village located in Eastern Belgium and use both secondary and primary data sources. A sinkhole inventory as well as data about the prevention costs provided by the municipality was used. To estimate the recreational values of the quarries, visitor data was obtained from the tourist office of Riemst. Next, two surveys were conducted among inhabitants and four real estate agents and one notary. The direct and indirect damages were assessed using respectively the repair cost and production and real estate value losses. The total yearly direct and indirect damage equals €415000 (±€85000) and more than half of it can be attributed to the depreciation of real estate (€230000). The quarries have recreational, cultural-historical and ecological values and thus generate societal benefits. The yearly recreational value was at least €613000 in 2012 values. The ecological and cultural-historical values augment to €180000 per year (in 2012 values). Further, our study indicates that the gains from filling up the quarries below the houses located above an underground limestone quarry outweigh the costs in the case study area. The net gain from filling up the underground quarry ranges €38700 to €101700 per house. This is only the lower bound of the net gain from filling up these underground quarries since preventive filling makes future collapses less likely so that future direct repair costs will be most likely smaller.