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Introduction: The p.(Arg85Trp) variant-specific phenotype of hepatocyte nuclear factor 4 alpha shows a complex clinical picture affecting three different organ systems and their corresponding metabolisms. Little is known about the molecular mechanisms involved and their relationship with the diverse symptoms seen in the context of this specific variant. Here, we present data of a new patient that expand the clinical phenotype, suggesting possible disease mechanisms. Case Presentation: Clinical data were extracted from the patient’s charts. The liver, kidney, and muscle were analyzed with routine histology and electron microscopy. Mitochondrial function was assessed by respirometric analyses and enzymatic activity assays. Structure and sequence analyses of this specific variant were investigated by in silico analyses. Our patient showed the known features of the variant-specific phenotype, including macrosomia, congenital hyperinsulinism, transient hepatomegaly, and renal Fanconi syndrome. In addition to that, she showed liver cirrhosis, chronic kidney failure, and altered mitochondrial morphology and function. The clinical and biochemical phenotype had features of a new type of glycogen storage disease. Discussion: This case expands the p.(Arg85Trp) variant-specific phenotype. Possible pathomechanistic explanations for the documented multiorgan involvement and changes of symptoms and signs during development of this ultra-rare but instructive disorder are discussed.

Zusammenfassung Hintergrund Eine generalisierte Hypermobilität liegt vor, wenn die Beweglichkeit in mehreren Gelenken das übliche Maß übersteigt. Bis zu 30 % der Frauen und 10 % der Männer sind davon betroffen. Hypermobilität ist keine Pathologie, wenn sie jedoch mit Schmerzen und weiteren Symptomen einhergeht, kann sie die Gesundheit und Alltagsfunktionen beeinträchtigen. Zur physiotherapeutischen Behandlung gibt es wenige Studien, wobei Krafttraining eine mögliche Intervention sein könnte. Ziel Erfassung der Machbarkeit und des Effekts eines Krafttrainings für Frauen mit generalisierter Hypermobilität. Methode Pre-post-Studie, in der hypermobile Frauen (Beighton-Score > 5) zwischen 20 und 40 Jahren während 12 Wochen ein Krafttraining an Geräten, fokussiert auf Beine und Rücken, absolvierten. Mithilfe eines Protokolls und wöchentlicher Fragebogen wurden das Training und dadurch ausgelöste Beschwerden analysiert. Vor und nach dem Training wurde die Kraft der Knieflexoren und -extensoren sowie der Muskelquerschnitt am Oberschenkel gemessen. Die Analyse erfolgte primär deskriptiv, zusätzlich erfolgte ein Vergleich von 2 Subgruppen mittels Mann-Whitney-U und Chi2-Test. Ergebnisse 46 Teilnehmerinnen (26,3 ± 4,3 Jahre) absolvierten das Training. 6 davon brachen die Studie vorzeitig ab, davon eine wegen Rückenschmerzen aufgrund einer Diskushernie. 72,5 % der verbleibenden 40 Teilnehmerinnen absolvierten 20 oder mehr Trainings. In 34 % der Trainingswochen wurden geringe Beschwerden angegeben, mehrheitlich an Knie und Rücken. Der Einsatz der verwendeten Gewichte war oft tief, so wurde auf der Legpress mit durchschnittlich 44,8 % des Körpergewichts begonnen, nach 12 Wochen lag das Trainingsgewicht im Mittel bei 52,2 kg, was 85,7 % des Körpergewichts entspricht. Bei der Kraft und beim Muskelquerschnitt wurden keine signifikanten Verbesserungen erreicht, wobei bis zu 17 Teilnehmerinnen (42,5 %) eine Verbesserung von mehr als 10 % erreichten. Schlussfolgerung Das Krafttraining war für die meisten Teilnehmerinnen machbar und gut verträglich. Das mehrheitlich selbstgesteuerte Training war zu wenig intensiv, um eindeutige Auswirkungen auf Kraft oder Muskelmasse zu erreichen, obwohl einzelne Teilnehmerinnen durchaus davon profitierten. In weiteren Studien sollten individuellere und enger begleitete Trainingsprogramme untersucht werden.

ObjectivesThe individual and socioeconomic burden of sarcopenia in rheumatoid arthritis (RA) is most relevant. However, longitudinal cohort data are scarce.MethodsProspective, single-center, controlled, observational cohort study of consecutive 124 postmenopausal women, 53 with RA, 71 healthy controls (HC). Low muscle mass and low muscle strengths was defined according to the European working group on sarcopenia in older people 2019 (appendicular lean mass index [ALMI] via dual-energy x-ray absorptiometry < 5.5 Kg/m2; handgrip strength via dynamometer < 16 Kg). Linear regression models were calculated including demographic and anthropometric data, comorbidities, and co-medication as confounders.ResultsMedian age was 63 (IQR 56, 70), follow-up 2.1 (IQR 2.0, 5.3) years. At baseline, median ALMI was 6.2 (IQR 6.0, 6.5) Kg/m2in RA patients, 6.3 (IQR 5.6, 6.9) Kg/m2in HC (p = 0.64) with no difference in rates of low muscle mass (RA 16.2 % vs. HC 15.1 %). In the fully adjusted model, mean change in ALMI per year was -0.05 (95%CI -0.10 to -0.01) Kg/m2in RA patients and 0.00 (95%CI -0.02 to 0.03) Kg/m2in HC resulting in a differential loss of -0.06 (95%CI -0.11 to -0.01) Kg/m2per year (p = 0.027). For RA patients, the adjusted OR of experiencing any loss of muscle mass was 3.98 (95%CI 1.47 to 10.77) compared to HC (p = 0.007). On average, RA patients lost 0.78 % of muscle mass per year. At baseline, low grip strength was seen in 27.3 % of RA patients and in 2.9 % of HC (p = 0.002). In both groups, grip strength did not decline during study period. TNFα inhibitors were associated with less, T-cell inhibition with greater loss of muscle mass. Low mass at baseline, disease duration and disease activity were not associated with loss of muscle mass.ConclusionPostmenopausal women with RA have a significant risk of accelerated loss of muscle mass over time.

Background loss of skeletal muscle function, strength and mass is common in older adults, with important socioeconomic impacts. Subclinical hypothyroidism is common with increasing age and has been associated with reduced muscle strength. Yet, no randomized placebo-controlled trial (RCT) has investigated whether treatment of subclinical hypothyroidism affects muscle function and mass. Methods this is an ancillary study within two RCTs conducted among adults aged ≥65 years with persistent subclinical hypothyroidism (thyrotropin (TSH) 4.60–19.99 mIU/l, normal free thyroxine). Participants received daily levothyroxine with TSH-guided dose adjustment or placebo and mock titration. Primary outcome was gait speed at final visit (median 18 months). Secondary outcomes were handgrip strength at 1-year follow-up and yearly change in muscle mass. Results we included 267 participants from Switzerland and the Netherlands. Mean age was 77.5 years (range 65.1–97.1), 129 (48.3%) were women, and their mean baseline TSH was 6.36 mIU/l (standard deviation [SD] 1.9). At final visit, mean TSH was 3.8 mIU/l (SD 2.3) in the levothyroxine group and 5.1 mIU/l (SD 1.8, P Conclusions in this ancillary analysis of two RCTs, treatment of subclinical hypothyroidism did not affect muscle function, strength and mass in individuals 65 years and older.

Generalized joint hypermobility (GJH) has a prevalence in women of 15% to 35%. GJH may lead to impaired movement control, frequent sprains or subluxations and pain, and can be associated with early osteoarthritis or chronic fatigue. Aim of this project was to analyse muscle strength, muscle cross-sectional area (mCSA) and daily function in women with GJH and to analyse correlations between these measurements.Descriptive cross-sectional study of women with GJH, defined by Beighton score ≥6/9. Assessments included muscle strength, mCSA by peripheral Quantitative Computed Tomography (pQCT), stair climbing, as well as two questionnaires. Spearman's correlations between parameters were calculated.51 women with a mean age of 26.5 years participated, whereof 18 (35%) had a Beighton score of 9/9 and 17 (33%) attained 8/9. Internal correlations between strength measurements were high, whereas pQCT parameters were less correlated. Strength was moderately correlated with mCSA, while correlations with stair climbing and SF-36 were not significant.This study provides insight into the muscle and bone properties of women with GJH. Only slight differences were seen compared to normative values. Correlations between various dimensions were middle or low, indicating the complex relationship between strength, muscle properties and function.

The effect of levothyroxine (LT4) therapy for subclinical hypothyroidism (SHypo) on appendicular bone geometry and volumetric density has so far not been studied. In a nested study within the randomized, placebocontrolled Thyroid Hormone Replacement for Subclinical Hypothyroidism (TRUST) trial, we assessed the effect of LT4 therapy on bone geometry as measured by peripheral quantitative computed tomography (pQCT). In the TRUST trial, community-dwelling adults aged >= 65 years with SHypo were randomized to LT4 with dose titration vs. placebo with mock titration. We analyzed data from participants enrolled at the TRUST site in Bern, Switzerland who had bone pQCT measured at baseline and at 1 to 2 years follow-up. The primary outcomes were the annual percentage changes of radius and tibia epi- and diaphysis bone geometry (total and cortical crosssectional area (CSA) and cortical thickness), and of volumetric bone mineral density (bone mineral content (BMC) and total, trabecular and cortical volumetric bone mineral density (vBMD)). We performed linear regression of the annual percentage changes adjusted for sex, LT4 dose at randomization and muscle crosssectional area. The 98 included participants had a mean age of 73.9 (+/- SD 5.4) years, 45.9% were women, and 12% had osteoporosis. They were randomized to placebo (n = 48) or LT4 (n = 50). Annual changes in BMC and vBMD were similar between placebo and LT4-treated groups, without significant difference in bone geometry or volumetric bone mineral density changes, neither at the diaphysis, nor at the epiphysis. For example, in the placebo group, epiphyseal BMC (radius) decreased by a mean 0.2% per year, with a similar decrease of 0.5% per year in the LT4 group (between-group difference in %Delta BMC 0.3, 95% CI -0.70 to 1.21, p = 0.91). Compared to placebo, LT4 therapy for an average 14 months had no significant effect on bone mass, bone geometry and volumetric density in older adults with subclinical hypothyroidism. Trial registration: The trial was registered on ClinicalTrials.gov numbers NCT01660126 (TRUST Thyroid trial) and NCT02491008 (Skeletal outcomes).

Disorders of isolated mineralocorticoid deficiency causing potentially life-threatening salt-wasting crisis early in life have been associated with gene variants of aldosterone biosynthesis or resistance, but in some patients no such variants are found. WNT/β-catenin signaling is crucial for differentiation and maintenance of the aldosterone producing adrenal zona glomerulosa (zG). We describe a highly consanguineous family with multiple perinatal deaths or infants presenting at birth with failure to thrive, severe salt-wasting crises associated with isolated hypoaldosteronism, nail anomalies, short stature, and deafness. Whole exome sequencing revealed a homozygous splice variant in the R-SPONDIN receptor LGR4 gene (c.618-1G>C) regulating WNT signaling. The resulting transcripts affected protein function and stability, and resulted in loss of Wnt/β-catenin signaling in vitro. The impact of LGR4 inactivation was analyzed by adrenal cortex specific ablation of Lgr4, using Lgr4Flox/Flox mated with Sf1:Cre mice. Inactivation of Lgr4 within the adrenal cortex in the mouse model caused decreased WNT signaling, aberrant zonation with deficient zG and reduced aldosterone production. Thus, human LGR4 mutations establish a direct link between LGR4 inactivation and decreased canonical WNT signaling with abnormal zG differentiation and endocrine function. Therefore, variants in WNT signaling and its regulators should systematically be considered in familial hyperreninemic hypoaldosteronism.

OBJECTIVE This study explored the impact of time-restricted eating (TRE) versus standard dietary advice (SDA) on bone health. METHODS Adults with ≥1 component of metabolic syndrome were randomized to TRE (ad libitum eating within 12 hours) or SDA (food pyramid brochure). Bone turnover markers and bone mineral content/density by dual energy x-ray absorptiometry were assessed at baseline and 6-month follow-up. Statistical analyses were performed in the total population and by weight loss response. RESULTS In the total population (n = 42, 76% women, median age 47 years [IQR: 31-52]), there were no between-group differences (TRE vs. SDA) in any bone parameter. Among weight loss responders (≥0.6 kg weight loss), the bone resorption marker β-carboxyterminal telopeptide of type I collagen tended to decrease after TRE but increase after SDA (between-group differences p = 0.041), whereas changes in the bone formation marker procollagen type I N-propeptide did not differ between groups. Total body bone mineral content decreased after SDA (p = 0.028) but remained unchanged after TRE (p = 0.31) in weight loss responders (between-group differences p = 0.028). Among nonresponders (

BackgroundMorbidity and mortality of COVID-19 is increased in patients with B-cell depleting therapies, the majority of which also show compromised vaccination-induced immune responses. Herein, we report on the trajectories of anti-SARS-CoV-2 antibodies in patients from the original RituxiVac study compared to healthy volunteers and investigate the immunogenicity of a third vaccination in previously non-responding patients.MethodsA follow-up evaluation was performed in volunteers and patients from the RituxiVac Study (NCT04877496), which investigated the humoral and cell-mediated immune response after SARS-CoV-2 mRNA vaccination in patients with a history with anti-CD20 depleting therapies (rituximab or ocrelizumab). The current population included 33 patients and 26 healthy volunteers with initial humoral vaccine response and 32 non-responding patients. Primary outcome was anti-SARS-CoV-2 antibody trajectories in vaccine responders 4.3 months (median; interquartile range [IQR]: 3.6 – 4.8 months) after first evaluation and humoral responses after a third vaccine dose in previous non-responders. Antibody decay rates were compared using analysis of covariance in linear regression.ResultsIn patients with detectable anti-spike IgG antibodies after two-dose vaccination, circulating anti-spike IgG persisted in 88% (29/33) of patients 5.6 months after the second vaccination (median; IQR: 5.1-6.7) compared to 92% (24/26) of healthy volunteers 6.8 months after the second dose (IQR: 6.0-7.1) (p=0.7). Antibody decay rates were comparable between patients and controls with −0.54 signal/cut-off (s/c) units per month (IQR −0.72 to −0.45) and −0.60 s/c units per month (IQR: −0.88 to −0.44), p=0.70. Two-dose responders with loss of circulating antibodies at follow-up (n=4/33, 12%) had lower initial antibody concentrations (pConclusionThe present study reveals comparable antibody reduction rates between patients with CD20-depleting treatment history and healthy volunteers, but inefficient humoral responses to a third dose of SARS-CoV-2 mRNA vaccines in the majority of two-dose non-responders. There is a need for individually tailored vaccination strategies in immunocompromised patients that could be stratified by B cell counts and initial level of antibody titers. (Funded by Bern University Hospital, ClinicalTrials.gov number, NCT04877496)

Background B-cell-depleting therapies increase the risk of morbidity and mortality due to COVID-19. Evidence-based SARS-CoV-2 vaccination strategies for patients on B-cell-depleting therapies are scarce. We aimed to investigate humoral and cell-mediated immune responses to SARS-CoV-2 mRNA-based vaccines in patients receiving CD20-targeted B-cell-depleting agents for autoimmune disease, malignancy, or transplantation. Methods The RituxiVac study was an investigator-initiated, single-centre, open-label study done at the Bern University Hospital (Bern, Switzerland). Patients with a treatment history of anti-CD20-depleting agents (rituximab or ocrelizumab) and with no previous history of SARS-CoV-2 infection were enrolled between April 26 and June 30, 2021, for analysis of humoral and cell-mediated immune responses (by interferon-γ [IFNγ] release assay) at least 4 weeks after completing vaccination against SARS-CoV-2. Healthy controls without a history of SARS-CoV-2 infection were also enrolled at least 4 weeks after completing vaccination against SARS-CoV-2. All study participants received two doses of either the Pfizer-BioNTech BNT162b2 vaccine or the Moderna mRNA-1273 vaccine. The primary outcome was the proportion of patients with a history of anti-CD20 treatment who showed a humoral immune response against the SARS-CoV-2 spike protein in comparison with immunocompetent controls. Prespecified secondary endpoints were the effect of anti-CD20 therapy (including time since last treatment and cumulative dose) on humoral or cell-mediated immune responses to SARS-CoV-2 vaccination, and biomarkers of immunocompetence. This study is registered with ClinicalTrials.gov, NCT04877496. Findings The final study population comprised 96 patients and 29 immunocompetent controls. The median age of patients was 67 years (IQR 57-72) and of controls was 54 years (45-62), and 51 (53%) of 96 patients and 19 (66%) of 29 controls were female. The median time since last anti-CD20 treatment was 1·07 years (IQR 0·48-2·55) and the median cumulative dose of an anti-CD20 depleting agent was 2·80 g (1·50-5·00). Anti-spike IgG antibodies were detected in 47 (49%) of 96 patients 1·79 months (IQR 1·16-2·48) after the second vaccine dose compared to 29 (100%) of 29 controls 1·81 months (1·17-2·48) after the second vaccine dose (p7·6 months; positive predictive value 0·78), peripheral CD19+ cell count (>27 cells per μL; positive predictive value 0·70), and CD4+ lymphocyte count (>653 cells per μL; positive predictive value 0·71) were predictive of humoral vaccine response (area under the curve [AUC] 67% [95% CI 56-78] for time since last anti-CD20 therapy, 67% [55-80] for peripheral CD19+ count, and 66% [54-79] for CD4+ count). Interpretation This study provides further evidence of blunted humoral and cell-mediated immune responses elicited by SARS-CoV-2 mRNA vaccines in patients with a history of CD20 B-cell-depleting treatment. Lymphocyte subpopulation counts were associated with vaccine response in this highly vulnerable population. On validation, these results could help guide both the administration of SARS-CoV-2 vaccines and B-cell-depleting agents in this population. Funding Bern University Hospital.

BackgroundB-cell depleting therapies increase COVID19 morbidity and mortality. For this specific population, evidence-based vaccination strategies are lacking. Here, we investigated humoral and cell mediated immune responses to SARS-CoV2 mRNA-based vaccines in patients receiving CD20-B-cell depleting agents for autoimmune disease, malignancy, or transplantation.MethodsPatients at the Bern University Hospital with a treatment history of anti-CD20 depleting agents (rituximab or ocrelizumab) were enrolled for analysis of humoral and cell-mediated immune responses (by interferon-γ release assay) after completing vaccination against SARS-CoV2. Primary outcome was the the anti-spike antibody response in anti-CD20-treated patients (n=96) in comparison to immunocompetent controls (n=29).ResultsAnti-spike IgG antibodies were detected in 49% of patients 1.79 months after the second vaccine dose (interquartile range, IQR: 1.16-2.48) compared to 100% of controls (p27/µl), and CD4+ lymphocyte count (>653/µl) predicted humoral vaccine response (area under the curve [AUC]: 67% [CI 56-78], 67% [CI 55-80] and 66% [CI 54-79], (positive predictive value [PPV]: 0.78, 0.7 and 0.71).ConclusionThis study provides evidence for blunted humoral and cell-mediated immune responses elicited by SARS-CoV2 mRNA vaccines in patients with CD20-depleting treatment history. Lymphocyte subpopulation counts are associated with vaccine response in this highly vulnerable population. (Funded by Bern University Hospital, ClinicalTrials.gov number, NCT04877496)

Anaemia affects quality of life and radiographic outcome in rheumatoid arthritis (RA). In a cross-sectional study with 779 patients, we assessed the prognostic potential of the major haematopoietic regulators, hepcidin and erythropoietin, comparing their serum concentrations with respect to different anaemia types, inflammatory activity, anti-cytokine-specific treatment effects and iron deficiency (ID) indices. The results showed that clinical disease activity was more closely associated with haemoglobin levels than with anti-tumour necrosis factor-alpha or interleukin 6 receptor effects. In ID, hepcidin was suppressed, independently of inflammation. Erythropoietin levels were inappropriately low in relation to the degree of anaemia, but, in contrast to low haemoglobin, not directly associated with joint damage progression. Hepcidin and erythropoietin levels are intimately connected with inflammation and ID. Interventional studies on these important targets are already in progress.

Background Generalized joint hypermobility is defined as an excessive range of motion in several joints. Having joint hypermobility is not a pathology, but when associated with pain and other symptoms, it might affect health and function. Evidence for physiotherapy management is sparse and resistance training might be a possible intervention. Thus, the effects of 12-week resistance-training on muscle properties and function in women with generalized joint hypermobility were evaluated. Methods In this single-blind randomized controlled trial women between 20 and 40 years with generalized joint hypermobility (Beighton score at least 6/9) were included. Participants were randomly allocated to 12-week resistance training twice weekly (experimental) or no lifestyle change (control). Resistance training focused on leg and trunk muscles. Primary outcome was muscle strength; additional outcomes included muscle properties, like muscle mass and density, functional activities, pain and disability. Training adherence and adverse events were recorded. Results Of 51 participating women 27 were randomised to training and 24 into the control group. In each group 11 women had joint hypermobility syndrome, fulfilling the Brighton criteria, while 24 (89%) in the training group and 21 (88%) in the control group mentioned any pain. The mean strength of knee extensors varied in the training group from 0.63 (sd 0.16) N/bm before training to 0.64 (sd 0.17) N/bm after training and in the control group from 0.53 (sd 0.14) N/bm to 0.54 (sd 0.15) N/bm. For this and all other outcome measures, no significant differences between the groups due to the intervention were found, with many variables showing high standard deviations. Adherence to the training was good with 63% of participants performing more than 80% of sessions. One adverse event occurred during training, which was not clearly associated to the training. Four participants had to stop the training early. Conclusions No improvement in strength or muscle mass by self-guided resistance training was found. Low resistance levels, as well as the choice of outcome measures were possible reasons. A more individualized and better guided training might be important. However, program adherence was good with few side effects or problems triggered by the resistance training. Trial registration This trial was prospectively registered in the ISRCTN registry (www.isrctn.com, BMC, Springer Nature) on July 16, 2013 as ISRCTN90224545. The first participant was enrolled at October 25, 2013.

Weight loss is key to controlling the increasing prevalence of metabolic syndrome (MS) and its components, i.e., central obesity, hypertension, prediabetes and dyslipidaemia. The goals of our study were two-fold. First, we characterised the relationships between eating duration, unprocessed and processed food consumption and metabolic health. During 4 weeks of observation, 213 adults used a smartphone application to record food and drink consumption, which was annotated for food processing levels following the NOVA classification. Low consumption of unprocessed food and low physical activity showed significant associations with multiple MS components. Second, in a pragmatic randomised controlled trial, we compared the metabolic benefits of 12 h time-restricted eating (TRE) to standard dietary advice (SDA) in 54 adults with an eating duration &gt, 14 h and at least one MS component. After 6 months, those randomised to TRE lost 1.6% of initial body weight (SD 2.9, p = 0.01), compared to the absence of weight loss with SDA (−1.1%, SD 3.5, p = 0.19). There was no significant difference in weight loss between TRE and SDA (between-group difference −0.88%, 95% confidence interval −3.1 to 1.3, p = 0.43). Our results show the potential of smartphone records to predict metabolic health and highlight that further research is needed to improve individual responses to TRE such as a shorter eating window or its actual clock time.

The effect of rheumatoid arthritis (RA) on peripheral muscle parameters is not completely understood. This study aimed to elucidate the influence of RA on peripheral muscle area and whole body skeletal muscle mass index (SMI) using peripheral quantitative computed tomography and dual-energy X-ray absorptiometry in postmenopausal women. This cross-sectional study included 54 postmenopausal women with RA and 86 healthy controls. Peripheral quantitative computed tomography and dual-energy X-ray absorptiometry were used to measure the muscle cross-sectional area and skeletal muscle mass. Muscle strength was assessed using a handheld dynamometer. Additionally, the effects of RA on muscle area and density as well as the bone / muscle area ratio were analyzed using multivariate models. The muscle area index of the thigh and forearm were correlated between both groups (RA: r = 0.357, p = 0.030; and healthy controls: r = 0.608, p < 0.001) and each index correlated with SMI in RA and healthy controls (p < 0.001). Bone / muscle area ratio correlated between forearms and thighs in health controls only (r = 0.547, p < 0.001). The RA group had a decreased thigh muscle area (p = 0.014); the fat area and fat muscle area ratio at the thigh and forearm were significantly increased (all p < 0.001), as well as thigh bone / muscle area ratio (p = 0.015). The RA group also had significantly lower forearm muscle density (p < 0.001). A sensitivity analysis excluding those on bisphosphonates led to similar results. Independent of RA, the thigh and forearm muscle area correlate with each other and with SMI. Differences in the bone / muscle ratio between RA and healthy controls may indicate regional muscle effects of inflammation and inactivity.

Bone protective effects of TNFα inhibition in rheumatoid arthritis are thought to be mediated by inhibiting synovial osteoclast differentiation and activity. However, it has not been addressed, if TNFα inhibitors alter the pool of peripheral osteoclast precursor cells (OPCs). Here, we blocked TNFα function in C57BL/6 mice with antigen induced arthritis (AIA) using the soluble TNFα receptor etanercept. Synovial bone lesions and osteoclasts were markedly reduced upon Etanercept in the early chronic phase of AIA. Unexpectedly this was not associated with a reduced recruitment of circulating OPCs to the arthritic joint nor to reduced synovial inflammation. In contrast we found that OPC numbers in bone marrow and blood were significantly reduced. Overall our study suggests that arrest of osteoclast mediated bone lesions upon inhibition of TNFα is, at least initially, based on reduced OPC availability in the periphery, and not on OPC recruitment or local anti-inflammatory effects in the arthritic joint.

Background There is an ongoing discussion about incorporating additional risk factors to established WHO fracture risk assessment tool (FRAX) to improve the prediction accuracy in clinical subgroups. We aimed to reach an expert consensus on possible additional predictive parameters for specific clinical subgroups. Methods Two-round modified Delphi survey: We generated a shortlist of experts from the authors’ lists of the pertinent literature and complemented the list with experts known to the authors. Participants were asked to name possible relevant risk factors besides the FRAX-parameters for the occurrence of osteoporotic fractures. Experts specified these possible predictors for specific subgroups of patients. In the second round the expert panel was asked to weight each parameter of every subgroup assigning a number between one (not important) to ten (very important). We defined the threshold for an expert consensus if the interquartile range (IQR) of a predictor was ≤2. The cut-off value of the median attributed weights for a relevant predictor was set at ≥7. Results Eleven experts of seven countries completed both rounds of the Delphi. The participants agreed on nine additional parameters for seven categories. For the category “secondary osteoporosis”, “older adults” and “nursing home patients”, there was a consensus that history of previous falls was relevant, while for men and postmenopausal women, there was a consensus that the spine fracture status was important. For the group “primary and secondary osteoporosis” the experts agreed on the parameters “high risk of falls”, “lumbar spine bone mineral density (BMD)” and “sarcopenia”. Conclusion This Delphi survey reached a consensus on various parameters that could be used to refine the currently existing FRAX for specific clinical situations or patient groups. The results may be useful for studies aiming at improving the predictive properties of instruments for fracture prediction.

Context Both thyroid dysfunction and levothyroxine (LT4) therapy have been associated with bone loss, but studies on the effect of LT4 for subclinical hypothyroidism (SHypo) on bone yielded conflicting results. Objective To assess the effect of LT4 treatment on bone mineral density (BMD), Trabecular Bone Score (TBS), and bone turnover markers (BTMs) in older adults with SHypo. Design and Intervention Planned nested substudy of the double-blind placebo-controlled TRUST trial. Participants with SHypo were randomized to LT4 with dose titration versus placebo with computerized mock titration. Setting and Participants 196 community-dwelling adults over 65 years enrolled at the Swiss TRUST sites had baseline and 1-year follow-up bone examinations; 4 participants withdrew due to adverse events not related to treatment. Main Outcome Measures One-year percentage changes of BMD, TBS, and 2 serum BTMs (serum CTX-1 [sCTX] and procollagen type 1 N-terminal polypeptide [P1NP]). Student’s t-test for unadjusted analyses and linear regression adjusted for clinical center and sex were performed. Results Mean age was 74.3 years ± 5.7, 45.4% were women, and 19.6% were osteoporotic. The unadjusted 1-year change in lumbar spine BMD was similar between LT4 (+0.8%) and placebo-treated groups (–0.6%; between-groups difference +1.4%: 95% confidence interval [CI] –0.1 to 2.9, P = .059). Likewise, there were no between-group differences in 1-year change in TBS (–1.3%: 95% CI –3.1 to 0.6, P = .19), total hip BMD (–0.2%: 95% CI –1.1 to 0.1, P = .61), or BTMs levels (sCTX +24.1%: 95% CI –7.9 to 56.2, P = .14), or after adjustment for clinical centers and sex. Conclusions Over 1-year levothyroxine had no effect on bone health in older adults with SHypo. Registration ClinicalTrial.gov NCT01660126 and NCT02491008

Objective This study aimed to elucidate the effects of changes in the geometry and density of the metacarpal bone of patients with rheumatoid arthritis (RA). Methods This prospective study included consecutive postmenopausal RA patients who met the American College of Rheumatology Criteria and healthy controls (HC). Peripheral quantitative computed tomography scans at 50% of the total metacarpal shaft (third metacarpal bone) were obtained at baseline and follow-ups. Use of bisphosphonates (BP), glucocorticoids (GC), biologics, and disease-modifying anti-rheumatic drugs (DMARD) was monitored (baseline to follow-up). Total cross-sectional area (CSA), cortical-transitional zone and compact zone CSA, cortical volumetric bone mineral density, and compact cortex porosity were measured. A linear mixed-effects model was used to determine significant differences in the rate of change in the RA and control groups and in RA patient subgroups. Results Thirty-nine RA patients and 42 consecutive postmenopausal HC were followed for 63 months. RA and HC depicted a time-dependent increase of medullary CSA (+0.41 mm2/year, P Conclusion Increase in medullary metacarpal CSA and thinning of the cortical CSA are physiological and time dependent. RA status is associated with loss in cortical density. Even upon biological therapy, low glucocorticoid dose affects metacarpal bone shaft geometry and density over time.

De nombreuses infections virales peuvent provoquer des arthralgies. La distinction clinique entre ceux dans le cadre d’une reaction systemique a une infection virale et une arthrite virale a proprement parler est difficile.

Viele virale Infektionen konnen Arthralgien auslosen. Die klinische Differenzierung zwischen Arthralgien im Rahmen einer Systemreaktion auf eine virale Infektion und einer per se viralen Arthritis ist schwierig.

Multicentric carpotarsal osteolysis (MCTO) is an autosomal dominant disease of the skeleton characterised by progressive destruction of carpal and tarsal bones. Recently, it has been demonstrated that this disease is caused by heterozygous mutations in the gene for the transcriptional repressor MAFB. We analysed genomic DNA and RNA from leucocytes of a female patient diagnosed with MCTO. We identified the mutation c.161C>T in the genomic sequence and in the expressed messenger RNA for MAFB. This is the second report of the c.161C>T mutation in a MCTO patient. Since the parents do not possess this mutation, the daughter must have acquired a de novo mutation. At the level of the gene, this mutation is found at a CpG dinucleotide sequence, suggesting that DNA methylation was involved in the occurrence of the DNA aberration. At the level of the protein, the mutation exchanges a serine with a leucine residue at a position on MAFB that can become phosphorylated in the wild-type protein. MAFB negatively regulates the RANKL-dependent differentiation of monocytes into osteoclasts. It is likely that the mutation will affect the phosphorylation status of the protein and its biological activity. When the activity of the transcriptional repressor is reduced, osteoclastogenesis will be increased, which might explain the carpotarsal bone destruction observed in the patient.

OBJECTIVE To investigate the effects of interleukin-17A (IL-17A) on osteoclastogenesis in vitro. METHODS Bone marrow cells (BMCs) were isolated from the excised tibia and femora of wild-type C57BL/6J mice, and osteoblasts were obtained by sequential digestion of the calvariae of ddY, C57BL/6J, and granulocyte-macrophage colony-stimulating factor-knockout (GM-CSF(-/-)) mice. Monocultures of BMCs or cocultures of BMCs and osteoblasts were supplemented with or without 1,25-dihydroxyvitamin D(3)(1,25[OH](2)D(3)), recombinant human macrophage colony-stimulating factor (M-CSF), RANKL, and IL-17A. After 5-6 days, the cultures were fixed with 4% paraformaldehyde and subsequently stained for the osteoclast marker enzyme tartrate-resistant acid phosphatase (TRAP). Osteoprotegerin (OPG) and GM-CSF expression were measured by enzyme-linked immunosorbent assay, and transcripts for RANK and RANKL were detected by real-time polymerase chain reaction. RESULTS In both culture systems, IL-17A alone did not affect the development of osteoclasts. However, the addition of IL-17A plus 1,25(OH)(2)D(3) to cocultures inhibited early osteoclast development within the first 3 days of culture and induced release of GM-CSF into the culture supernatants. Furthermore, in cocultures of GM-CSF(-/-) mouse osteoblasts and wild-type mouse BMCs, IL-17A did not affect osteoclast development, corroborating the role of GM-CSF as the mediator of the observed inhibition of osteoclastogenesis by IL-17A. CONCLUSION These findings suggest that IL-17A interferes with the differentiation of osteoclast precursors by inducing the release of GM-CSF from osteoblasts.

Levels of circulating cytokines are elevated in inflammatory diseases. Previously, it was shown that interleukin (IL-)17A, in synergism with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and tumor necrosis factor α (TNFα), induces the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) by murine osteoblasts in vitro. In this study, we further analyzed the effects of GM-CSF on osteoclast development in vitro. The effects of IL-17A, TNFα, and 1,25(OH)2D3 on the regulation of osteoclast development were investigated in cocultures of bone marrow-derived osteoclast progenitor cells (OPC) and mouse calvarial osteoblasts. Additionally, OPC were grown for 3days in media containing macrophage colony-stimulating factor (M-CSF), GM-CSF, or M-CSF/GM-CSF. Subsequently, the osteoclastogenic potential and the capacity to dissolve amorphous calcium phosphate were assessed in each of the three populations of OPC. IL-17A, in synergism with TNFα and 1,25(OH)2D3, inhibited the development of osteoclasts in cocultures by stimulating the osteoblast lineage cells to release GM-CSF. GM-CSF-treated OPC expressed traits characteristic of dendritic cells. Upon removal of GM-CSF and supplementation of the culture media with M-CSF/RANKL, the cells lost their dendritic cell characteristics and differentiated into osteoclasts. OPC pretreated with GM-CSF and M-CSF/GM-CSF exhibited delayed development to osteoclasts and an extended proliferation phase. Elevated levels of GM-CSF in systemic inflammatory diseases may cause an expansion of the OPC pools in the bone, bone marrow, and blood. Upon homing to the bone, this may lead to an increase in the number of osteoclasts and in bone resorption.

BACKGROUND There is evidence that postmenopausal women with rheumatoid arthritis (RA) on glucocorticoid (GC) therapy and bisphosphonate (BP) have an increased risk for atypical subtrochanteric and atypical diaphyseal femoral fracture (AFF). The underlying mechanism has not been elucidated so far. Using peripheral quantitative computed tomography (pQCT), the aim of the present study was to compare bone geometry, volumetric bone mineral density (vBMD) and bone strength of femoral shaft in BP-treated and BP-naïve postmenopausal women with RA. METHODS Prospective cross-sectional pQCT scans were taken at 33 % of total femur of BP-treated and BP-naïve RA patients. Bone parameters of the two groups were compared and correlated to disease characteristics and muscle cross-sectional area (CSA). RESULTS A total of 60 consecutive postmenopausal RA patients, 20 with BP therapy and 40 BP-naïve, were included in the study. The median age of the subjects was 63.5 years (range 48-85 years), and median disease duration (RA) was 12.0 years (range 2-47 years). Height and weight of the patients of the two groups were comparable. Women in the BP group were on average 4.3 years older (p = 0.044), and duration since menopause was on average 5.76 years longer (p = 0.045). In the BP group, there was a 13.31 % reduced muscle cross-sectional area around the proximal thigh (p = 0.013); cortical CSA was smaller by 5.3 % (p = 0.043); however, total and medullary CSA, as well as cortical vBMD and the polar bone stress-strain index of the femoral shaft were similar in the two groups. In regression analysis, age, time since menopause and muscular CSA were significant factors determining cortical CSA, cortical thickness and femoral index (p

We present a 44-year-old female patient with recurrent fragility fractures including an intercondylar femoral fracture and with normal planar bone densitometry. Diagnosis of hypophosphatasia was suggested by low volumetric cortical bone mineral density and laboratory findings. DNA sequencing revealed heterozygous mutations in the exons 5, 6 and 9 of the ALPL gene, thus confirming the suspected diagnosis.

Central nervous system involvement is a rare and serious complication of Behçet's disease (BD). Herein, we describe a patient with an atypical central lesion, who experienced progressive hypesthesia of the right arm and sensory loss of the trigeminal nerve together with intense headache. A repeated biopsy was necessary to conclusively establish the diagnosis of BD. Therapy with infusions of infliximab led to a remarkable full remission. TNFα-blocking therapy was successfully replaced by azathioprine. The present well-illustrated case demonstrates the difficulty of establishing the diagnosis of BD with central nervous system involvement, the dramatic benefit of short given TNF-α-blocking agent, and the long-term remission with azathioprin.

Objectives. Recent studies have suggested that areal BMD (aBMD) measured by DXA is elevated in patients with DISH. We used peripheral QCT (pQCT) to assess volumetric BMD (vBMD) and bone geometry of the radius, tibia and the third metacarpal bone. Methods. Patients with established DISH and a control group of healthy individuals were recruited. pQCT measurements were performed at the distal epiphyses and mid-shafts of the radius, the tibia and the third metacarpal bone. At the epiphyses cross-sectional area (CSA), total BMD and trabecular BMD were measured. At the shafts, total bone CSA, cortical CSA, cortical wall thickness and cortical BMD were determined. In addition, muscle and fat CSA of the forearm and lower leg were assessed. Bone parameters were compared between the two groups using independent t-tests. Results. Thirty DISH patients and 30 controls comparable with regard to age and height were included in this study. None of the measured bone parameters differed between groups. Conclusions. In contrast to suggestions based on DXA, pQCT revealed that DISH patients do not have increased vBMD and bone geometry in the appendicular skeleton. Ossification at tendon or ligament insertion sites may lead to overestimation of aBMD if assessed by DXA.

Background Extraspinal manifestations of diffuse idiopathic skeletal hyperostosis (DISH) have been described previously. We aimed to assess the prevalence of elbow hyperostotic spurs, to search for sites discriminating for elbow DISH and to analyze the effect of physical activities, handedness and sex. Methods Out of 284 patients hospitalized for extraskeletal disorders, 85 patients (33 with and 52 without thoracospinal DISH) agreed to bilateral elbow X-rays in two projections. Clinical information was collected by a standardized questionnaire and X-rays were graded blindly. Results A total of 400 hyperostotic spurs (210 unilateral, 95 bilateral) were present at 11 predefined sites. The most frequent sites affected were the olecranon (20.8 %), lateral epicondyle (17.8 %) and medial epicondyle (15.5 %). In carriers of thoracospinal DISH significantly more hyperostotic spurs were present at the lateral and medial epicondyle compared to non-DISH carriers (OR 4.01 [95 % CI 1.35–12.34] and 2.88 [1.03–8.24], respectively). The olecranon, lateral and medial epicondyle contributed significantly to the classification of elbow DISH (OR 22.2 [4.1–144.7], 9.6 [1.9–61.2] and 10.1 [2.2–52.1], respectively). The prevalence of elbow hyperostotic spurs was higher in 45 patients with a history of heavy physical activities (24.4 % versus 18.0 %, OR 1.48 [1.17–1.86]), at the right elbow (24.2 % versus 18.6 %, OR 1.39 [1.11–1.75]) and in 62 males (22.8 % versus 17.6 %, OR 1.38 [1.06–1.81]). Conclusions Hyperostotic spurs at the olecranon, lateral and medial epicondyle had the highest prevalence and disclosed the most pronounced discrimination for elbow DISH. Mechanical factors such as physical activities and handedness, and sex influenced the formation of these spurs. Electronic supplementary material The online version of this article (doi:10.1186/s12891-015-0575-5) contains supplementary material, which is available to authorized users.

The pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) is induced by glucocorticoids (GCs), but it was not previously known if MIF regulates cellular sensitivity to GC. Here we show in GC and LPS-treated peritoneal macrophages derived from MIF−/− and wt mice that the absence of endogenous MIF is associated with increased sensitivity to GC of TNF release. This is associated with increased expression of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), concomitant decreased phosphorylation of p38 MAPK, but no effect of MIF on nuclear factor κB (NF-κB). These results demonstrate that MIF regulates GC sensitivity by phosphorylation of p38, and provides a cellular mechanism for this observation, indicating that MKP-1 is a central target of this regulation.

Introduction On sait peu de choses des personnes qui presentent une hyper-mobilite generale des articulations. Elles sont souvent soumises a des restrictions au sport ou au travail du fait de douleurs ou d’un handicap. Une force musculaire adequate pour controler le mouvement pourrait permettre de surmonter ces restrictions. L’entrainement en resistance peut ameliorer la force musculaire. A ce jour, aucune etude n’a examine l’influence de ce type d’entrainement sur la force et la taille des muscles chez les femmes atteintes d’hyper-mobilite generale des articulations ; c’etait donc le but de cette recherche. Methode Cette etude randomisee controlee comprenait 51 femmes atteintes d’hyper-mobilite generale des articulations (moyenne d’âge : 26,5 ans). Vingt-sept ont entrepris un entrainement en resistance deux fois par semaine pendant 12 semaines ; 24 n’ont pas fait d’exercice. Les mesures ont porte sur la force isometrique maximale des muscles du genou, la surface maximale de section musculaire de la cuisse et sur le questionnaire de qualite de vie SF-36. Les donnees ont ete analysees en intention de traiter au moyen d’une analyse de variance multivariee (MANOVA). Les resultats sont presentes comme la difference moyenne entre groupes avec des intervalles de confiance de 95 % (IC) et des ampleurs de l’effet (ae). Resultats Au depart, les groupes sont comparables. L’analyse de variance ne revele aucune difference importante au sein des 5 variables principales. La difference de modification de force isometrique maximale entre les groupes est de 43,9 N (IC : −4,2 a 92,2 ; ae = 0,36) pour l’extenseur du genou, de 29,2 N (IC : −5,9 a 64,18 ; ae = 0,33) pour les flechisseurs du genou, en faveur du groupe qui a suivi l’entrainement. L’ecart moyen de modification de la surface maximale de section musculaire est de 131,2 mm2 (IC : −13,0 a 275,3 ; ae = 0,37) en faveur du groupe qui a suivi l’entrainement. L’ecart moyen de modification de la composante physique du SF-36 est de 0,5 (IC : −1,6 a 2,6 ; ae = 0,09), celui de la composante mentale de −4,2 (IC : −0,8 a −7,5 ; ae = 0,50), ce qui favorise le groupe de controle. Conclusions L’entrainement en resistance pendant 12 semaines ne modifie pas la force isometrique maximale, ni la surface maximale de section musculaire de la cuisse. Les grandes variations dues a la grande variabilite entre les sujets peuvent etre responsables de resultats statistiquement non significatifs. Le fait que l’entrainement etait dynamique, alors que les mesures etaient isometriques pourrait aussi expliquer le manque de difference de force mesuree. Par ailleurs, l’analyse des protocoles d’entrainement montre que les participantes ont fait de l’exercice a faible resistance. A titre d’exemple, sur une « leg press » unilaterale, la resistance moyenne a la fin des 12 semaines est de 83 % du poids du corps (de 65 a 160 %). Trois seances de formation etaient probablement insuffisantes pour gagner de la masse musculaire et pour conserver la motivation a s’exercer jusqu’a ses limites de force personnelles. Signification L’entrainement en resistance n’a pas modifie la force ni la taille des muscles chez des femmes atteintes d’hyper-mobilite generale des articulations. Des instructions plus detaillees pendant l’entrainement sont certainement necessaires pour conserver la motivation a s’exercer avec suffisamment de resistance pour gagner de la force et de la masse musculaire.

Introduction Le renforcement musculaire est utilise en physiotherapie chez differents patients, par exemple pour le mal de dos et l’arthrose. La question se pose egalement en termes economiques : dans quelle mesure les patients doivent-ils etre intensivement suivis pour suivre un entrainement efficace ? Il n’existe actuellement que tres peu d’etudes sur le renforcement musculaire au sein de groupes de patients bien definis. L’hyper-mobilite articulaire generalisee peut etre traitee au moyen d’un renforcement musculaire. Le but de cette etude etait d’examiner comment cet entrainement peut etre execute. Methode Quarante-sept femmes atteintes d’hyper-mobilite articulaire generalisee (26,5 ± 4,5 ans ; taille 1,68 ± 0,06 m ; poids 62,4 ± 10,1 kg) se sont entrainees durant 12 semaines (2 seances par semaine) dans le but d’atteindre une hypertrophie. Les exercices consistaient exercices sur leg press, extension et flexion des genoux, abduction de la hanche et position sur la pointe des pieds. Par ailleurs, les muscles abdominaux et les extenseurs dorsaux ont ete globalement entraines. Une physiotherapeute experimentee a fourni une formation d’une heure lors de la premiere seance, puis un controle et une adaptation d’une demi-heure au cours de la 3 e et de la 6 e semaine. Les participantes devaient augmenter la resistance elles-memes. Elles notaient chaque semaine les eventuelles douleurs et genes causees par l’entrainement. L’evaluation a ete faite de maniere descriptive. Resultats Les participantes ont effectue une moyenne de 19,3 entrainements durant 78 jours. La resistance initiale de la leg press se situe entre 7 et 111 % du poids corporel par jambe ; elle atteint 25–160 % apres 12 semaines. A la fin du programme, 13 femmes s’entrainent avec plus que le poids de leur propre corps ; 18 n’augmentent plus la resistance entre les semaines 7 et 12. Au cours de l’entrainement, 22 femmes indiquent avoir des douleurs aux genoux, 13 au niveau du dos. Dix eprouvent une ou plusieurs fois des courbatures. Une participante doit interrompre l’entrainement en raison de douleurs au dos ; elle se fera operer d’une hernie discale plus tard. Trois femmes arretent prematurement l’entrainement en raison d’une trop forte sollicitation. Conclusions L’entrainement peut etre bien execute par la plupart des femmes et les genes ne sont que minimes. Pour la patiente qui a arrete l’entrainement, la question du rapport entre la hernie discale et l’entrainement reste ouverte. Beaucoup de femmes s’entrainent avec une resistance basse ; la seance d’instruction et les deux coachings ne conduisent pas a un accroissement adequat de la resistance chez toutes les participantes. Signification Un accompagnement intensif semble necessaire pour atteindre un entrainement ideal d’hypertrophie chez les femmes atteintes d’hyper-mobilite articulaire generalisee. En meme temps, des adaptations frequentes et ciblees ont contribue a ce que moins de genes n’apparaissent, ce qui a probablement pu faire augmenter la motivation.

Objective: To evaluate routinely applicable criteria to predict fragmentation of renal calculi by extracorporeal shock wave lithotripsy (ESWL). Patients and Methods: Two hundred and two consecutive patients (121 men, 81 women), median age 48 (range 19–81) years, were treated with the original Dornier HM-3 lithotriptor at a single stone center. Inclusion criteria were: solitary stones, 10–30 mm in greatest diameter, located in renal pelvis or calyces. Based on plain radiographs, the calculi were classified according to their size, form, location, density (compared to the 12th rib), structure and surface. Furthermore, age of the patient, gender and body mass index were also considered for evaluation. Disintegration was documented on day 1 after ESWL by plain X-ray. A multivariate regression analysis was applied to all preoperative parameters, based on the dual variable stone free versus residual fragments. Results: The overall disintegration rate was 95.5%; 42 patients (20.8%) were completely stone free, and 151 patients (74.7%) had clinically insignificant residual fragments (5 mm or smaller). 14.9% of men and 29.6% of women were stone free (p = 0.01). All other parameters did not reach statistical significance. Conclusions: The disintegration rate of the HM-3 is excellent for kidney stones; women did significantly better than men. However, because of this high disintegration rate, a much larger series would be necessary to define possible differences between preinterventional parameters, if there were any at all.

Background: Hepatic angiosarcomas are rare tumors most often associated with exposure to vinyl chloride or other carcinogens. Only a few cases have been published without such a history. Case Report: We report the case of a 73-year-old woman who was admitted to our medical department with unclear upper abdominal pain, thrombocytopenia and anemia. Both computed tomography and magnet resonance imaging revealed a giant hemangioma in the right liver with multiple small hemangiomas. To cure the problem of thrombocytopenia due to sequestration of blood cells in the hemangioma, we decided to resect the large tumor. Intraoperatively, however, the diagnosis of angiosarcoma with multiple metastases was made. The patient died 6 weeks after surgery. Conclusion: Problems in diagnosing angiosarcoma include the brief duration of antecedent symptoms, difficulties in radiological diagnosis, and patients without a history of professional exposure to carcinogens.

Gemass WHO wird Osteoporose uber die Knochendichte definiert. Eine tiefe Knochendichte allein hat jedoch fur die Betroffenen keinen spurbaren Krankheitswert. Es stellt sich deshalb die Frage, wo die Grenze zwischen gesund und krank zu ziehen ist. Verschiedene klinische Risikofaktoren beeinflussen das Risiko fur Fragilitatsfrakturen auch unabhangig von der Knochendichte.

D’apres l’OMS, l’osteoporose se definit au moyen de la densite osseuse. Toutefois, une faible densite osseuse a elle seule n’a pas valeur de maladie reellement perceptible pour les personnes touchees.Differents facteurs de risque cliniques ont une influence sur le risque de fractures de fragilite et ce, independamment de la densite osseuse.

Glucokortikoide fuhren innerhalb weniger Monate zu einem Verlust von trabekularen Knochenstrukturen, insbesondere an der Wirbelsaule. Ausserdem erhohen Glucokortikoide auch die Porositat der Kortikalis und verstarken die insuffiziente Adaptation des Knochens an mechanische Belastungen. Diese Veranderungen sind mit einem stark erhohten Frakturrisiko assoziiert.

En l’espace de quelques mois, les glucocorticoides entrainent une perte de structure osseuse trabeculaire, plus particulierement au niveau de la colonne vertebrale. Outre la perte de structure osseuse trabeculaire les glucocorticoides peuvent egalement causer une augmentation de la porosite de l’os cortical et une adaptation osseuse insuffisante aux contraintes mecaniques. Ces modifications sont associees avec un risque de fracture fortement accru.