Chronisch-entzündliche Darmerkrankungen (CED) sind häufig mit extraintestinalen Manifestationen assoziiert. Diese treten meist im Verlauf oder zeitgleich mit der intestinalen Erkrankung auf. Das Vorliegen mehrerer assoziierter Autoimmunerkrankungen vor der Manifestation einer CED ist hingegen selten und ungewöhnlich. Wir berichten über eine 22-jährige Patientin, die initial wegen einer beidseitigen Uveitis anterior rheumatologisch vorgestellt wurde. In der Vorgeschichte bestanden eine Autoimmunpankreatitis Typ 2 sowie persistierend erhöhte Cholestaseparameter. Im weiteren Verlauf wurde eine primär sklerosierende Cholangitis diagnostiziert. Wenige Wochen später manifestierte sich klinisch und histologisch ein Morbus Crohn. Retrospektiv zeigten sich bereits zuvor bildgebende Hinweise auf eine entzündliche Dünndarmerkrankung. Der Fall unterstreicht die Bedeutung einer interdisziplinären Diagnostik bei jungen Patientinnen und Patienten mit multiplen Autoimmunmanifestationen. Eine zugrundeliegende chronisch-entzündliche Darmerkrankung sollte auch bei initial fehlender gastrointestinaler Symptomatik in Betracht gezogen werden.

Recent advancements in tissue engineering have led to sophisticated in vitro models that better replicate physiological conditions. Bone regeneration remains a key research area due to its complex remodeling and biomechanical properties. Traditional models often fail to capture these dynamics, limiting their translational potential. Here, a modular bioreactor platform designed to simulate bone homeostasis and disease states with integrated mechanical load simulation is presented, featuring a 3D-printed microfluidic chamber, dynamic dual perfusion, and a mechanical compression device, enabling precise control of environmental parameters via a web interface. Applied to an in vitro fracture healing model, the setup prolonged viability by facilitating the inflammatory-to-anti-inflammatory transition. Additionally, the setup allowed for generating functional bone models through controlled mechanical stimulation, revealing mechanobiological insights. The dual perfusion approach further enhanced composite tissue incubation. This system advances in vitro tissue modeling by combining perfusion with mechanical stimulation, improving nutrient delivery, mechanotransduction, and scalability. It holds promise for preclinical research, drug testing, and regenerative medicine, bridging the gap between static in vitro models and physiologically relevant conditions.

Pathologische Frakturen unter antiosteoporotischer und unter antirheumatischer Therapie sind sehr seltene Ereignisse. Dennoch treten atypische Femurfrakturen unter antiresorptiver Therapie mit Bisphosphonaten oder Denosumab auf, Letztere v. a. bei mit Bisphosphonaten vorbehandelten Patienten. Eine Behandlung mit Teriparatid kann hilfreich sein. Während Glukokortikoide einen gut bekannten Einfluss auf die Entstehung einer Osteoporose und damit auch Frakturen haben, ist die wahrscheinlich unproblematische Anwendung im Niedrigdosisbereich bislang wenig akzeptiert. Eine Methotrexat-induzierte Osteopathie ist ebenfalls ein selten auftretendes Phänomen, dennoch mittlerweile gut akzeptiert und bekannt. Für die Behandlung einer Glukokortikoid-induzierten Osteoporose gibt es verschiedene zugelassene Medikamente, bei der Methotrexat-induzierten Osteopathie ist insbesondere das Absetzen von Methotrexat essenziell.

Pregnancy and lactation-associated osteoporosis (PLO) is a rare but serious condition. Multiple fractures often occur, mostly in the form of vertebral fractures, the mother is severely restricted and caring for the infant is barely possible without assistance. The fractures causing the complaints usually occur in the last trimester of the first pregnancy or in the first weeks of lactation. Magnetic resonance imaging (MRI) can be used to detect vertebral fractures and also edematous vertebrae. Bone densitometry is helpful for the diagnostics and assessment of progression. It is extremely important to distinguish PLO from other secondary forms of osteoporosis that can also be manifested during pregnancy and lactation. The mother is advised to stop breastfeeding immediately in order to interrupt calcium mobilization from bone and to achieve a normalization of hormone levels. Calcium and vitamin D should be supplemented and adequate pain treatment and physiotherapy should be initiated. The quality of data is poor due to the rarity of the disease, all available anti-osteoporotic drugs have been used in case reports but overall, in the last decade off-label treatment with teriparatide has been proven to be helpful and safe.

Selenoprotein P (SELENOP) controls selenium (Se) transport, and glutathione peroxidase 3 (GPx3) elicits antioxidant activity in blood. Inflammation associates with Se deficiency, but knowledge concerning selenoproteins in inflammatory rheumatic musculoskeletal diseases (iRMD) is limited. We compared three Se biomarkers in patients with rheumatoid (RA), psoriatic (PsA), and juvenile idiopathic arthritis (JIA) in comparison to osteoarthritis (OA) and healthy subjects, to improve the data base on selenoprotein expression in iRMD.The cross-sectional study enrolled n=272 patients with RA (n=131), PsA (n=67), JIA (n=22) and OA (n=52). Serum Se was quantified by total reflection X-ray fluorescence, SELENOP by ELISA and GPx3 by an enzymatic test. Data from the EPIC trial served as reference. Impairment of daily life was assessed by the Functional Ability Questionnaire (FfbH).Serum SELENOP and Se concentrations correlated linearly in all groups and were below the average measured in EPIC. Se concentration was not different between the patient groups. Compared to controls, SELENOP levels were low in iRMD patients. GPx3 activity was particularly low in JIA and PsA. Seropositive but not seronegative RA patients displayed a disrupted interaction between GPx3 and Se or SELENOP. SELENOP associated with the functional status measured by the FfbH, most pronounced in OA (R=0.76, P < .01).The data indicate selenoprotein deficiency in the majority of patients with iRMD, and a positive relation of SELENOP with functional status in OA. Since increased Se supply improves selenoprotein biosynthesis, a personalized correction of diagnosed deficiency merits consideration to improve Se transport and ameliorate disease burden.

Schwangerschafts- und Stillzeit-assoziierte Osteoporose ist ein seltenes, jedoch durchaus schwerwiegendes Krankheitsbild. Oft treten mehrere Frakturen auf, meist in Form von Wirbelkörperfrakturen, die Mutter ist stark eingeschränkt und die Versorgung des Säuglings kaum ohne Hilfe möglich. Meistens treten die Beschwerden verursachenden Frakturen im letzten Trimenon der ersten Schwangerschaft auf oder in den ersten Wochen der Stillzeit. MRT(Magnetresonanztomographie)-morphologisch können Wirbelkörperfrakturen, aber auch stark ödematöse Wirbelkörper detektiert werden. Eine Osteodensitometrie ist zur Diagnostik und zur Verlaufsbeurteilung hilfreich. Extrem wichtig ist die Abgrenzung zu anderen sekundären Osteoporoseformen, die sich auch in der Schwangerschaft/Stillzeit manifestieren können. Der Mutter wird zum sofortigen Abstillen geraten, um die starke Kalziummobilisation aus dem Knochen zu durchbrechen und eine Normalisierung des hormonellen Status zu erreichen. Kalzium und Vitamin D sollten supplementiert und eine adäquate Schmerztherapie sowie Physiotherapie initiiert werden. Die Datenqualität ist aufgrund der Seltenheit der Erkrankung dürftig, alle zur Verfügung stehenden Antiosteoporotika wurden in Fallbeschreibungen eingesetzt, insgesamt hat sich jedoch in der letzten Dekade eine Off-label-Therapie mit Teriparatid als hilfreich und sicher bewährt.

Pathological fractures under anti-osteoporotic and antirheumatic treatment are very rare events. Nevertheless, atypical femoral fractures occur during antiresorptive treatment with bisphosphonates or denosumab, the latter especially in patients previously treated with bisphosphonates. Treatment with teriparatide can be helpful. While glucocorticoids have a well-known influence on the development of osteoporosis and thus also fractures, the probably unproblematic use in the low-dose range has so far found little acceptance. Methotrexate-induced osteopathy is also a rare phenomenon but is now well accepted and known. There are several approved medications for the treatment of glucocorticoid-induced osteoporosis and for methotrexate-induced osteopathy, discontinuation of methotrexate is particularly essential.

Fractures, with a yearly incidence of 1.2%, can lead to healing complications in up to 10% of cases. The angiogenic stimulant deferoxamine (DFO) is recognized for enhancing bone healing when administered into the fracture gap. This systematic review with meta-analysis investigates the effect of local DFO application on bone healing in rat and mouse models. EMBASE, MEDLINE (PubMed), and Web of Science are systematically searched in January 2024. The study is prospectively registered in PROSPERO (CRD42024492533), and the SYRCLE tool is used to assess study quality and risk of bias. Outcome values contain the primary endpoint bone volume fraction (BV/TV) as well as the secondary endpoints bone volume, tissue volume, bone mineral density, trabecular separation, trabecular thickness, vessel formation and the mechanical properties, assessed by µCT, angiography and mechanical strength tests. Out of 21 included studies, 18 qualify for meta-analysis, involving 539 animals. DFO-treated groups exhibit significantly higher BV/TV values (p < 0.0001) compared to controls, with similarly significant improvements in secondary outcomes. These findings highlight the substantial benefit of DFO in promoting bone healing, especially after radiotherapy. Rapid clinical implementation is recommended to help patients at high risk of fracture healing complications.

The remitting seronegative symmetric synovitis with pitting edema (RS3PE) syndrome is a rare inflammatory rheumatic disease of older adults, which can also be paraneoplastic. The main symptom is a rapidly progressing symmetric edematous swelling of both hands, sometimes also both feet, accompanied by (teno-)synovitis. Autoimmune serologies (rheumatic factor, antibodies against cyclic citrullinated peptides, antinuclear antibodies) typically remain negative. When a diagnosis of RS3PE is made, age-appropriate screening investigations for malignancies should be carried out. In addition, a comprehensive history should be taken and physical examination should be performed focusing on signs of neoplasia, followed by further investigations if necessary. The RS3PE syndrome typically shows an excellent response to treatment with glucocorticoids. A drug-free remission is frequently achieved but sometimes treatment with disease-modifying antirheumatic drugs (DMARDs) is necessary.

Background Accurate and rapid diagnosis of rheumatic diseases is essential for further treatment decision. Different rheumatic diseases present characteristic patterns (image features) in fluorescence optical imaging (FOI). We developed an atlas of FOI image features and tested its ability to differentiate various rheumatic diseases.Methods FOI images from patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), connective tissue diseases (CTD) and osteoarthritis (OA) were analysed by two readers blinded for diagnosis and calibrated against each other, using the prima vista mode (PVM) and an automated 5-phase model. Twenty-six different reoccurring typical signal enhancement patterns (features) indicating inflamed joints, nail or skin were defined and all FOI images were scored accordingly. The feature frequency in each patient cohort and phase (PVM, 5-phase) was counted. Contingency tables were created with categorical variable counts and diagnosis using common formulae.Findings Four hundred thirty-eight patients with RA (n=117), PsA (n=110), CTD (n=121) and OA (n=90) were included. Once the data had been categorised, a two-step diagnostic pathway was developed: in the first step, OA was best distinguished from the other diseases with high specificity by five patterns (specificity >0.9, diagnostic OR between 2.34 and 8.24). In a second step, the remaining autoimmune diseases were differentiated from each other by a certain number of features (five for RA, 12 for PsA and four for CTD).Interpretation This was the first study to show that feature analysis in FOI helps to differentiate typical rheumatic diseases from each other, potentially simplifying and speeding up the diagnostic process. Therefore, FOI could be considered an additional component of a wider range of imaging techniques used in rheumatology.

Osteoporosis is a bone disease characterized by low bone mass and changes in bone architecture, often leading to fractures and thereby decreased functional status in affected patients. About 200 million people worldwide suffer from osteoporosis, with women being affected earlier in life and more often than men. Various factors, such as genetic background, comorbidities, alcohol abuse, and medications such as glucocorticoids, are known to contribute to the development of osteoporosis. Due to the changing demographics, osteoporosis is becoming increasingly prevalent, and with this, the rate of fractures is expected to increase in the coming years. To investigate therapeutic options for treatment and to elucidate disease-causing mechanisms, various in vivo and in vitro osteoporosis models have been developed. In vivo models, in particular small animal models, remain the gold standard for osteoporosis research and the most used model to illustrate osteoporosis is the ovariectomized mouse. While in vivo models largely reflect the systemic and biological conditions, the transferability of findings to human patients is low and ethical concerns for laboratory animals must be considered. Thanks to tremendous technological improvements, such as on-a-chip platforms and high-end bioreactor systems, sophisticated in vitro models are of growing interest. These models offer the possibility of using complex cell systems, human cells from single donors, and 3D models, thus bridging the transferability gap, providing a platform for the introduction of personalized precision medicine, and ultimately replacing animal testing. Here, we summarize and discuss recent in vivo, in vitro, and in silico osteoporosis research approaches.

Das RS3PE(„remitting seronegative symmetric synovitis with pitting edema“)-Syndrom ist eine seltene entzündlich rheumatische Erkrankung des älteren Menschen, die auch paraneoplastisch auftreten kann. Leitsymptom ist die rasch progrediente, symmetrische ödematöse Schwellung beider Hände, teils auch beider Füße, begleitet durch (Teno-)Synovitiden. Autoimmunserologien (Rheumafaktoren, Antikörper gegen zyklische citrullinierte Peptide, antinukleäre Antikörper) bleiben typischerweise negativ. Wird die Diagnose eines RS3PE-Syndroms gestellt, sollten bislang ausgebliebene altersentsprechende Malignom-Screening-Untersuchungen nachgeholt werden. Zudem sollten eine ausführliche Anamnese und körperliche Untersuchung mit der Frage nach Hinweisen für eine Neoplasie durchgeführt werden, gegebenenfalls gefolgt von weiteren Untersuchungen. Das RS3PE-Syndrom spricht typischerweise exzellent auf eine Therapie mit Glukokortikoiden an. Häufig wird eine medikamentenfreie Remission erreicht, teils ist eine Therapie mit DMARDs („disease-modifying antirheumatic drugs“) notwendig.

Einleitung: Knochenbrüche, welche mit einer jährlichen Inzidenz von 1,2 % auftreten, bergen in bis zu 10 % der Fälle das Potenzial für Heilungsstörungen oder gar Non-Unions. Das angiogene Stimulans Deferoxamin (DFO), das durch direkte Injektion oder hochentwickelte Vektorsysteme in den Frakturspalt verabreicht wird, ist für seine positiven Auswirkungen auf die Osteogenese bekannt. Dies ist auf den Einfluss auf die Neovaskularisierung durch Eisen-Chelation und somit Aktivierung des Hypoxie-induzierbaren Faktor-1alpha-Signalwegs zurückzuführen. Dieses systematische Review mit Meta-Analyse befasst sich mit der Frage, ob die lokale Applikation von DFO in den Frakturspalt die Knochenheilung in Ratten- und Mausmodellen verbessert.

IntroductionDiabetes mellitus (DM) is a chronic metabolic disorder that increases fragility fracture risk. Conventional DXA-based areal bone mineral density (aBMD) assessments often underestimate this risk. Cortical Backscatter (CortBS) ultrasound, a radiation-free technique, non-invasively analyzes cortical bone’s viscoelastic and microstructural properties. This study aimed to evaluate CortBS’s discriminative performance in DM patients compared to DXA and characterize changes in cortical bone microstructure in Type 1 and Type 2 DM (T1DM, T2DM) patients.MethodsThis in-vivo study included 89 DM patients (T1DM = 39, T2DM = 48) and 76 age- and sex-matched controls. DXA measured aBMD, while CortBS measurements were taken at the anteromedial tibia using a medical ultrasound scanner with custom software. Multivariate analysis of variance assessed the impact of DM type on CortBS and DXA measurement results. Partial least squares discriminant analyses with cross-validation were used to compare the discrimination performance for vertebral, non-vertebral, and any fragility fractures, adjusting for gender, age, and anthropometric parameters (weight, height, BMI).ResultsFractures occurred in 8/23 T1DM, 17/18 T2DM, and 16/55 controls. DXA parameters were reduced in fracture patients, with significant diabetes impact. T2DM was associated with altered CortBS parameters, reduced scatterer density, and larger pores. CortBS outperformed DXA in discriminating fracture risk (0.61 ≤ AUC(DXA) ≤ 0.63, 0.68 ≤ AUC(CortBS) ≤ 0.69).ConclusionsBoth T1DM and T2DM showed altered bone metabolism, with T2DM linked to impaired tissue formation. CortBS provides insights into pathophysiological changes in diabetic bone and provided superior fracture risk assessment in DM patients compared to DXA.

The role of uric acid (UA) on bone metabolism is controversially discussed. Higher UA levels have been associated with higher T-scores and a reduced incidence of fractures in postmenopausal women. However, in the context of rheumatoid arthritis (RA), the role of UA remains unclear. This pilot study aimed to investigate the association of UA levels with bone mineral density in RA female and male patients. This pilot study analyzed patients with RA to explore preliminary associations. We utilized data from the Rh-GIOP cohort, a prospective monocentric observational study focusing on bone health in chronic rheumatic diseases. To assess the association between UA levels and the lowest T-scores measured at the lumbar spine, hip, or femur, we used linear regression with adjustment for various confounders. An interaction term was included to evaluate differential associations in pre- and postmenopausal women. Data on dual X-ray absorptiometry (DXA) measurements and serum UA levels were analyzed in a total of 206 patients. Among the 167 women 16 were premenopausal (age 40 ± 8 years) and 149 postmenopausal (age 65 ± 10 years). As expected, postmenopausal had lower T-scores than premenopausal patients (-1.53 ± 1.01 versus − 0.41 ± 1.29, respectively). No association of UA levels with T-scores was found when analyzing the whole cohort (Slope β: -0.04; p = 0.45). However, a significant negative correlation of UA with T-scores in premenopausal (Slope β: -0.98; p = 0.014), but not postmenopausal (Slope β: -0.04; p > 0.05) women was found. Uric acid appears to be negatively associated with bone mineral density in premenopausal but not in postmenopausal women with RA. Thus, the impact of UA on bone health seems to depend on the hormonal status of women. Further investigations are required to validate these results in a larger cohort of patients and to investigate the underlying mechanisms.