Background: Osteoporosis is a frequent age-related skeletal disorder, wielding an enormous influence on the quality of life of many women, but also men. Osteoporosis results from a shifted ratio between the activity of osteoblasts and osteoclasts resulting in an increased degradation of bone. This leads to a systemic impairment of bone mass and microarchitecture. Currently only a small number of patients with osteoporosis is treated adequately, making the disease an enormous economic burden. This implies the urgent need of developing new treatment strategies and application mechanisms. Therefore, animal models are of great importance for the investigation and treatment of bone diseases. Summary: In this narrative review we focus on animal models specially used for age-related osteoporosis including mice, fish and large animal models. Key Message: With this manuscript we want to contribute to the identification of novel treatment strategies for the treatment of age-related osteoporosis.

Introduction: Osteoarthritis is a classical age-related disease, which affects millions of patients worldwide. To further understand the pathophysiology and to develop therapeutic strategies for this disease, animal models play a significant role. Nothobranchius furzeri is an established model for accelerated aging that spontaneously develops spinal deformities. Although the bone properties of N. furzeri are well described, characteristics of the intervertebral discs are still unknown. The aim of this study was to investigate the characteristics of the intervertebral discs of healthy and deformed N. furzeri. Material and Methods: Intervertebral properties of healthy and deformed N. furzeri were investigated in 8-, 12-, 18- and 21.5-week-old male fish of the GRZ strain. For histological evaluations the fish were decalcified, paraffin-embedded and stained with (1) hematoxylin and eosin, (2) toluidine blue and (3) alcian blue/picrosirius red. Results: 8-week-old and deformed N. furzeri showed spongy-like tissue containing vacuolated notochord cells and a beginning formation of fibrous tissue in the central area. Older healthy fish showed fibrous tissue in the central region and a spongy-like tissue in the peripheral region. Conclusion: Our study revealed age- and disease-related alterations of the vertebral discs in N. furzeri. Further studies should investigate the utility of N. furzeri as a model for degenerative spine diseases.

A huge number of inbred mouse strains with different bone properties have become available for musculoskeletal research. C57Bl/6J and C3H/HeOuJ mice show a significant difference in their bone characteristics. Nevertheless, there is a lack of knowledge on the molecular basis of these strain differences. The aim of this study is to determine the gene expression of selected regulators expressed in the bone marrow as well as bone microstructure of C57Bl/6J and C3H/HeOuJ mice. Bone properties were investigated in 20-week-old female C57Bl/6J and C3H/HeOuJ mice. Total RNA was extracted from the bone marrow of the tibia and gene expression of the following genes was determined by quantitative real-time PCR: SOST, DKK1, OPN, FGF23, RANKL, IL6, TNF, IL17a, and OPG. The femur and third lumbar vertebral body (L3) were investigated by μCT. Bone histomorphometric evaluations were performed in tartrate-resistant acid phosphatase/toluidine blue stained fourth lumbar vertebral bodies (L4). C57Bl/6J and C3H/HeOuJ mice showed significant differences in the gene expression of DKK1, FGF23, IL-6, TNF, and OPG. When compared with C57Bl/6J mice, C3H/HeOuJ mice had a stronger cortical and trabecular bone microstructure at the femur. In contrast, at L3 bone volume/total volume (BV/TV) and trabecular number were significantly higher in C57Bl/6J than in C3H/HeOuJ mice. Bone histomorphometry of L4 revealed significantly higher BV/TV, trabecular number, and thickness in C57Bl/6J mice. Furthermore, the number of osteoblasts and the number of osteoclasts/bone perimeter were higher in the C57Bl/6J mice. This study shows that C57Bl/6J and C3H/HeOuJ mice exhibit a differential expression of cytokines present in the bone marrow. Bone properties differ not only between both strains but also in relation to the investigated bone region.

Einleitung Mausmodelle werden häufig in der Osteoporoseforschung eingesetzt; zur Beurteilung der Knocheneigenschaften werden meist Wirbelkörper, Femora oder Tibiae herangezogen. Im Gegensatz dazu wurde der Humerus, obwohl er eine klinisch wichtige Frakturlokalisation darstellt, kaum untersucht. Ziel dieser Studie war es, den Humerus bei verschiedenen Mausstämmen mittels Histomorphometrie zu analysieren. Wir stellten die Hypothese auf, dass die Mikroarchitektur des Humerus alters- und stammesbezogene Unterschiede aufweist. Methode In dieser Studie wurde der trabekuläre Anteil von 53 Humeri von weiblichen Mäusen der Stämme DBA/2JRj, C3H/J und C57BL/6J histomorphometrisch untersucht. Nach Euthanasie der Tiere im Alter von 8, 16 und 24 Wochen wurden Dünnschnittpräparate angefertigt, mit Toluidinblau und TRAP gefärbt und anschließend mit Hilfe des OsteomeasureTM Systems ausgewertet. Ergebnisse Bei den acht Wochen alten Mäusen wies der DBA-Stamm ein signifikant höheres Trabekelvolumen (p = 0,013), eine höhere Trabekelanzahl, und einen geringeren Trabekelabstand gegenüber den C3H-Mäusen auf. Acht Wochen alte DBA-Mäuse zeigten die höchste Trabekelanzahl, demgegenüber war die Zahl der Trabekel bei älteren DBA-Mäusen signifikant vermindert (p = 0,005). C57BL Mäuse wiesen im Vergleich zu dem C3H-Stamm eine signifikant höhere Osteoklastenanzahl auf (p = 0,035). Diskussion Zusammenfassend konnten in dieser Arbeit signifikante stammes- und altersbezogene Unterschiede bei histomorphometrischen Parametern des Humerus der Maus nachgewiesen werden. Diese Daten stellen eine Grundlage für zukünftige weitere Analysen des Humerus in Mausmodellen dar. Finanzielle Unterstützung Dieses Projekt wurde durch den Fonds zur Förderung der wissenschaftlichen Forschung (FWF; P35262) unterstützt. Keywords Mikroarchitektur, Humerus, Mausmodell, Osteoklasten, Histomorphometrie Korrespondenzadresse Katharina Gelles, Medizinische Universität Wien, Institut für Pathophysiologie und Allergieforschung, Währinger Gürtel 18-20/3Q, 1090 Wien, Österreich, E-Mail: katharina.gelles@meduniwien.ac.at Article published online: 16 June 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany

Age-related osteoporosis is characterized by progressive loss of bone mass and deterioration of bone microarchitecture, leading to enhanced skeletal fragility. Cytokines regulate bone remodeling through distinct signaling pathways. Baricitinib, a selective JAK1/2 inhibitor effective in inflammatory disorders such as rheumatoid arthritis, suppresses cytokine signaling, but its role in age-related osteoporosis remains insufficiently defined. In our study a total of 60 eight-month-old female SAMP8 mice were randomized to receive baricitinib (10 mg/kg) or vehicle twice daily by oral gavage for six weeks. Bone outcomes were evaluated by high-resolution micro-computed tomography (µCT) and static histomorphometry. Intracellular cytokine production by splenocytes was determined via flow cytometry. We found that baricitinib substantially reduced T-cell cytokine production, decreasing IL-6, IL-17, IFN-γ, and IL-21 in CD4⁺ T cells and IL-6 in CD8⁺ T cells, accompanied by lower IFN-γ/IL-17 and IL-21/IL-6 ratios, respectively. µCT analyses showed no significant intergroup differences in BV/TV, whereas histomorphometry demonstrated higher BV/TV in the baricitinib group. Overall, baricitinib was found to effectively suppressed proinflammatory cytokines in aged SAMP8 mice but did not consistently enhance bone parameters, indicating reduced skeletal responsiveness during aging.