Journal of Osteoporosis and Physical Activity
Open Access

Zebrafish Insights into Osteoporosis and Bone Recovery

Ferga Widaa^{* *}Correspondence: Ferga Widaa, Department of Orthopaedics and Traumatology, University of Innsbruck, Innsbruck, Austria, Email:

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Description

Osteoporosis, a condition characterized by reduced bone density and increased fracture risk, is a significant public health concern, particularly in aging populations. To develop effective treatments, scientists often turn to animal models that mimic the disease's progression and response to therapies. Among these, zebrafish (Danio rerio) have emerged as a powerful model for studying bone biology, including fracture healing and bone regeneration in osteoporotic conditions. Zebrafish have unique characteristics that make them a valuable model for studying bone health and regeneration. The transparent bodies of zebrafish larvae allow researchers to observe bone development and healing in real time. Zebrafish bones develop quickly, enabling studies to be conducted over shorter timeframes compared to mammalian models. Zebrafish share many genes involved in bone formation and remodelling with humans. Zebrafish bones undergo remodelling processes similar to human bones, including the activity of osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells). Techniques such as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) allow researchers to create zebrafish models with specific genetic mutations linked to osteoporosis.

Osteoporosis and fracture healing in the zebrafish model

To study osteoporosis, researchers induce bone loss in zebrafish using various methods, such as, genetic mutations in genes involved in bone metabolism (e.g., col1a1 or BMP-2) create zebrafish with osteoporotic phenotypes. Drugs like glucocorticoids, which are known to induce bone loss in humans, are used to simulate osteoporosis in zebrafish. Low-calcium diets can mimic the effects of nutritional deficiencies on bone health. These models exhibit reduced bone density, impaired bone regeneration, and susceptibility to fractures, closely mirroring human osteoporosis. Fracture healing is a complex process involving inflammation, bone repair, and remodelling. In zebrafish, this process can be studied with remarkable clarity due to their regenerative capabilities.

Inflammatory phase: After a fracture, immune cells are recruited to the site to clear debris and initiate healing.

Bone formation: Osteoblasts and chondrocytes (cartilage-forming cells) create a cartilage template that is later replaced by bone.

Remodelling phase: Osteoclasts reshape the newly formed bone, restoring its structure and strength.

In osteoporotic zebrafish, this process is often delayed or incomplete due to impaired cellular activity and reduced bone mineral density. This makes them a valuable model for studying how osteoporosis impacts fracture healing and identifying interventions to improve outcomes.

Bone regeneration and advancing osteoporosis treatment in zebrafish

One of the most remarkable features of zebrafish is their ability to regenerate bone. Unlike mammals, zebrafish can regrow entire fin rays (which contain bone) following amputation. This regeneration process shares many molecular pathways with bone healing in humans, including, Wnt/β-catenin pathway as important regulator of bone formation. BMP signalling promotes the differentiation of osteoblasts and chondrocytes. VEGF pathway supports angiogenesis, which is essential for delivering nutrients and cells to the injury site. Studying these pathways in zebrafish helps researchers understand the mechanisms of bone regeneration and identify potential therapeutic targets for enhancing bone repair in osteoporotic patients. Zebrafish models are instrumental in developing and testing new treatments for osteoporosis and impaired fracture healing. Key applications include, zebrafish are used to test the efficacy and safety of drugs aimed at enhancing bone density and promoting fracture healing. By manipulating genes involved in bone metabolism, researchers can identify novel targets for therapy. Studies on dietary supplements such as calcium, vitamin D, and omega-3 fatty acids provide insights into how nutrition impacts bone health. While zebrafish offer many advantages, there are limitations to their use in osteoporosis research, such as, anatomical differences. For example, zebrafish lack weight-bearing bones, which are most affected by osteoporosis in humans and in translational challenges, not all findings in zebrafish can be directly applied to human medicine. To address these challenges, researchers are combining zebrafish studies with other models, such as mice, and developing advanced techniques like 3D imaging and single-cell analysis to deepen their understanding of bone biology.

Conclusion

The zebrafish osteoporosis model is a promising tool for studying fracture healing and bone regeneration. Its unique advantages-transparency, rapid development, and genetic manipulability, allow researchers to explore the underlying mechanisms of bone repair and identify innovative treatments for osteoporosis. As our understanding of zebrafish bone biology grows, so does the potential to translate these findings into therapies that improve bone health and quality of life for individuals with osteoporosis.