Isovitexin, a natural adiponectin agonist, prevents glucocorticoid-induced osteosarcopenia.

PURPOSE: Isovitexin is an agonist of adiponectin receptors (AdipoRs). Adiponectin has been shown to have beneficial effects on bone and muscle function, in addition to its positive impact on metabolic health. However, the preclinical and clinical application of adiponectin faces scalability challenges, prompting the investigation of isovitexin in a methylprednisolone (MP)-induced osteoporosis model.

METHODS

A rat model of MP-induced osteoporosis was developed to evaluate isovitexin's effects on bone health, including bone mass & microarchitecture (MicroCT), turnover markers (P1NP and CTX-1), strength (three-point bending, and nanoindentation), and quality (FTIR). We also investigated the muscle protective effects of isovitexin by measuring key muscle catabolic (atrogenes) proteins.

RESULTS

Isovitexin effectively prevented MP-induced osteopenia in critical weight-bearing, fracture-prone sites, such as the proximal femur and lumbar vertebrae. Bone turnover markers revealed its osteogenic and anti-resorptive properties, crucial for countering glucocorticoid-induced bone loss. Isovitexin treatment preserved the mineral and material composition of bone, indicating that it helps maintain the tissue integrity and mechanical strength. Hitherto observed effects of isovitexin likely resulted in the preservation of bone quality, demonstrated by preserving mechanical behavior and bone strength, which are essential for preventing fractures. MP treatment led to muscle atrophy, evidenced by reduced gastrocnemius diameter and cross-sectional area. Isovitexin countered these effects and inhibited atrogenes (atrogin-1 and MuRF-1) induction.

CONCLUSION

Isovitexin not only mitigates osteopenia but also maintains overall bone quality and composition, exhibiting dual osteogenic and anti-resorptive effects. Its capacity to reduce muscle atrophy underscores its potential as a comprehensive treatment for glucocorticoid-induced osteoporosis and sarcopenia.