Molecular Hydrogen Prevents Osteoclast Activation in a Glucocorticoid-Induced Osteoporosis Zebrafish Scale Model

Antioxidants represent a powerful tool for many human diseases and, in particular, molecular hydrogen has unique characteristics that make it a very promising therapeutic agent against osteoporosis. Zebrafish scales offer an innovative model in which new therapeutic approaches against secondary osteoporosis are tested. Scale bone loss obtained by prednisolone (PN) treatment is characterized by increased osteoclast activity and decreased osteoblast activity highlighted with bone enzymatic assays. We used this read-out system to test the therapeutic effects of hydrogen-rich water (HRW), an innovative antioxidant approach. HRW prevented osteoclast activation and bone loss in PN-treated fish scales, as verified by both biochemical and histochemical tartrate-resistant alkaline phosphatase assays. On the other hand, HRW treatment did not prevent PN-dependent osteoblast suppression, as measured by alkaline phosphatase activity. Moreover, HRW treatment did not facilitate the reparation of resorption lacunae induced in scales by PN. Our study highlighted a specific effect of HRW on adult osteoclast activity but not in osteoblasts, introducing an intriguing new antioxidant preventive approach against osteoporosis.