Therapeutic Potential of Hydrogen Sulfide in Bone Deficiency

H₂S, recognized as the third gaseous signaling molecule following NO and CO, holds significant potential for therapeutic applications in diseases characterized by bone deficiency. Considerable advancements have been achieved in the development of bone scaffold materials incorporating H₂S donors, as well as in the creation of innovative H₂S-releasing pharmacological agents. Exogenous supplementation of H₂S has exhibited pronounced bone-protective effects in animal models of osteoporosis, fractures, and periodontitis. These therapeutic effects are mediated through various mechanisms, including anti-inflammatory and antioxidant activities, alongside the bidirectional regulation of bone metabolic balance. Mechanistically, H₂S plays a critical role throughout the entire bone remodeling process-encompassing the resorption, reversal, and formation phases-by modulating osteoclast generation and activation, osteoblast differentiation and maturation, and maintaining mesenchymal stem cell function. This modulation occurs via key signaling pathways, such as the RANKL/OPG, the Wnt/β-catenin, and the p38-MAPK signaling pathway. A deeper understanding of the role of H₂S in bone deficiency can lead to the discovery of new therapeutic targets, while innovative H₂S donors offer highly promising new treatments for patients with bone deficiency.