Dual Chemical Regulations for Combined Anti-Resorption and Osteo-Anabolism to Reverse Osteoporosis

Osteoporosis is characterized by serious calcium loss in bone, where osteoclast-induced bone resorption overwhelms osteoblast-based bone formation. Herein, a dual chemical regulation strategy is proposed for reversing osteoporosis by antioxidation to inhibit osteoclastic bone resorption, in combination with pro-mineralization to favor osteoblast-based anabolic bone formation, synergistically functioning to remodel bone homeostasis. Such a dual chemical approach is achieved by an elaborately engineered nanomedicine, which can degrade in the acidic region of osteoporosis, releasing Mn 2+, epicatechin (EC), and silicate species. Mn 2+ coordinated by EC significantly enhances its antioxidant activity, thereby scavenging excessive reactive oxygen species in the osteoclast and inhibiting bone resorption. Additionally, the silicate species released from the nanoplatform promote mineralization reaction to facilitate osteoblast-based new bone formation. Such a nanomedicine is capable of efficiently reversing osteoporosis, as demonstrated by both in vitro and in vivo results. This work provides a feasible approach for osteoporosis treatment by a dual chemical regulation approach.