Cell death regulation: A new way for natural products to treat osteoporosis

Osteoporosis is a common metabolic bone disease that results from the imbalance of homeostasis within the bone. Intra-bone homeostasis is dependent on a precise dynamic balance between bone resorption by osteoclasts and bone formation by mesenchymal lineage osteoblasts, which comprises a series of complex and highly standardized steps. Programmed cell death (PCD) (e.g., apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis) is a cell death process that involves a cascade of gene expression events with tight structures. These events play a certain role in regulating bone metabolism by determining the fate of bone cells. Moreover, existing research has suggested that natural products derived from a wide variety of dietary components and medicinal plants modulate the PCDs based on different mechanisms, which show great potential for the prevention and treatment of osteoporosis, thus revealing the emergence of more acceptable complementary and alternative drugs with lower costs, fewer side effects and more long-term application. Accordingly, this review summarizes the common types of PCDs in the field of osteoporosis. Moreover, from the perspective of targeting PCDs, this review also discussed the roles of currently reported natural products in the treatment of osteoporosis and the involved mechanisms. Based on this, this review provides more insights into new molecular mechanisms of osteoporosis and provides a reference for developing more natural anti-osteoporosis drugs in the future.