Targeting autophagy in osteoporosis: From pathophysiology to potential therapy

Osteoporosis is a highly prevalent disorder characterized by the loss of bone mass and microarchitecture deterioration of bone tissue, attributed to various factors, including menopause (primary), aging (primary) and adverse effects of relevant medications (secondary). In recent decades, knowledge regarding the etiological mechanisms underpinning osteoporosis emphasizes that bone cellular homeostasis, including the maintenance of cell functions, differentiation, and the response to stress, is tightly regulated by autophagy, which is a cell survival mechanism for eliminating and recycling damaged proteins and organelles. With the important roles in the maintenance of cellular homeostasis and organ function, autophagy has emerged as a potential target for the prevention and treatment of osteoporosis. In this review, we update and discuss the pathophysiology of autophagy in normal bone cell life cycle and metabolism. Then, the alternations of autophagy in primary and secondary osteoporosis, and the accompanied pathological process are discussed. Finally, we discuss current strategies, limitations, and challenges involved in targeting relevant pathways and propose strategies by which such hurdles may be circumvented in the future for their translation into clinical validations and applications for the prevention and treatment of osteoporosis.