Indole derivatives intervene osteoporosis via gut-bone axis.

Osteoporosis is a systemic skeletal disease characterized by low bone mass, deterioration of bone microarchitecture, and increased fracture risk, which imposes a heavy burden on global public health, especially in postmenopausal women and the elderly. The gut-bone axis, a bidirectional regulatory network between the gut microbiota and bone metabolism, has emerged as a novel therapeutic target for osteoporosis. Indole derivatives, a class of bioactive compounds derived from tryptophan metabolism by gut microbiota or plant secondary metabolism, have attracted increasing attention due to their extensive biological activities, including anti-inflammatory, antioxidant, and metabolic regulatory effects. Accumulating evidence indicates that indole derivatives can regulate bone homeostasis through the gut-bone axis, providing a new strategy for the prevention and treatment of osteoporosis. This review systematically summarizes the types of indole derivative, elaborates their molecular mechanisms in the treatment of osteoporosis via the gut-bone axis (including regulating gut microbiota composition, maintaining intestinal barrier integrity, modulating immune-inflammatory responses, and mediating key signaling pathways), and discusses the current translational progress, existing challenges, and future prospects. This review aims to provide a comprehensive theoretical basis for the clinical application of indole derivatives in osteoporosis treatment and the development of novel targeted drugs.