Deciphering Multitarget Mechanisms of Phytochemical Flavonoids From Traditional Chinese Medicine: Emerging Insights Into Osteoporosis Therapeutics

Osteoporosis is a common metabolic bone disorder characterized by reduced bone mass and compromised skeletal microstructure, increasing fracture risk. Current therapies, such as bisphosphonates and hormone replacement, have limitations and side effects, highlighting the need for safer alternatives. Flavonoids, bioactive compounds in traditional Chinese medicine, show promise due to their antioxidant, anti-inflammatory, and estrogen-mimetic properties. However, their complex interactions with bone metabolism pathways require systematic exploration. This review evaluates the regulatory effects of flavonoids on osteoporosis, focusing on their ability to enhance osteoblast-mediated bone formation while inhibiting osteoclast-driven resorption. We categorize major flavonoid subfamilies (flavones, flavonols, flavanones, and isoflavones) and detail their molecular mechanisms and signaling pathways contributing to clinical efficacy. Additionally, we address challenges related to flavonoid bioavailability, explore strategies for optimizing drug delivery, and highlight the integration of advanced technologies-such as network pharmacology and artificial intelligence-to uncover synergistic mechanisms in herbal formulations. These discussions provide a mechanistic framework supporting the role of flavonoids as multitarget modulators in osteoporosis therapy, offering insights for future pharmacological research and clinical applications.