Analysis of the Molecular Mechanisms by Flavonoids with Potential Use for Osteoporosis Prevention or Therapy

Background: Osteoporosis is the most common skeletal disorder worldwide. Flavonoids have the potential to alleviate bone alterations in osteoporotic patients with the advantage of being safer and less expensive than conventional therapies. Objective: The main objective is to analyze the molecular mechanisms triggered in bone by different subclasses of flavonoids. In addition, this review provides an up-to-date overview of the cellular and molecular aspects of osteoporotic bones versus healthy bones, and a brief description of some epidemiological studies indicating that flavonoids could be useful for osteoporosis treatment. Methods: The PubMed database was searched in 2001- 2021 using the keywords osteoporosis, flavonoids, and their subclasses such as flavones, flavonols, flavanols, isoflavones, flavanones and anthocyanins, focusing the data on the molecular mechanisms triggered in bone. Results: Although flavonoids comprise many compounds that differ in structure, their effects on bone loss in postmenopausal women or in ovariectomized-induced osteoporotic animals are quite similar. Most of them increase bone mineral density and bone strength, which occur through an enhancement of osteoblastogenesis and osteoclast apoptosis, a decrease in osteoclastogenesis, as well as an increase in neovascularization on the site of the osteoporotic fracture. Conclusion: Several molecules of signaling pathways are involved in the effect of flavonoids on osteoporotic bone. Whether all flavonoids have a common mechanism or they act as ligands of estrogen receptors remains to be established. More clinical trials are necessary to know better their safety, efficacy, delivery and bioavailability in humans, as well as comparative studies with conventional therapies.