Phytoestrogens as Potential Anti-Osteoporosis Nutraceuticals: Major Sources and Mechanism(s) of Action.

Abstract

By 2050, the global aging population is predicted to reach 1.5 billion, highlighting the need to enhance elderly quality of life. Osteoporotic fractures are projected to affect one in three women and one in five men over aged 50. Initial treatments for osteoporosis in postmenopausal women include antiresorptive agents such as bisphosphonates, strontium ranelate, estrogen replacement therapy (ERT) and selective estrogen receptor modulators (SERMs). However, these do not rebuild bone, limiting their effectiveness. Denosumab, an FDA-approved antiresorptive monoclonal antibody, also has drawbacks including high costs, biannual subcutaneous injections, slow healing, impaired bone growth, and side effects like eczema, flatulence, cellulitis, osteonecrosis of the jaw (ONJ), and an increased risk of spinal fractures after treatment discontinuation. Nutraceuticals, particularly phytoestrogens, are gaining attention for their health benefits and safety in osteoporosis prevention. Phytoestrogens, plant metabolites similar to mammalian estrogens, include isoflavones, coumestans, lignans, stilbenes, and flavonoids. They interact with estrogen receptor isoforms ERα and ERβ, acting as agonists or antagonists based on concentration and bioavailability. Their tissue-selective activities are particularly significant: anti-estrogenic effects in reproductive tissues may lower the risk of hormone-related cancers (such as ovarian, uterine, breast, and prostate cancers), while estrogenic effects on bone could contribute to the preservation of bone mineral density.Phytoestrogens are, thus, used in managing breast and prostate cancers, cardiovascular diseases, menopause, and osteoporosis. The presentreview focuses on the botanical origin,classification, sources and mechanism(s) of action of major phytoestrogens, their potential in prevention and management of osteoporosis and the requirement for additional clinical trials to achieve more definitive outcomes in order to confirm their efficacy and dosage safety.