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Isoflavones Potentials for the Treatment of Osteoporosis: An Update on In-vivoStudies

Hamid Reza Chaboki, Farideh Akbarian, and Hossein Kazemi Mehrjerdi*

Department of Clinical Sciences, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran



In plant-derived compounds, phytoestrogens are biologically active substances that exhibit various estrogenic and antiestrogenic effects. With the increasing prevalence of osteoporosis among older women caused by estrogen deficiency, identifying natural substances that can potentially treat the disease is of utmost significance.This review study aimed to explore how phytoestrogen metabolites mimic mammalian estrogens and prevent bone loss following menopause. Phytoestrogens derived from plants have gained considerable attention due to their similarity to mammalian estrogens and lower impact on sensitive tissues, such as the uterus and breasts. One well-establishedapproach to simulate postmenopausal conditions is by using ovariectomized rats or mice (OVX). The administration of phytoestrogens in the OVX murine model has inhibited osteoclast differentiation, activation, and Pyridinoline secretion. Furthermore, thesecompounds have been shown to enhance bone formation and increase bone mineral density and the expression levels of various osteoblast markers, such as alkaline phosphatase, osteocalcin, osteopontin, and alpha-1 collagen. Several natural phytoestrogen compounds in plants possess a chemical structure akin to 17 beta-estradiol, a steroid hormone. In postmenopausal women with osteoporosis, isoflavones, a type of phytoestrogen, can potentially treat the disease by binding to estrogen receptors on the surface oftarget cells. Mechanistic investigations have demonstrated that phytoestrogens can retard bone resorption and promote bone formation. Novel approaches in phytoestrogen research could involve investigating the synergistic effects of combining different phytoestrogen compounds, exploring their interactions with other signaling pathways, or assessing their effects on various bone types. Furthermore, identifying novel sources of phytoestrogens could lead to the discovery of new compounds with potent osteoprotective effects.

1. Introduction:

There are several subtypes of osteoporosis, such as senile osteoporosis and postmenopausal osteoporosis1. In older and postmenopausal women, osteoporosis is one of the most prevalent skeletal diseases2. In addition to decreased bone mass and deteriorated microarchitecture, osteoporosis also increases the risk of fractures3. As one of the most serious issues facing women, postmenopausal osteoporosis is difficult to prevent4. It has been shown that hormone replacement therapy and pharmacological supplements of calcium, vitamins D and K can reduce bone loss and hip fracture complications after menopause, as well as select estrogen-receptor modulators, estrogen analogs or bisphosphonates, calcium, and parathyroid hormone5-7. Several nonpharmacological interventions are also available, including dietary modification, physical activity, hip protectors, and orthopedic treatment of fractures8. Osteoporosis can be treated with estrogen and related compounds9. Still, these are primarily aimed at blunting bone resorption, a tightly coupled process involving bone formation and resorption, largely the aim of current treatments10. Osteoporosis is currently treated with various drugs, which act as antiresorptive agents to prevent bone loss. These include bisphosphonates, estrogen, selective estrogen receptor modulators, and statins11,12. Most osteoporosis cases are caused by estrogen loss13. A well-established and reproducible method of simulating postmenopausal conditions is using ovariectomized (OVX) rats or mice14,15. Models like these simulate the decline of cancellous bone during postmenopause16.

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