Soy Isoflavones and Bone Health: Focus on the RANKL/RANK/OPG Pathway.

Bone remodels via resorption and formation, two phenomena that continuously occur in bone turnover. The RANKL/RANK/OPG pathway is one of the several mechanisms that affect bone turnover. The RANKL/OPG ratio has a substantial role in bone resorption. An imbalance between formation and resorption is related to an increased RANKL/OPG balance. OPG, a member of this system, can bind to RANKL and suppress RANK-RANKL interaction, and subsequently, inhibit further osteoclastogenesis. The serum levels of RANKL and OPG in the bone microenvironment are vital for osteoclasts formation. The RANK/RANKL/OPG system plays a role in the pathogenesis of bone disorders. This system can be considered a new treatment target for bone disorders. Soy isoflavones affect the RANK/RANKL/OPG system through numerous mechanisms. Soy isoflavones decrease RANKL levels and increase OPG levels. Therefore, isoflavones improve bone metabolism and decrease bone resorption. Soy isoflavones decrease serum markers of bone resorption and improve bone metabolism. However, while the available data are promising, the results of several studies reported no change in RANKL and OPG levels with isoflavones supplementation. In this regard, current evidence is insufficient for conclusive approval of the efficacy of isoflavones on RANKL/RANK/OPG and further research, including animal and human studies, are needed to confirm the effect of soy isoflavones on the RANKL/RANK/OPG pathway. This study was a review of available evidence to determine the role of isoflavones in bone hemostasis and the RANK/RANKL/OPG pathway. The identification of the effects of isoflavones on the RANKL/RANK/OPG pathway directs future studies and leads to the development of effective treatment strategies for bone disorders.

Potential of natural products in osteosarcoma treatment: Focus on molecular mechanisms.

Osteosarcoma is the most frequent type of bone cancer found in children and adolescents, and commonly arises in the metaphyseal region of tubular long bones. Standard therapeutic approaches, such as surgery, chemotherapy, and radiation therapy, are used in the management of osteosarcoma. In recent years, the mortality rate of osteosarcoma has decreased due to advances in treatment methods. Today, the scientific community is investigating the use of different naturally derived active principles against various types of cancer. Natural bioactive compounds can function against cancer cells in two ways. Firstly they can act as classical cytotoxic compounds by non-specifically affecting macromolecules, such as DNA, enzymes, and microtubules, which are also expressed in normal proliferating cells, but to a greater extent by cancer cells. Secondly, they can act against oncogenic signal transduction pathways, many of which are activated in cancer cells. Some bioactive plant-derived agents are gaining increasing attention because of their anti-cancer properties. Moreover, some naturally-derived compounds can significantly promote the effectiveness of standard chemotherapy drugs, and in certain cases are able to ameliorate drug-induced adverse effects caused by chemotherapy. In the present review we summarize the effects of various naturally-occurring bioactive compounds against osteosarcoma.