Resveratrol is a stilbene found in red grapes. It has often been shown to have a protective role in osteoporosis. Several studies have shown the beneficial effects of resveratrol.

An in vivo study demonstrated that resveratrol significantly increased bone mineral density (BMD) and femoral porosity in osteoporotic experimental models. It led to significant reduction in the serum levels of alkaline phosphatase (ALP) and osteocalcin (OC) in these models. Resveratrol treatment also improved the protein expression of sirtuin 1 (SIRT1), led to the suppression of nuclear factor (NF)-κB and activated the NF-κB inhibitor (IkB) α protein expression.

Resveratrol protects against the deterioration of the trabecular microarchitecture. It seems to interfere with the cells that have a role in bone remodeling and decreases bone resorption. It enhances the differentiation of mesenchymal cells in osteoblasts, and inhibits the formation of osteoclasts. In ovariectomized experimental models, treatment with resveratrol for 12 weeks has been shown to inhibit the reduction of BMD.

Resveratrol is a potent antioxidant. It prevents bone loss by checking the damage caused by oxidative stress. It has been found to minimize receptor activator of nuclear factor-κB ligand (RANKL) and tartrate-resistant acid phosphatase‑5b (TRAP‑5b) levels, and increase the osteoprotegerin (OPG) level, thus mitigating bone microarchitecture damage. It has also been shown to upregulate FoxO1 transcriptional activity by inhibition of the PI3K/AKT signaling pathway. This enhances resistance to oxidative damage.

Resveratrol thus seems to exert a protective effect on osteoporosis and this effect could be attributed to several mechanisms. This substance can be explored further as a treatment for osteoporosis.