Sodium p-hydroxybenzoate alleviates osteoporosis through inhibiting bone metabolism and oxidative stress via activating ERα.

As the population ages, the incidence of osteoporosis (OP) gradually increases and is becoming a growing public health problem. Meanwhile, although traditional pharmacological therapy is extremely efficient in the treatment of OP, its application is constrained because of irreversible adverse drug reactions. Therefore, scientists should actively develop safer drugs while ensuring the therapeutic effect of OP. Previous studies have shown that p-hydroxybenzoic acid (HA) can upregulate the expression of estrogen receptor (ER). Sodium p-hydroxybenzoate (DSN160) is a sodium salt of HA with a lethal dose greater than 5g/kg. However, whether DSN160 has demonstrable anti-osteoporotic activities remains unclear. In this study, DSN160 increased the organ index, length and diameter of the bone and bone mineral density and improved bone microstructure in retinoic acid-induced OP rats. Furthermore, DSN160 reduced bone metabolism-related indicators. In addition, fulvestrant (a specific antagonist of ER) blocked the anti-OP effect of DSN160. In conclusion, our findings showed that DSN160 exerts anti-OP effect through inhibiting bone metabolism and oxidative stress via activating ERα.