Cinnamic acid suppresses bone loss via induction of osteoblast differentiation with alteration of gut microbiota

Osteoporosis, a disease characterized by low bone density that poses a high risk of bone fractures, is associated with aging, diet, and menopause. Despite the various known therapeutic methods for osteoporosis treatment, the development of a new therapeutic agent without side effects in long-term use is required. Cinnamic acid (CA) is a phytochemical found in cinnamon. In this study, we evaluated the effect of CA on osteoporosis and demonstrated its mechanism in MC3T3E1 preosteoblasts and ovariectomized mice. CA treatment induced osteoblast differentiation with elevation of osteogenic markers both in vitro and in vivo. CA treatment ameliorated bone loss resulting in better bone indices, increased gut microbial diversity, and recovered changes in the gut microbial composition induced by ovariectomy. These changes were accompanied by an increase in BMP/TGFβ/Smad signaling. Therefore, CA has the potential to suppress the progress of bone loss via the enhancement of bone density through the regulation of gut microbiota.