<scp>d</scp>-limonene suppresses RANKL-induced osteoclast differentiation and promotes osteoblast activity <i>in vitro</i>

Treatments for osteoporosis are typically given postfracture. Therefore, identifying safe prophylactic interventions to reduce fracture risk would be beneficial. One approach is to utilize the bioactive properties of natural compounds to modify osteoclast and osteoblast activity. d-limonene a well-tolerated, anti-inflammatory monoterpene found in citrus fruits holds promise due to its suppressive effect on NFκB, a key regulator of bone cell activity. We found that limonene promoted osteoblast differentiation and bone nodule formation and inhibited RANKL-induced osteoclast formation and bone resorption in vitro. Limonene also reduced the proresorptive signal provided by osteoblast, augmenting markers of osteoblast differentiation (alkaline phosphatase, osterix, and osteocalcin) and significantly decreasing osteoclastogenic cytokine production (PTHrP, IL-1β, and TNF-α). Therefore, limonene supplementation represents a potential route in combination with current interventions to optimize bone cell activity to maintain or enhance bone mass.