D-limonene suppresses RANKL-induced osteoclast differentiation and promotes osteoblast activity in-vitro

Treatments for osteoporosis are typically given post-fracture. Therefore, identifying safe prophylactic interventions to reduce fracture risk would be beneficial. One approach is to utilise 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-indued osteoclast formation and bone resorption in-vitro. Limonene also reduced the pro-resorptive signal provided by osteoblast, augmenting markers of osteoblast differentiation (alkaline phosphatase, osterix and osteocalcin) and significantly decreased osteoclastogenic cytokine production (PTHrP, IL-1β and TNF-α). Therefore, limonene supplementation represents a potential route in combination with current interventions to optimise bone cell activity to maintain or enhance bone mass.