The alpha and the omega (6 lipids): discovering dietary drivers of heterotopic ossification

Bone formation in soft tissues, known as heterotopic ossification (HO), can occur as a complication of trauma or burn injury and can cause pain and functional limitations in the affected site. HO remains an unmet clinical challenge due to a general lack of specific medical therapies. In this issue of the JCI, a study by Moye et al. identified obesity as a risk factor for HO and further found that the association with obesity was driven not by caloric surplus, but instead by dietary omega-6 lipids, which are characteristically elevated in the Western diet. These omega-6 lipids accumulated directly at the incipient HO site, where they served as substrates for prostaglandin E2 (PGE2), fueling aberrant osteoblast differentiation. Overall, this work provides compelling support for dietary intervention or pharmacologic therapy directed at downstream PGE2 signaling as approaches to reduce HO in at-risk patients.