Upwards of 10% of all bone fractures fail to heal properly, with dysfunctional repair even more common in individuals with metabolic defects. Vitamin D has been implicated in fracture healing, which involves formation of a soft callus at the fracture site that is later mineralized and ossified. In this episode, René St-Arnaud and colleagues determined that ossification is impaired in Cyp24a1-deficient mice, which are unable to synthesize the vitamin D metabolite 24R,25-dihydroxyvitamin D3, following traumatic bone injury. FAM57B2 was upregulated in the fracture callus of Cyp24a1-deficient mice, and an interaction between FAM57B2 and 24R,25-dihydroxyvitamin D3 in chondrocytes produced lactosylceramide, which supports callus mineralization. Importantly, lactosylceramide supplementation improved mineralization in both Cyp24a1- and Fam57b2-deficient calluses, suggesting that this 24R,25-dihydroxyvitamin D3–dependent pathway has potential to be targeted to optimize bone repair after fracture.
