A video abstract is available with the new study by Florio et al. in JBJS:
Bone fracture repair involves reactivation of the Wnt pathway. Bone formation can be hindered, however, by inhibitors of the pathway including sclerostin and Dickkopf-1 (DKK1). Prior work with rodent models demonstrated that the inhibition of sclerostin and DKK1 increased bone volume and strength. In a new JBJS study, Florio et al. test the dual inhibition of sclerostin and DKK1 in nonhuman primates.
As concluded by the authors, “DKK1-Ab [anti-DKK1 antibody] increased BMD and strength at the ulnar osteotomy site, Scl-Ab [anti-sclerostin antibody] increased bone formation and BMD at uninjured skeletal sites, and Scl-Ab plus DKK1-Ab combination therapy induced all of these effects, in some cases to a greater degree versus 1 or both monotherapies. These results in nonhuman primates suggest that DKK1 preferentially regulates bone healing while sclerostin preferentially regulates systemic bone mass.”
Additional perspective on this study is provided by Andre J. van Wijnen, PhD and Parisa Dashti, MSc in their commentary article, Next-Generation Bone Stimulation: Doubling Down on Bone Anabolics.