Pharmacological blockade of the Wnt signalling inhibitor sclerostin improves bone mineral density and bone strength via dual effects: a rapid but transient increase in bone formation, and a sustained reduction in bone resorption. New research suggests that drug-mediated repression of platelet-derived growth factor receptor (PDGFR) signalling in osteoblast lineage cells could explain the uncoupling of the anabolic and anti-resorptive effects of long-term sclerostin blockade.

Previous work had shown that PDGFRs are activated by sclerostin in osteoblast lineage cells and that PDGFR signalling in these cells regulates bone resorption by stimulating the secretion of M-CSF. These observations led the researchers to hypothesize that PDGFRs mediate the sustained antiresorptive effects of anti-sclerostin antibody.