Close negative correlation of local and circulating Dickkopf-1 and Sclerostin levels during human fracture healing

Abstract

Abstract Objective This study investigates the role of Wnt signaling in human fracture healing by examining local and circulating levels of Dickkopf-1 (DKK1) and its association with sclerostin (SOST). Methods This study includes 69 patients who underwent surgical stabilization of long bone fractures, with six experiencing impaired healing. Patient data on factors influencing DKK1 and SOST were recorded. DKK1 and SOST concentrations were measured at the fracture site and in circulation using enzyme-linked immunosorbent assay (ELISA). Results A negative correlation between DKK1 and SOST was observed. Immediately after trauma and in the fracture hematoma, DKK1 levels decreased significantly, while SOST levels increased compared to healthy controls. Postoperatively, DKK1 peaked at week 2, and SOST peaked at week 8, demonstrating a negative correlation. Age and smoking influenced the DKK1-SOST balance, while type 2 diabetes and sex showed no impact. In younger patients (< 50 years), non-union was associated with early postoperative elevation of SOST without compensatory DKK1 decrease. Conclusion The study highlights the inverse correlation and rapid dynamics of DKK1 and SOST during human fracture healing. The findings support the idea that dual-blockade of DKK1 and SOST could be essential for the therapeutic efficacy of Wnt-targeted therapies in fracture healing.