FRACTURE HEALING AND SCLEROSTIN DEPLETION

Background Sclerostin is a secreted glycoprotein that inhibits the intracellular Wnt signaling pathway, which when inactivated bone formation is stimulated. This stimulation has been proven in fracture studies, showing larger and stronger calluses with accelerated fracture healing, both in sclerostin knockout and sclerostin antibody injection models. The effects of these two mechanisms have not been compared to assess the accurate effect of the Scl-Ab injections. Therefore we designed a study to compare the effect of sclerostin depletion (sclerostin knockout) and inhibition (Scl-Ab injection). Methods 10-week-old male SOST knockout (KO) (N=20) and Wild-type (WT) (N=40) mice underwent insertion of a tibial intramedullary pin after which a mid-shaft tibial osteotomy was performed. The mice were divided into three groups: SOST KO (N=20), WT with Scl-Ab injection “intravenous dose of 100mg/kg weekly” (N=20) and WT with saline injection (N=20). Each group was managed and sacrificed according to the specified protocol. Results Both Scl-Ab and KO groups showed significantly increased trabecular bone volume/ total volume at the fracture site compared to the saline group at all time points and also showed no significant difference between them (except at 28 days postoperative). On biomechanical testing the Scl-Ab and KO groups showed significant increased strength in stiffness at days 14, 28 and 35 compared to the saline group. Discussion and Conclusion Scl-Ab injections showed promising results, which were comparable to the complete depletion of sclerostin, especially at earlier stages of the healing process and thus completing the process of healing at an earlier time point.