Sclerostin antibody treatment improves fracture outcomes in a Type I diabetic mouse model

• DOI: 10.1016/j.bone.2015.04.048
• Publication Date: 2015-05-05T00:50:22Z
• Authors: Cristal S. Yee; LiQin Xie; Sarah Hatsell; Nicholas Hum; Deepa Murugesh; Aris N. Economides; Gabriela G. Loots; Nicole M. Collette
• Keywords: Sclerostin; RUNX2; Osteopenia

Type 1 diabetes mellitus (T1DM) patients have osteopenia and impaired fracture healing due to decreased osteoblast activity. Further, no adequate treatments are currently available that can restore in T1DM; hence a significant need exists investigate new therapeutics for treatment of orthopedic complications. Sclerostin (SOST), WNT antagonist, negatively regulates bone formation, SostAb is potent anabolic agent. To determine whether SOST antibody (SostAb) improves streptozotocin (STZ) induced T1DM mice, we administered twice weekly up 21days post-fracture, examined quality callus outcomes at 42days post-fracture (11 14weeks age, respectively). Here show parameters; these improvements persist after cessation treatment. Markers differentiation such as Runx2, collagen I, osteocalcin, DMP1 were reduced, while an abundant number SP7/osterix-positive early osteoblasts observed on the surface STZ calluses. These results suggest calluses poor osteogenesis resulting from failure fully differentiate produce mineralized matrix, which produces less callus. enhanced both normal groups, STZ+SostAb also reversed lower mineralization seen Micro-CT analysis revealed improved parameters with treatment, was comparable Controls. Additionally, found sclerostin levels be elevated mice β-catenin activity reduced. Consistent its function activity, but increased circulation. Our indicate rescues model by facilitating bone.