Localized sclerostin accumulation in osteocyte lacunar-canalicular system is associated with cortical bone microstructural alterations and bone fragility in db/db male mice

This study investigates how localized accumulation of sclerostin within the osteocyte lacunar–canalicular system contributes to cortical bone fragility in a type 2 diabetes (db/db) mouse model. Diabetic mice exhibited impaired cortical bone microarchitecture, reduced canalicular density, and altered osteocyte ultrastructure despite relatively preserved bone mineral density. Mechanical testing revealed reduced whole-bone stiffness, strength, and elastic modulus, accompanied by decreased tissue-level hardness and Young’s modulus. Elevated sclerostin accumulation correlated with increased expression of matrix-degrading enzymes, suggesting that localized osteocyte-driven matrix remodeling contributes to diabetic bone fragility.