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Transpedicular fixation can be challenging in the osteoporotic spine as reduced bone mineral density compromises the mechanical stability of the pedicle screw. Here, we sought to investigate the biomechanical and histological properties of stabilization of expandable pedicle screw (EPS) in the osteoporotic spine in sheep. EPSs and standard pedicle screws, SINO screws, were inserted on the vertebral bodies in four female ovariectomized sheep. Pull-out and cyclic bending resistance test were performed to compare the holding strength of these pedicle screws. High-resolution micro-computed tomography (CT) was performed for three-dimensional image reconstruction. We found that the EPSs provided a 59.6% increase in the pull-out strength over the SINO screws. Moreover, the EPSs withstood a greater number of cycles or load with less displacement before loosening. Micro-CT image reconstruction showed that the tissue mineral density, bone volume fraction, bone surface/bone volume ratio, trabecular thickness, and trabecular separation were significantly better in the expandable portion of the EPSs than those in the anterior portion of the SINO screws ( P < 0.05). Furthermore, the trabecular architecture in the screw-bone interface was denser in the expandable portion of the EPS than that in the anterior portion of the SINO screw. Histologically, newly formed bone tissues grew into the center of EPS and were in close contact with the EPS. Our results show that the EPS demonstrates improved biomechanical and histological properties over the standard screw in the osteoporotic spine. The EPS may be of value in treating patients with osteoporosis and warrants further clinical studies. [ABSTRACT FROM AUTHOR]