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Thirty\u2010one skeletally mature mice underwent PS, with circumferential removal of periosteum from an 8\u2010mm segment of the mid\u2010diaphysis of the left femur. Thirty\u2010one control mice underwent sham surgery in which the femur was isolated without manipulation of the periosteum. At 2, 6, 12, or 26 weeks following surgery, the left femora were examined by micro\u2010CT to quantify cortical thickness (CtTh), cross\u2010sectional area (CSA), bone volume (BV), and polar moment of inertia (PMI). Three\u2010point mechanical bend testing was performed and peak load, stiffness, and energy to failure were determined. PS resulted in significantly decreased CtTh, CSA, BV, and PMI at all time points. Peak load, stiffness, and energy to failure were significantly reduced at 2, 6, and 12 weeks. There were no significant differences in mechanical properties at 26 weeks. In this mouse model, extensive circumferential PS resulted in sustained changes in bone structure that were still evident after 6 months, accompanied by reductions in bone strength that persisted for at least 3 months. \u00a9 2011 Orthopaedic Research Society. \u00a9 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. 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