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Raloxifene Enhances Material-Level Mechanical Properties of Femoral Cortical and Trabecular Bone

Departments of Anatomy and Cell Biology (M.R.A., A.S.K., M.C.K., D.B.B.) and Orthopedic Surgery (D.B.B.), Indiana University School of Medicine, and Department of Biomedical Engineering (D.B.B.), Indiana University-Purdue University at Indianapolis, Indianapolis, Indiana 46202; and Department of Mechanical Engineering (H.A.H., W.A.H.), Texas A&M University, College Station, Texas 77843

Address all correspondence and requests for reprints to: Matthew R. Allen, Ph.D., Department of Anatomy and Cell Biology, MS 5035, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, Indiana 46202. E-mail: matallen{at}iupui.edu.

We have previously documented that raloxifene enhances the mechanical properties of dog vertebrae independent of changes in bone mass, suggesting a positive effect of raloxifene on material-level mechanical properties. The goal of this study was to determine the separate effects of raloxifene on the material-level mechanical properties of trabecular and cortical bone from the femur of beagle dogs. Skeletally mature female beagles (n = 12 per group) were treated daily for 1 yr with oral doses of vehicle or raloxifene (0.50 mg/kg·d). Trabecular bone mechanical properties were measured at the femoral neck using reduced platen compression, a method that allows the trabecular bone to be tested without coring specimens. Cortical bone properties were assessed on prismatic beam specimens machined from the femoral diaphysis using both monotonic and dynamic (cyclic relaxation) four-point bending tests. Trabecular bone from raloxifene-treated animals had significantly higher ultimate stress (+130%), modulus (+89%), and toughness (+152%) compared with vehicle-treated animals. Cortical bone from raloxifene-treated animals had significantly greater toughness (+62%) compared with vehicle, primarily as a function of increased postyield displacement (+100%). There was no significant difference between groups in the percentage of stiffness loss during cortical bone cyclic relaxation tests. These results are consistent with previous data from the vertebrae of these same animals, showing raloxifene has positive effects on biomechanical properties independent of changes in bone volume/density. This may help explain how raloxifene reduces osteoporotic fractures despite modest changes in bone mass.