Sclerostin Antibody Increases Bone Volume and Enhances Implant Fixation in a Rat Model

• DOI: 10.2106/jbjs.k.00344
• Publication Date: 2012-11-15T20:57:05Z
• Authors: Amarjit S Virdi; Min Liu; Kotaro Sena; James Maletich; Margaret McNulty; Hua Zhu Ke; Dale R Sumner
• Keywords: Male; Titanium; 0301 basic medicine; Dose-Response Relationship, Drug; Antibodies, Monoclonal; X-Ray Microtomography; Risk Assessment; Drug Administration Schedule; Biomechanical Phenomena; Rats; Prosthesis Implantation; Rats, Sprague-Dawley; Disease Models, Animal; Random Allocation; 03 medical and health sciences; Treatment Outcome; Osteogenesis; Reference Values; Tensile Strength; Animals; Femur

Previous studies have demonstrated that sclerostin blockade is anabolic for bone. This study examined whether systemic administration of sclerostin antibody would increase implant fixation and peri-implant bone volume in a rat model.Titanium cylinders were placed in the femoral medullary canal of ninety male Sprague-Dawley rats. One-half of the rats (n=45) received murine sclerostin antibody (Scl-Ab, 25 mg/kg, twice weekly) and the other one-half (n=45) received saline solution. Equal numbers of rats from both groups were sacrificed at two, four, or eight weeks after the implant surgery and the femora were examined by microcomputed tomography, mechanical pull-out testing, and histology.Fixation strength in the two groups was similar at two weeks but was 1.9-fold greater at four weeks (p=0.024) and 2.2-fold greater at eight weeks (p<0.001) in the rats treated with sclerostin antibody. At two weeks, antibody treatment led to increased cortical area, with later increases in cortical thickness and total cross-sectional area. Significant differences in peri-implant trabecular bone were not evident until eight weeks but included increased bone volume per total volume, bone structure that was more plate-like, and increased trabecular thickness and number. Changes in bone architecture in the intact contralateral femur tended to precede the peri-implant changes. The peri-implant bone properties accounted for 61% of the variance in implant fixation strength, 32% of the variance in stiffness, and 63% of the variance in energy to failure. The implant fixation strength at four weeks was approximately equivalent to the strength in the control group at eight weeks.Sclerostin antibody treatment accelerated and enhanced mechanical fixation of medullary implants in a rat model by increasing both cortical and trabecular bone volume.