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Scientific Articles   |    
Sclerostin Antibody Increases Bone Volume and Enhances Implant Fixation in a Rat Model
Amarjit S. Virdi, PhD1; Min Liu, PhD2; Kotaro Sena, DDS, PhD1; James Maletich, BS1; Margaret McNulty, PhD1; Hua Zhu Ke, MD2; Dale R. Sumner, PhD1
1 Department of Anatomy and Cell Biology, Rush Medical College, Rush University Medical Center, 600 South Paulina Street, Room 507, AcFac, Chicago, IL 60612. E-mail address for D.R. Sumner: rick_sumner@rush.edu
2 Metabolic Disorders Research, Mail Stop 29-M-B, Amgen, One Amgen Center Drive, Thousand Oaks, CA 91320
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  • Disclosure statement for author(s): PDF

Investigation performed at the Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, Illinois



Disclosure: One or more of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of an aspect of this work. In addition, one or more of the authors, or his or her institution, has had a financial relationship, in the thirty-six months prior to submission of this work, with an entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. No author has had any other relationships, or has engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

Copyright © 2012 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2012 Sep 19;94(18):1670-1680. doi: 10.2106/JBJS.K.00344
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Abstract

Background: 

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.

Methods: 

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.

Results: 

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.

Conclusions: 

Sclerostin antibody treatment accelerated and enhanced mechanical fixation of medullary implants in a rat model by increasing both cortical and trabecular bone volume.

Clinical Relevance: 

Sclerostin antibody treatment may be useful for improving implant fixation.

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    References

    Accreditation Statement
    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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