0
Scientific Articles   |    
Local Administration of Ibandronate and Bone Morphogenetic Protein-2 After Ischemic Osteonecrosis of the Immature Femoral HeadA Combined Therapy That Stimulates Bone Formation and Decreases Femoral Head Deformity
Jacob S. Vandermeer1; Nobuhiro Kamiya, MD, PhD1; James Aya-ay, MS2; Amanda Garces3; Richard Browne, PhD1; Harry K.W. Kim, MD, MSc1
1 Center for Excellence in Hip Disorders, Texas Scottish Rite Hospital for Children, 2222 Welborn Street, Dallas, TX 75219. E-mail address for H.K.W. Kim: harry.kim@tsrh.org
2 Department of Immunology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612
3 Department of Pathology and Cell Biology, University of South Florida, Health COM MDC 61, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612
View Disclosures and Other Information

Investigation performed at Texas Scottish Rite Hospital for Children, Dallas, Texas

A commentary by Keith M. Baumgarten, MD, is linked to the online version of this article at jbjs.org.



Disclosure: The authors did not receive any outside funding or grants in support of their research for or preparation of this work. In support of their research in the past, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from Roche Pharmaceuticals. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity.

Copyright © 2011 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2011 May 18;93(10):905-913. doi: 10.2106/JBJS.J.00716
A commentary by Keith M. Baumgarten, MD, is available here
5 Recommendations (Recommend) | 3 Comments | Saved by 3 Users Save Case

Abstract

Background: 

Bisphosphonate therapy has been shown to preserve the osteonecrotic femoral head in experimental and short-term clinical studies. However, a lack of new bone formation within the preserved femoral head due to the inhibition of bone remodeling is a concern. The purpose of this investigation was to determine if combined therapy consisting of ibandronate and bone morphogenetic protein-2 (BMP-2) can preserve the shape of the femoral head and stimulate new bone formation in an immature animal model of ischemic osteonecrosis.

Methods: 

Ischemic osteonecrosis was surgically induced in immature pigs. Four groups were studied: normal, treated with saline solution, treated with ibandronate, and treated with both ibandronate and BMP-2 (the ibandronate + BMP-2 group). The animals were killed eight weeks after surgery. Radiographic, histological, and histomorphometric assessments were performed.

Results: 

Radiographic assessment showed better preservation of the femoral head shape—i.e., a 54% (CI [95% confidence interval]: 22%, 86%) higher mean epiphyseal quotient—in the ibandronate + BMP-2 group than in the saline group. Histological assessment showed increased trabecular bone in the ibandronate + BMP-2 group as compared with that in the saline group. The mean values for trabecular bone volume, thickness, and number and for osteoblast surface were an average of 400% (CI: 242%, 558%), 212% (CI: 166%, 259%), 71% (CI: 6%, 137%), and 2402% (CI: 2113%, 2693%) higher, respectively, in the ibandronate + BMP-2 group than in the saline group. The osteoclast number was significantly reduced in the ibandronate + BMP-2 group compared with that in the saline group (−59% [CI: −75%, −42%]). The mean osteoblast surface value in the ibandronate + BMP-2 group was significantly higher (2567% [CI: 2258%, 2877%]) than that in the ibandronate group. Heterotopic ossifications were present in the capsule of the hip joint in the ibandronate + BMP-2 group.

Conclusions: 

A combination of ibandronate and BMP-2 decreased femoral head deformity while stimulating bone formation in an immature animal model of ischemic osteonecrosis.

Clinical Relevance: 

The findings provide a proof of concept that a combination of antiresorptive and anabolic agents can significantly improve bone healing and decrease deformity following ischemic osteonecrosis in the immature femoral head of a pig. Additional studies are needed to investigate whether heterotopic ossification can be prevented.

Figures in this Article
    Sign In to Your Personal ProfileSign In To Access Full Content
    Not a Subscriber?
    Get online access for 30 days for $35
    New to JBJS?
    Sign up for a full subscription to both the print and online editions
    Register for a FREE limited account to get full access to all CME activities, to comment on public articles, or to sign up for alerts.
    Register for a FREE limited account to get full access to all CME activities
    Have a subscription to the print edition?
    Current subscribers to The Journal of Bone & Joint Surgery in either the print or quarterly DVD formats receive free online access to JBJS.org.
    Forgot your password?
    Enter your username and email address. We'll send you a reminder to the email address on record.

     
    Forgot your username or need assistance? Please contact customer service at subs@jbjs.org. If your access is provided
    by your institution, please contact you librarian or administrator for username and password information. Institutional
    administrators, to reset your institution's master username or password, please contact subs@jbjs.org

    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.
    CME Activities Associated with This Article
    Submit a Comment
    Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
    Comments are moderated and will appear on the site at the discretion of JBJS editorial staff.

    * = Required Field
    (if multiple authors, separate names by comma)
    Example: John Doe





    Related Content
    The Journal of Bone & Joint Surgery
    JBJS Case Connector
    Related Audio and Videos
    PubMed Articles
    Clinical Trials
    Readers of This Also Read...
    JBJS Jobs
    02/28/2014
    DC - Children's National Medical Center
    03/17/2014
    CT - Orthopaedic Foundation
    04/02/2014
    IL - Hinsdale Orthopaedics