HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Sign In to gain access to subscriptions and/or personal tools.

This Article Full Text Full Text (PDF) All Versions of this Article: 35/4/597    most recent 0363546506296312v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Ma, C. B. Articles by Rodeo, S. A. Search for Related Content PubMed PubMed Citation Articles by Ma, C. B. Articles by Rodeo, S. A. Related Collections Reconstruction Graft fixation

Bone Morphogenetic Proteins-Signaling Plays a Role in Tendon-to-Bone Healing

A Study of rhBMP-2 and Noggin

C. Benjamin Ma, MD^,*, Sumito Kawamura, MD, Xiang-Hua Deng, MD, Ling Ying, MD, Jason Schneidkraut, MD, Peyton Hays, MD and Scott A. Rodeo, MD

From the Department of Orthopaedic Surgery, University of California, San Francisco, California, and the Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, New York

^* Address correspondence to C. Benjamin Ma, MD, University of California, San Francisco, Department of Orthopaedic Surgery, 500 Parnassus Avenue, MU 320W, San Francisco, CA 94143 (e-mail: maben{at}orthosurg.ucsf.edu).

Background: Successful anterior cruciate ligament reconstruction requires secure healing between tendon and bone.

Hypothesis: Bone morphogenetic protein-signaling plays an important role in tendon-to-bone healing. rhBMP-2, a powerful osteoinductive agent, can improve tendon-bone interdigitation.

Study Design: Controlled laboratory study.

Methods: The study was designed in 2 phases: Phase I consisted of a dose-response study where 21 New Zealand White rabbits underwent bilateral anterior cruciate ligament reconstructions. Rabbits received either rhBMP-2 (11.5, 50, or 115 µg) or noggin (10, 15, 30, or 100 ng) (a potent bone morphogenetic proteins inhibitor) delivered in an injectable calcium phosphate matrix. Animals were sacrificed at 2 weeks and histomorphometric analyses were performed. In phase II, 60 rabbits underwent bilateral anterior cruciate ligament reconstructions and were assigned to 3 groups: rhBMP-2 (115 µg), noggin (30 ng) in a calcium phosphate carrier, and calcium phosphate carrier alone. Animals were sacrificed at 2, 4, and 8 weeks and histomorphometric and biomechanical analyses were performed.

Results: rhBMP-2 treatment led to a significant increase in the width of new bone formation at the tendon-bone interface in a dose-dependent fashion (0.24–0.35 mm vs 0.13–0.16 mm in controls). All dosages of noggin inhibited new bone formation (0.06–0.1 mm vs 0.15–0.16 mm in controls); however, there was no dose-dependent effect in the concentrations studied. In the phase II study, rhBMP-2 resulted in a significant increase in new bone formation (81%, 89%, and 113%) at increasing time periods compared with controls. Tunnel diameters in the rhBMP-2 group were significantly smaller (15%–45%) than in the carrier group. The negative effect of noggin was not sustained, as new bone formation increased with time. The rhBMP-2 group demonstrated significantly increased stiffness at 8 weeks, while there was no significant difference in ultimate tensile load when compared with the other 2 groups.

Conclusion: rhBMP-2 demonstrated a strong, positive dose-dependent effect on osteointegration at the tendon-bone junction. In contrast, noggin decreased osteointegration. No tunnel widening was detected with rhBMP-2 using the calcium phosphate carrier.

Clinical Relevance: Further studies are needed to investigate the potential clinical application of enhancing healing and decreasing recovery time using bone morphogenetic proteins in soft tissue ligament reconstruction.

Key Words: BMP-2 • noggin • tendon-to-bone healing • ACL

This article has been cited by other articles:

				L. V. Gulotta, D. Kovacevic, L. Ying, J. R. Ehteshami, S. Montgomery, and S. A. Rodeo Augmentation of Tendon-to-Bone Healing With a Magnesium-Based Bone Adhesive Am. J. Sports Med., July 1, 2008; 36(7): 1290 - 1297. [Abstract] [Full Text] [PDF]

				M. E. Steiner, M. M. Murray, and S. A. Rodeo Strategies to Improve Anterior Cruciate Ligament Healing and Graft Placement Am. J. Sports Med., January 1, 2008; 36(1): 176 - 189. [Abstract] [Full Text] [PDF]

				L. V. Gulotta, C. Hidaka, S. A. Maher, M. E. Cunningham, and S. A. Rodeo What's New in Orthopaedic Research J. Bone Joint Surg. Am., September 1, 2007; 89(9): 2092 - 2101. [Full Text] [PDF]