The Journal of Bone and Joint Surgery (American). 2007;89:2250-2259.
doi:10.2106/JBJS.F.00409
© 2007 The Journal of Bone and Joint Surgery, Inc.
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The Effect of Osteoclastic Activity on Tendon-to-Bone Healing: An Experimental Study in Rabbits

Scott A. Rodeo, MD1, Sumito Kawamura, MD1, C. Benjamin Ma, MD1, Xiang-hua Deng, MD1, Patrick S. Sussman, MD1, Peyton Hays, BS1 and Liang Ying, BS1

1 The Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021. E-mail address for S.A. Rodeo: rodeos{at}hss.edu

Investigation performed at The Laboratory for Soft Tissue Research, The Hospital for Special Surgery, New York, NY

Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from the Orthopaedic Research and Education Foundation and the National Institutes of Health (a Pilot and Feasibility Grant as part of a NIH Core Centers grant [1P30AR46121-01]; in addition, this investigation was conducted in a facility constructed with support from Research Facilities Improvement Program Grant Number C06-RR12538-01 from the National Center for Research Resources, NIH). 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. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

Background: Healing of a tendon graft in a bone tunnel depends on bone ingrowth into the interface between tendon and bone. Excessive osteoclastic activity may contribute to bone resorption, tunnel widening, and impaired healing. We hypothesized that inhibition of osteoclastic activity by osteoprotegerin (OPG) would increase bone formation around a tendon graft in anterior cruciate ligament reconstruction in a rabbit model, while increased osteoclastic activity due to the aplication of receptor activator of nuclear factor-kappa B ligand (RANKL) would impair bone ingrowth.

Methods: Sixty skeletally mature, male New Zealand White rabbits underwent bilateral anterior cruciate ligament reconstruction. OPG (100 µg per tunnel) or RANKL (10 µg per tunnel) was delivered to the tendon-bone interface with use of a synthetic calcium phosphate carrier vehicle. Twenty animals were killed at two, four, and eight weeks after surgery. Two rabbits from each group were prepared for histological evaluation, and the other rabbits were used for biomechanical testing.

Results: A significantly greater amount of bone surrounded the tendon at the healing tendon-bone interface in the OPG-treated limbs compared with the controls and the RANKL-treated limbs at all time-points (p < 0.05). There were significantly fewer osteoclasts in the OPG-treated limbs compared with the controls and the RANKL-treated limbs (p < 0.05). The average tunnel area in the OPG group was significantly smaller than that in the RANKL group (p = 0.003 at two weeks and p = 0.004 at four weeks). The femur-anterior cruciate ligament-tibia complex of the OPG-treated limbs had significantly increased stiffness compared with RANKL-treated limbs at eight weeks (p = 0.04).

Conclusions: Osteoprotegerin significantly improves bone formation around the grafted tendon and improves the stiffness at the healing tendon-bone junction in a rabbit model.

Clinical Relevance: Inhibition of excessive osteoclastic activity may improve tendon-to-bone healing.


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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.
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