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Effect of Selective Sensory Denervation on Fracture-HealingAn Experimental Study of Rats
Peter J. Apel, MD1; Daniel Crane, BS1; Casey N. Northam, BS1; Michael Callahan, PhD1; Thomas L. Smith, PhD1; Robert D. Teasdall, MD1
1 Department of Orthopaedic Surgery, Wake Forest University School of Medicine, 1 Medical Center Boulevard, Winston-Salem, NC 27157. E-mail address for P.J. Apel: papel@wfubmc.edu
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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 Trauma Association and the Department of Surgery, Wake Forest University School of Medicine. 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.
Investigation performed at the Department of Orthopaedic Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina

The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2009 Dec 01;91(12):2886-2895. doi: 10.2106/JBJS.H.01878
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Background: Interactions between the peripheral nervous system and the healing skeleton are poorly understood. Various clinical observations suggest that the nervous system interacts with and promotes fracture-healing. The purpose of this study was to examine the effect of selective sensory denervation on fracture-healing.

Methods: Fifty-one Sprague-Dawley rats underwent unilateral placement of an intramedullary rod followed by creation of a standardized femoral fracture. One group of these rats underwent sensory denervation by means of a localized capsaicin injection, and the other did not. Subgroups were allocated for analysis of mRNA expression of collagen I and II and osteocalcin at three, seven, and fourteen days after the fracture. Additionally, histological examination was performed at four weeks; micro-computed tomography, at five weeks; and biomechanical testing, at six weeks.

Results: The sensory-denervated group had significantly less collagen-I upregulation than the sensory-intact group at three days after the fracture (difference in means, forty-four-fold [95% confidence interval = 22.7 to 65.5-fold]; p < 0.001) and significantly less collagen-II upregulation at seven days after the fracture (difference in means, ninefold [95% confidence interval = 4.3 to 13.8-fold]; p < 0.001). In the sensory-denervated group, the fracture callus had a significantly larger cross-sectional area (difference in means, 15.6 mm2 [95% confidence interval = 0.78 to 30.5 mm2]; p = 0.043) and was less dense. Biomechanical testing revealed that sensory denervation significantly decreased the load to failure (difference in means, 28.7 N [95% confidence interval = 1.2 to 56.2 N]; p = 0.022).

Conclusions: Sensory denervation negatively affects fracture-healing. These results offer insight into the nerve-bone interaction following injury.

Clinical Relevance: These results are relevant to clinicians and researchers who are seeking to improve fracture-healing in patients with associated peripheral nerve injury or peripheral neuropathy.

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    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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