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Epiphysiodesis with Infusion of Stromal Cell-Derived Factor-1 in Rabbit Growth Plates
Mark C. Lee, MD1; Adam D. Bier, MD1; Florian Nickisch, MD2; Craig P. Eberson, MD1; Michael G. Ehrlich, MD1; Qian Chen, PhD3
1 Department of Orthopaedics, Rhode Island Hospital and Brown University School of Medicine, 593 Eddy Street, Providence, RI 02908
2 Division of Orthopaedic Surgery, Duke University Medical Center, Box 3093, Durham, NC 27705
3 Department of Orthopaedics, Rhode Island Hospital and Brown University School of Medicine, CORO West, 1 Hoppin Street, 402A, Providence, RI 02903. E-mail address: Qian_Chen@brown.edu
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Disclosure: The authors did not receive grants or outside funding in support of their research for or preparation of this manuscript. They did not receive 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, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.
Investigation performed at the Department of Orthopaedics, Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island

The Journal of Bone and Joint Surgery, Incorporated
J Bone Joint Surg Am, 2007 Jan 01;89(1):102-113. doi: 10.2106/JBJS.F.00198
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Background: The mechanism of physeal closure is poorly understood, although both mechanical and biological factors may play a role in the process. In this study, we evaluated the effect of the application of a chemokine stromal cell-derived factor-1 (SDF-1) to rabbit physes in vivo with regard to growth inhibition.

Methods: A continuous infusion system consisting of a fenestrated catheter and an osmotic pump were implanted into the right proximal tibial physis of twenty six-week-old New Zealand White rabbits. Ten of the pumps were loaded with human recombinant SDF-1a, and ten were loaded with phosphate-buffered saline solution (sham treatment). The left leg was used as the uninvolved control. The growth of the tibiae was followed radiographically for eight weeks, and histologic analysis was performed for both the SDF-1-treated rabbits and the sham-treated rabbits at two, four, and eight-week time-points.

Results: Radiographic evaluation showed a significant growth inhibition in the SDF-1a-treated physes (4.5 ± 3.0 mm; p = 0.007) compared with the sham-treated physes after eight weeks. No difference was noted when the sham-treated leg was compared with the contralateral, control leg (0.2 ± 2.9 mm; p = 0.465). Histologic evaluation showed marked physeal disorganization, narrowing, and proteoglycan loss and a significant decrease in physeal height (p < 0.0001) for the SDF-1-treated group. Reversible growth slowing was noted in the uninvolved, control leg of the SDF-1-treated group at six weeks, with resolution of the difference by eight weeks.

Conclusions: SDF-1 may be used to induce physeal closure through a targeted infusion system. However, transient systemic effects of SDF-1 may exist and must be evaluated further prior to its clinical use for epiphysiodesis.

Clinical Relevance: The use of biologic agents to effect physeal closure could offer a biological therapeutic alternative to mechanical ablation of the physis for the treatment of limb-length inequality in children.

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    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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