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Enlargement of Growth Plate Chondrocytes Modulated by Sustained Mechanical Loading

Investigation performed at the University of Vermont, Burlington, Vermont

Ian A. Stokes, PhD
James C. Iatridis, PhD
David D. Aronsson, MD
Department of Orthopaedics and Rehabilitation (I.A.S. and D.D.A.) and Department of Mechanical Engineering (J.C.I.), University of Vermont, Burlington, VT 05405

Peter L. Mente, PhD
Department of Biological and Agricultural Engineering, North Carolina State University, Raleigh, NC 27695-7625

Cornelia E. Farnum, DVM, PhD
College of Veterinary Medicine, Cornell University, Ithaca, NY 14853

In support of their research or preparation of this manuscript, one or more of the authors received National Institutes of Health Grants R01 AR 46543, R55 HD 34460, and F32 AR 08453 and a Bristol-Myers Squibb/Zimmer Institutional Excellence Grant. None of the authors 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, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

Background: Mechanical compression and distraction forces are known to modulate growth in vertebral growth plates, and they have been implicated in the progression of scoliosis. This study was performed to test the hypothesis that growth differences produced by sustained compression or distraction loading of vertebrae are associated with alterations in the amount of increase in the height of growth plate chondrocytes in the growth direction.

Methods: Compression or distraction force of nominally 60% of body weight was maintained for four weeks on a caudad vertebra of growing rats by an external apparatus attached, by means of transcutaneous pins, to the two vertebrae cephalad and caudad to it. Growth of the loaded and control vertebrae was measured radiographically. After four weeks, the animals were killed and histological sections of the loaded and control vertebrae were prepared to measure the height of the hypertrophic zone (average separation between zonal boundaries), the mean height of hypertrophic chondrocytes, and the amount of increase in cell height in the growth direction.

Results: Over the four weeks of the experiment, the growth rates of the compressed and distracted vertebrae averaged 52% and 113% of the control rates, respectively. The reduction in the growth rate of the compressed vertebrae was significant (p = 0.002). In the compressed vertebrae, the height of the hypertrophic zone, the mean chondrocyte height, and the amount of increase in cell height averaged 87%, 85%, and 78% of the control values, respectively, and all were significantly less than the corresponding control values. In the distracted vertebrae, these measurements did not differ significantly from the control values. The height of the hypertrophic zone and the mean chondrocyte height correlated with the growth rate (r ² = 0.29 [p = 0.03] and r ² = 0.23 [p = 0.06], respectively), when each variable was expressed as a proportion of the control value. The percentage changes in the measurements of the chondrocytic dimensions relative to the control values were smaller than the percentage changes in the growth rates, a finding that suggested that the rate of chondrocytic proliferation was also modulated by the mechanical loading.

Conclusions: Mechanical loading of tail vertebrae in rats modulated their growth rate, which correlated with changes in the height of hypertrophic chondrocytes. The effects of compression were greater than those of distraction.

Clinical Relevance: Information about the growth rate and chondrocytic response to mechanical loads in rat vertebrae undergoing mechanically modulated growth will be helpful in determining how human vertebral growth might respond to altered loading states during progression or treatment of scoliosis and other growth-related angular skeletal deformities.

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