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Spinal cord injury causes rapid osteoclastic resorption and growth plate abnormalities in growing rats (SCI-induced bone loss in growing rats)

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Abstract

Summary

Spinal cord injury causes severe bone loss. We report osteoclast resorption with severe trabecular and cortical bone loss, decreased bone mineral apposition, and growth plate abnormalities in a rodent model of contusion spinal cord injury. These findings will help elucidate the mechanisms of osteoporosis following neurological trauma.

Introduction

Limited understanding of the mechanism(s) that underlie spinal cord injury (SCI)-induced bone loss has led to few treatment options. As SCI-induced osteoporosis carries significant morbidity and can worsen already profound disability, there is an urgency to advance knowledge regarding this pathophysiology.

Methods

A clinically relevant contusion model of experimental spinal cord injury was used to generate severe lower thoracic SCI by weight-drop (10 g × 50 mm) in adolescent male Sprague-Dawley rats. Body weight and gender-matched naïve (no surgery) rats served as controls. Bone microarchitecture was determined by micro-computed tomographic imaging. Mature osteoclasts were identified by TRAP staining and bone apposition rate was determined by dynamic histomorphometry.

Results

At 10 days post-injury we detected a marked 48% decrease in trabecular bone and a 35% decrease in cortical bone at the distal femoral metaphysis by micro-CT. A 330% increase in the number of mature osteoclasts was detected at the growth plate in the injured animals that corresponded with cellular disorganization at the chondro-osseous junction. Appositional growth studies demonstrated decreased new bone formation with a mineralization defect indicative of osteoblast dysfunction.

Conclusions

Contusion SCI results in a rapid bone loss that is the result of increased bone resorption and decreased bone formation.

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Acknowledgements

We would like to thank Dr. M.van der Vlies and Justine Dobeck for technical assistance and the Swiss National Science Foundation.

Funding

Grant sponsor: NIH/NICHD Grant number K12 HD001097-08 (L.M.);

Grant sponsor: VABLR&D121F (Y.D.T.);

Grant sponsor: NIH Grant number R21NS53935 (Y.D.T.);

Grant sponsor: NIH/NICDR Grant number DE007378-18 (P.S.)

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Authors and Affiliations

  1. Department of Physical Medicine and Rehabilitation, Harvard Medical School and Spaulding Rehabilitation Hospital, 140 The Fenway, Boston, MA, 02115, USA

    L. Morse, Y. D. Teng & W.-L. Liao

  2. Department of Neurosurgery, Harvard Medical School and Brigham and Women’s Hospital/Children’s Hospital, Boston, MA, USA

    Y. D. Teng, K. Newton & D. Yu

  3. Division of Spinal Cord Injury Research, VA Boston Healthcare System, Boston, MA, USA

    Y. D. Teng, K. Newton, D. Yu & W.-L. Liao

  4. Institute for Biomechanics, ETH Zurich, Zurich, Switzerland

    T. Kohler & R. Müller

  5. Boston University School of Dental Medicine, Boston, MA, USA

    D. Graves

  6. Department of Cytokine Biology, Forsyth Institute, Boston, MA, USA

    L. Pham, P. Stashenko & R. Battaglino

Authors
  1. L. Morse
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  2. Y. D. Teng
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  3. L. Pham
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  4. K. Newton
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  5. D. Yu
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  6. W.-L. Liao
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  7. T. Kohler
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  8. R. Müller
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  9. D. Graves
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  10. P. Stashenko
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  11. R. Battaglino
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Corresponding author

Correspondence to L. Morse.

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Morse, L., Teng, Y.D., Pham, L. et al. Spinal cord injury causes rapid osteoclastic resorption and growth plate abnormalities in growing rats (SCI-induced bone loss in growing rats). Osteoporos Int 19, 645–652 (2008). https://doi.org/10.1007/s00198-007-0494-x

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  • DOI: https://doi.org/10.1007/s00198-007-0494-x

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