Spinal cord injury causes rapid osteoclastic resorption and growth plate abnormalities in growing rats (SCI-induced bone loss in growing rats)
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.
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.
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.
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.
Contusion SCI results in a rapid bone loss that is the result of increased bone resorption and decreased bone formation.
KeywordsBone Osteoclast Osteoporosis Rehabilitation medicine Spinal cord injury
We would like to thank Dr. M.van der Vlies and Justine Dobeck for technical assistance and the Swiss National Science Foundation.
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.)
- 30.Choi H, Liao WL, Newton KM, Onario RC, King AM, Desilets FC, Woodard EJ, Eichler ME, Frontera WR, Sabharwal S, Teng YD (2005) Respiratory abnormalities resulting from midcervical spinal cord injury and their reversal by serotonin 1A agonists in conscious rats. J Neurosci 25(18):4550–4559, May 4PubMedCrossRefGoogle Scholar