Trabecular Bone Integrity at the Proximal Tibia Following a Contusion Spinal Cord Injury in Rats

Abstract

Bone loss following spinal cord injury (SCI) is a major contributor to bone fracture risk, particularly at the proximal tibia. PURPOSE: To determine longitudinal changes in trabecular bone integrity at the proximal tibia in a rodent contusion SCI model. METHODS: 16-week old male Sprague-Dawley rats (n = 28) were randomized to receive no surgery (Non-Surgical Controls), T9 laminectomy (SHAM), or T9 laminectomy plus severe (250 kdyne) contusion SCI using a computer-guided impactor and were euthanized 2- or 4-weeks (w) post-surgery. Hindlimb locomotion was assessed weekly using the BBB locomotor scale and trabecular bone integrity at the proximal tibia was assessed weekly using in vivo microCT. Comparisons were made using one-way ANOVAs and post-hoc analyses were done when appropriate. RESULTS: SCI animals exhibited significant losses in hindlimb locomotor function [BBB score < 6 (0-21 scale); p<0.01 vs SHAM at all time points]. Percent cancellous bone volume (cBV/TV) was 32% lower at 2-w and 42% lower at 4-w in SCI vs SHAM animals (p<0.01). This bone loss was exemplified by progressively lower trabecular thickness (Tb.Th) and trabecular number (Tb.N) at 2- and 4-w (p<0.01) and higher trabecular separation (Tb.Sp) (p<0.01 at 4-w only). No differences in trabecular pattern factor (Tb.Pf), an inverse indicator of trabecular network connectedness, were present at 1-w. However, Tb.Pf was higher at 2- and 4-w in SCI vs SHAM (p<0.01). Structure model index (SMI) was higher at 2- and 4-w in SCI vs SHAM (p<0.01), indicating transition from rod- to plate-shaped trabecular spicules. Similarly, in SCI animals, cBV/TV was 48-75% lower, Tb.Th was 15-27% lower, Tb.N was 36-62% lower across the 4-w period in comparison with Non-Surgical Controls (p<0.01 for all), while Tb.Sp was progressively higher in SCI animals (p<0.05 for 2- and 4-w). Higher Tb.Pf and SMI were also found in SCI vs Non-Surgical Controls at all timepoints (p<0.05). Only cBV/TV was lower in SHAM vs Non-Surgical Controls across the 4-w period (p<0.01). CONCLUSION: Our findings indicate that trabecular bone integrity at the proximal tibia was significantly impaired in rats following a severe contusion SCI due to both bone loss and diminished bone quality. As such, our rodent model may be useful to examine effectiveness of strategies intended to prevent SCI-induced bone loss.