Bone Mechanical Strength Deficits Following a Contusion Spinal Cord Injury in Rats

Abstract

Sublesional bone loss occurs rapidly following spinal cord injury (SCI) and contributes to a 20-100 fold greater bone fracture risk. PURPOSE: To determine the time course of bone strength deficits at different femoral test sites in a rodent contusion SCI model. METHODS: Sixty 16-week old male Sprague-Dawley rats received SHAM surgery or T9 laminectomy plus severe (250 kilodyne) contusion SCI using a computer-guided impactor and were euthanized 1-, 2-, or 3-months (m) post-surgery. Hindlimb locomotion was assessed weekly using the BBB locomotor scale and bone strength was assessed ex vivo at the distal femur, femoral midshaft, and femoral neck. SCI vs SHAM comparisons were made at each time point using independent t-tests. RESULTS: SCI animals exhibited persistent hindlimb locomotor deficits [BBB score < 6 (0-21 scale), p < 0.01 vs SHAMs at all time points], characterized by an inability to support the hindlimbs in stance or to perform hindlimb weight supported stepping. Bone strength deficits were observed at all testing sites after SCI in a somewhat variable pattern. At the distal femur, maximal breaking load (N) was 19% lower at 1-m (p < 0.05), 10% lower at 2-m (p < 0.05), and 16% lower at 3-m (p < 0.01) in SCI vs SHAM animals using a cantilever bending test. In addition, displacement at max load was 29% lower at 1-m (p < 0.05) and 22% lower at 3-m (p < 0.05). At the femoral neck, maximal breaking load was 22% lower at 1-m in SCI vs SHAM (p < 0.05), but was not different at 2-m or 3-m post-surgery. At the femoral midshaft, maximal breaking load was not different at 1-m post-surgery, but was 11% lower at 2-m (p < 0.05), and 23% lower at 3-m (p < 0.05) in SCI vs SHAMs, using a 3-point breaking test. No other differences in displacement or stiffness were observed among groups. CONCLUSION: In our SCI model, femoral skeletal integrity is compromised 1-m post-injury, with strength deficits dependent upon the skeletal site and the tests that were utilized. The distal femur cantilever test yielded less variability and typifies a common site of fracture in humans after SCI, suggesting this test is clinically-relevant. Interventions focused on preventing bone loss after SCI should initiate therapy soon after the injury occurs to ensure maintenance of skeletal integrity. Supported by VA RR&D SPiRE 1I21RX001373-01 to JFY.