Chapter 7 - Gene expression and bone loss following spinal cord injury

Abstract

Spinal cord injury (SCI) leads to several molecular and cellular disruptions, resulting in systemic changes, and a complex disease that requires multi-professional care treatment. The mechanisms underlying SCI have not yet been fully elucidated, and effective therapies for SCI are lacking. Two phases characterize the damages following the injury. The primary damage is the mechanical injury itself, and the secondary damage phase results from biochemical processes following the primary damage. SCI individuals experience motor, sensory, and autonomic impairments, which cause musculoskeletal disorders post-injury and progress throughout their lifetime. The specific aim of this review is to gain a better understanding of the mechanisms driving bone loss post-SCI. Bone remodeling corresponds to an ingenious mechanism in which the bone contributes to the circulatory levels of calcium, and in parallel, ensures bone renewal. In ideal conditions, adult individuals restore bone resorption by an adequate amount of bone formation, guaranteeing bone strength maintenance. Bone loss following SCI is certainly unique in its magnitude and rapidity, which may be explained by the concomitant effects of the absence of mechanical loading to the vascular changes, muscle atrophy, neural, and endocrine components. Uncoupled bone turnover was identified in SCI individuals and animals, with a predominance of resorption over formation. The highly uncoupled bone turnover due to SCI, associated with muscle atrophy and vascular disorder, potentially increases the risk for low-impact fractures in the sublesional bones in these individuals. Although major advances in understanding the pathogenesis, prevention, and treatment of SCI-induced bone loss have risen, the high risk of low-energy fracture in SCI individuals remains an important complication of SCI-induced bone loss. Maintaining bone integrity and preventing fractures are crucial for individuals with SCI in order to fully benefit from future advances in paralysis cure research and robotic exoskeletons, brain–computer interfaces, and other evolving technologies.