Disuse Bone Loss After Spinal Cord Injury: Scope and Challenges, Potential Mechanisms, Treatment, and Future Directions

Traumatic spinal cord injury (SCI) is a major insult that causes motor and sensory neurological deficits and multisystem dysfunction. The skeletal system is severely affected after SCI, with disuse bone loss being one of the most common and challenging complications. Changes in bone mass and structure after SCI are progressive and involve both trabecular and cortical components of the long bones below the lesion. The weight-bearing trabecular regions of the distal femur and proximal tibia are the most compromised sites with the highest incidence of fracture. Furthermore, SCI-associated bone loss is resistant to currently available pharmacologic and rehabilitative treatment, especially during the chronic phase after injury. Therefore, there is a need to highlight the scale of this clinical problem in the SCI patient population and address the challenges. Protection against bone loss during the early phases and restoration of bone structure in the later or chronic phases of SCI are necessary to reduce the risk of fracture and avoid the associated morbidities and mortalities and allow safe use of walking aids and exoskeletal ReWalk devices. Identifying the potential mechanisms underlying SCI-induced bone loss is critical so that new and more effective therapeutic strategies can be developed. The goal of this review is to provide an up-to-date overview of SCI bone loss and discuss challenges, potential mechanisms, and progress in pharmacological treatment.