Developing and Investigating a Nanovibration Intervention for the Prevention/Reversal of Bone Loss Following Spinal Cord Injury

Abstract

Osteoporosis disrupts the fine-tuned balance between bone formation and resorption leading to reductions in bone quantity and quality, ultimately leading to increased fracture risk. Prevention and treatment of osteoporotic fractures is essential, for reductions in mortality, morbidity and the economic burden, particularly considering the ageing global population. Extreme bone loss that mimics time-accelerated osteoporosis develops in the paralysed limbs following complete spinal cord injury (SCI). In vitro nanoscale vibration (1 kHz, 30- or 90 nm amplitude) has been shown to drive differentiation of mesenchymal stem cells towards osteoblast-like phenotypes, enhancing osteogenesis, and inhibiting osteoclastogenesis, simultaneously. Here we develop and characterise a wearable device designed to deliver continuous nano-amplitude vibration to the hindlimb long bones of rats with complete SCI. We investigate whether a clinically feasible dose of nanovibration (4-hours/day, 5-days/week for 6 weeks) is effective at reversing the established SCI-induced osteoporosis. Laser interferometry and finite element analysis confirmed transmission of nanovibration into the bone, and micro-computed tomography and serum bone formation and resorption markers assessed effectiveness. The intervention did not reverse SCI-induced osteoporosis. However, serum analysis indicated an elevated concentration of the bone formation marker procollagen type 1 N-terminal propeptide (P1NP) in rats receiving 40 nm amplitude nanovibration, suggesting increased synthesis of type 1 collagen, the major organic component of bone. Therefore, enhanced doses of nanovibrational stimulus may yet prove beneficial in attenuating/reversing osteoporosis, particularly in less severe forms of osteoporosis.