Administration of low intensity vibration and a rankl inhibitor, alone or in combination, reduces bone loss after spinal cord Injury-induced Immobilization in rats.

Authors: PENG, YUANZHEN - James J Peters Vamc; BRAMLETT, HELEN - Bruce W Carter Miami Veteran Affairs Medical Center; DIETRICH, DALTON - University Of Miami; MARCILLO, ALEX - University Of Miami; SANCHEZ-MOLANO, JULIANA - University Of Miami; FURONES-ALONSO, OFELIA - University Of Miami; Cao, Jay; FENG, JIAN - Texas A&M University; BAUMAN, WILLIAM - The Icahn School Of Medicine At Mount Sinai; QIN, WEIPING - James J Peters Vamc

Submitted to: Bone Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/1/2024
Publication Date: 10/7/2024
Citation: Peng, Y., Bramlett, H.M., Dietrich, D.W., Marcillo, A., Sanchez-Molano, J., Furones-Alonso, O., Cao, J.J., Feng, J.Q., Bauman, W.A., Qin, W. 2024. Administration of low intensity vibration and a rankl inhibitor, alone or in combination, reduces bone loss after spinal cord Injury-induced Immobilization in rats.. Journal of Bone and Mineral Research. 23:Article e101808. https://doi.org/10.1016/j.bonr.2024.101808.
DOI: https://doi.org/10.1016/j.bonr.2024.101808

Interpretive Summary: Low-intensity vibration training has been used as an alternative exercise modality to improve musculoskeletal health in various conditions of muscle weakness and bone loss. We investigated the extent to which eight-week low-intensity vibration affects bone loss after spinal core injury in a rat model. We demonstrated that low-intensity vibration increases bone formation, osteoblast differentiation and inhibits bone resorption. The combined administration of low-intensity vibration and the inhibitor of receptor activator of nuclear factor-kB ligand (RANKL), a bone resorption regulating gene, has greater beneficial effects than low-intensity vibration or RANKL inhibitor on bone. The findings of this study provide a new approach to improve bone health.

Technical Abstract: We previous reported an ability of low-intensity vibration (LIV) to improve selected biomarkers of bone turnover and gene expression and reduce osteoclastogenesis but lacking of evident bone accrual. In this study, we demonstrate that a prolonged course of LIV for 8 weeks can protect against bone loss after SCI in rats. LIV stimulates bone formation and improves osteoblast differentiation potential of bone marrow stromal stem cells while inhibiting osteoclast differentiation potential of marrow hematopoietic progenitors to reduce bone resorption. We further demonstrate that the combination of LIV and RANKL antibody reduces SCI-related bone loss more than each intervention alone. Our findings that LIV is efficacious in maintaining sublesional bone mass suggests that such physical-based intervention approach would be a noninvasive, simple, inexpensive and practical intervention to treat bone loss after SCI. Because the combined administration of LIV and RANKL inhibition better preserved sublesional bone after SCI than either intervention alone, this work provides the impetus for the development of future clinical protocols based on the potential greater therapeutic efficacy of combining non-pharmacological (e.g., LIV) and pharmacological (e.g., RANKL inhibitor or other agents) approaches to treat osteoporosis after SCI or other conditions associated with severe immobilization.