Administration of low intensity vibration and a RANKL inhibitor, alone or in combination, reduces bone loss after spinal cord injury-induced immobilization in rats
Yuanzhen Peng,
Helen M. Bramlett,
W. Dalton Dietrich,
Alex Marcillo,
Juliana Sanchez-Molano,
Ofelia Furones-Alonso,
Jay J. Cao,
Jenney Huang,
Andrew A. Li,
Jian Q. Feng,
William A. Bauman,
Weiping Qin
Affiliations
Yuanzhen Peng
Spinal Cord Damage Research Center, James J. Peters Veteran Affairs Medical Center, Bronx, New York, USA
Helen M. Bramlett
Bruce W. Carter Miami VA Medical Center, Miami, Florida, USA; Miami Project to Cure Paralysis, USA; Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
W. Dalton Dietrich
Miami Project to Cure Paralysis, USA; Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
Alex Marcillo
Miami Project to Cure Paralysis, USA; Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
Juliana Sanchez-Molano
Miami Project to Cure Paralysis, USA; Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
Ofelia Furones-Alonso
Miami Project to Cure Paralysis, USA; Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
Jay J. Cao
USDA-ARS Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota, USA
Jenney Huang
Townsend Harris High School, New York, USA
Andrew A. Li
Bronx high school of science, New York, USA
Jian Q. Feng
Baylor College of Dentistry, TX A&M, Dallas, TX, USA
William A. Bauman
Departments of Medicine, USA; Rehabilitation and Human Performance, Icahn School of Medicine at Mount Sinai, New York, USA
Weiping Qin
Spinal Cord Damage Research Center, James J. Peters Veteran Affairs Medical Center, Bronx, New York, USA; Departments of Medicine, USA; Corresponding author at: James J. Peters Veteran Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA.
We previously 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 that initiated at 2 weeks post-injury and continued 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.
