Transient muscle paralysis degrades bone via rapid osteoclastogenesis

The FASEB Journal • Research Communication

Transient muscle paralysis degrades bone via rapid osteoclastogenesis Antonios O. Aliprantis,*,† Marina Stolina,‡ Paul J. Kostenuik,‡ Sandra L. Poliachik,§ Sarah E. Warner,§ Steven D. Bain,§ and Ted S. Gross§,1 *Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA; †Department of Infectious Diseases and Immunology, Harvard School of Public Health, Boston, Massachusetts, USA; ‡Metabolic Disorders, Amgen, Inc., Thousand Oaks, California, USA; and §Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, Washington, USA A unilateral injection of botulinum toxin A (BTxA) in the calf induces paralysis and profound loss of ipsalateral trabecular bone within days. However, the cellular mechanism underlying acute muscle paralysis-induced bone loss (MPIBL) is poorly understood. We hypothesized that MPIBL arises via rapid and extensive osteoclastogenesis. We performed a series of in vivo experiments to explore this thesis. First, we observed elevated levels of the proosteoclastogenic cytokine receptor activator for nuclear factor-␬B ligand (RANKL) within the proximal tibia metaphysis at 7 d after muscle paralysis (ⴙ113%, P