Dmitriev et al. respond

Abstract

We appreciate the interest in our work by Salisbury et al. The role of bone morphogenetic protein-2 (BMP-2) in bone formation has been extensively characterized over the last 30 years [ 1 Boden S.D. Bioactive factors for bone tissue engineering. Clin Orthop Relat Res. 1999; : S84-S94 Crossref PubMed Scopus (136) Google Scholar , 2 Axelrad T.W. Einhorn T.A. Bone morphogenetic proteins in orthopaedic surgery. Cytokine Growth Factor Rev. 2009; 20: 481-488 Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar ]. The neuroscience field has also found significant involvement of BMPs in development, maturation, and repair of the peripheral nervous system (PNS) and central nervous system (CNS) [ 3 Hall A.K. Miller R.H. Emerging roles for bone morphogenetic proteins in central nervous system glial biology. J Neurosci Res. 2004; 76: 1-8 Crossref PubMed Scopus (61) Google Scholar , 4 Setoguchi T. Yone K. Matsuoka E. et al. Traumatic injury-induced BMP7 expression in the adult rat spinal cord. Brain Res. 2001; 921: 219-225 Crossref PubMed Scopus (105) Google Scholar , 5 Fuller M.L. Dechant A.K. Rothstein B. et al. Bone morphogenetic proteins promote gliosis in demyelinating spinal cord lesions. Ann Neurol. 2007; 62: 288-300 Crossref PubMed Scopus (105) Google Scholar ]. Although the direct influence of the PNS on bone homeostasis is well described, the interactions through which peripheral neurons may influence bone formation or repair remain to be fully defined [ 6 Togari A. Arai M. Pharmacological topics of bone metabolism: the physiological function of the sympathetic nervous system in modulating bone resorption. J Pharmacol Sci. 2008; 106: 542-546 Crossref PubMed Scopus (69) Google Scholar , 7 Li J. Kreicbergs A. Bergström J. et al. Site-specific CGRP innervation coincides with bone formation during fracture healing and modeling: a study in rat angulated tibia. J Orthop Res. 2007; 25: 1204-1212 Crossref PubMed Scopus (69) Google Scholar , 8 Li J. Ahmed M. Bergstrom J. Ackermann P. et al. Occurrence of substance P in bone repair under different load comparison of straight and angulated fracture in rat tibia. J Orthop Res. 2010; 28: 1643-1650 Crossref PubMed Scopus (20) Google Scholar ]. We would agree that further study of neuron-bone interaction could be highly significant for the orthopedic world. However, the potential role of BMPs in this interaction is largely unexplored. Adverse events and bone morphogenetic protein-2The Spine JournalVol. 11Issue 8PreviewRecently, a number of adverse events have been reported in the use of recombinant bone morphogenetic protein-2 (BMP-2) in spinal fusion [1–4]. We have been studying new bone formation after delivery of physiologic levels of BMP-2 using a cell therapy approach and have found this to rely on very selective neurogenic inflammation. We would like to suggest that this is actually a normal physiologic event in bone formation and fracture repair rather than an adverse event associated with delivery of this protein. Full-Text PDF