title: Short-term application of dexamethasone enhances bone morphogenetic protein-7-induced ectopic bone formation in vivo.
abstract: BACKGROUND
  Long-term administration of glucocorticoids may lead to bone loss and osteoporosis as reported in previous experimental and clinical studies. On the other hand, several in vitro studies have demonstrated that dexamethasone treatment induces proliferation and differentiation of human and murine osteoblast precursors. Thereby, a positive interaction of dexamethasone with the osteoinductive bone morphogenetic proteins (BMPs) is reported in vitro, but in vivo studies are still missing. Thus, the aim of this study was to determine whether short-term application of dexamethasone may improve BMP-7-induced bone formation in vivo.
  
  
  METHODS
  Ectopic bone formation was induced in control and dexamethasone-treated mice by application of BMP-7 into the hamstring muscles. After 20 days of treatment, each ectopic bone nodule was analyzed by contact radiography, microcomputed tomography, and histomorphometry. Furthermore, mice were subjected to histomorphometric analyses of their lumbar vertebrae and proximal tibiae to assess the systemic effect of short-term dexamethasone treatment on bone metabolism.
  
  
  RESULTS
  Dexamethasone application significantly increased the bone volume and osteoblast number of the ectopic bone nodules compared with untreated controls. Histomorphometric analyses of the lumbar vertebrae and proximal tibiae revealed no significant differences between the control and dexamethasone-treated mice.
  
  
  CONCLUSIONS
  This study demonstrates that BMP-7-induced ectopic bone formation is significantly enhanced by systemic short-term application of dexamethasone. These in vivo data confirm the results of previous in vitro studies and could be of interest for further studies with the intention to improve BMP-induced bone formation by short-term application of dexamethasone.
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Spiro
authors.forename: F Timo
authors.initials: FT
authors.lastname: Beil
authors.forename: F
authors.initials: F
authors.lastname: Timo Beil
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schinke
authors.forename: Arndt F
authors.initials: AF
authors.lastname: Schilling
authors.forename: Christine
authors.initials: C
authors.lastname: Eulenburg
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Rueger
authors.forename: Michael
authors.initials: M
authors.lastname: Amling
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D013848:Thigh / Q000000981:diagnostic imaging; D055114:X-Ray Microtomography
chemical_list: D055419:Bone Morphogenetic Protein 7; D005938:Glucocorticoids; D003907:Dexamethasone