title: Sclerostin antibody treatment enhances bone strength but does not prevent growth retardation in young mice treated with dexamethasone.
abstract: OBJECTIVE
  Exposure to supraphysiologic levels of glucocorticoid drugs is known to have detrimental effects on bone formation and linear growth. Patients with sclerosteosis lack the bone regulatory protein sclerostin, have excessive bone formation, and are typically above average in height. This study was undertaken to characterize the effects of a monoclonal antibody to sclerostin (Scl-AbI) in mice exposed to dexamethasone (DEX).
  
  
  METHODS
  Young mice were concomitantly treated with DEX (or vehicle control) and Scl-AbI antibody (or isotype-matched control antibody [Ctrl-Ab]) in 2 independent studies. Linear growth, the volume and strength of the bones, and the levels of bone turnover markers were analyzed.
  
  
  RESULTS
  In DEX-treated mice, Scl-AbI had no significant effect on linear growth when compared to control treatment (Ctrl-Ab). However, in mice treated with DEX and Scl-ABI, a significant increase in trabecular bone at the femoral metaphysis (bone volume/total volume +117% versus Ctrl-Ab-treated mice) and in the width and volume of the cortical bone at the femoral diaphysis (+24% and +20%, respectively, versus Ctrl-Ab-treated mice) was noted. Scl-AbI treatment also improved mechanical strength (as assessed by 4-point bending studies) at the femoral diaphysis in DEX-treated mice (maximum load +60% and ultimate strength +47% in Scl-AbI-treated mice versus Ctrl-Ab-treated mice). Elevated osteocalcin levels were not detected in DEX-treated mice that received Scl-AbI, although levels of type 5b tartrate-resistant acid phosphatase were significantly lower than those observed in mice receiving DEX and Ctrl-Ab.
  
  
  CONCLUSIONS
  Scl-AbI treatment does not prevent the detrimental effects of DEX on linear growth, but the antibody does increase both cortical and trabecular bone and improves bone mechanical properties in DEX-treated mice.
authors.affiliation: UCB Celltech, Slough, UK.
authors.forename: M
authors.initials: M
authors.lastname: Marenzana
authors.forename: K
authors.initials: K
authors.lastname: Greenslade
authors.forename: A
authors.initials: A
authors.lastname: Eddleston
authors.forename: R
authors.initials: R
authors.lastname: Okoye
authors.forename: D
authors.initials: D
authors.lastname: Marshall
authors.forename: A
authors.initials: A
authors.lastname: Moore
authors.forename: M K
authors.initials: MK
authors.lastname: Robinson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D015519:Bone Density / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D005269:Femur / Q000187:drug effects* / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology*; D006023:Glycoproteins / Q000276:immunology*; D006128:Growth / Q000187:drug effects* / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D005938:Glucocorticoids; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C486030:Sost protein, mouse; D003907:Dexamethasone