title: The effect of oxandrolone treatment on human osteoblastic cells.
abstract: OBJECTIVE
  Oxandrolone, administered to severely burned children over the first year postburn, produces increased lean body mass by 6 months; however, an increase in total body bone mineral requires 12 months. Consequently, this bone mineral response may be due to increased muscle mass. Alternatively, oxandrolone may act directly on bone. The current study seeks to determine whether oxandrolone can transactivate the androgen receptor in osteoblasts.
  
  
  METHODS
  Collagen, alkaline phosphatase, osteocalcin, osteoprotegerin, and androgen receptor abundance were determined by qRT-PCR, confocal laser scanning microscopy, or immunoquantitative assay. To determine the effect of oxandrolone on gene expression in differentiated cells, osteocytic cultures were grown to confluence in differentiation medium and then treated 24 hours or 5 days with 15 microg/mL oxandrolone.
  
  
  RESULTS
  Increased nuclear fluorescence of the androgen receptor and increased cellular type I collagen were observed with oxandrolone at 15 and 30 microg/mL but not at lower doses. Alkaline phosphatase (7%-20%) and osteocalcin (13%-18%) increases were modest but significant. Short-term treatment produced no significant effects, but at 5 days androgen receptor levels were increased while collagen levels were significantly decreased, with little effect on alkaline phosphatase, osteocalcin, or osteoprotegerin.
  
  
  CONCLUSIONS
  These data suggest oxandrolone can stimulate production of osteoblast differentiation markers in proliferating osteoblastic cells, most likely through the androgen receptor; however, with longer treatment in mature cells, oxandrolone decreases collagen expression. Thus it is possible that oxandrolone given to burned children acts directly on immature osteoblasts to stimulate collagen production, but also may have positive effects to increase bone mineral through other mechanisms.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Texas Medical Branch, Galveston, TX, USA. lbi@utmb.edu
authors.forename: Lian Xiang
authors.initials: LX
authors.lastname: Bi
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Wiren
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Zhang
authors.forename: Gisele V
authors.initials: GV
authors.lastname: Oliveira
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Klein
authors.forename: Elgene G
authors.initials: EG
authors.lastname: Mainous
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon