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The effect of oxandrolone treatment on human osteoblastic cells.

Bi LX, Wiren KM, Zhang XW, Oliveira GV, Klein GL, Mainous EG, Herndon DN - J Burns Wounds (2007)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral and Maxillofacial Surgery, University of Texas Medical Branch, Galveston, TX, USA. lbi@utmb.edu

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.

No MeSH data available.


Related in: MedlinePlus

Increased osteocalcin levels after oxandrolone treatment. Human osteoblastic cultures were exposed to oxandrolone (0, 1, 5, 10, and 15 μg/mL) for 24 hours. Data are expressed as mean ± SEM of 6 determinations.
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Figure 3: Increased osteocalcin levels after oxandrolone treatment. Human osteoblastic cultures were exposed to oxandrolone (0, 1, 5, 10, and 15 μg/mL) for 24 hours. Data are expressed as mean ± SEM of 6 determinations.

Mentions: To determine the effect of oxandrolone on additional markers of osteoblast activity, osteoblastic cultures were treated with or without oxandrolone. Alkaline phosphatase activity was determined in cells treated with oxandrolone for 24 hours (Fig 2), and there was an increase (7%–20%) in activity in a dose-dependent manner. The differences were statistically significant (P < .05) but the changes were minor compared to the control group. We also performed immunoquantitative assays for type I collagen and osteocalcin on osteoblastic cells. In cultures treated with oxandrolone (10 or 15 μg/mL), collagen was increased 21% to 35% (Fig 3; P < .05). There were no differences in the groups treated with low concentrations of oxandrolone (1 or 5 μg/mL) compared to control group. Thus, after multiple repetitions of the experiment, the data confirmed the results observed using immunofluorescence.


The effect of oxandrolone treatment on human osteoblastic cells.

Bi LX, Wiren KM, Zhang XW, Oliveira GV, Klein GL, Mainous EG, Herndon DN - J Burns Wounds (2007)

Increased osteocalcin levels after oxandrolone treatment. Human osteoblastic cultures were exposed to oxandrolone (0, 1, 5, 10, and 15 μg/mL) for 24 hours. Data are expressed as mean ± SEM of 6 determinations.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1828036&req=5

Figure 3: Increased osteocalcin levels after oxandrolone treatment. Human osteoblastic cultures were exposed to oxandrolone (0, 1, 5, 10, and 15 μg/mL) for 24 hours. Data are expressed as mean ± SEM of 6 determinations.
Mentions: To determine the effect of oxandrolone on additional markers of osteoblast activity, osteoblastic cultures were treated with or without oxandrolone. Alkaline phosphatase activity was determined in cells treated with oxandrolone for 24 hours (Fig 2), and there was an increase (7%–20%) in activity in a dose-dependent manner. The differences were statistically significant (P < .05) but the changes were minor compared to the control group. We also performed immunoquantitative assays for type I collagen and osteocalcin on osteoblastic cells. In cultures treated with oxandrolone (10 or 15 μg/mL), collagen was increased 21% to 35% (Fig 3; P < .05). There were no differences in the groups treated with low concentrations of oxandrolone (1 or 5 μg/mL) compared to control group. Thus, after multiple repetitions of the experiment, the data confirmed the results observed using immunofluorescence.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral and Maxillofacial Surgery, University of Texas Medical Branch, Galveston, TX, USA. lbi@utmb.edu

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.

No MeSH data available.


Related in: MedlinePlus