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Testosterone delivered with a scaffold is as effective as bone morphologic protein-2 in promoting the repair of critical-size segmental defect of femoral bone in mice.

Cheng BH, Chu TM, Chang C, Kang HY, Huang KE - PLoS ONE (2013)

Bottom Line: Micro-computed tomography and histological examinations revealed that testosterone treatment caused similar degrees of callus formation as BMP-2 treatment in wildtype mice, but had no such effect in ARKO mice, suggesting that the androgen receptor is required for testosterone to initiate fracture healing.These results demonstrate that testosterone is as effective as BMP-2 in promoting the healing of critical-size segmental defects and that combination therapy with testosterone and BMP-2 is superior to single therapy.Results of this study may provide a foundation to develop a cost effective and efficient therapeutic modality for treatment of bone fractures with segmental defects.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.

ABSTRACT
Loss of large bone segments due to fracture resulting from trauma or tumor removal is a common clinical problem. The goal of this study was to evaluate the use of scaffolds containing testosterone, bone morphogenetic protein-2 (BMP-2), or a combination of both for treatment of critical-size segmental bone defects in mice. A 2.5-mm wide osteotomy was created on the left femur of wildtype and androgen receptor knockout (ARKO) mice. Testosterone, BMP-2, or both were delivered locally using a scaffold that bridged the fracture. Results of X-ray imaging showed that in both wildtype and ARKO mice, BMP-2 treatment induced callus formation within 14 days after initiation of the treatment. Testosterone treatment also induced callus formation within 14 days in wildtype but not in ARKO mice. Micro-computed tomography and histological examinations revealed that testosterone treatment caused similar degrees of callus formation as BMP-2 treatment in wildtype mice, but had no such effect in ARKO mice, suggesting that the androgen receptor is required for testosterone to initiate fracture healing. These results demonstrate that testosterone is as effective as BMP-2 in promoting the healing of critical-size segmental defects and that combination therapy with testosterone and BMP-2 is superior to single therapy. Results of this study may provide a foundation to develop a cost effective and efficient therapeutic modality for treatment of bone fractures with segmental defects.

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Micro-CT analyses of femurs of wildtype (AR+/Y) and ARKO (AR−/Y) mice with segmental bone defect treated with a 2.5-mm scaffold containing BMP-2 (5 µg), testosterone (100 µg), or testosterone plus BMP-2 for 35 days.Each femur was scanned for 260 slices each above and below the midpoint of the scaffold for a total of 8.2 mm in length. Upper panel shows reconstructed 3-D images of the region containing the scaffold. The volumes of regenerated callus and bone in the scanned region are shown in column graphs in the lower panel. *: p<0.05. ND: not determined.
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pone-0070234-g003: Micro-CT analyses of femurs of wildtype (AR+/Y) and ARKO (AR−/Y) mice with segmental bone defect treated with a 2.5-mm scaffold containing BMP-2 (5 µg), testosterone (100 µg), or testosterone plus BMP-2 for 35 days.Each femur was scanned for 260 slices each above and below the midpoint of the scaffold for a total of 8.2 mm in length. Upper panel shows reconstructed 3-D images of the region containing the scaffold. The volumes of regenerated callus and bone in the scanned region are shown in column graphs in the lower panel. *: p<0.05. ND: not determined.

Mentions: Micro-CT analyses were performed at day 35 after surgery. In wildtype mice, no callus or bone formation was detected if the fracture was treated with a scaffold containing no BMP-2 or testosterone. An average of 8 mm3, 9 mm3, and 16.2 mm3 of callus (Tissue Volume, TV) was formed if the scaffold was loaded with BMP-2, testosterone, or testosterone plus BMP-2, respectively (Fig. 3). Similar results in mineralized bone in callus were observed with an average of 4.2 mm3, 4 mm3 and 6.8 mm3 of bone (Bone volume, BV) formed if the scaffold was loaded with BMP-2, testosterone, or testosterone plus BMP-2, respectively. Statistically, there was no difference in effects between BMP-2 and testosterone, whereas treatment with the combination of BMP-2 and testosterone resulted in a significantly higher levels of both callus and BV formation than the treatment with either BMP-2 or testosterone alone (Fig. 3).


Testosterone delivered with a scaffold is as effective as bone morphologic protein-2 in promoting the repair of critical-size segmental defect of femoral bone in mice.

Cheng BH, Chu TM, Chang C, Kang HY, Huang KE - PLoS ONE (2013)

Micro-CT analyses of femurs of wildtype (AR+/Y) and ARKO (AR−/Y) mice with segmental bone defect treated with a 2.5-mm scaffold containing BMP-2 (5 µg), testosterone (100 µg), or testosterone plus BMP-2 for 35 days.Each femur was scanned for 260 slices each above and below the midpoint of the scaffold for a total of 8.2 mm in length. Upper panel shows reconstructed 3-D images of the region containing the scaffold. The volumes of regenerated callus and bone in the scanned region are shown in column graphs in the lower panel. *: p<0.05. ND: not determined.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3733987&req=5

pone-0070234-g003: Micro-CT analyses of femurs of wildtype (AR+/Y) and ARKO (AR−/Y) mice with segmental bone defect treated with a 2.5-mm scaffold containing BMP-2 (5 µg), testosterone (100 µg), or testosterone plus BMP-2 for 35 days.Each femur was scanned for 260 slices each above and below the midpoint of the scaffold for a total of 8.2 mm in length. Upper panel shows reconstructed 3-D images of the region containing the scaffold. The volumes of regenerated callus and bone in the scanned region are shown in column graphs in the lower panel. *: p<0.05. ND: not determined.
Mentions: Micro-CT analyses were performed at day 35 after surgery. In wildtype mice, no callus or bone formation was detected if the fracture was treated with a scaffold containing no BMP-2 or testosterone. An average of 8 mm3, 9 mm3, and 16.2 mm3 of callus (Tissue Volume, TV) was formed if the scaffold was loaded with BMP-2, testosterone, or testosterone plus BMP-2, respectively (Fig. 3). Similar results in mineralized bone in callus were observed with an average of 4.2 mm3, 4 mm3 and 6.8 mm3 of bone (Bone volume, BV) formed if the scaffold was loaded with BMP-2, testosterone, or testosterone plus BMP-2, respectively. Statistically, there was no difference in effects between BMP-2 and testosterone, whereas treatment with the combination of BMP-2 and testosterone resulted in a significantly higher levels of both callus and BV formation than the treatment with either BMP-2 or testosterone alone (Fig. 3).

Bottom Line: Micro-computed tomography and histological examinations revealed that testosterone treatment caused similar degrees of callus formation as BMP-2 treatment in wildtype mice, but had no such effect in ARKO mice, suggesting that the androgen receptor is required for testosterone to initiate fracture healing.These results demonstrate that testosterone is as effective as BMP-2 in promoting the healing of critical-size segmental defects and that combination therapy with testosterone and BMP-2 is superior to single therapy.Results of this study may provide a foundation to develop a cost effective and efficient therapeutic modality for treatment of bone fractures with segmental defects.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.

ABSTRACT
Loss of large bone segments due to fracture resulting from trauma or tumor removal is a common clinical problem. The goal of this study was to evaluate the use of scaffolds containing testosterone, bone morphogenetic protein-2 (BMP-2), or a combination of both for treatment of critical-size segmental bone defects in mice. A 2.5-mm wide osteotomy was created on the left femur of wildtype and androgen receptor knockout (ARKO) mice. Testosterone, BMP-2, or both were delivered locally using a scaffold that bridged the fracture. Results of X-ray imaging showed that in both wildtype and ARKO mice, BMP-2 treatment induced callus formation within 14 days after initiation of the treatment. Testosterone treatment also induced callus formation within 14 days in wildtype but not in ARKO mice. Micro-computed tomography and histological examinations revealed that testosterone treatment caused similar degrees of callus formation as BMP-2 treatment in wildtype mice, but had no such effect in ARKO mice, suggesting that the androgen receptor is required for testosterone to initiate fracture healing. These results demonstrate that testosterone is as effective as BMP-2 in promoting the healing of critical-size segmental defects and that combination therapy with testosterone and BMP-2 is superior to single therapy. Results of this study may provide a foundation to develop a cost effective and efficient therapeutic modality for treatment of bone fractures with segmental defects.

Show MeSH
Related in: MedlinePlus