Related Articles Testosterone dose-dependently prevents bone and muscle loss in rodents following spinal cord injury.
J Neurotrauma. 2013 Dec 30;
Authors: Yarrow JF, Conover CF, Beggs LA, Beck DT, Otzel DM, Balaez A, Combs SM, Miller JR, Ye F, Aguirre JI, Neuville KG, Williams AA, Conrad BP, Gregory CM, Wronski TJ, Bose PK, Borst SE
Abstract
Androgen administration protects against musculoskeletal deficits in models of sex-steroid deficiency and injury/disuse. However, it remains unknown whether testosterone prevents bone loss accompanying spinal cord injury (SCI), a condition that results in a near universal occurrence of osteoporosis. Our primary purpose was to determine whether testosterone-enanthate (TE) attenuates hind limb bone loss in a rodent moderate/severe contusion SCI model. Forty (n=10/group), 14 week old male Sprague-Dawley rats were randomized to receive: 1) Sham surgery (T9 laminectomy), 2) moderate/severe (250 kdyne) SCI, 3) SCI+Low-dose TE (2.0mg/week), or 4) SCI+High-dose TE (7.0mg/week). Twenty-one days post-injury, SCI animals exhibited a 77-85% reduction in hind limb cancellous bone volume at the distal femur (measured via µCT) and proximal tibia (measured via histomorphometry), characterized by a >70% reduction in trabecular number, 13-27% reduction in trabecular thickness, and increased trabecular separation. A 57% reduction in cancellous volumetric bone mineral density (vBMD) at the distal femur and a 20% reduction in vBMD at the femoral neck were also observed. TE dose-dependently prevented hind limb bone loss after SCI, with high-dose TE fully preserving cancellous bone structural characteristics and vBMD at all skeletal sites examined. Animals receiving SCI also exhibited a 35% reduction in hind limb weight bearing (triceps surae) muscle mass and a 22% reduction in sublesional non-weight bearing [levator ani/bulbocavernosus (LABC)] muscle mass, and reduced prostate mass. Both TE doses fully preserved LABC mass, while only high-dose TE ameliorated hind limb muscle losses. TE also dose-dependently increased prostate mass. Our findings provide the first evidence indicating that high-dose TE fully prevents hind limb cancellous bone loss and concomitantly ameliorates muscle loss following SCI, while low-dose TE produces much less profound musculoskeletal benefit. However, testosterone-induced prostate enlargement represents a potential barrier to the clinical implementation of high-dose TE as a means of preserving musculoskeletal tissue after SCI.
PMID: 24378197 [PubMed - as supplied by publisher]
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J Neurotrauma. 2013 Dec 30;
Authors: Yarrow JF, Conover CF, Beggs LA, Beck DT, Otzel DM, Balaez A, Combs SM, Miller JR, Ye F, Aguirre JI, Neuville KG, Williams AA, Conrad BP, Gregory CM, Wronski TJ, Bose PK, Borst SE
Abstract
Androgen administration protects against musculoskeletal deficits in models of sex-steroid deficiency and injury/disuse. However, it remains unknown whether testosterone prevents bone loss accompanying spinal cord injury (SCI), a condition that results in a near universal occurrence of osteoporosis. Our primary purpose was to determine whether testosterone-enanthate (TE) attenuates hind limb bone loss in a rodent moderate/severe contusion SCI model. Forty (n=10/group), 14 week old male Sprague-Dawley rats were randomized to receive: 1) Sham surgery (T9 laminectomy), 2) moderate/severe (250 kdyne) SCI, 3) SCI+Low-dose TE (2.0mg/week), or 4) SCI+High-dose TE (7.0mg/week). Twenty-one days post-injury, SCI animals exhibited a 77-85% reduction in hind limb cancellous bone volume at the distal femur (measured via µCT) and proximal tibia (measured via histomorphometry), characterized by a >70% reduction in trabecular number, 13-27% reduction in trabecular thickness, and increased trabecular separation. A 57% reduction in cancellous volumetric bone mineral density (vBMD) at the distal femur and a 20% reduction in vBMD at the femoral neck were also observed. TE dose-dependently prevented hind limb bone loss after SCI, with high-dose TE fully preserving cancellous bone structural characteristics and vBMD at all skeletal sites examined. Animals receiving SCI also exhibited a 35% reduction in hind limb weight bearing (triceps surae) muscle mass and a 22% reduction in sublesional non-weight bearing [levator ani/bulbocavernosus (LABC)] muscle mass, and reduced prostate mass. Both TE doses fully preserved LABC mass, while only high-dose TE ameliorated hind limb muscle losses. TE also dose-dependently increased prostate mass. Our findings provide the first evidence indicating that high-dose TE fully prevents hind limb cancellous bone loss and concomitantly ameliorates muscle loss following SCI, while low-dose TE produces much less profound musculoskeletal benefit. However, testosterone-induced prostate enlargement represents a potential barrier to the clinical implementation of high-dose TE as a means of preserving musculoskeletal tissue after SCI.
PMID: 24378197 [PubMed - as supplied by publisher]
This is an automated post
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