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A combined treatment with selective androgen and estrogen receptor modulators prevents bone loss in orchiectomized rats

PURPOSE: Enobosarm (EN), a selective androgen receptor modulator and raloxifene (RAL), a selective estrogen receptor modulator, have been shown to improve bone tissue in osteoporotic males. The present study evaluated the effects of a combination therapy of EN and RAL on bone properties in orchiecto...

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Autores principales: Komrakova, M., Büchler, G., Böker, K. O., Lehmann, W., Schilling, A. F., Roch, P. J., Taudien, S., Hoffmann, D. B., Sehmisch, S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9646546/
https://www.ncbi.nlm.nih.gov/pubmed/35867330
http://dx.doi.org/10.1007/s40618-022-01865-9
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author Komrakova, M.
Büchler, G.
Böker, K. O.
Lehmann, W.
Schilling, A. F.
Roch, P. J.
Taudien, S.
Hoffmann, D. B.
Sehmisch, S.
author_facet Komrakova, M.
Büchler, G.
Böker, K. O.
Lehmann, W.
Schilling, A. F.
Roch, P. J.
Taudien, S.
Hoffmann, D. B.
Sehmisch, S.
author_sort Komrakova, M.
collection PubMed
description PURPOSE: Enobosarm (EN), a selective androgen receptor modulator and raloxifene (RAL), a selective estrogen receptor modulator, have been shown to improve bone tissue in osteoporotic males. The present study evaluated the effects of a combination therapy of EN and RAL on bone properties in orchiectomized rats compared to the respective single treatments. METHODS: Eight-month-old male Sprague–Dawley rats were either left intact (Non-Orx) or orchiectomized (Orx). The Orx rats were divided into four groups (n = 15 each): 1) Orx, 2) EN treatment (Orx + EN), 3) RAL treatment (Orx + RAL), 4) combined treatment (Orx + EN + RAL). EN and RAL (0.4 mg and 7 mg/kg body weight/day) were applied immediately after Orx with a soy-free pelleted diet for up to 18 weeks. The lumbar spine and femora were examined by micro-CT, biomechanical, histomorphological, ashing, and gene expression analyses. RESULTS: EN exhibited an anabolic effect on bone, improving some of its parameters in Orx rats, but did not affect biomechanical properties. RAL exhibited antiresorptive activity, maintaining the biomechanical and trabecular parameters of Orx rats at the levels of Non-Orx rats. EN + RAL exerted a stronger effect than the single treatments, improving most of the bone parameters. Liver weight increased after all treatments; the kidney, prostate, and levator ani muscle weights increased after EN and EN + RAL treatments. BW was reduced due to a decreased food intake in the Orx + RAL group and due a reduced visceral fat weight in the Orx + EN + RAL group. CONCLUSION: The EN + RAL treatment appeared to be promising in preventing male osteoporosis, but given the observed side effects on liver, kidney, and prostate weights, it requires further investigation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40618-022-01865-9.
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spelling pubmed-96465462022-11-15 A combined treatment with selective androgen and estrogen receptor modulators prevents bone loss in orchiectomized rats Komrakova, M. Büchler, G. Böker, K. O. Lehmann, W. Schilling, A. F. Roch, P. J. Taudien, S. Hoffmann, D. B. Sehmisch, S. J Endocrinol Invest Original Article PURPOSE: Enobosarm (EN), a selective androgen receptor modulator and raloxifene (RAL), a selective estrogen receptor modulator, have been shown to improve bone tissue in osteoporotic males. The present study evaluated the effects of a combination therapy of EN and RAL on bone properties in orchiectomized rats compared to the respective single treatments. METHODS: Eight-month-old male Sprague–Dawley rats were either left intact (Non-Orx) or orchiectomized (Orx). The Orx rats were divided into four groups (n = 15 each): 1) Orx, 2) EN treatment (Orx + EN), 3) RAL treatment (Orx + RAL), 4) combined treatment (Orx + EN + RAL). EN and RAL (0.4 mg and 7 mg/kg body weight/day) were applied immediately after Orx with a soy-free pelleted diet for up to 18 weeks. The lumbar spine and femora were examined by micro-CT, biomechanical, histomorphological, ashing, and gene expression analyses. RESULTS: EN exhibited an anabolic effect on bone, improving some of its parameters in Orx rats, but did not affect biomechanical properties. RAL exhibited antiresorptive activity, maintaining the biomechanical and trabecular parameters of Orx rats at the levels of Non-Orx rats. EN + RAL exerted a stronger effect than the single treatments, improving most of the bone parameters. Liver weight increased after all treatments; the kidney, prostate, and levator ani muscle weights increased after EN and EN + RAL treatments. BW was reduced due to a decreased food intake in the Orx + RAL group and due a reduced visceral fat weight in the Orx + EN + RAL group. CONCLUSION: The EN + RAL treatment appeared to be promising in preventing male osteoporosis, but given the observed side effects on liver, kidney, and prostate weights, it requires further investigation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40618-022-01865-9. Springer International Publishing 2022-07-22 2022 /pmc/articles/PMC9646546/ /pubmed/35867330 http://dx.doi.org/10.1007/s40618-022-01865-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Komrakova, M.
Büchler, G.
Böker, K. O.
Lehmann, W.
Schilling, A. F.
Roch, P. J.
Taudien, S.
Hoffmann, D. B.
Sehmisch, S.
A combined treatment with selective androgen and estrogen receptor modulators prevents bone loss in orchiectomized rats
title A combined treatment with selective androgen and estrogen receptor modulators prevents bone loss in orchiectomized rats
title_full A combined treatment with selective androgen and estrogen receptor modulators prevents bone loss in orchiectomized rats
title_fullStr A combined treatment with selective androgen and estrogen receptor modulators prevents bone loss in orchiectomized rats
title_full_unstemmed A combined treatment with selective androgen and estrogen receptor modulators prevents bone loss in orchiectomized rats
title_short A combined treatment with selective androgen and estrogen receptor modulators prevents bone loss in orchiectomized rats
title_sort combined treatment with selective androgen and estrogen receptor modulators prevents bone loss in orchiectomized rats
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9646546/
https://www.ncbi.nlm.nih.gov/pubmed/35867330
http://dx.doi.org/10.1007/s40618-022-01865-9
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