Treatment of osteoporosis using a selective androgen receptor modulator ostarine in an orchiectomized rat model.
Orchiectomized (Orx) rat model
Ostarine
Osteoporosis
Selective androgen receptor modulator (SARM)
Journal
Endocrine
ISSN: 1559-0100
Titre abrégé: Endocrine
Pays: United States
ID NLM: 9434444
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
12
12
2022
accepted:
10
06
2023
medline:
7
8
2023
pubmed:
28
6
2023
entrez:
28
6
2023
Statut:
ppublish
Résumé
The selective androgen receptor modulator ostarine has been shown to have advantageous effects on skeletal tissue properties, reducing muscle wasting and improving physical function in males. However, data on effects in male osteoporosis remain limited. In this study, the effects of ostarine on osteoporotic bone were evaluated in a rat model of male osteoporosis and compared with those of testosterone treatments. Eight-month-old male Sprague-Dawley rats were either non-orchiectomized to serve as a healthy control (Non-Orx, Group 1) or orchiectomized (Orx, Groups 2-6) and then grouped (n = 15/group): (1) Non-Orx, (2) Orx, (3) Ostarine Therapy, (4) Testosterone Therapy, (5) Ostarine Prophylaxis and (6) Testosterone Prophylaxis. Prophylaxis treatments started directly after orchiectomy and continued for 18 weeks, whereas Therapy treatments were initiated 12 weeks after Orx. Ostarine and Testosterone were applied orally at daily doses of 0.4 and 50 mg/kg body weight, respectively. The lumbar vertebral bodies and femora were analyzed using biomechanical, micro-CT, ashing, and gene expression analyses. Ostarine Prophylaxis showed positive effects in preventing osteoporotic changes in cortical and trabecular bone (femoral trabecular density: 26.01 ± 9.1% vs. 20.75 ± 1.2% in Orx and in L4: 16.3 ± 7.3% vs 11.8 ± 2.9% in Orx); biomechanical parameters were not affected; prostate weight was increased (0.62 ± 0.13 g vs 0.18 ± 0.07 g in Orx). Ostarine Therapy increased solely the cortical density of the femur (1.25 ± 0.03 g/cm Ostarine Prophylaxis could be further investigated as a preventative treatment for male osteoporosis, but an androgenic effect on the prostate should be taken into consideration, and combination therapies with other anti-osteoporosis agents could be considered.
Identifiants
pubmed: 37378829
doi: 10.1007/s12020-023-03422-7
pii: 10.1007/s12020-023-03422-7
pmc: PMC10403398
doi:
Substances chimiques
Receptors, Androgen
0
ostarine
O3571H3R8N
Androgens
0
Testosterone
3XMK78S47O
Androgen Antagonists
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
579-591Informations de copyright
© 2023. The Author(s).
Références
J Clin Endocrinol Metab. 2010 Jan;95(1):3-10
pubmed: 20056806
J Comp Physiol Psychol. 1976 Jan;90(1):18-25
pubmed: 965512
Am J Physiol Endocrinol Metab. 2014 Apr 15;306(8):E937-44
pubmed: 24619882
J Clin Endocrinol Metab. 2001 Feb;86(2):724-31
pubmed: 11158037
Osteoporos Int. 2010 Feb;21(2):251-61
pubmed: 19436940
Expert Opin Investig Drugs. 2006 Apr;15(4):377-87
pubmed: 16548787
Prz Menopauzalny. 2017 Jun;16(2):70-73
pubmed: 28721134
World J Urol. 2009 Aug;27(4):547-55
pubmed: 19221760
Sci Rep. 2018 May 16;8(1):7712
pubmed: 29769600
Front Endocrinol (Lausanne). 2020 Sep 17;11:556581
pubmed: 33042018
J Cachexia Sarcopenia Muscle. 2011 Sep;2(3):153-161
pubmed: 22031847
Calcif Tissue Int. 2016 Oct;99(4):408-22
pubmed: 27272029
Calcif Tissue Int. 2000 Feb;66(2):100-3
pubmed: 10652955
Bone. 2009 Oct;45(4):669-76
pubmed: 19539794
Osteoporos Int. 2006 Dec;17(12):1726-33
pubmed: 16983459
Spine (Phila Pa 1976). 2009 Sep 1;34(19):2014-21
pubmed: 19730209
J Bone Miner Metab. 2019 Mar;37(2):243-255
pubmed: 29785666
J Endocrinol. 2011 Apr;209(1):9-19
pubmed: 21233300
Clin Interv Aging. 2014 Apr 08;9:593-601
pubmed: 24748777
Int J Endocrinol. 2013;2013:213234
pubmed: 23573086
J Bone Miner Res. 2006 Jan;21(1):89-96
pubmed: 16355277
Lancet Diabetes Endocrinol. 2017 Nov;5(11):908-923
pubmed: 28689768
Pharm Res. 2007 Feb;24(2):328-35
pubmed: 17063395
Vet World. 2022 Mar;15(3):627-633
pubmed: 35497966
Endocr Rev. 1994 Jun;15(3):275-300
pubmed: 8076582
J Bone Miner Res. 2013 Jan;28(1):2-17
pubmed: 23197339
J Bone Miner Res. 2007 Aug;22(8):1155-64
pubmed: 17488197
Endocrinology. 2005 Nov;146(11):4887-97
pubmed: 16099859
Endocrinology. 2007 Jan;148(1):363-73
pubmed: 17023534
J Endocrinol Invest. 2022 Dec;45(12):2299-2311
pubmed: 35867330
Keio J Med. 2004 Mar;53(1):12-7
pubmed: 15096723
Osteoporos Int. 2007 Jan;18(1):77-84
pubmed: 17048064
J Bone Miner Res. 1997 Jan;12(1):89-95
pubmed: 9240730
Biol Pharm Bull. 2012;35(7):1096-104
pubmed: 22791158
Calcif Tissue Int. 2020 Dec;107(6):593-602
pubmed: 32876707
J Clin Endocrinol Metab. 2002 Feb;87(2):589-98
pubmed: 11836290
Nutrients. 2018 Jun 21;10(7):
pubmed: 29933617
Lancet Oncol. 2013 Apr;14(4):335-45
pubmed: 23499390
Arch Orthop Trauma Surg. 1996;115(5):262-9
pubmed: 8836458
J Bone Miner Res. 2012 Dec;27(12):2535-43
pubmed: 22836391
Bone. 2017 Aug;101:134-144
pubmed: 28455215
Am J Physiol. 1969 Sep;217(3):865-70
pubmed: 5807713
Curr Opin Investig Drugs. 2006 Oct;7(10):873-81
pubmed: 17086931
Calcif Tissue Int. 2015 Oct;97(4):391-401
pubmed: 26084691
Mol Cell Endocrinol. 2018 Apr 15;465:134-142
pubmed: 28624515
J Bone Miner Res. 2009 Feb;24(2):231-40
pubmed: 18847323
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
Osteoporos Int. 1991 Oct;2(1):20-5
pubmed: 1790416
J Bone Miner Res. 2015 Jul;30(7):1138-49
pubmed: 25704845
Yonsei Med J. 2003 Jun 30;44(3):508-16
pubmed: 12833590
Calcif Tissue Int. 2016 Mar;98(3):235-43
pubmed: 26746477
J Endocrinol Invest. 2022 Aug;45(8):1555-1568
pubmed: 35429299
J Am Geriatr Soc. 2003 Jan;51(1):101-15; discussion 115
pubmed: 12534854
J Appl Physiol (1985). 2018 Jan 1;124(1):118-130
pubmed: 28860177
J Clin Endocrinol Metab. 1997 Oct;82(10):3493-7
pubmed: 9329391
Calcif Tissue Int. 2008 Feb;82(2):108-15
pubmed: 18084692
Calcif Tissue Int. 1980;32(1):77-82
pubmed: 6775783
Pharm Res. 2009 Nov;26(11):2471-7
pubmed: 19728047
Physiol Behav. 1979 Mar;22(3):583-93
pubmed: 379889
J Bone Miner Res. 1997 Jan;12(1):16-23
pubmed: 9240721