title: β-Ecdysone Augments Peak Bone Mass in Mice of Both Sexes.
abstract: BACKGROUND
  One of the strongest predictors for osteoporosis is peak bone mass. Interventions to augment peak bone mass have yet to be developed. β-Ecdysone (βEcd), a natural steroid-like compound produced by arthropods to initiate metamorphosis, is believed to have androgenic effects and so may be used to augment bone mass.
  
  
  OBJECTIVE
  The purpose of this study was to use both male and female (1) gonadal-sufficient; and (2) -insufficient mice to investigate sex differences in terms of bone development and structure after βEcd administration.
  
  
  METHODS
  Two-month-old male and female Swiss-Webster mice were randomized to receive either vehicle or βEcd (0.5 mg/kg) for 3 weeks. In a separate experiment to evaluate the effects of βEcd on sex hormone-deficient mice, gonadectomy was performed in male (orchiectomy [ORX]) and female mice (ovariectomy [OVX]). Sham-operated and the ORX/OVX mice were then treated for 3 weeks with βEcd. Primary endpoints for the study were trabecular bone structure and bone strength.
  
  
  RESULTS
  In male mice, the trabecular bone volume was 0.18±0.02 in the placebo-treated (PL) and 0.23±0.02 in the βEcd-treated group (p<0.05 versus PL); and 0.09±0.01 in the ORX group (p<0.05 versus PL) and 0.12±0.01 in the ORX+βEcd group. Vertebral bone strength (maximum load) was 43±2 in PL and 51±1 in the βEcd-treated group (p<0.05 versus PL); and 30±4 in the ORX group (p<0.05 versus PL) and 37±3 in the ORX+βEcd group. In female mice, trabecular bone volume was 0.23±0.02 in PL and 0.26±0.02 in the βEcd-treated group (p<0.05 versus PL); and 0.15±0.01 in the OVX group (p<0.05 versus PL) and 0.14±0.01 in the OVX+βEcd group. Maximum load of the vertebrae was 45±2 in PL and 48±4 in the βEcd-treated group; and 39±4 in the OVX group (p<0.05 versus PL) and 44±4 in the OVX+βEcd group.
  
  
  CONCLUSIONS
  These findings suggest the potential use of βEcd in the augmentation of bone mass in growing male and female mice. It may also partially prevent the detrimental effects of gonadectomy on trabecular bone.
  
  
  CONCLUSIONS
  Our results support the potential use of βEcd or nature products that are rich in βEcd to augment peak bone mass. βEcd may differ from the other anabolic hormone treatments that may have severe side effects such as serious cardiac complications. However, its effects on humans remain to be determined.
authors.affiliation: Department of Science and Technology, Integrative Medicine Discipline, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, PR China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Dai
authors.forename: HongLiang
authors.initials: H
authors.lastname: Zhang
authors.forename: Zhendong A
authors.initials: ZA
authors.lastname: Zhong
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.forename: Haiyan
authors.initials: H
authors.lastname: Chen
authors.forename: Yu-An Evan
authors.initials: YA
authors.lastname: Lay
authors.forename: Alexander
authors.initials: A
authors.lastname: Kot
authors.forename: Robert O
authors.initials: RO
authors.lastname: Ritchie
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Lane
authors.forename: Wei
authors.initials: W
authors.lastname: Yao
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D004441:Ecdysterone / Q000008:administration & dosage*; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000254:growth & development; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000254:growth & development; D008297:Male; D051379:Mice; D009919:Orchiectomy; D010012:Osteogenesis / Q000187:drug effects*; D010052:Ovariectomy; D012737:Sex Factors; D055114:X-Ray Microtomography
chemical_list: D004441:Ecdysterone
references.citation: Genes Dev. 2006 Sep 15;20(18):2492-506
references.pmid: 16980579
references.citation: Bone. 2000 Sep;27(3):437-44
references.pmid: 10962357
references.citation: J Bone Miner Res. 2001 Dec;16(12):2267-75
references.pmid: 11760841
references.citation: Osteoporos Int. 1993;3 Suppl 1:54-5
references.pmid: 8461578
references.citation: Lancet. 2001 Oct 13;358(9289):1208-12
references.pmid: 11675056
references.citation: Nat Prod Commun. 2011 May;6(5):707-18
references.pmid: 21615037
references.citation: J Bone Miner Res. 1999 Oct;14(10):1672-9
references.pmid: 10491214
references.citation: J Steroid Biochem Mol Biol. 2002 Feb;80(2):175-89
references.pmid: 11897502
references.citation: Bone. 1993 Jul-Aug;14(4):595-608
references.pmid: 8274302
references.citation: J Bone Miner Res. 2006 Mar;21(3):466-76
references.pmid: 16491295
references.citation: Nat Rev Endocrinol. 2013 Dec;9(12):699-712
references.pmid: 24042328
references.citation: J Steroid Biochem Mol Biol. 2009 Apr;114(3-5):180-5
references.pmid: 19429449
references.citation: Endocrinology. 2012 Nov;153(11):5325-33
references.pmid: 23015293
references.citation: Nat Med. 2012 Mar;18(3):456-62
references.pmid: 22306732
references.citation: J Endocrinol. 2006 May;189(2):279-87
references.pmid: 16648295
references.citation: Biosci Biotechnol Biochem. 2010;74(11):2226-31
references.pmid: 21071854
references.citation: Phytother Res. 2013 Jan;27(1):107-11
references.pmid: 22495969
references.citation: Bone. 2007 Nov;41(5):804-12
references.pmid: 17825637
references.citation: Arthritis Rheum. 2008 Nov;58(11):3485-97
references.pmid: 18975341
references.citation: J Bone Miner Res. 2001 Nov;16(11):1962-71
references.pmid: 11697792
references.citation: Obstet Gynecol Int. 2015;2015:713295
references.pmid: 25685151
references.citation: Phytomedicine. 2010 Sep;17(11):884-9
references.pmid: 20554186
references.citation: Arch Insect Biochem Physiol. 2009 Nov;72(3):126-41
references.pmid: 19771554
references.citation: JAMA. 2002 Jul 17;288(3):321-33
references.pmid: 12117397
references.citation: Endocrinology. 2010 Jun;151(6):2641-9
references.pmid: 20410195
references.citation: Phytomedicine. 2010 Apr;17(5):350-5
references.pmid: 20171072
references.citation: Curr Med Chem. 2008;15(1):75-91
references.pmid: 18220764
references.citation: J Clin Endocrinol Metab. 1999 Jun;84(6):2002-7
references.pmid: 10372701
references.citation: Bone. 2007 Oct;41(4):496-504
references.pmid: 17870038
references.citation: J Agric Food Chem. 2008 May 28;56(10):3532-7
references.pmid: 18444661
references.citation: Arthritis Rheum. 2008 Dec;58(12):3809-19
references.pmid: 19035511
references.citation: PLoS One. 2010;5(7):e11410
references.pmid: 20625385
references.citation: Stem Cells. 2013 Sep;31(9):2003-14
references.pmid: 23818248
references.citation: Bone. 2015 May;74:48-57
references.pmid: 25585248
references.citation: J Endocrinol. 2006 Oct;191(1):1-8
references.pmid: 17065383
references.citation: Am J Clin Nutr. 2005 Jan;81(1):175-88
references.pmid: 15640478
references.citation: Vitam Horm. 2005;73:1-30
references.pmid: 16399406
references.citation: J Cell Biol. 2007 Apr 9;177(1):73-86
references.pmid: 17420291
references.citation: JAMA. 2013 Oct 2;310(13):1353-68
references.pmid: 24084921
references.citation: J Bone Miner Res. 2010 Feb;25(2):190-9
references.pmid: 19594295
references.citation: Mini Rev Med Chem. 2002 Jun;2(3):285-93
references.pmid: 12370070
references.citation: J Clin Endocrinol Metab. 1998 Dec;83(12):4274-9
references.pmid: 9851763
references.citation: J Biol Chem. 2007 Sep 14;282(37):27285-97
references.pmid: 17623659
references.citation: FASEB J. 2011 Oct;25(10):3708-19
references.pmid: 21746867
references.citation: Int J Sports Med. 2005 Jun;26(5):332-8
references.pmid: 15895314
references.citation: Endocrinology. 2004 Apr;145(4):1980-7
references.pmid: 14715712