title: Substrain-specific differences in survival and osteonecrosis incidence in a mouse model.
abstract: We previously reported strain-specific susceptibility to dexamethasone-induced osteonecrosis in mice. Here we report that BALB/cJ and BALB/cAnNHsd mice display substrain-specific differences in dexamethasone-induced adverse effects. As compared with BALB/cJ mice, BALB/cAnNHsd weighed more (16.6 g compared with 13.7 g) at the beginning of dexamethasone administration on postnatal day 28 and fewer died during the dexamethasone regimen (10% compared with 50%). Although the 2 substrains had similar plasma concentrations of dexamethasone, BALB/cJ mice were more susceptible to developing dexamethasone-induced osteonecrosis. A higher dose of dexamethasone (8 mg/L) throughout the treatment period compared with a lower dose (8 mg/L loading dose during week 1 followed by 4 mg/L for the remainder of the treatment period) and earlier start of treatment (postnatal day 24 compared with postnatal day 28) was required to induce osteonecrosis with a similar frequency in BALB/cAnNHsd mice as in BALB/cJ mice. Our results show, for the first time, substrain-specific differences in the development of osteonecrosis in mice.
authors.affiliation: Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Jitesh D
authors.initials: JD
authors.lastname: Kawedia
authors.forename: Laura
authors.initials: L
authors.lastname: Janke
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Funk
authors.forename: Laura B
authors.initials: LB
authors.lastname: Ramsey
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Liu
authors.forename: David
authors.initials: D
authors.lastname: Jenkins
authors.forename: Kelli L
authors.initials: KL
authors.lastname: Boyd
authors.forename: Mary V
authors.initials: MV
authors.lastname: Relling
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight; D003907:Dexamethasone / Q000009:adverse effects* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008807:Mice, Inbred BALB C; D010020:Osteonecrosis / Q000139:chemically induced* / Q000473:pathology*; D013045:Species Specificity; D016019:Survival Analysis
chemical_list: D003907:Dexamethasone
references.citation: J Pharmacol Exp Ther. 1995 Dec;275(3):1484-9
references.pmid: 8531119
references.citation: Immunogenetics. 1999 Dec;50(5-6):354-7
references.pmid: 10630301
references.citation: J Pharmacol Exp Ther. 1986 Jun;237(3):809-19
references.pmid: 3712280
references.citation: J Pharmacol Exp Ther. 2001 Jul;298(1):148-55
references.pmid: 11408536
references.citation: J Neuroimmunol. 1994 Jun;52(1):19-24
references.pmid: 8207118
references.citation: Arthritis Rheum. 2001 Mar;44(3):682-92
references.pmid: 11263784
references.citation: J Orthop Res. 2009 Feb;27(2):169-75
references.pmid: 18683891
references.citation: Comp Med. 2011 Aug;61(4):356-60
references.pmid: 22330251
references.citation: J Pharmacol Exp Ther. 2007 Jan;320(1):124-32
references.pmid: 17038508
references.citation: J Physiol. 2009 Sep 1;587(Pt 17):4159-67
references.pmid: 19491248
references.citation: Psychopharmacology (Berl). 1997 Jul;132(2):161-8
references.pmid: 9266613
references.citation: Immunogenetics. 1990;32(1):34-40
references.pmid: 1973683
references.citation: Blood. 2011 Feb 24;117(8):2340-7; quiz 2556
references.pmid: 21148812