Alendronate and omeprazole in combination reduce angiogenic and growth signals from osteoblasts.
Alendronate
Bisphosphonates
Bone repair
Omeprazole
Osteonecrosis
Proton pump inhibitors
Journal
Bone reports
ISSN: 2352-1872
Titre abrégé: Bone Rep
Pays: United States
ID NLM: 101646176
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
received:
24
09
2020
revised:
06
01
2021
accepted:
21
01
2021
entrez:
8
2
2021
pubmed:
9
2
2021
medline:
9
2
2021
Statut:
epublish
Résumé
Due to gastrointestinal side effects of oral bisphosphonates (BPs), proton pump inhibitors (PPIs) are often prescribed. PPIs may enhance the risk of osteonecrosis of the jaw, a rare side effect of BPs. Therefore, the objective of this study was to evaluate the effects of the oral BP alendronate (ALN) and the PPI omeprazole (OME) alone and in combination on primary human osteoblasts and gingival fibroblasts in vitro. Human gingival fibroblasts and normal human osteoblasts were incubated with either 5 μM of ALN or 1 μM of OME, or ALN + OME for 1, 3, 7 or 14 days. Effect on viability was evaluated by the lactate dehydrogenase activity in the medium and on proliferation by quantifying 3H-thymidin incorporation. Multianalyte profiling of proteins in cell culture media was performed using the Luminex 200TM system to assess the effect on selected bone markers and cytokines. The proliferation of osteoblasts and fibroblasts was reduced upon exposure to ALN + OME. ALN induced an early, temporary rise in markers of inflammation, and OME and ALN + OME promoted a transient decline. An initial increase in IL-13 occurred after exposure to all three options, whereas ALN + OME promoted IL-8 release after 7 days. OME and ALN + OME promoted a transient reduction in vascular endothelial growth factor (VEGF) from osteoblasts, whereas ALN and ALN + OME induced a late rise in VEGF from fibroblasts. Osteoprotegerin release was enhanced by ALN and suppressed by OME and ALN + OME. ALN + OME seemed to exaggerate the negative effects of each drug alone on human osteoblasts and gingival fibroblasts. The anti-proliferative effects, modulation of inflammation and impairment of angiogenesis, may induce unfavorable conditions in periodontal tissue facilitating development of osteonecrosis.
Identifiants
pubmed: 33553512
doi: 10.1016/j.bonr.2021.100750
pii: S2352-1872(21)00005-X
pmc: PMC7856318
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100750Informations de copyright
© 2021 The Author(s).
Déclaration de conflit d'intérêts
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Références
Rheumatology (Oxford). 2012 Sep;51(9):1571-9
pubmed: 22596210
J Oral Maxillofac Surg. 2003 Sep;61(9):1115-7
pubmed: 12966493
Oral Maxillofac Surg Clin North Am. 2015 Nov;27(4):489-96
pubmed: 26412796
J Oral Maxillofac Surg. 2020 Dec;78(12):2138-2146
pubmed: 32919953
EFORT Open Rev. 2018 Sep 12;3(9):494-500
pubmed: 30305933
Biol Pharm Bull. 2017;40(6):739-750
pubmed: 28566618
Osteoporos Int. 2017 Oct;28(10):2921-2928
pubmed: 28664276
Nat Med. 2004 Oct;10(10):1095-103
pubmed: 15378055
Head Face Med. 2010 Jul 09;6:12
pubmed: 20618968
Arch Intern Med. 2011 Jun 13;171(11):998-1004
pubmed: 21321287
Bone. 2010 Aug;47(2):169-80
pubmed: 20493982
J Craniomaxillofac Surg. 2018 Apr;46(4):538-546
pubmed: 29454604
Clin Orthop Relat Res. 1994 May;(302):189-93
pubmed: 8168299
Support Care Cancer. 2009 Dec;17(12):1553-7
pubmed: 19653010
Sci Rep. 2017 Apr 07;7:46322
pubmed: 28387378
J Biol Chem. 2009 Mar 6;284(10):6038-42
pubmed: 19112107
Clin Oral Investig. 2013 Nov;17(8):1829-37
pubmed: 23114879
Bone. 2016 Oct;91:30-8
pubmed: 27353702
J Clin Periodontol. 2016 Feb;43(2):193-203
pubmed: 26725944
J Orthop Surg Res. 2014 Jun 05;9:45
pubmed: 24902588
J Craniomaxillofac Surg. 2019 Sep;47(9):1464-1474
pubmed: 31327558
Int J Mol Sci. 2019 Nov 28;20(23):
pubmed: 31795299
Calcif Tissue Int. 2012 Jun;90(6):507-14
pubmed: 22527206
Oral Dis. 2014 Jul;20(5):446-52
pubmed: 23837828
J Bone Miner Res. 2015 Jan;30(1):3-23
pubmed: 25414052
Clin Ther. 2007 Aug;29(8):1548-58
pubmed: 17919538
J Orthop Res. 2019 Jan;37(1):35-50
pubmed: 30370699
J Transl Med. 2019 Nov 20;17(1):381
pubmed: 31747953
Curr Drug Saf. 2008 Sep;3(3):178-84
pubmed: 18690998
Anat Rec (Hoboken). 2008 Jan;291(1):1-5
pubmed: 18085627
Clin Cancer Res. 2002 May;8(5):1080-4
pubmed: 12006522
FEBS J. 2013 Oct;280(20):5052-64
pubmed: 23937530
J Dent Res. 2015 Feb;94(2):252-60
pubmed: 25477311
Int J Clin Exp Med. 2015 Apr 15;8(4):4899-910
pubmed: 26131063
J Bone Miner Res. 1997 Oct;12(10):1700-7
pubmed: 9333131
Rheumatol Int. 2013 Sep;33(9):2255-60
pubmed: 23455632
J Natl Cancer Inst Monogr. 2019 Aug 1;2019(53):
pubmed: 31425596
J Korean Assoc Oral Maxillofac Surg. 2019 Jun;45(3):135-140
pubmed: 31334101
Exp Mol Med. 2002 May 31;34(2):145-51
pubmed: 12085990
Eur J Case Rep Intern Med. 2019 Oct 14;6(10):001279
pubmed: 31742205
Int J Med Sci. 2018 Feb 12;15(4):359-367
pubmed: 29511371
Ther Adv Med Oncol. 2019 Jun 09;11:1758835919855235
pubmed: 31217825
Clin Oral Investig. 2012 Feb;16(1):79-86
pubmed: 20938793
Biomol Concepts. 2018 May 30;9(1):64-79
pubmed: 29856726
Acta Odontol Scand. 2016 Oct;74(7):550-557
pubmed: 27546224
Bone Res. 2020 Mar 11;8:14
pubmed: 32195012
Curr Osteoporos Rep. 2018 Oct;16(5):584-595
pubmed: 30155844
Nat Rev Rheumatol. 2012 Jan 31;8(3):133-43
pubmed: 22293759
Bone. 2001 Mar;28(3):268-74
pubmed: 11248656
Exp Cell Res. 2007 Feb 1;313(3):486-99
pubmed: 17126831
Bratisl Lek Listy. 2017;118(12):724-731
pubmed: 29322803
Oral Surg Oral Med Oral Pathol Oral Radiol. 2019 Feb;127(2):117-135
pubmed: 30393090
J Oral Maxillofac Surg. 2012 May;70(5):1081-92
pubmed: 21856057
J Int Med Res. 2009 Mar-Apr;37(2):407-16
pubmed: 19383235
Bone. 2016 May;86:119-30
pubmed: 26946132
Bone Joint J. 2013 Nov;95-B(11):1575-80
pubmed: 24151282
J Bone Miner Res. 2008 Nov;23(11):1765-74
pubmed: 18597629
Front Bioeng Biotechnol. 2017 Nov 03;5:68
pubmed: 29164110
J Clin Oncol. 2019 Sep 1;37(25):2270-2290
pubmed: 31329513
Curr Osteoporos Rep. 2007 Sep;5(3):98-104
pubmed: 17925190
Arch Oral Biol. 2011 May;56(5):491-8
pubmed: 21146154
Curr Osteoporos Rep. 2019 Dec;17(6):538-547
pubmed: 31713180