title: Safety of Anti-Diabetic Therapies on Bone.
abstract: Osteoporosis and diabetic disease have reached epidemic proportion and create significant public health concerns. The prevalence of these diseases is alarming, and indicates that in the US, 50% of elderly individuals are osteoporotic and almost 20% of population has either diabetic or prediabetic conditions (Centers for Disease Control and Prevention; http://www.cdc.gov). Osteoporosis and diabetes share many features including genetic predispositions and molecular mechanisms. The linkage between these two chronic diseases, which stems from overlapping molecular controls involved in bone homeostasis and energy metabolism, creates a possibility that certain anti-diabetic therapies may affect bone. This concurs with recent findings indicating that bone status is closely linked to regulation of energy metabolism and insulin sensitivity. Indeed, bone and energy homeostasis are under the control of the same regulatory factors, including insulin, peroxisome proliferator activated receptor gamma (PPARγ), gastrointestinal hormones such as glucose inhibitory protein (GIP) and glucagon inhibitory peptide (GLP), and bone derived hormone osteocalcin. These factors and related mechanisms control glucose homeostasis and fatty acids metabolism in fat tissue, pancreas and intestine, which are pharmacological targets for anti-diabetic therapies. The same factors contribute to the bone quality by their effect on bone cell differentiation and bone remodeling process. This implies that bone should be considered as a vital target for therapies which modulate energy metabolism. This review is summarizing available data on the skeletal effects of clinically approved anti-diabetic therapies.
authors.affiliation: Department of Orthopaedic Surgery, Department of Physiology and Pharmacology, Center for Diabetes and Endocrine Research, University of Toledo College of Medicine, 3000 Arlington Avenue, Toledo, OH 43614.
authors.forename: Beata
authors.initials: B
authors.lastname: Lecka-Czernik
keywords: BMD; DPP-4 inhibitors; PPAR; TZDs; anti-diabetic therapy; bone; fractures; glyburide; incretins; insulin; metformin
references.citation: Endocrinology. 2002 Jun;143(6):2376-84
references.pmid: 12021203
references.citation: EMBO Rep. 2004 Oct;5(10):1007-12
references.pmid: 15359271
references.citation: J Bone Miner Res. 2005 Sep;20(9):1497-506
references.pmid: 16059621
references.citation: Endocrinology. 2007 Feb;148(2):903-11
references.pmid: 17122083
references.citation: Oncogene. 2009 Jan 29;28(4):479-91
references.pmid: 18978811
references.citation: J Cell Biochem. 1994 Jul;55(3):273-86
references.pmid: 7962158
references.citation: Am J Epidemiol. 2007 Sep 1;166(5):495-505
references.pmid: 17575306
references.citation: Rev Endocr Metab Disord. 2006 Jun;7(1-2):1-16
references.pmid: 17051438
references.citation: Aging Cell. 2004 Dec;3(6):379-89
references.pmid: 15569355
references.citation: CMAJ. 2009 Jan 6;180(1):32-9
references.pmid: 19073651
references.citation: Cell. 1997 May 30;89(5):747-54
references.pmid: 9182762
references.citation: Am J Physiol Endocrinol Metab. 2007 Feb;292(2):E543-8
references.pmid: 17003233
references.citation: J Biol Chem. 2001 Oct 12;276(41):37731-4
references.pmid: 11459852
references.citation: Horm Metab Res. 2004 Nov-Dec;36(11-12):761-5
references.pmid: 15655705
references.citation: J Cell Biochem. 2009 Feb 1;106(2):232-46
references.pmid: 19115254
references.citation: Am J Manag Care. 2009 Aug;15(8):491-6
references.pmid: 19670952
references.citation: Nat Med. 2001 Sep;7(9):1028-34
references.pmid: 11533706
references.citation: J Bone Miner Res. 2006 Apr;21(4):495-500
references.pmid: 16598367
references.citation: J Clin Endocrinol Metab. 2006 Sep;91(9):3349-54
references.pmid: 16608888
references.citation: N Engl J Med. 2006 Dec 7;355(23):2427-43
references.pmid: 17145742
references.citation: Nature. 2002 Jul 4;418(6893):41-9
references.pmid: 12077603
references.citation: Am J Clin Nutr. 2010 Jan;91(1):267S-272S
references.pmid: 19906796
references.citation: J Clin Endocrinol Metab. 2001 Jan;86(1):32-8
references.pmid: 11231974
references.citation: J Clin Invest. 2004 Mar;113(6):846-55
references.pmid: 15067317
references.citation: J Clin Endocrinol Metab. 2009 Aug;94(8):2792-8
references.pmid: 19470635
references.citation: Acta Diabetol. 2013 Feb;50(1):47-52
references.pmid: 22042129
references.citation: Cell. 2007 Aug 10;130(3):456-69
references.pmid: 17693256
references.citation: Bone. 2010 Apr;46(4):1138-45
references.pmid: 20044046
references.citation: J Clin Endocrinol Metab. 2010 Feb;95(2):592-600
references.pmid: 20061432
references.citation: Calcif Tissue Int. 2009 Jan;84(1):45-55
references.pmid: 19067021
references.citation: J Clin Endocrinol Metab. 2010 Jan;95(1):134-42
references.pmid: 19875477
references.citation: Endocrinology. 2004 Jan;145(1):401-6
references.pmid: 14500573
references.citation: Diabetes. 1995 Jul;44(7):775-82
references.pmid: 7789645
references.citation: N Engl J Med. 2004 Sep 9;351(11):1106-18
references.pmid: 15356308
references.citation: Stem Cells. 2001;19(3):180-92
references.pmid: 11359943
references.citation: IDrugs. 2010 Nov;13(11):793-801
references.pmid: 21046527
references.citation: Nat Rev Immunol. 2010 May;10(5):365-76
references.pmid: 20414208
references.citation: J Clin Endocrinol Metab. 2012 Jan;97(1):234-41
references.pmid: 22031520
references.citation: Endocrinology. 2008 Feb;149(2):574-9
references.pmid: 18039776
references.citation: N Engl J Med. 2007 Jun 14;356(24):2457-71
references.pmid: 17517853
references.citation: Cell. 2010 Jul 23;142(2):309-19
references.pmid: 20655471
references.citation: Diabetes Care. 2002 Oct;25(10):1749-54
references.pmid: 12351472
references.citation: Nat Rev Genet. 2003 Aug;4(8):638-49
references.pmid: 12897775
references.citation: Curr Opin Investig Drugs. 2009 Oct;10(10):1085-90
references.pmid: 19777397
references.citation: Annu Rev Biochem. 2008;77:289-312
references.pmid: 18518822
references.citation: J Clin Invest. 2007 Jan;117(1):24-32
references.pmid: 17200703
references.citation: Arch Intern Med. 2009 Aug 10;169(15):1395-402
references.pmid: 19667303
references.citation: Cell. 1994 Dec 30;79(7):1147-56
references.pmid: 8001151
references.citation: Diabetes Obes Metab. 2011 Nov;13(11):1036-46
references.pmid: 21682834
references.citation: Eur J Pharmacol. 2011 Oct 15;668(3):477-85
references.pmid: 21839072
references.citation: J Bone Miner Res. 2008 Aug;23(8):1334-42
references.pmid: 18348689
references.citation: Endocrinology. 2005 Mar;146(3):1226-35
references.pmid: 15591153
references.citation: Bone. 2011 Apr 1;48(4):885-93
references.pmid: 21147283
references.citation: J Clin Endocrinol Metab. 2008 Mar;93(3):1013-9
references.pmid: 18160470
references.citation: J Clin Endocrinol Metab. 2008 May;93(5):1696-701
references.pmid: 18285411
references.citation: J Cell Biochem. 1999 Sep 1;74(3):357-71
references.pmid: 10412038
references.citation: Genes Dev. 2002 Jan 1;16(1):27-32
references.pmid: 11782442
references.citation: Diabetes Care. 2008 May;31(5):845-51
references.pmid: 18223031
references.citation: Rev Endocr Metab Disord. 2001 Jan;2(1):81-94
references.pmid: 11704982
references.citation: J Cell Biochem. 2011 Oct;112(10):2902-9
references.pmid: 21618594
references.citation: Bone. 2007 May;40(5):1352-60
references.pmid: 17321229
references.citation: Endocrinology. 2001 Jul;142(7):2731-3
references.pmid: 11415989
references.citation: JAMA. 2007 Sep 12;298(10):1180-8
references.pmid: 17848652
references.citation: Endocrinology. 2011 Feb;152(2):457-67
references.pmid: 21177828
references.citation: ChemMedChem. 2009 Jun;4(6):951-6
references.pmid: 19326383
references.citation: Nat Med. 2007 Dec;13(12):1496-503
references.pmid: 18059282
references.citation: Cancer Res. 2005 Feb 15;65(4):1325-34
references.pmid: 15735018
references.citation: Diabetes Obes Metab. 2011 Apr;13(4):374-7
references.pmid: 21205127
references.citation: Curr Osteoporos Rep. 2010 Dec;8(4):178-84
references.pmid: 20809203
references.citation: Calcif Tissue Int. 2004 Oct;75(4):329-37
references.pmid: 15549648
references.citation: J Clin Endocrinol Metab. 2007 Apr;92(4):1305-10
references.pmid: 17264176
references.citation: Cell. 1997 May 30;89(5):755-64
references.pmid: 9182763
references.citation: Arch Intern Med. 2008 Apr 28;168(8):820-5
references.pmid: 18443256
references.citation: Front Biosci. 2008 Jan 01;13:2435-43
references.pmid: 17981724
references.citation: J Bone Miner Res. 2009 Apr;24(4):702-9
references.pmid: 19049338
references.citation: J Endocrinol. 2004 Oct;183(1):203-16
references.pmid: 15525588
references.citation: PLoS Med. 2009 Sep;6(9):e1000154
references.pmid: 19787025
references.citation: Bone. 2006 Jan;38(1):74-84
references.pmid: 16137931
references.citation: J Musculoskelet Neuronal Interact. 2005 Oct-Dec;5(4):316
references.pmid: 16340119
references.citation: Bone. 2007 Mar;40(3):723-9
references.pmid: 17081815
references.citation: Osteoporos Int. 2010 Dec;21(12):2013-8
references.pmid: 20130841
references.citation: Clin Pharmacol Ther. 2010 Aug;88(2):197-203
references.pmid: 20336066
references.citation: Diabetes Care. 2011 Nov;34(11):2474-6
references.pmid: 22025784
references.citation: J Bone Miner Res. 2011 Apr;26(4):677-80
references.pmid: 21433069
references.citation: Cell. 2010 Jul 23;142(2):296-308
references.pmid: 20655470
references.citation: Calcif Tissue Int. 2010 May;86(5):343-9
references.pmid: 20354684
references.citation: Endocrinology. 2007 Jun;148(6):2669-80
references.pmid: 17332064