Skip to main content
Top
Published in: Osteoporosis International 8/2015

01-08-2015 | Review

Oral anti-diabetic drugs and fracture risk, cut to the bone: safe or dangerous? A narrative review

Authors: A. Palermo, L. D’Onofrio, R. Eastell, A. V. Schwartz, P. Pozzilli, N. Napoli

Published in: Osteoporosis International | Issue 8/2015

Login to get access

Abstract

Fracture risk is higher in older adults with type 2 diabetes and may be influenced by treatments for diabetes. Oral anti-diabetic drugs have different effects on bone metabolism. The purpose of this review is to describe the effects of these drugs on bone metabolism and fracture risk. Osteoporosis is a progressive skeletal disorder that is characterized by compromised bone strength and increased risk of fracture. This condition has become an important global health problem, affecting approximately 200 million people worldwide. Another chronic and highly prevalent condition is diabetes mellitus, which affects more than 380 million people; both type 1 and type 2 diabetes are risk factors for fracture. Type 2 diabetes, in particular, is associated with impaired bone strength, although it is characterized by normal or elevated bone mineral density. Several therapeutic strategies are available to achieve the best outcomes in the management of diabetes mellitus but these have different effects on bone metabolism. The purpose of this narrative review is to describe the effects of oral hypoglycemic agents (metformin, sulfonylureas, thiazolidinediones, meglitinides, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium-dependent glucose transporter 2 inhibitors) on bone metabolism and on the risk of developing fragility fractures in patients with type 2 diabetes. Both diabetes and osteoporosis represent a significant burden in terms of healthcare costs and quality of life. It is very important to choose therapies for diabetes that ensure good metabolic control whilst preserving skeletal health.
Literature
1.
2.
go back to reference Hernlund E, Svedbom A, Ivergård M et al (2013) Osteoporosis in the european union: medical management, epidemiology and economic burden. A report prepared in collaboration with the international osteoporosis foundation (IOF) and the European federation of pharmaceutical industry associations (EFPIA). Arch Osteoporos 8:136. doi:10.1007/s11657-013-0136-1 PubMedCentralPubMed Hernlund E, Svedbom A, Ivergård M et al (2013) Osteoporosis in the european union: medical management, epidemiology and economic burden. A report prepared in collaboration with the international osteoporosis foundation (IOF) and the European federation of pharmaceutical industry associations (EFPIA). Arch Osteoporos 8:136. doi:10.​1007/​s11657-013-0136-1 PubMedCentralPubMed
3.
5.
go back to reference Janghorbani M, Van Dam RM, Willett WC, Hu FB (2007) Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol 166:495–505. doi:10.1093/aje/kwm106 PubMed Janghorbani M, Van Dam RM, Willett WC, Hu FB (2007) Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol 166:495–505. doi:10.​1093/​aje/​kwm106 PubMed
6.
go back to reference Burghardt AJ, Issever AS, Schwartz AV et al (2010) High-resolution peripheral quantitative computed tomographic imaging of cortical and trabecular bone microarchitecture in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 95:5045–5055. doi:10.1210/jc.2010-0226 PubMedCentralPubMed Burghardt AJ, Issever AS, Schwartz AV et al (2010) High-resolution peripheral quantitative computed tomographic imaging of cortical and trabecular bone microarchitecture in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 95:5045–5055. doi:10.​1210/​jc.​2010-0226 PubMedCentralPubMed
8.
10.
go back to reference Forsén L, Meyer HE, Midthjell K, Edna TH (1999) Diabetes mellitus and the incidence of hip fracture: results from the Nord-Trøndelag Health Survey. Diabetologia 42:920–925. doi:10.1007/s001250051248 PubMed Forsén L, Meyer HE, Midthjell K, Edna TH (1999) Diabetes mellitus and the incidence of hip fracture: results from the Nord-Trøndelag Health Survey. Diabetologia 42:920–925. doi:10.​1007/​s001250051248 PubMed
11.
go back to reference De Liefde II, van der Klift M, de Laet CEDH et al (2005) Bone mineral density and fracture risk in type-2 diabetes mellitus: the Rotterdam Study. Osteoporos Int 16:1713–1720. doi:10.1007/s00198-005-1909-1 PubMed De Liefde II, van der Klift M, de Laet CEDH et al (2005) Bone mineral density and fracture risk in type-2 diabetes mellitus: the Rotterdam Study. Osteoporos Int 16:1713–1720. doi:10.​1007/​s00198-005-1909-1 PubMed
13.
go back to reference Oei L, Zillikens MC, Dehghan A et al (2013) High bone mineral density and fracture risk in type 2 diabetes as skeletal complications of inadequate glucose control: the Rotterdam study. Diabetes Care 36:1619–1628. doi:10.2337/dc12-1188 PubMedCentralPubMed Oei L, Zillikens MC, Dehghan A et al (2013) High bone mineral density and fracture risk in type 2 diabetes as skeletal complications of inadequate glucose control: the Rotterdam study. Diabetes Care 36:1619–1628. doi:10.​2337/​dc12-1188 PubMedCentralPubMed
14.
go back to reference Kim JH, Choi HJ, Ku EJ, et al (2014) Trabecular bone score as an indicator for skeletal deterioration in diabetes. J Clin Endocrinol Metab jc20142047. doi: 10.1210/jc.2014-2047 Kim JH, Choi HJ, Ku EJ, et al (2014) Trabecular bone score as an indicator for skeletal deterioration in diabetes. J Clin Endocrinol Metab jc20142047. doi: 10.​1210/​jc.​2014-2047
16.
go back to reference Liberati A, Altman DG, Tetzlaff J et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 62:e1–e34. doi:10.1016/j.jclinepi.2009.06.006 PubMed Liberati A, Altman DG, Tetzlaff J et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 62:e1–e34. doi:10.​1016/​j.​jclinepi.​2009.​06.​006 PubMed
18.
go back to reference Kanazawa I, Yamaguchi T, Yano S et al (2008) Metformin enhances the differentiation and mineralization of osteoblastic MC3T3-E1 cells via AMP kinase activation as well as eNOS and BMP-2 expression. Biochem Biophys Res Commun 375:414–419. doi:10.1016/j.bbrc.2008.08.034 PubMed Kanazawa I, Yamaguchi T, Yano S et al (2008) Metformin enhances the differentiation and mineralization of osteoblastic MC3T3-E1 cells via AMP kinase activation as well as eNOS and BMP-2 expression. Biochem Biophys Res Commun 375:414–419. doi:10.​1016/​j.​bbrc.​2008.​08.​034 PubMed
21.
go back to reference Molinuevo MS, Schurman L, McCarthy AD et al (2010) Effect of metformin on bone marrow progenitor cell differentiation: in vivo and in vitro studies. J Bone Miner Res 25:211–221. doi:10.1359/jbmr.090732 PubMed Molinuevo MS, Schurman L, McCarthy AD et al (2010) Effect of metformin on bone marrow progenitor cell differentiation: in vivo and in vitro studies. J Bone Miner Res 25:211–221. doi:10.​1359/​jbmr.​090732 PubMed
22.
go back to reference Schurman L, McCarthy AD, Sedlinsky C et al (2008) Metformin reverts deleterious effects of advanced glycation end-products (AGEs) on osteoblastic cells. Exp Clin Endocrinol Diabetes 116:333–340. doi:10.1055/s-2007-992786 PubMed Schurman L, McCarthy AD, Sedlinsky C et al (2008) Metformin reverts deleterious effects of advanced glycation end-products (AGEs) on osteoblastic cells. Exp Clin Endocrinol Diabetes 116:333–340. doi:10.​1055/​s-2007-992786 PubMed
26.
go back to reference Tolosa MJ, Chuguransky SR, Sedlinsky C et al (2013) Insulin-deficient diabetes-induced bone microarchitecture alterations are associated with a decrease in the osteogenic potential of bone marrow progenitor cells: preventive effects of metformin. Diabetes Res Clin Pract 101:177–186. doi:10.1016/j.diabres.2013.05.016 PubMed Tolosa MJ, Chuguransky SR, Sedlinsky C et al (2013) Insulin-deficient diabetes-induced bone microarchitecture alterations are associated with a decrease in the osteogenic potential of bone marrow progenitor cells: preventive effects of metformin. Diabetes Res Clin Pract 101:177–186. doi:10.​1016/​j.​diabres.​2013.​05.​016 PubMed
27.
go back to reference Kasai T, Bandow K, Suzuki H et al (2009) Osteoblast differentiation is functionally associated with decreased AMP kinase activity. J Cell Physiol 221:740–749. doi:10.1002/jcp.21917 PubMed Kasai T, Bandow K, Suzuki H et al (2009) Osteoblast differentiation is functionally associated with decreased AMP kinase activity. J Cell Physiol 221:740–749. doi:10.​1002/​jcp.​21917 PubMed
29.
go back to reference Mai Q-G, Zhang Z-M, Xu S et al (2011) Metformin stimulates osteoprotegerin and reduces RANKL expression in osteoblasts and ovariectomized rats. J Cell Biochem 112:2902–2909. doi:10.1002/jcb.23206 PubMed Mai Q-G, Zhang Z-M, Xu S et al (2011) Metformin stimulates osteoprotegerin and reduces RANKL expression in osteoblasts and ovariectomized rats. J Cell Biochem 112:2902–2909. doi:10.​1002/​jcb.​23206 PubMed
30.
go back to reference Liu L, Zhang C, Hu Y, Peng B (2012) Protective effect of metformin on periapical lesions in rats by decreasing the ratio of receptor activator of nuclear factor kappa B ligand/osteoprotegerin. J Endod 38:943–947. doi:10.1016/j.joen.2012.03.010 PubMed Liu L, Zhang C, Hu Y, Peng B (2012) Protective effect of metformin on periapical lesions in rats by decreasing the ratio of receptor activator of nuclear factor kappa B ligand/osteoprotegerin. J Endod 38:943–947. doi:10.​1016/​j.​joen.​2012.​03.​010 PubMed
31.
go back to reference Wu W, Ye Z, Zhou Y, Tan W-S (2011) AICAR, a small chemical molecule, primes osteogenic differentiation of adult mesenchymal stem cells. Int J Artif Organs 34:1128–1136. doi:10.5301/ijao.5000007 PubMed Wu W, Ye Z, Zhou Y, Tan W-S (2011) AICAR, a small chemical molecule, primes osteogenic differentiation of adult mesenchymal stem cells. Int J Artif Organs 34:1128–1136. doi:10.​5301/​ijao.​5000007 PubMed
32.
go back to reference Patel JJ, Butters OR, Arnett TR (2014) PPAR agonists stimulate adipogenesis at the expense of osteoblast differentiation while inhibiting osteoclast formation and activity. Cell Biochem Funct. doi:10.1002/cbf.3025 PubMed Patel JJ, Butters OR, Arnett TR (2014) PPAR agonists stimulate adipogenesis at the expense of osteoblast differentiation while inhibiting osteoclast formation and activity. Cell Biochem Funct. doi:10.​1002/​cbf.​3025 PubMed
34.
go back to reference Zinman B, Haffner SM, Herman WH et al (2010) Effect of rosiglitazone, metformin, and glyburide on bone biomarkers in patients with type 2 diabetes. J Clin Endocrinol Metab 95:134–142. doi:10.1210/jc.2009-0572 PubMed Zinman B, Haffner SM, Herman WH et al (2010) Effect of rosiglitazone, metformin, and glyburide on bone biomarkers in patients with type 2 diabetes. J Clin Endocrinol Metab 95:134–142. doi:10.​1210/​jc.​2009-0572 PubMed
35.
go back to reference Van Lierop AH, Hamdy NAT, van der Meer RW et al (2012) Distinct effects of pioglitazone and metformin on circulating sclerostin and biochemical markers of bone turnover in men with type 2 diabetes mellitus. Eur J Endocrinol 166:711–6. doi:10.1530/EJE-11-1061 PubMed Van Lierop AH, Hamdy NAT, van der Meer RW et al (2012) Distinct effects of pioglitazone and metformin on circulating sclerostin and biochemical markers of bone turnover in men with type 2 diabetes mellitus. Eur J Endocrinol 166:711–6. doi:10.​1530/​EJE-11-1061 PubMed
37.
go back to reference Vestergaard P, Rejnmark L, Mosekilde L (2005) Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk. Diabetologia 48:1292–1299. doi:10.1007/s00125-005-1786-3 PubMed Vestergaard P, Rejnmark L, Mosekilde L (2005) Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk. Diabetologia 48:1292–1299. doi:10.​1007/​s00125-005-1786-3 PubMed
40.
go back to reference Kanazawa I, Yamaguchi T, Yamamoto M, Sugimoto T (2010) Relationship between treatments with insulin and oral hypoglycemic agents versus the presence of vertebral fractures in type 2 diabetes mellitus. J Bone Miner Metab 28:554–560. doi:10.1007/s00774-010-0160-9 PubMed Kanazawa I, Yamaguchi T, Yamamoto M, Sugimoto T (2010) Relationship between treatments with insulin and oral hypoglycemic agents versus the presence of vertebral fractures in type 2 diabetes mellitus. J Bone Miner Metab 28:554–560. doi:10.​1007/​s00774-010-0160-9 PubMed
42.
go back to reference Monami M, Cresci B, Colombini A et al (2008) Bone fractures and hypoglycemic treatment in type 2 diabetic patients: a case–control study. Diabetes Care 31:199–203. doi:10.2337/dc07-1736 PubMed Monami M, Cresci B, Colombini A et al (2008) Bone fractures and hypoglycemic treatment in type 2 diabetic patients: a case–control study. Diabetes Care 31:199–203. doi:10.​2337/​dc07-1736 PubMed
45.
46.
go back to reference Kahn SE, Zinman B, Lachin JM et al (2008) Rosiglitazone-associated fractures in type 2 diabetes: an analysis from A diabetes outcome progression trial (ADOPT). Diabetes Care 31:845–851. doi:10.2337/dc07-2270 PubMed Kahn SE, Zinman B, Lachin JM et al (2008) Rosiglitazone-associated fractures in type 2 diabetes: an analysis from A diabetes outcome progression trial (ADOPT). Diabetes Care 31:845–851. doi:10.​2337/​dc07-2270 PubMed
47.
go back to reference Monami M, Dicembrini I, Kundisova L et al (2014) A meta-analysis of the hypoglycemic risk in randomized controlled trials with sulphonylureas in patients with type 2 diabetes. Diabetes Obes Metab. doi:10.1111/dom.12287 Monami M, Dicembrini I, Kundisova L et al (2014) A meta-analysis of the hypoglycemic risk in randomized controlled trials with sulphonylureas in patients with type 2 diabetes. Diabetes Obes Metab. doi:10.​1111/​dom.​12287
50.
54.
go back to reference Feige JN, Gelman L, Michalik L et al (2006) From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions. Prog Lipid Res 45:120–159. doi:10.1016/j.plipres.2005.12.002 PubMed Feige JN, Gelman L, Michalik L et al (2006) From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions. Prog Lipid Res 45:120–159. doi:10.​1016/​j.​plipres.​2005.​12.​002 PubMed
55.
go back to reference Willson TM, Brown PJ, Sternbach DD, Henke BR (2000) The PPARs: from orphan receptors to drug discovery. J Med Chem 43:527–550PubMed Willson TM, Brown PJ, Sternbach DD, Henke BR (2000) The PPARs: from orphan receptors to drug discovery. J Med Chem 43:527–550PubMed
56.
go back to reference Michalik L, Auwerx J, Berger JP et al (2006) International union of pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacol Rev 58:726–741. doi:10.1124/pr.58.4.5 PubMed Michalik L, Auwerx J, Berger JP et al (2006) International union of pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacol Rev 58:726–741. doi:10.​1124/​pr.​58.​4.​5 PubMed
57.
58.
go back to reference Shockley KR, Lazarenko OP, Czernik PJ et al (2009) PPARgamma2 nuclear receptor controls multiple regulatory pathways of osteoblast differentiation from marrow mesenchymal stem cells. J Cell Biochem 106:232–246. doi:10.1002/jcb.21994 PubMedCentralPubMed Shockley KR, Lazarenko OP, Czernik PJ et al (2009) PPARgamma2 nuclear receptor controls multiple regulatory pathways of osteoblast differentiation from marrow mesenchymal stem cells. J Cell Biochem 106:232–246. doi:10.​1002/​jcb.​21994 PubMedCentralPubMed
59.
go back to reference Johnson TE, Vogel R, Rutledge SJ et al (1999) Thiazolidinedione effects on glucocorticoid receptor-mediated gene transcription and differentiation in osteoblastic cells. Endocrinology 140:3245–3254. doi:10.1210/endo.140.7.6797 PubMed Johnson TE, Vogel R, Rutledge SJ et al (1999) Thiazolidinedione effects on glucocorticoid receptor-mediated gene transcription and differentiation in osteoblastic cells. Endocrinology 140:3245–3254. doi:10.​1210/​endo.​140.​7.​6797 PubMed
60.
go back to reference Suzawa M, Takada I, Yanagisawa J et al (2003) Cytokines suppress adipogenesis and PPAR-gamma function through the TAK1/TAB1/NIK cascade. Nat Cell Biol 5:224–230. doi:10.1038/ncb942 PubMed Suzawa M, Takada I, Yanagisawa J et al (2003) Cytokines suppress adipogenesis and PPAR-gamma function through the TAK1/TAB1/NIK cascade. Nat Cell Biol 5:224–230. doi:10.​1038/​ncb942 PubMed
62.
go back to reference Cho E-S, Kim M-K, Son Y-O et al (2012) The effects of rosiglitazone on osteoblastic differentiation, osteoclast formation and bone resorption. Mol Cell 33:173–181. doi:10.1007/s10059-012-2240-z Cho E-S, Kim M-K, Son Y-O et al (2012) The effects of rosiglitazone on osteoblastic differentiation, osteoclast formation and bone resorption. Mol Cell 33:173–181. doi:10.​1007/​s10059-012-2240-z
64.
go back to reference Ali AA, Weinstein RS, Stewart SA et al (2005) Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation. Endocrinology 146:1226–1235. doi:10.1210/en.2004-0735 PubMed Ali AA, Weinstein RS, Stewart SA et al (2005) Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation. Endocrinology 146:1226–1235. doi:10.​1210/​en.​2004-0735 PubMed
65.
go back to reference Wang L, Li L, Gao H, Li Y (2012) Effect of pioglitazone on transdifferentiation of preosteoblasts from rat bone mesenchymal stem cells into adipocytes. J Huazhong Univ Sci Technolog Med Sci 32:530–533. doi:10.1007/s11596-012-0091-x PubMed Wang L, Li L, Gao H, Li Y (2012) Effect of pioglitazone on transdifferentiation of preosteoblasts from rat bone mesenchymal stem cells into adipocytes. J Huazhong Univ Sci Technolog Med Sci 32:530–533. doi:10.​1007/​s11596-012-0091-x PubMed
66.
go back to reference Seth A, Sy V, Pareek A et al (2013) Thiazolidinediones (TZDs) affect osteoblast viability and biomarkers independently of the TZD effects on aromatase. Horm Metab Res 45:1–8. doi:10.1055/s-0032-1321874 PubMed Seth A, Sy V, Pareek A et al (2013) Thiazolidinediones (TZDs) affect osteoblast viability and biomarkers independently of the TZD effects on aromatase. Horm Metab Res 45:1–8. doi:10.​1055/​s-0032-1321874 PubMed
69.
71.
go back to reference Gallagher EJ, Sun H, Kornhauser C et al (2014) The effect of dipeptidyl peptidase-IV inhibition on bone in a mouse model of type 2 diabetes. Diabetes Metab Res Rev 30:191–200. doi:10.1002/dmrr.2466 PubMed Gallagher EJ, Sun H, Kornhauser C et al (2014) The effect of dipeptidyl peptidase-IV inhibition on bone in a mouse model of type 2 diabetes. Diabetes Metab Res Rev 30:191–200. doi:10.​1002/​dmrr.​2466 PubMed
73.
go back to reference Benvenuti S, Cellai I, Luciani P et al (2007) Rosiglitazone stimulates adipogenesis and decreases osteoblastogenesis in human mesenchymal stem cells. J Endocrinol Invest 30:RC26–RC30PubMed Benvenuti S, Cellai I, Luciani P et al (2007) Rosiglitazone stimulates adipogenesis and decreases osteoblastogenesis in human mesenchymal stem cells. J Endocrinol Invest 30:RC26–RC30PubMed
74.
go back to reference Gustafson B, Eliasson B, Smith U (2010) Thiazolidinediones increase the wingless-type MMTV integration site family (WNT) inhibitor Dickkopf-1 in adipocytes: a link with osteogenesis. Diabetologia 53:536–540. doi:10.1007/s00125-009-1615-1 PubMed Gustafson B, Eliasson B, Smith U (2010) Thiazolidinediones increase the wingless-type MMTV integration site family (WNT) inhibitor Dickkopf-1 in adipocytes: a link with osteogenesis. Diabetologia 53:536–540. doi:10.​1007/​s00125-009-1615-1 PubMed
79.
go back to reference Lecka-Czernik B, Ackert-Bicknell C, Adamo ML et al (2007) Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) by rosiglitazone suppresses components of the insulin-like growth factor regulatory system in vitro and in vivo. Endocrinology 148:903–911. doi:10.1210/en.2006-1121 PubMedCentralPubMed Lecka-Czernik B, Ackert-Bicknell C, Adamo ML et al (2007) Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) by rosiglitazone suppresses components of the insulin-like growth factor regulatory system in vitro and in vivo. Endocrinology 148:903–911. doi:10.​1210/​en.​2006-1121 PubMedCentralPubMed
80.
go back to reference Tsirella E, Mavrakanas T, Rager O et al (2012) Low dose pioglitazone does not affect bone formation and resorption markers or bone mineral density in streptozocin-induced diabetic rats. J Physiol Pharmacol 63:201–204PubMed Tsirella E, Mavrakanas T, Rager O et al (2012) Low dose pioglitazone does not affect bone formation and resorption markers or bone mineral density in streptozocin-induced diabetic rats. J Physiol Pharmacol 63:201–204PubMed
82.
go back to reference Sottile V, Seuwen K, Kneissel M (2004) Enhanced marrow adipogenesis and bone resorption in estrogen-deprived rats treated with the PPARgamma agonist BRL49653 (rosiglitazone). Calcif Tissue Int 75:329–337. doi:10.1007/s00223-004-0224-8 PubMed Sottile V, Seuwen K, Kneissel M (2004) Enhanced marrow adipogenesis and bone resorption in estrogen-deprived rats treated with the PPARgamma agonist BRL49653 (rosiglitazone). Calcif Tissue Int 75:329–337. doi:10.​1007/​s00223-004-0224-8 PubMed
83.
go back to reference Syversen U, Stunes AK, Gustafsson BI et al (2009) Different skeletal effects of the peroxisome proliferator activated receptor (PPAR)alpha agonist fenofibrate and the PPARgamma agonist pioglitazone. BMC Endocr Disord 9:10. doi:10.1186/1472-6823-9-10 PubMedCentralPubMed Syversen U, Stunes AK, Gustafsson BI et al (2009) Different skeletal effects of the peroxisome proliferator activated receptor (PPAR)alpha agonist fenofibrate and the PPARgamma agonist pioglitazone. BMC Endocr Disord 9:10. doi:10.​1186/​1472-6823-9-10 PubMedCentralPubMed
85.
go back to reference Rubin GL, Zhao Y, Kalus AM, Simpson ER (2000) Peroxisome proliferator-activated receptor gamma ligands inhibit estrogen biosynthesis in human breast adipose tissue: possible implications for breast cancer therapy. Cancer Res 60:1604–1608PubMed Rubin GL, Zhao Y, Kalus AM, Simpson ER (2000) Peroxisome proliferator-activated receptor gamma ligands inhibit estrogen biosynthesis in human breast adipose tissue: possible implications for breast cancer therapy. Cancer Res 60:1604–1608PubMed
86.
go back to reference Seto-Young D, Paliou M, Schlosser J et al (2005) Direct thiazolidinedione action in the human ovary: insulin-independent and insulin-sensitizing effects on steroidogenesis and insulin-like growth factor binding protein-1 production. J Clin Endocrinol Metab 90:6099–6105. doi:10.1210/jc.2005-0469 PubMed Seto-Young D, Paliou M, Schlosser J et al (2005) Direct thiazolidinedione action in the human ovary: insulin-independent and insulin-sensitizing effects on steroidogenesis and insulin-like growth factor binding protein-1 production. J Clin Endocrinol Metab 90:6099–6105. doi:10.​1210/​jc.​2005-0469 PubMed
87.
go back to reference Seto-Young D, Avtanski D, Parikh G et al (2011) Rosiglitazone and pioglitazone inhibit estrogen synthesis in human granulosa cells by interfering with androgen binding to aromatase. Horm Metab Res 43:250–256. doi:10.1055/s-0030-1270525 PubMed Seto-Young D, Avtanski D, Parikh G et al (2011) Rosiglitazone and pioglitazone inhibit estrogen synthesis in human granulosa cells by interfering with androgen binding to aromatase. Horm Metab Res 43:250–256. doi:10.​1055/​s-0030-1270525 PubMed
88.
go back to reference Grey A, Bolland M, Gamble G et al (2007) The peroxisome proliferator-activated receptor-gamma agonist rosiglitazone decreases bone formation and bone mineral density in healthy postmenopausal women: a randomized, controlled trial. J Clin Endocrinol Metab 92:1305–1310. doi:10.1210/jc.2006-2646 PubMed Grey A, Bolland M, Gamble G et al (2007) The peroxisome proliferator-activated receptor-gamma agonist rosiglitazone decreases bone formation and bone mineral density in healthy postmenopausal women: a randomized, controlled trial. J Clin Endocrinol Metab 92:1305–1310. doi:10.​1210/​jc.​2006-2646 PubMed
90.
go back to reference Berberoglu Z, Yazici AC, Demirag NG (2010) Effects of rosiglitazone on bone mineral density and remodelling parameters in Postmenopausal diabetic women: a 2-year follow-up study. Clin Endocrinol (Oxf) 73:305–312. doi:10.1111/j.1365-2265.2010.03784.x Berberoglu Z, Yazici AC, Demirag NG (2010) Effects of rosiglitazone on bone mineral density and remodelling parameters in Postmenopausal diabetic women: a 2-year follow-up study. Clin Endocrinol (Oxf) 73:305–312. doi:10.​1111/​j.​1365-2265.​2010.​03784.​x
91.
go back to reference Berberoglu Z, Gursoy A, Bayraktar N et al (2007) Rosiglitazone decreases serum bone-specific alkaline phosphatase activity in postmenopausal diabetic women. J Clin Endocrinol Metab 92:3523–3530. doi:10.1210/jc.2007-0431 PubMed Berberoglu Z, Gursoy A, Bayraktar N et al (2007) Rosiglitazone decreases serum bone-specific alkaline phosphatase activity in postmenopausal diabetic women. J Clin Endocrinol Metab 92:3523–3530. doi:10.​1210/​jc.​2007-0431 PubMed
92.
go back to reference Gruntmanis U, Fordan S, Ghayee HK et al (2010) The peroxisome proliferator-activated receptor-gamma agonist rosiglitazone increases bone resorption in women with type 2 diabetes: a randomized, controlled trial. Calcif Tissue Int 86:343–349. doi:10.1007/s00223-010-9352-5 PubMed Gruntmanis U, Fordan S, Ghayee HK et al (2010) The peroxisome proliferator-activated receptor-gamma agonist rosiglitazone increases bone resorption in women with type 2 diabetes: a randomized, controlled trial. Calcif Tissue Int 86:343–349. doi:10.​1007/​s00223-010-9352-5 PubMed
93.
go back to reference Bilezikian JP, Josse RG, Eastell R et al (2013) Rosiglitazone decreases bone mineral density and increases bone turnover in postmenopausal women with type 2 diabetes mellitus. J Clin Endocrinol Metab 98:1519–1528. doi:10.1210/jc.2012-4018 PubMed Bilezikian JP, Josse RG, Eastell R et al (2013) Rosiglitazone decreases bone mineral density and increases bone turnover in postmenopausal women with type 2 diabetes mellitus. J Clin Endocrinol Metab 98:1519–1528. doi:10.​1210/​jc.​2012-4018 PubMed
95.
go back to reference Kanazawa I, Yamaguchi T, Yano S et al (2010) Baseline atherosclerosis parameter could assess the risk of bone loss during pioglitazone treatment in type 2 diabetes mellitus. Osteoporos Int 21:2013–2018. doi:10.1007/s00198-009-1161-1 PubMed Kanazawa I, Yamaguchi T, Yano S et al (2010) Baseline atherosclerosis parameter could assess the risk of bone loss during pioglitazone treatment in type 2 diabetes mellitus. Osteoporos Int 21:2013–2018. doi:10.​1007/​s00198-009-1161-1 PubMed
96.
go back to reference Glintborg D, Andersen M, Hagen C et al (2008) Association of pioglitazone treatment with decreased bone mineral density in obese premenopausal patients with polycystic ovary syndrome: a randomized, placebo-controlled trial. J Clin Endocrinol Metab 93:1696–1701. doi:10.1210/jc.2007-2249 PubMed Glintborg D, Andersen M, Hagen C et al (2008) Association of pioglitazone treatment with decreased bone mineral density in obese premenopausal patients with polycystic ovary syndrome: a randomized, placebo-controlled trial. J Clin Endocrinol Metab 93:1696–1701. doi:10.​1210/​jc.​2007-2249 PubMed
97.
100.
go back to reference Bone HG, Lindsay R, McClung MR et al (2013) Effects of pioglitazone on bone in postmenopausal women with impaired fasting glucose or impaired glucose tolerance: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 98:4691–4701. doi:10.1210/jc.2012-4096 PubMed Bone HG, Lindsay R, McClung MR et al (2013) Effects of pioglitazone on bone in postmenopausal women with impaired fasting glucose or impaired glucose tolerance: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 98:4691–4701. doi:10.​1210/​jc.​2012-4096 PubMed
101.
go back to reference Grey A, Bolland M, Fenwick S et al (2014) The skeletal effects of pioglitazone in type 2 diabetes or impaired glucose tolerance: a randomized controlled trial. Eur J Endocrinol 170:255–262. doi:10.1530/EJE-13-0793 PubMed Grey A, Bolland M, Fenwick S et al (2014) The skeletal effects of pioglitazone in type 2 diabetes or impaired glucose tolerance: a randomized controlled trial. Eur J Endocrinol 170:255–262. doi:10.​1530/​EJE-13-0793 PubMed
102.
go back to reference Schwartz AV, Sellmeyer DE, Vittinghoff E et al (2006) Thiazolidinedione (TZD) use and bone loss in older diabetic adults. J Clin Endocrinol Metab 91:3349–3354PubMedCentralPubMed Schwartz AV, Sellmeyer DE, Vittinghoff E et al (2006) Thiazolidinedione (TZD) use and bone loss in older diabetic adults. J Clin Endocrinol Metab 91:3349–3354PubMedCentralPubMed
110.
go back to reference Hsiao F-Y, Mullins CD (2010) The association between thiazolidinediones and hospitalisation for fracture in type 2 diabetic patients: a Taiwanese population-based nested case–control study. Diabetologia 53:489–496. doi:10.1007/s00125-009-1609-z PubMed Hsiao F-Y, Mullins CD (2010) The association between thiazolidinediones and hospitalisation for fracture in type 2 diabetic patients: a Taiwanese population-based nested case–control study. Diabetologia 53:489–496. doi:10.​1007/​s00125-009-1609-z PubMed
111.
go back to reference Jones SG, Momin SR, Good MW et al (2009) Distal upper and lower limb fractures associated with thiazolidinedione use. Am J Manag Care 15:491–496PubMed Jones SG, Momin SR, Good MW et al (2009) Distal upper and lower limb fractures associated with thiazolidinedione use. Am J Manag Care 15:491–496PubMed
114.
go back to reference Yaturu S, Bryant B, Jain SK (2007) Thiazolidinedione treatment decreases bone mineral density in type 2 diabetic men. Diabetes Care 30:1574–1576. doi:10.2337/dc06-2606 PubMed Yaturu S, Bryant B, Jain SK (2007) Thiazolidinedione treatment decreases bone mineral density in type 2 diabetic men. Diabetes Care 30:1574–1576. doi:10.​2337/​dc06-2606 PubMed
115.
go back to reference Borges JLC, Bilezikian JP, Jones-Leone AR et al (2011) A randomized, parallel group, double-blind, multicentre study comparing the efficacy and safety of Avandamet (rosiglitazone/metformin) and metformin on long-term glycaemic control and bone mineral density after 80 weeks of treatment in drug-naïve type 2 d. Diabetes Obes Metab 13:1036–1046. doi:10.1111/j.1463-1326.2011.01461.x PubMed Borges JLC, Bilezikian JP, Jones-Leone AR et al (2011) A randomized, parallel group, double-blind, multicentre study comparing the efficacy and safety of Avandamet (rosiglitazone/metformin) and metformin on long-term glycaemic control and bone mineral density after 80 weeks of treatment in drug-naïve type 2 d. Diabetes Obes Metab 13:1036–1046. doi:10.​1111/​j.​1463-1326.​2011.​01461.​x PubMed
116.
go back to reference Home PD, Pocock SJ, Beck-Nielsen H et al (2009) Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet 373:2125–2135. doi:10.1016/S0140-6736(09)60953-3 PubMed Home PD, Pocock SJ, Beck-Nielsen H et al (2009) Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet 373:2125–2135. doi:10.​1016/​S0140-6736(09)60953-3 PubMed
118.
go back to reference Bray GA, Smith SR, Banerji MA et al (2013) Effect of pioglitazone on body composition and bone density in subjects with prediabetes in the ACT NOW trial. Diabetes Obes Metab 15:931–937. doi:10.1111/dom.12099 PubMed Bray GA, Smith SR, Banerji MA et al (2013) Effect of pioglitazone on body composition and bone density in subjects with prediabetes in the ACT NOW trial. Diabetes Obes Metab 15:931–937. doi:10.​1111/​dom.​12099 PubMed
119.
go back to reference Grey A, Beckley V, Doyle A et al (2012) Pioglitazone increases bone marrow fat in type 2 diabetes: results from a randomized controlled trial. Eur J Endocrinol 166:1087–1091. doi:10.1530/EJE-11-1075 PubMed Grey A, Beckley V, Doyle A et al (2012) Pioglitazone increases bone marrow fat in type 2 diabetes: results from a randomized controlled trial. Eur J Endocrinol 166:1087–1091. doi:10.​1530/​EJE-11-1075 PubMed
121.
go back to reference Dormandy J, Bhattacharya M, van Troostenburg De Bruyn A-R (2009) Safety and tolerability of pioglitazone in high-risk patients with type 2 diabetes: an overview of data from PROactive. Drug Saf 32:187–202PubMed Dormandy J, Bhattacharya M, van Troostenburg De Bruyn A-R (2009) Safety and tolerability of pioglitazone in high-risk patients with type 2 diabetes: an overview of data from PROactive. Drug Saf 32:187–202PubMed
122.
go back to reference Nissen SE, Nicholls SJ, Wolski K et al (2008) Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA 299:1561–1573. doi:10.1001/jama.299.13.1561 PubMed Nissen SE, Nicholls SJ, Wolski K et al (2008) Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA 299:1561–1573. doi:10.​1001/​jama.​299.​13.​1561 PubMed
125.
go back to reference Kim J-Y, Lee S-K, Jo K-J et al (2013) Exendin-4 increases bone mineral density in type 2 diabetic OLETF rats potentially through the down-regulation of SOST/sclerostin in osteocytes. Life Sci 92:533–540. doi:10.1016/j.lfs.2013.01.001 PubMed Kim J-Y, Lee S-K, Jo K-J et al (2013) Exendin-4 increases bone mineral density in type 2 diabetic OLETF rats potentially through the down-regulation of SOST/sclerostin in osteocytes. Life Sci 92:533–540. doi:10.​1016/​j.​lfs.​2013.​01.​001 PubMed
126.
go back to reference Nuche-Berenguer B, Portal-Núñez S, Moreno P et al (2010) Presence of a functional receptor for GLP-1 in osteoblastic cells, independent of the cAMP-linked GLP-1 receptor. J Cell Physiol 225:585–592. doi:10.1002/jcp.22243 PubMed Nuche-Berenguer B, Portal-Núñez S, Moreno P et al (2010) Presence of a functional receptor for GLP-1 in osteoblastic cells, independent of the cAMP-linked GLP-1 receptor. J Cell Physiol 225:585–592. doi:10.​1002/​jcp.​22243 PubMed
127.
go back to reference Sanz C, Vázquez P, Blázquez C et al (2010) Signaling and biological effects of glucagon-like peptide 1 on the differentiation of mesenchymal stem cells from human bone marrow. Am J Physiol Endocrinol Metab 298:E634–E643. doi:10.1152/ajpendo.00460.2009 PubMed Sanz C, Vázquez P, Blázquez C et al (2010) Signaling and biological effects of glucagon-like peptide 1 on the differentiation of mesenchymal stem cells from human bone marrow. Am J Physiol Endocrinol Metab 298:E634–E643. doi:10.​1152/​ajpendo.​00460.​2009 PubMed
128.
go back to reference Nuche-Berenguer B, Moreno P, Esbrit P et al (2009) Effect of GLP-1 treatment on bone turnover in normal, type 2 diabetic, and insulin-resistant states. Calcif Tissue Int 84:453–461. doi:10.1007/s00223-009-9220-3 PubMed Nuche-Berenguer B, Moreno P, Esbrit P et al (2009) Effect of GLP-1 treatment on bone turnover in normal, type 2 diabetic, and insulin-resistant states. Calcif Tissue Int 84:453–461. doi:10.​1007/​s00223-009-9220-3 PubMed
129.
go back to reference Nuche-Berenguer B, Lozano D, Gutiérrez-Rojas I et al (2011) GLP-1 and exendin-4 can reverse hyperlipidic-related osteopenia. J Endocrinol 209:203–210. doi:10.1530/JOE-11-0015 PubMed Nuche-Berenguer B, Lozano D, Gutiérrez-Rojas I et al (2011) GLP-1 and exendin-4 can reverse hyperlipidic-related osteopenia. J Endocrinol 209:203–210. doi:10.​1530/​JOE-11-0015 PubMed
130.
go back to reference Ma X, Meng J, Jia M et al (2013) Exendin-4, a glucagon-like peptide-1 receptor agonist, prevents osteopenia by promoting bone formation and suppressing bone resorption in aged ovariectomized rats. J Bone Miner Res 28:1641–1652. doi:10.1002/jbmr.1898 PubMed Ma X, Meng J, Jia M et al (2013) Exendin-4, a glucagon-like peptide-1 receptor agonist, prevents osteopenia by promoting bone formation and suppressing bone resorption in aged ovariectomized rats. J Bone Miner Res 28:1641–1652. doi:10.​1002/​jbmr.​1898 PubMed
131.
go back to reference Mabilleau G, Mieczkowska A, Irwin N et al (2013) Optimal bone mechanical and material properties require a functional glucagon-like peptide-1 receptor. J Endocrinol 219:59–68. doi:10.1530/JOE-13-0146 PubMed Mabilleau G, Mieczkowska A, Irwin N et al (2013) Optimal bone mechanical and material properties require a functional glucagon-like peptide-1 receptor. J Endocrinol 219:59–68. doi:10.​1530/​JOE-13-0146 PubMed
132.
go back to reference Raun K, von Voss P, Gotfredsen CF et al (2007) Liraglutide, a long-acting glucagon-like peptide-1 analog, reduces body weight and food intake in obese candy-fed rats, whereas a dipeptidyl peptidase-IV inhibitor, vildagliptin, does not. Diabetes 56:8–15. doi:10.2337/db06-0565 PubMed Raun K, von Voss P, Gotfredsen CF et al (2007) Liraglutide, a long-acting glucagon-like peptide-1 analog, reduces body weight and food intake in obese candy-fed rats, whereas a dipeptidyl peptidase-IV inhibitor, vildagliptin, does not. Diabetes 56:8–15. doi:10.​2337/​db06-0565 PubMed
133.
go back to reference Yamada C, Yamada Y, Tsukiyama K et al (2008) The murine glucagon-like peptide-1 receptor is essential for control of bone resorption. Endocrinology 149:574–579. doi:10.1210/en.2007-1292 PubMed Yamada C, Yamada Y, Tsukiyama K et al (2008) The murine glucagon-like peptide-1 receptor is essential for control of bone resorption. Endocrinology 149:574–579. doi:10.​1210/​en.​2007-1292 PubMed
134.
go back to reference Sbaraglini ML, Molinuevo MS, Sedlinsky C et al (2014) Saxagliptin affects long-bone microarchitecture and decreases the osteogenic potential of bone marrow stromal cells. Eur J Pharmacol 727C:8–14. doi:10.1016/j.ejphar.2014.01.028 Sbaraglini ML, Molinuevo MS, Sedlinsky C et al (2014) Saxagliptin affects long-bone microarchitecture and decreases the osteogenic potential of bone marrow stromal cells. Eur J Pharmacol 727C:8–14. doi:10.​1016/​j.​ejphar.​2014.​01.​028
135.
go back to reference Cusick T, Mu J, Pennypacker BL et al (2013) Bone loss in the oestrogen-depleted rat is not exacerbated by sitagliptin, either alone or in combination with a thiazolidinedione. Diabetes Obes Metab 15:954–957. doi:10.1111/dom.12109 PubMed Cusick T, Mu J, Pennypacker BL et al (2013) Bone loss in the oestrogen-depleted rat is not exacerbated by sitagliptin, either alone or in combination with a thiazolidinedione. Diabetes Obes Metab 15:954–957. doi:10.​1111/​dom.​12109 PubMed
136.
137.
go back to reference Glorie L, Behets GJ, Baerts L et al (2014) DPP IV inhibitor treatment attenuates bone loss and improves mechanical bone strength in male diabetic rats. Am J Physiol Endocrinol Metab 307:E447–E455. doi:10.1152/ajpendo.00217.2014 PubMed Glorie L, Behets GJ, Baerts L et al (2014) DPP IV inhibitor treatment attenuates bone loss and improves mechanical bone strength in male diabetic rats. Am J Physiol Endocrinol Metab 307:E447–E455. doi:10.​1152/​ajpendo.​00217.​2014 PubMed
141.
go back to reference Henriksen DB, Alexandersen P, Hartmann B et al (2009) Four-month treatment with GLP-2 significantly increases hip BMD: a randomized, placebo-controlled, dose-ranging study in postmenopausal women with low BMD. Bone 45:833–842. doi:10.1016/j.bone.2009.07.008 PubMed Henriksen DB, Alexandersen P, Hartmann B et al (2009) Four-month treatment with GLP-2 significantly increases hip BMD: a randomized, placebo-controlled, dose-ranging study in postmenopausal women with low BMD. Bone 45:833–842. doi:10.​1016/​j.​bone.​2009.​07.​008 PubMed
142.
go back to reference Gottschalck IB, Jeppesen PB, Hartmann B et al (2008) Effects of treatment with glucagon-like peptide-2 on bone resorption in colectomized patients with distal ileostomy or jejunostomy and short-bowel syndrome. Scand J Gastroenterol 43:1304–1310. doi:10.1080/00365520802200028 PubMed Gottschalck IB, Jeppesen PB, Hartmann B et al (2008) Effects of treatment with glucagon-like peptide-2 on bone resorption in colectomized patients with distal ileostomy or jejunostomy and short-bowel syndrome. Scand J Gastroenterol 43:1304–1310. doi:10.​1080/​0036552080220002​8 PubMed
143.
144.
go back to reference Mabilleau G, Mieczkowska A, Chappard D (2014) Use of glucagon-like peptide-1 receptor agonists and bone fractures: a meta-analysis of randomized clinical trials (−1:meta). J Diabetes 6:260–266. doi:10.1111/1753-0407.12102 PubMed Mabilleau G, Mieczkowska A, Chappard D (2014) Use of glucagon-like peptide-1 receptor agonists and bone fractures: a meta-analysis of randomized clinical trials (−1:meta). J Diabetes 6:260–266. doi:10.​1111/​1753-0407.​12102 PubMed
145.
go back to reference Su B, Sheng H, Zhang M et al (2014) Risk of bone fractures associated with glucagon-like peptide-1 receptor agonists’ treatment: a meta-analysis of randomized controlled trials. Endocrine. doi:10.1007/s12020-014-0361-4 Su B, Sheng H, Zhang M et al (2014) Risk of bone fractures associated with glucagon-like peptide-1 receptor agonists’ treatment: a meta-analysis of randomized controlled trials. Endocrine. doi:10.​1007/​s12020-014-0361-4
146.
147.
go back to reference Hirshberg B, Parker A, Edelberg H et al (2013) Safety of saxagliptin: events of special interest in 9156 patients with type 2 diabetes mellitus. Diabetes Metab Res Rev. doi:10.1002/dmrr.2502 PubMed Hirshberg B, Parker A, Edelberg H et al (2013) Safety of saxagliptin: events of special interest in 9156 patients with type 2 diabetes mellitus. Diabetes Metab Res Rev. doi:10.​1002/​dmrr.​2502 PubMed
148.
go back to reference Tirmenstein M, Dorr TE, Janovitz EB et al (2013) Nonclinical toxicology assessments support the chronic safety of dapagliflozin, a first-in-class sodium-glucose cotransporter 2 inhibitor. Int J Toxicol 32:336–350. doi:10.1177/1091581813505331 PubMed Tirmenstein M, Dorr TE, Janovitz EB et al (2013) Nonclinical toxicology assessments support the chronic safety of dapagliflozin, a first-in-class sodium-glucose cotransporter 2 inhibitor. Int J Toxicol 32:336–350. doi:10.​1177/​1091581813505331​ PubMed
149.
go back to reference Yokono M, Takasu T, Hayashizaki Y et al (2014) SGLT2 selective inhibitor ipragliflozin reduces body fat mass by increasing fatty acid oxidation in high-fat diet-induced obese rats. Eur J Pharmacol 727C:66–74. doi:10.1016/j.ejphar.2014.01.040 Yokono M, Takasu T, Hayashizaki Y et al (2014) SGLT2 selective inhibitor ipragliflozin reduces body fat mass by increasing fatty acid oxidation in high-fat diet-induced obese rats. Eur J Pharmacol 727C:66–74. doi:10.​1016/​j.​ejphar.​2014.​01.​040
150.
go back to reference Kwon H (2013) Canaglifozin: clinical efficacy and safety. Endocrinol. Metab. Drugs Advis. Comm. Meet. 2013. www.fda.gov/ downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ Endocrinol. Kwon H (2013) Canaglifozin: clinical efficacy and safety. Endocrinol. Metab. Drugs Advis. Comm. Meet. 2013. www.​fda.​gov/​ downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ Endocrinol.
151.
go back to reference Ljunggren Ö, Bolinder J, Johansson L et al (2012) Dapagliflozin has no effect on markers of bone formation and resorption or bone mineral density in patients with inadequately controlled type 2 diabetes mellitus on metformin. Diabetes Obes Metab 14:990–999. doi:10.1111/j.1463-1326.2012.01630.x PubMed Ljunggren Ö, Bolinder J, Johansson L et al (2012) Dapagliflozin has no effect on markers of bone formation and resorption or bone mineral density in patients with inadequately controlled type 2 diabetes mellitus on metformin. Diabetes Obes Metab 14:990–999. doi:10.​1111/​j.​1463-1326.​2012.​01630.​x PubMed
152.
go back to reference Bolinder J, Ljunggren O, Johansson L et al (2013) Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab. doi:10.1111/dom.12189 PubMed Bolinder J, Ljunggren O, Johansson L et al (2013) Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab. doi:10.​1111/​dom.​12189 PubMed
154.
go back to reference Kohan DE, Fioretto P, Tang W, List JF (2013) Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney Int. doi:10.1038/ki.2013.356 PubMedCentralPubMed Kohan DE, Fioretto P, Tang W, List JF (2013) Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney Int. doi:10.​1038/​ki.​2013.​356 PubMedCentralPubMed
155.
go back to reference (2013) INVOKANA® (canaglifozin) [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 1–41 (2013) INVOKANA® (canaglifozin) [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 1–41
Metadata
Title
Oral anti-diabetic drugs and fracture risk, cut to the bone: safe or dangerous? A narrative review
Authors
A. Palermo
L. D’Onofrio
R. Eastell
A. V. Schwartz
P. Pozzilli
N. Napoli
Publication date
01-08-2015
Publisher
Springer London
Published in
Osteoporosis International / Issue 8/2015
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-015-3123-0

Other articles of this Issue 8/2015

Osteoporosis International 8/2015 Go to the issue