Skip to main content
Erschienen 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

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

Erschienen in: Osteoporosis International | Ausgabe 8/2015

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat IDF (2013) IDF Diabetes Atlas, 6th edn IDF (2013) IDF Diabetes Atlas, 6th edn
2.
Zurück zum Zitat 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.
Zurück zum Zitat Vestergaard P (2007) Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a meta-analysis. Osteoporos Int 18:427–444. doi:10.1007/s00198-006-0253-4 PubMed Vestergaard P (2007) Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a meta-analysis. Osteoporos Int 18:427–444. doi:10.​1007/​s00198-006-0253-4 PubMed
5.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat Giangregorio LM, Leslie WD, Lix LM et al (2012) FRAX underestimates fracture risk in patients with diabetes. J Bone Miner Res 27:301–308. doi:10.1002/jbmr.556 PubMed Giangregorio LM, Leslie WD, Lix LM et al (2012) FRAX underestimates fracture risk in patients with diabetes. J Bone Miner Res 27:301–308. doi:10.​1002/​jbmr.​556 PubMed
10.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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
28.
29.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat Ma P, Xiong W, Liu H et al (2011) Extrapancreatic roles of glimepiride on osteoblasts from rat manibular bone in vitro: regulation of cytodifferentiation through PI3-kinases/Akt signalling pathway. Arch Oral Biol 56:307–316. doi:10.1016/j.archoralbio.2010.10.009 PubMed Ma P, Xiong W, Liu H et al (2011) Extrapancreatic roles of glimepiride on osteoblasts from rat manibular bone in vitro: regulation of cytodifferentiation through PI3-kinases/Akt signalling pathway. Arch Oral Biol 56:307–316. doi:10.​1016/​j.​archoralbio.​2010.​10.​009 PubMed
54.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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
61.
62.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat Sorocéanu MA, Miao D, Bai X-Y et al (2004) Rosiglitazone impacts negatively on bone by promoting osteoblast/osteocyte apoptosis. J Endocrinol 183:203–216. doi:10.1677/joe.1.05723 PubMed Sorocéanu MA, Miao D, Bai X-Y et al (2004) Rosiglitazone impacts negatively on bone by promoting osteoblast/osteocyte apoptosis. J Endocrinol 183:203–216. doi:10.​1677/​joe.​1.​05723 PubMed
71.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat Li H, Cui R, Cai H et al (2010) The effect of thiazolidinediones on bone mineral density in Chinese older patients with type 2 diabetes. J Bone Miner Metab 28:77–81. doi:10.1007/s00774-009-0104-4 PubMed Li H, Cui R, Cai H et al (2010) The effect of thiazolidinediones on bone mineral density in Chinese older patients with type 2 diabetes. J Bone Miner Metab 28:77–81. doi:10.​1007/​s00774-009-0104-4 PubMed
100.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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
123.
125.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat Bunck MC, Poelma M, Eekhoff EM et al (2012) Effects of vildagliptin on postprandial markers of bone resorption and calcium homeostasis in recently diagnosed, well-controlled type 2 diabetes patients. J Diabetes 4:181–185. doi:10.1111/j.1753-0407.2011.00168.x PubMed Bunck MC, Poelma M, Eekhoff EM et al (2012) Effects of vildagliptin on postprandial markers of bone resorption and calcium homeostasis in recently diagnosed, well-controlled type 2 diabetes patients. J Diabetes 4:181–185. doi:10.​1111/​j.​1753-0407.​2011.​00168.​x PubMed
144.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat (2013) INVOKANA® (canaglifozin) [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 1–41 (2013) INVOKANA® (canaglifozin) [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 1–41
Metadaten
Titel
Oral anti-diabetic drugs and fracture risk, cut to the bone: safe or dangerous? A narrative review
verfasst von
A. Palermo
L. D’Onofrio
R. Eastell
A. V. Schwartz
P. Pozzilli
N. Napoli
Publikationsdatum
01.08.2015
Verlag
Springer London
Erschienen in
Osteoporosis International / Ausgabe 8/2015
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-015-3123-0

Weitere Artikel der Ausgabe 8/2015

Osteoporosis International 8/2015 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Mehr Frauen im OP – weniger postoperative Komplikationen

21.05.2024 Allgemeine Chirurgie Nachrichten

Ein Frauenanteil von mindestens einem Drittel im ärztlichen Op.-Team war in einer großen retrospektiven Studie aus Kanada mit einer signifikanten Reduktion der postoperativen Morbidität assoziiert.

„Übersichtlicher Wegweiser“: Lauterbachs umstrittener Klinik-Atlas ist online

17.05.2024 Klinik aktuell Nachrichten

Sie sei „ethisch geboten“, meint Gesundheitsminister Karl Lauterbach: mehr Transparenz über die Qualität von Klinikbehandlungen. Um sie abzubilden, lässt er gegen den Widerstand vieler Länder einen virtuellen Klinik-Atlas freischalten.

Klinikreform soll zehntausende Menschenleben retten

15.05.2024 Klinik aktuell Nachrichten

Gesundheitsminister Lauterbach hat die vom Bundeskabinett beschlossene Klinikreform verteidigt. Kritik an den Plänen kommt vom Marburger Bund. Und in den Ländern wird über den Gang zum Vermittlungsausschuss spekuliert.

TEP mit Roboterhilfe führt nicht zu größerer Zufriedenheit

15.05.2024 Knie-TEP Nachrichten

Der Einsatz von Operationsrobotern für den Einbau von Totalendoprothesen des Kniegelenks hat die Präzision der Eingriffe erhöht. Für die postoperative Zufriedenheit der Patienten scheint das aber unerheblich zu sein, wie eine Studie zeigt.

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.