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Osteoporosis International
Published in: Osteoporosis International 12/2018

Open Access 01-12-2018 | Review

Diagnosis and management of bone fragility in diabetes: an emerging challenge

Authors: S.L. Ferrari, B. Abrahamsen, N. Napoli, K. Akesson, M. Chandran, R. Eastell, G. El-Hajj Fuleihan, R. Josse, D.L. Kendler, M. Kraenzlin, A. Suzuki, D.D. Pierroz, A.V. Schwartz, W.D. Leslie, on behalf of the Bone and Diabetes Working Group of IOF

Published in: Osteoporosis International | Issue 12/2018

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Abstract

Fragility fractures are increasingly recognized as a complication of both type 1 and type 2 diabetes, with fracture risk that increases with disease duration and poor glycemic control. Yet the identification and management of fracture risk in these patients remains challenging. This review explores the clinical characteristics of bone fragility in adults with diabetes and highlights recent studies that have evaluated bone mineral density (BMD), bone microstructure and material properties, biochemical markers, and fracture prediction algorithms (i.e., FRAX) in these patients. It further reviews the impact of diabetes drugs on bone as well as the efficacy of osteoporosis treatments in this population. We finally propose an algorithm for the identification and management of diabetic patients at increased fracture risk.
Literature
1.
International Diabetes Federation (2017) IDF diabetes atlas - Eighth Edition
2.
3.
Weber DR, Haynes K, Leonard MB, Willi SM, Denburg MR (2015) Type 1 diabetes is associated with an increased risk of fracture across the life span: a population-based cohort study using The Health Improvement Network (THIN). Diabetes Care 38:1913–1920PubMedPubMedCentralCrossRef
4.
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 48:1292–1299CrossRefPubMed
5.
Bonds DE, Larson JC, Schwartz AV, Strotmeyer ES, Robbins J, Rodriguez BL, Johnson KC, Margolis KL (2006) Risk of fracture in women with type 2 diabetes: the Women's Health Initiative Observational Study. J Clin Endocrinol Metab 91:3404–3410PubMedCrossRef
6.
Fraser LA, Pritchard J, Ioannidis G, Giangegorio LM, Adachi JD, Papaioannou A, Leslie WD (2011) Clinical risk factors for fracture in diabetes: a matched cohort analysis. J Clin Densitom 14:416–421PubMedPubMedCentralCrossRef
7.
Oei L, Zillikens MC, Dehghan A, Buitendijk GHS, Castano-Betancourt MC, Estrada K, Stolk L, Oei EHG, van Meurs JBJ, Janssen JAMJL, Hofman A, van Leeuwen JPTM, Witteman JCM, Pols HAP, Uitterlinden AG, Klaver CCW, Franco OH, Rivadeneira F (2013) High bone mineral density and fracture risk in type 2 diabetes as skeletal complications of inadequate glucose control: the Rotterdam Study. Diabetes Care 36:1619–1628PubMedPubMedCentralCrossRef
8.
Holmberg AH, Johnell O, Nilsson PM, Nilsson J, Berglund G, Akesson K (2006) Risk factors for fragility fracture in middle age. A prospective population-based study of 33,000 men and women. Osteoporos Int 17:1065–1077PubMedCrossRef
9.
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 166:495–505PubMedCrossRef
10.
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 18:427–444PubMedCrossRef
11.
Johnston SS, Conner C, Aagren M, Ruiz K, Bouchard J (2012) Association between hypoglycaemic events and fall-related fractures in Medicare-covered patients with type 2 diabetes. Diabetes Obes Metab 14:634–643PubMedCrossRef
12.
Chamberlain JJ, Kalyani RR, Leal S, Rhinehart AS, Shubrook JH, Skolnik N, Herman WH (2017) Treatment of type 1 diabetes: synopsis of the 2017 American Diabetes Association Standards of Medical Care in Diabetes. Ann Intern Med 167:493–498PubMedCrossRef
13.
de Liefde I, van der Klift M, de Laet CE, van Daele PL, Hofman A, Pols HA (2005) Bone mineral density and fracture risk in type-2 diabetes mellitus: the Rotterdam Study. Osteoporos Int 16:1713–1720PubMedCrossRef
14.
Strotmeyer ES, Cauley JA, Schwartz AV, Nevitt MC, Resnick HE, Bauer DC, Tylavsky FA, de Rekeneire N, Harris TB, Newman AB (2005) Nontraumatic fracture risk with diabetes mellitus and impaired fasting glucose in older white and black adults: the health, aging, and body composition study. Arch Intern Med 165:1612–1617PubMedCrossRef
15.
Leslie WD, Morin SN, Lix LM, Majumdar SR (2014) Does diabetes modify the effect of FRAX risk factors for predicting major osteoporotic and hip fracture? Osteoporos Int 25:2817–2824PubMedCrossRef
16.
Kanis JA (2008) Assessment of osteoporosis at the primary health care level. World Health Organization Scientific Group. University of Sheffield, WHO Collaborating Centre for Metabolic Bone Diseases
17.
Ivers RQ, Cumming RG, Mitchell P, Peduto AJ (2001) Diabetes and risk of fracture: The Blue Mountains Eye Study. Diabetes Care 24:1198–1203PubMedCrossRef
18.
Leslie WD, Lix LM, Prior HJ, Derksen S, Metge C, O'Neil J (2007) Biphasic fracture risk in diabetes: a population-based study. Bone 40:1595–1601PubMedCrossRef
19.
Majumdar SR, Leslie WD, Lix LM, Morin SN, Johansson H, Oden A, McCloskey EV, Kanis JA (2016) Longer duration of diabetes strongly impacts fracture risk assessment: The Manitoba BMD Cohort. J Clin Endocrinol Metab 101:4489–4496PubMedPubMedCentralCrossRef
20.
Schneider AL, Williams EK, Brancati FL, Blecker S, Coresh J, Selvin E (2013) Diabetes and risk of fracture-related hospitalization: the Atherosclerosis Risk in Communities Study. Diabetes Care 36:1153–1158PubMedPubMedCentralCrossRef
21.
Li CI, Liu CS, Lin WY, Meng NH, Chen CC, Yang SY, Chen HJ, Lin CC, Li TC (2015) Glycated hemoglobin level and risk of hip fracture in older people with type 2 diabetes: a competing risk analysis of Taiwan Diabetes Cohort Study. J Bone Miner Res 30:1338–1346PubMedCrossRef
22.
Schwartz AV, Margolis KL, Sellmeyer DE, Vittinghoff E, Ambrosius WT, Bonds DE, Josse RG, Schnall AM, Simmons DL, Hue TF, Palermo L, Hamilton BP, Green JB, Atkinson HH, O'Connor PJ, Force RW, Bauer DC (2012) Intensive glycemic control is not associated with fractures or falls in the ACCORD randomized trial. Diabetes Care 35:1525–1531PubMedPubMedCentralCrossRef
23.
Hu F, Jiang C, Shen J, Tang P, Wang Y (2012) Preoperative predictors for mortality following hip fracture surgery: a systematic review and meta-analysis. Injury 43:676–685PubMedCrossRef
24.
Huang YF, Shyu YI, Liang J, Chen MC, Cheng HS, Wu CC (2012) Diabetes and health outcomes among older Taiwanese with hip fracture. Rejuvenation Res 15:476–482PubMedCrossRef
25.
Shanbhogue VV, Hansen S, Frost M, Jorgensen NR, Hermann AP, Henriksen JE, Brixen K (2016) Compromised cortical bone compartment in type 2 diabetes mellitus patients with microvascular disease. Eur J Endocrinol 174:115–124PubMedCrossRef
26.
Napoli N, Strotmeyer ES, Ensrud KE, Sellmeyer DE, Bauer DC, Hoffman AR, Dam TTL, Barrett-Connor E, Palermo L, Orwoll ES, Cummings SR, Black DM, Schwartz AV (2014) Fracture risk in diabetic elderly men: the MrOS study. Diabetologia 57:2057–2065PubMedPubMedCentralCrossRef
27.
Zhu ZN, Jiang YF, Ding T (2014) Risk of fracture with thiazolidinediones: an updated meta-analysis of randomized clinical trials. Bone 68:115–123PubMedCrossRef
28.
29.
Su B, Sheng H, Zhang M, Bu L, Yang P, Li L, Li F, Sheng C, Han Y, Qu S, Wang J (2015) Risk of bone fractures associated with glucagon-like peptide-1 receptor agonists' treatment: a meta-analysis of randomized controlled trials. Endocrine 48:107–115PubMedCrossRef
30.
Monami M, Dicembrini I, Antenore A, Mannucci E (2011) Dipeptidyl peptidase-4 inhibitors and bone fractures: a meta-analysis of randomized clinical trials. Diabetes Care 34:2474–2476PubMedPubMedCentralCrossRef
31.
Mosenzon O, Wei C, Davidson J, Scirica BM, Yanuv I, Rozenberg A, Hirshberg B, Cahn A, Stahre C, Strojek K, Bhatt DL, Raz I (2015) Incidence of fractures in patients with type 2 diabetes in the SAVOR-TIMI 53 Trial. Diabetes Care 38:2142–2150PubMedCrossRef
32.
Watts NB, Bilezikian JP, Usiskin K, Edwards R, Desai M, Law G, Meininger G (2016) Effects of canagliflozin on fracture risk in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 101:157–166PubMedCrossRef
33.
Ljunggren O, Bolinder J, Johansson L, Wilding J, Langkilde AM, Sjostrom CD, Sugg J, Parikh S (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 14:990–999PubMedCrossRef
34.
Bilezikian JP, Watts NB, Usiskin K, Polidori D, Fung A, Sullivan D, Rosenthal N (2016) Evaluation of bone mineral density and bone biomarkers in patients with type 2 diabetes treated with canagliflozin. J Clin Endocrinol Metab 101:44–51PubMedCrossRef
35.
Monami M, Cresci B, Colombini A, Pala L, Balzi D, Gori F, Chiasserini V, Marchionni N, Rotella CM, Mannucci E (2008) Bone fractures and hypoglycemic treatment in type 2 diabetic patients: a case-control study. Diabetes Care 31:199–203PubMedCrossRef
36.
Kachroo S, Kawabata H, Colilla S, Shi L, Zhao Y, Mukherjee J, Iloeje U, Fonseca V (2015) Association between hypoglycemia and fall-related events in type 2 diabetes mellitus: analysis of a U.S. commercial database. J Manag Care Spec Pharm 21:243–253PubMed
37.
Wallander M, Axelsson KF, Nilsson AG, Lundh D, Lorentzon M (2017) Type 2 diabetes and risk of hip fractures and non-skeletal fall injuries in the elderly: a study from the Fractures and Fall Injuries in the Elderly Cohort (FRAILCO). J Bone Miner Res 32:449–460PubMedCrossRef
38.
Napoli N, Chandran M, Pierroz DD, Abrahamsen B, Schwartz AV, Ferrari SL, IOF Bone Diabetes Working G (2017) Mechanisms of diabetes mellitus-induced bone fragility. Nat Rev Endocrinol 13:208–219PubMedCrossRef
39.
Schwartz AV, Vittinghoff E, Sellmeyer DE, Feingold KR, Rekeneire N, Strotmeyer ES, Shorr RI, Vinik AI, Odden MC, Park SW, Faulkner KA, Harris TB, for the Health, Aging, and Body Composition Study (2008) Diabetes-related complications, glycemic control, and falls in older adults. Diabetes Care 31:391–396PubMedCrossRef
40.
Palermo A, D'Onofrio L, Eastell R, Schwartz AV, Pozzilli P, Napoli N (2015) Oral anti-diabetic drugs and fracture risk, cut to the bone: safe or dangerous? A narrative review. Osteoporos Int 26:2073–2089PubMedCrossRef
41.
Ruanpeng D, Ungprasert P, Sangtian J, Harindhanavudhi T (2017) Sodium-glucose cotransporter 2 (SGLT2) inhibitors and fracture risk in patients with type 2 diabetes mellitus: a meta-analysis. Diabetes Metab Res Rev 33CrossRef
42.
Hough FS, Pierroz DD, Cooper C, Ferrari SL, IOF CSA Bone and Diabetes Working Group (2016) Mechanisms in endocrinology: mechanisms and evaluation of bone fragility in type 1 diabetes mellitus. Eur J Endocrinol 174:R127–R138PubMedCrossRef
43.
Ma L, Oei L, Jiang L, Estrada K, Chen H, Wang Z, Yu Q, Zillikens MC, Gao X, Rivadeneira F (2012) Association between bone mineral density and type 2 diabetes mellitus: a meta-analysis of observational studies. Eur J Epidemiol 27:319–332PubMedPubMedCentralCrossRef
44.
Holmberg AH, Nilsson PM, Nilsson JA, Akesson K (2008) The association between hyperglycemia and fracture risk in middle age. A prospective, population-based study of 22,444 men and 10,902 women. J Clin Endocrinol Metab 93:815–822PubMedCrossRef
45.
Schwartz AV, Vittinghoff E, Bauer DC, Hillier TA, Strotmeyer ES, Ensrud KE, Donaldson MG, Cauley JA, Harris TB, Koster A, Womack CR, Palermo L, Black DM, Study of Osteoporotic Fractures (SOF) Research Group, Osteoporotic Fractures in Men (MrOS) Research Group, Health, Aging, and Body Composition (Health ABC) Research Group (2011) Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA 305:2184–2192PubMedPubMedCentralCrossRef
46.
Schacter GI, Leslie WD (2017) DXA-based measurements in diabetes: can they predict fracture risk? Calcif Tissue Int 100:150–164PubMedCrossRef
47.
Schwartz AV, Ewing SK, Porzig AM et al (2013) Diabetes and change in bone mineral density at the hip, calcaneus, spine, and radius in older women. Front Endocrinol (Lausanne) 4:62PubMedCentralCrossRef
48.
Leslie WD, Morin SN, Majumdar SR, Lix LM (2018) Effects of obesity and diabetes on rate of bone density loss. Osteoporos Int 29:61–67PubMedCrossRef
49.
Caffarelli C, Giambelluca A, Ghini V, Francolini V, Pitinca MDT, Nuti R, Gonnelli S (2017) In Type-2 diabetes subjects trabecular bone score is better associated with carotid intima-media thickness than BMD. Calcif Tissue Int 101:404–411PubMedCrossRef
50.
Leslie WD, Aubry-Rozier B, Lamy O, Hans D, Manitoba Bone Density P (2013) TBS (trabecular bone score) and diabetes-related fracture risk. J Clin Endocrinol Metab 98:602–609PubMedCrossRef
51.
Mazzetti G, Berger C, Leslie WD, Hans D, Langsetmo L, Hanley DA, Kovacs CS, Prior JC, Kaiser SM, Davison KS, Josse R, Papaioannou A, Adachi JR, Goltzman D, Morin SN, CaMos Research Group (2017) Densitometer-specific differences in the correlation between body mass index and lumbar spine trabecular bone score. J Clin Densitom 20:233–238PubMedCrossRef
52.
Tao B, Liu JM, Zhao HY, Sun LH, Wang WQ, Li XY, Ning G (2008) Differences between measurements of bone mineral densities by quantitative ultrasound and dual-energy X-ray absorptiometry in type 2 diabetic postmenopausal women. J Clin Endocrinol Metab 93:1670–1675PubMedCrossRef
53.
Yamaguchi T, Yamamoto M, Kanazawa I, Yamauchi M, Yano S, Tanaka N, Nitta E, Fukuma A, Uno S, Sho-no T, Sugimoto T (2011) Quantitative ultrasound and vertebral fractures in patients with type 2 diabetes. J Bone Miner Metab 29:626–632PubMedCrossRef
54.
Pritchard JM, Giangregorio LM, Atkinson SA, Beattie KA, Inglis D, Ioannidis G, Punthakee Z, Adachi JD, Papaioannou A (2012) Association of larger holes in the trabecular bone at the distal radius in postmenopausal women with type 2 diabetes mellitus compared to controls. Arthritis Care Res (Hoboken) 64:83–91CrossRef
55.
Burghardt AJ, Kazakia GJ, Sode M, de Papp AE, Link TM, Majumdar S (2010) A longitudinal HR-pQCT study of alendronate treatment in postmenopausal women with low bone density: relations among density, cortical and trabecular microarchitecture, biomechanics, and bone turnover. J Bone Miner Res 25:2558–2571PubMedPubMedCentralCrossRef
56.
Patsch JM, Burghardt AJ, Yap SP, Baum T, Schwartz AV, Joseph GB, Link TM (2013) Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures. J Bone Miner Res 28:313–324PubMedCrossRef
57.
Compston JE, Flahive J, Hosmer DW, Watts NB, Siris ES, Silverman S, Saag KG, Roux C, Rossini M, Pfeilschifter J, Nieves JW, Netelenbos JC, March L, LaCroix AZ, Hooven FH, Greenspan SL, Gehlbach SH, Díez-Pérez A, Cooper C, Chapurlat RD, Boonen S, Anderson FA Jr, Adami S, Adachi JD, for the GLOW Investigators (2014) Relationship of weight, height, and body mass index with fracture risk at different sites in postmenopausal women: the Global Longitudinal study of Osteoporosis in Women (GLOW). J Bone Miner Res 29:487–493PubMedCrossRef
58.
Nilsson AG, Sundh D, Johansson L, Nilsson M, Mellstrom D, Rudang R, Zoulakis M, Wallander M, Darelid A, Lorentzon M (2017) Type 2 diabetes mellitus is associated with better bone microarchitecture but lower bone material strength and poorer physical function in elderly women: a population-based study. J Bone Miner Res 32:1062–1071PubMedCrossRef
59.
Bala Y, Bui QM, Wang XF, Iuliano S, Wang Q, Ghasem-Zadeh A, Rozental TD, Bouxsein ML, Zebaze RM, Seeman E (2015) Trabecular and cortical microstructure and fragility of the distal radius in women. J Bone Miner Res 30:621–629PubMedCrossRef
60.
Yu EW, Putman MS, Derrico N, Abrishamanian-Garcia G, Finkelstein JS, Bouxsein ML (2015) Defects in cortical microarchitecture among African-American women with type 2 diabetes. Osteoporos Int 26:673–679PubMedCrossRef
61.
Heilmeier U, Cheng K, Pasco C, Parrish R, Nirody J, Patsch JM, Zhang CA, Joseph GB, Burghardt AJ, Schwartz AV, Link TM, Kazakia G (2016) Cortical bone laminar analysis reveals increased midcortical and periosteal porosity in type 2 diabetic postmenopausal women with history of fragility fractures compared to fracture-free diabetics. Osteoporos Int 27:2791–2802PubMedCrossRefPubMedCentral
62.
Furst JR, Bandeira LC, Fan WW, Agarwal S, Nishiyama KK, McMahon DJ, Dworakowski E, Jiang H, Silverberg SJ, Rubin MR (2016) Advanced glycation endproducts and bone material strength in type 2 diabetes. J Clin Endocrinol Metab 101:2502–2510PubMedPubMedCentralCrossRef
63.
64.
65.
Manavalan JS, Cremers S, Dempster DW, Zhou H, Dworakowski E, Kode A, Kousteni S, Rubin MR (2012) Circulating osteogenic precursor cells in type 2 diabetes mellitus. J Clin Endocrinol Metab 97:3240–3250PubMedPubMedCentralCrossRef
66.
Krakauer JC, McKenna MJ, Buderer NF, Rao DS, Whitehouse FW, Parfitt AM (1995) Bone loss and bone turnover in diabetes. Diabetes 44:775–782PubMedCrossRef
67.
Starup-Linde J (2013) Diabetes, biochemical markers of bone turnover, diabetes control, and bone. Front Endocrinol (Lausanne) 4:21CrossRef
68.
Reyes-Garcia R, Rozas-Moreno P, Lopez-Gallardo G, Garcia-Martin A, Varsavsky M, Aviles-Perez MD, Munoz-Torres M (2013) Serum levels of bone resorption markers are decreased in patients with type 2 diabetes. Acta Diabetol 50:47–52PubMedCrossRef
69.
Shu A, Yin MT, Stein E, Cremers S, Dworakowski E, Ives R, Rubin MR (2012) Bone structure and turnover in type 2 diabetes mellitus. Osteoporos Int 23:635–641PubMedCrossRef
70.
Kanazawa I, Yamaguchi T, Yamauchi M, Yamamoto M, Kurioka S, Yano S, Sugimoto T (2011) Serum undercarboxylated osteocalcin was inversely associated with plasma glucose level and fat mass in type 2 diabetes mellitus. Osteoporos Int 22:187–194PubMedCrossRef
71.
Zhou Y, Li Y, Zhang D, Wang J, Yang H (2010) Prevalence and predictors of osteopenia and osteoporosis in postmenopausal Chinese women with type 2 diabetes. Diabetes Res Clin Pract 90:261–269PubMedCrossRef
72.
Vashishth D (2007) The role of the collagen matrix in skeletal fragility. Curr Osteoporos Rep 5:62–66PubMedCrossRef
73.
Viguet-Carrin S, Roux JP, Arlot ME, Merabet Z, Leeming DJ, Byrjalsen I, Delmas PD, Bouxsein ML (2006) Contribution of the advanced glycation end product pentosidine and of maturation of type I collagen to compressive biomechanical properties of human lumbar vertebrae. Bone 39:1073–1079PubMedCrossRef
74.
Saito M, Fujii K, Mori Y, Marumo K (2006) Role of collagen enzymatic and glycation induced cross-links as a determinant of bone quality in spontaneously diabetic WBN/Kob rats. Osteoporos Int 17:1514–1523PubMedCrossRef
75.
Kerkeni M, Saidi A, Bouzidi H, Ben Yahya S, Hammami M (2012) Elevated serum levels of AGEs, sRAGE, and pentosidine in Tunisian patients with severity of diabetic retinopathy. Microvasc Res 84:378–383PubMedCrossRef
76.
Ng ZX, Chua KH, Iqbal T, Kuppusamy UR (2013) Soluble receptor for advanced glycation end-product (sRAGE)/pentosidine ratio: a potential risk factor determinant for type 2 diabetic retinopathy. Int J Mol Sci 14:7480–7491PubMedPubMedCentralCrossRef
77.
Yamamoto M, Yamaguchi T, Yamauchi M, Yano S, Sugimoto T (2008) Serum pentosidine levels are positively associated with the presence of vertebral fractures in postmenopausal women with type 2 diabetes. J Clin Endocrinol Metab 93:1013–1019PubMedCrossRef
78.
Schwartz AV, Garnero P, Hillier TA, Sellmeyer DE, Strotmeyer ES, Feingold KR, Resnick HE, Tylavsky FA, Black DM, Cummings SR, Harris TB, Bauer DC, Health, Aging, and Body Composition Study (2009) Pentosidine and increased fracture risk in older adults with type 2 diabetes. J Clin Endocrinol Metab 94:2380–2386PubMedPubMedCentralCrossRef
79.
Tanaka S, Kuroda T, Saito M, Shiraki M (2011) Urinary pentosidine improves risk classification using fracture risk assessment tools for postmenopausal women. J Bone Miner Res 26:2778–2784PubMedCrossRef
80.
Yamamoto M, Yamaguchi T, Yamauchi M, Sugimoto T (2009) Low serum level of the endogenous secretory receptor for advanced glycation end products (esRAGE) is a risk factor for prevalent vertebral fractures independent of bone mineral density in patients with type 2 diabetes. Diabetes Care 32:2263–2268PubMedPubMedCentralCrossRef
81.
Gennari L, Merlotti D, Valenti R, Ceccarelli E, Ruvio M, Pietrini MG, Capodarca C, Franci MB, Campagna MS, Calabrò A, Cataldo D, Stolakis K, Dotta F, Nuti R (2012) Circulating sclerostin levels and bone turnover in type 1 and type 2 diabetes. J Clin Endocrinol Metab 97:1737–1744PubMedCrossRef
82.
Ardawi MS, Akhbar DH, Alshaikh A, Ahmed MM, Qari MH, Rouzi AA, Ali AY, Abdulrafee AA, Saeda MY (2013) Increased serum sclerostin and decreased serum IGF-1 are associated with vertebral fractures among postmenopausal women with type-2 diabetes. Bone 56:355–362PubMedCrossRef
83.
Yamamoto M, Yamauchi M, Sugimoto T (2013) Elevated sclerostin levels are associated with vertebral fractures in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 98:4030–4037PubMedCrossRef
84.
Heilmeier U, Carpenter DR, Patsch JM, Harnish R, Joseph GB, Burghardt AJ, Baum T, Schwartz AV, Lang TF, Link TM (2015) Volumetric femoral BMD, bone geometry, and serum sclerostin levels differ between type 2 diabetic postmenopausal women with and without fragility fractures. Osteoporos Int 26:1283–1293PubMedCrossRef
85.
Starup-Linde J, Lykkeboe S, Gregersen S, Hauge EM, Langdahl BL, Handberg A, Vestergaard P (2016) Bone structure and predictors of fracture in type 1 and type 2 diabetes. J Clin Endocrinol Metab 101:928–936PubMedCrossRef
86.
Morales-Santana S, Garcia-Fontana B, Garcia-Martin A, Rozas-Moreno P, Garcia-Salcedo JA, Reyes-Garcia R, Munoz-Torres M (2013) Atherosclerotic disease in type 2 diabetes is associated with an increase in sclerostin levels. Diabetes Care 36:1667–1674PubMedPubMedCentralCrossRef
87.
Pepe J, Bonnet N, Herrmann FR, Biver E, Rizzoli R, Chevalley T, Ferrari SL (2018) Interaction between LRP5 and periostin gene polymorphisms on serum periostin levels and cortical bone microstructure. Osteoporos Int 29:339–346PubMedCrossRef
88.
Heilmeier U, Hackl M, Skalicky S, Weilner S, Schroeder F, Vierlinger K, Patsch JM, Baum T, Oberbauer E, Lobach I, Burghardt AJ, Schwartz AV, Grillari J, Link TM (2016) Serum miRNA signatures are indicative of skeletal fractures in postmenopausal women with and without type 2 diabetes and influence osteogenic and Adipogenic differentiation of adipose tissue-derived mesenchymal stem cells in vitro. J Bone Miner Res 31:2173–2192PubMedCrossRef
89.
Keegan TH, Schwartz AV, Bauer DC, Sellmeyer DE, Kelsey JL, fracture intervention t (2004) Effect of alendronate on bone mineral density and biochemical markers of bone turnover in type 2 diabetic women: the fracture intervention trial. Diabetes Care 27:1547–1553PubMedCrossRef
90.
Abrahamsen B, Rubin KH, Eiken PA, Eastell R (2013) Characteristics of patients who suffer major osteoporotic fractures despite adhering to alendronate treatment: a National Prescription registry study. Osteoporos Int 24:321–328PubMedCrossRef
91.
Vestergaard P, Rejnmark L, Mosekilde L (2011) Are antiresorptive drugs effective against fractures in patients with diabetes? Calcif Tissue Int 88:209–214PubMedCrossRef
92.
Inoue D, Muraoka R, Okazaki R, Nishizawa Y, Sugimoto T (2016) Efficacy and safety of Risedronate in osteoporosis subjects with comorbid diabetes, hypertension, and/or dyslipidemia: a post hoc analysis of phase III trials conducted in Japan. Calcif Tissue Int 98:114–122PubMedCrossRef
93.
Johnell O, Kanis JA, Black DM, Balogh A, Poor G, Sarkar S, Zhou C, Pavo I (2004) Associations between baseline risk factors and vertebral fracture risk in the Multiple Outcomes of Raloxifene Evaluation (MORE) Study. J Bone Miner Res 19:764–772PubMedCrossRef
94.
Ensrud KE, Stock JL, Barrett-Connor E, Grady D, Mosca L, Khaw KT, Zhao Q, Agnusdei D, Cauley JA (2008) Effects of raloxifene on fracture risk in postmenopausal women: the Raloxifene Use for the Heart Trial. J Bone Miner Res 23:112–120PubMedCrossRef
95.
Schwartz AV, Pavo I, Alam J, Disch DP, Schuster D, Harris JM, Krege JH (2016) Teriparatide in patients with osteoporosis and type 2 diabetes. Bone 91:152–158PubMedCrossRef
96.
Dagdelen S, Sener D, Bayraktar M (2007) Influence of type 2 diabetes mellitus on bone mineral density response to bisphosphonates in late postmenopausal osteoporosis. Adv Ther 24:1314–1320PubMedCrossRef
97.
Iwamoto J, Sato Y, Uzawa M, Takeda T, Matsumoto H (2011) Three-year experience with alendronate treatment in postmenopausal osteoporotic Japanese women with or without type 2 diabetes. Diabetes Res Clin Pract 93:166–173PubMedCrossRef
98.
Hansen S, Hauge EM, Beck Jensen JE, Brixen K (2013) Differing effects of PTH 1-34, PTH 1-84, and zoledronic acid on bone microarchitecture and estimated strength in postmenopausal women with osteoporosis: an 18-month open-labeled observational study using HR-pQCT. J Bone Miner Res 28:736–745PubMedCrossRef
99.
Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S, Hofbauer LC, Lau E, Lewiecki EM, Miyauchi A, Zerbini CAF, Milmont CE, Chen L, Maddox J, Meisner PD, Libanati C, Grauer A (2016) Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med 375:1532–1543PubMedCrossRef
100.
Hamann C, Rauner M, Hohna Y et al (2013) Sclerostin antibody treatment improves bone mass, bone strength, and bone defect regeneration in rats with type 2 diabetes mellitus. J Bone Miner Res 28:627–638PubMedCrossRef
101.
Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, Maddox J, Fan M, Meisner PD, Grauer A (2017) Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med 377:1417–1427PubMedCrossRef
102.
Giangregorio LM, Leslie WD, Lix LM, Johansson H, Oden A, McCloskey E, Kanis JA (2012) FRAX underestimates fracture risk in patients with diabetes. J Bone Miner Res 27:301–308PubMedCrossRef
103.
McCloskey EV, Oden A, Harvey NC, Leslie WD, Hans D, Johansson H, Kanis JA (2015) Adjusting fracture probability by trabecular bone score. Calcif Tissue Int 96:500–509PubMedCrossRef
104.
Leslie WD, Rubin MR, Schwartz AV, Kanis JA (2012) Type 2 diabetes and bone. J Bone Miner Res 27:2231–2237PubMedCrossRef
105.
Villareal DT, Chode S, Parimi N, Sinacore DR, Hilton T, Armamento-Villareal R, Napoli N, Qualls C, Shah K (2011) Weight loss, exercise, or both and physical function in obese older adults. N Engl J Med 364:1218–1229PubMedPubMedCentralCrossRef
106.
Armamento-Villareal R, Aguirre L, Napoli N, Shah K, Hilton T, Sinacore DR, Qualls C, Villareal DT (2014) Changes in thigh muscle volume predict bone mineral density response to lifestyle therapy in frail, obese older adults. Osteoporos Int 25:551–558PubMedCrossRef
107.
Scott D, Seibel M, Cumming R, Naganathan V, Blyth F, Le Couteur DG, Handelsman DJ, Waite LM, Hirani V (2017) Sarcopenic obesity and its temporal associations with changes in bone mineral density, incident falls, and fractures in older men: The Concord Health and Ageing in Men Project. J Bone Miner Res 32:575–583PubMedCrossRef
108.
Armamento-Villareal R, Sadler C, Napoli N, Shah K, Chode S, Sinacore DR, Qualls C, Villareal DT (2012) Weight loss in obese older adults increases serum sclerostin and impairs hip geometry but both are prevented by exercise training. J Bone Miner Res 27:1215–1221PubMedCrossRef
109.
Napoli N, Shah K, Waters DL, Sinacore DR, Qualls C, Villareal DT (2014) Effect of weight loss, exercise, or both on cognition and quality of life in obese older adults. Am J Clin Nutr 100:189–198PubMedPubMedCentralCrossRef
110.
Pozzilli P, Manfrini S, Crino A, Picardi A, Leomanni C, Cherubini V, Valente L, Khazrai M, Visalli N, group I (2005) Low levels of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 in patients with newly diagnosed type 1 diabetes. Horm Metab Res 37:680–683PubMedCrossRef
111.
Hurskainen AR, Virtanen JK, Tuomainen TP, Nurmi T, Voutilainen S (2012) Association of serum 25-hydroxyvitamin D with type 2 diabetes and markers of insulin resistance in a general older population in Finland. Diabetes Metab Res Rev 28:418–423PubMedCrossRef
112.
Berlie HD, Garwood CL (2010) Diabetes medications related to an increased risk of falls and fall-related morbidity in the elderly. Ann Pharmacother 44:712–717PubMedCrossRef
113.
Schwartz AV, Hillier TA, Sellmeyer DE, Resnick HE, Gregg E, Ensrud KE, Schreiner PJ, Margolis KL, Cauley JA, Nevitt MC, Black DM, Cummings SR (2002) Older women with diabetes have a higher risk of falls: a prospective study. Diabetes Care 25:1749–1754PubMedCrossRef
114.
115.
Pozzilli P, Leslie RD, Chan J, De Fronzo R, Monnier L, Raz I, Del Prato S (2010) The A1C and ABCD of glycaemia management in type 2 diabetes: a physician's personalized approach. Diabetes Metab Res Rev 26:239–244PubMedCrossRef
116.
Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR (2015) Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 38:140–149PubMedCrossRef
Metadata
Title
Diagnosis and management of bone fragility in diabetes: an emerging challenge
Authors
S.L. Ferrari
B. Abrahamsen
N. Napoli
K. Akesson
M. Chandran
R. Eastell
G. El-Hajj Fuleihan
R. Josse
D.L. Kendler
M. Kraenzlin
A. Suzuki
D.D. Pierroz
A.V. Schwartz
W.D. Leslie
on behalf of the Bone and Diabetes Working Group of IOF
Publication date
01-12-2018
Publisher
Springer London
Published in
Osteoporosis International / Issue 12/2018
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-018-4650-2

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