Abstract
Summary
Pentosidine levels were higher in diabetic patients with vertebral fractures. Trabecular bone scores were negatively associated with pentosidine levels in diabetic patients only. Our results provide further evidence that AGEs are associated with the pathogenesis of bone fragility in patients with T2DM.
Introduction
Type 2 diabetes mellitus (T2DM) is associated with fracture risk. Pentosidine, an advanced glycation end product (AGE), is associated with prevalent vertebral fractures (VFs) in patients with T2DM. Trabecular bone score (TBS) has been proposed as an index of bone microarchitecture associated with bone quality. This study evaluated the associations of urine pentosidine and TBS in T2DM and non-T2DM groups.
Methods
A total of 112 T2DM patients and 62 non-T2DM subjects were enrolled. TBS was calculated using TBS insight® software (version 2.1). Pentosidine levels were measured using high-performance liquid chromatography method. We compared the BMD, TBS, and pentosidine levels between those with and without VFs with or without adjustment for age and sex. The association with TBS, lumbar spine BMD, and pentosidine levels were also evaluated in both T2DM and non-T2DM groups.
Results
Pentosidine levels were significantly higher in T2DM patients with VFs. TBSs were significantly lower in patients with T2DM and VFs. In non-diabetic patients, there were no significant differences in TBS and pentosidine levels for those with and without VFs after adjustment for age and sex. Pentosidine levels were negatively associated with TBS only in patients with T2DM. In multivariate stepwise regression analysis, pentosidine levels were significantly associated with TBS in patients with T2DM.
Conclusions
TBS and pentosidine could be used as a method to assess bone quality to identify T2DM patients at risk of VFs. Our results also provide further evidence that AGEs are associated with the pathogenesis of bone fragility in patients with T2DM.
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References
Epstein S, Leroith D (2008) Diabetes and fragility fractures: a burgeoning epidemic? Bone 43(1):3–6. https://doi.org/10.1016/j.bone.2008.03.017
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(4):427–444. https://doi.org/10.1007/s00198-006-0253-4
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(5):495–505. https://doi.org/10.1093/aje/kwm106
Yamamoto M, Yamaguchi T, Yamauchi M, Kaji H, Sugimoto T (2009) Diabetic patients have an increased risk of vertebral fractures independent of BMD or diabetic complications. J Bone Miner Res 24(4):702–709. https://doi.org/10.1359/jbmr.081207
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(5):319–332. https://doi.org/10.1007/s10654-012-9674-x
Stein EM, Liu XS, Nickolas TL, Cohen A, McMahon DJ, Zhou B, Zhang C, Kamanda-Kosseh M, Cosman F, Nieves J, Guo XE, Shane E (2012) Microarchitectural abnormalities are more severe in postmenopausal women with vertebral compared to nonvertebral fractures. J Clin Endocrinol Metab 97(10):E1918–E1926. https://doi.org/10.1210/jc.2012-1968
Nishiyama KK, Macdonald HM, Hanley DA, Boyd SK (2013) Women with previous fragility fractures can be classified based on bone microarchitecture and finite element analysis measured with HR-pQCT. Osteoporos Int 24(5):1733–1740. https://doi.org/10.1007/s00198-012-2160-1
Silva BC, Leslie WD (2017) Trabecular bone score: a new DXA-derived measurement for fracture risk assessment. Endocrinol Metab Clin N Am 46(1):153–180. https://doi.org/10.1016/j.ecl.2016.09.005
Hans D, Barthe N, Boutroy S, Pothuaud L, Winzenrieth R, Krieg MA (2011) Correlations between trabecular bone score, measured using anteroposterior dual-energy X-ray absorptiometry acquisition, and 3-dimensional parameters of bone microarchitecture: an experimental study on human cadaver vertebrae. J Clin Densitom 14(3):302–312. https://doi.org/10.1016/j.jocd.2011.05.005
Pothuaud L, Carceller P, Hans D (2008) Correlations between grey-level variations in 2D projection images (TBS) and 3D microarchitecture: applications in the studyof human trabecular bone microarchitecture. Bone 42(4):775–787. https://doi.org/10.1016/j.bone.2007.11.018
Leslie WD, Aubry-Rozier B, Lamy O, Hans D, Manitoba Bone Density Program (2013) TBS (trabecular bone score) and diabetes-related fracture risk. J Clin Endocrinol Metab 98(2):602–609. https://doi.org/10.1210/jc.2012-3118
Silva BC, Broy SB, Boutroy S, Schousboe JT, Shepherd JA, Leslie WD (2015) Fracture risk prediction by non-BMD DXA measures: the 2015 ISCD official positions part 2: trabecular bone score. J Clin Densitom 18(3):309–330. https://doi.org/10.1016/j.jocd.2015.06.008
Yamamoto M, Sugimoto T (2016) Advanced glycation end products, diabetes, and bone strength. Curr Osteoporos Rep 14(6):320–326. https://doi.org/10.1007/s11914-016-0332-1
Saito M, Marumo K (2010) Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporos Int 21(2):195–214. https://doi.org/10.1007/s00198-009-1066-z
Dong XN, Qin A, Xu J, Wang X (2011) In situ accumulation of advanced glycation end products (AGEs) in bone matrix and its correlation with osteoclastic bone resorption. Bone 49(2):174–183. https://doi.org/10.1016/j.bone.2011.04.009
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(7):2380–2386
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(3):1013–1019. https://doi.org/10.1210/jc.2007-1270
Mehta JS, Reed MR, McVie JL, Sanderson PL (2004) Weight-bearing radiographs in thoracolumbar fractures: do they influence management? Spine (Phila Pa 1976) 29(5):564–567. https://doi.org/10.1097/01.BRS.0000113873.07484.5D
Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8(9):1137–1148. https://doi.org/10.1002/jbmr.5650080915
Du ES, Moon HS, Lim SJ, Chang SY, Kim SH (2016) High performance liquid chromatographic determination of YJC-10592, a new chemokine receptor 2 (CCR-2) antagonist, in biological samples. J Pharm Investig 46(5):495–504
Hanley DA, Brown JP, Tenenhouse A, Olszynski WP, Ioannidis G, Berger C, Prior JC, Pickard L, Murray TM, Anastassiades T, Kirkland S, Joyce C, Joseph L, Papaioannou A, Jackson SA, Poliquin S, Adachi JD, Canadian Multicentre Osteoporosis Study Research Group (2003) Associations among disease conditions, bone mineral density, and prevalent vertebral deformities in men and women 50 years of age and older: cross sectional results from the Canadian multicentre osteoporosis study. J Bone Miner Res 18(4):784–790. https://doi.org/10.1359/jbmr.2003.18.4.784
Koh WP, Wang R, Ang LW, Heng D, Yuan JM, Yu MC (2010) Diabetes and risk of hip fracture in the Singapore Chinese health study. Diabetes Care 33(8):1766–1770. https://doi.org/10.2337/dc10-0067
Melton LJ III, Leibson CL, Achenbach SJ, Therneau TM, Khosla S (2008) Fracture risk in type 2 diabetes: update of a population-based study. J Bone Miner Res 23(8):1334–1342
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(9):3404–3410. https://doi.org/10.1210/jc.2006-0614
Yamamoto M, Yamaguchi T, Yamauchi M, Kaji H, Sugimoto T (2009) Diabetic patients have an increased risk of vertebral fractures independent of BMD or diabetic complications. J Bone Miner Res 24(4):702–709. https://doi.org/10.1359/jbmr.081207
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(7):2380–2386
Shiraki M, Kuroda T, Tanaka S, Saito M, Fukunaga M, Nakamura T (2008) Nonenzymatic collagen cross-links induced by glycoxidation (pentosidine) predicts vertebral fractures. J Bone Miner Metab 26(1):93–100. https://doi.org/10.1007/s00774-007-0784-6
Cohen A, Dempster DW, Müller R, Guo XE, Nickolas TL, Liu XS, Zhang XH, Wirth AJ, van Lenthe GH, Kohler T, McMahon DJ, Zhou H, Rubin MR, Bilezikian JP, Lappe JM, Recker RR, Shane E (2015) Assessment of trabecular and cortical architecture and mechanical competence of bone by high-resolution peripheral computed tomography: comparison with transiliac bone biopsy. Osteoporos Int 21(2):263–273
Choi YJ, Chung YS (2016) Type 2 diabetes mellitus and bone fragility: special focus on bone imaging. Osteoporos Sarcopenia 2(1):20–24. https://doi.org/10.1016/j.afos.2016.02.001
Choi YJ, Ock SY, Chung YS (2016) Trabecular bone score (TBS) and TBS-adjusted fracture risk assessment tool are potential supplementary tools for the discrimination of morphometric vertebral fractures in postmenopausal women with type 2 diabetes. J Clin Densitom 19(4):507–514. https://doi.org/10.1016/j.jocd.2016.04.001
Iki M, Tamaki J, Kadowaki E, Sato Y, Dongmei N, Winzenrieth R, Kagamimori S, Kagawa Y, Yoneshima H (2014) Trabecular bone score (TBS) predicts vertebral fractures in Japanese women over 10 years independently of bone density and prevalent vertebral deformity: the Japanese population-based osteoporosis (JPOS) cohort study. J Bone Miner Res 29(2):399–407. https://doi.org/10.1002/jbmr.2048
Viguet-Carrin S, Follet H, Gineyts E, Roux JP, Munoz F, Chapurlat R, Delmas PD, Bouxsein ML (2010) Association between collagen cross-links and trabecular microarchitecture properties of human vertebral bone. Bone 46(2):342–347. https://doi.org/10.1016/j.bone.2009.10.001
Farlay D, Armas LA, Gineyts E, Akhter MP, Recker RR, Boivin G (2016) Nonenzymatic glycation and degree of mineralization are higher in bone from fractured patients with type 1 diabetes mellitus. J Bone Miner Res 31(1):190–195. https://doi.org/10.1002/jbmr.2607
Devlin MJ, Van Vliet M, Motyl K, Karim L, Brooks DJ, Louis L, Conlon C, Rosen CJ, Bouxsein ML (2014) Early-onset type 2 diabetes impairs skeletal acquisition in the male TALLYHO/JngJ mouse. Endocrinology 155(10):3806–3816. https://doi.org/10.1210/en.2014-1041
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(10):1514–1523. https://doi.org/10.1007/s00198-006-0155-5
Tang SY, Allen MR, Phipps R, Burr DB, Vashishth D (2009) Changes in non-enzymatic glycation and its association with altered mechanical properties following 1-year treatment with risedronate or alendronate. Osteoporos Int 20(6):887–894. https://doi.org/10.1007/s00198-008-0754-4
Odetti P, Rossi S, Monacelli F, Poggi A, Cirnigliaro M, Federici M, Federici A (2005) Advanced glycation end products and bone loss during aging. Ann N Y Acad Sci 1043(1):710–717. https://doi.org/10.1196/annals.1333.082
Acknowledgements
This research was partly supported by the Korea Health Technology R&D Project (HI16C0992), through the Korea Health Industry Development Institute (KHIDI), which is funded by the Ministry of Health and Welfare, Republic of Korea (So Hee Kim). The authors are grateful to the technologist, Byung Joo Lee, for his assistance with the analyses of trabecular bone score. The authors are also grateful to professor Yunhwan Lee for his advice on the statistical analyses.
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Receiver operating characteristic curve analysis of pentosidine with VFs. (GIF 14 kb)
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Choi, Y.J., Ock, S.Y., Jin, Y. et al. Urinary Pentosidine levels negatively associates with trabecular bone scores in patients with type 2 diabetes mellitus. Osteoporos Int 29, 907–915 (2018). https://doi.org/10.1007/s00198-017-4359-7
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DOI: https://doi.org/10.1007/s00198-017-4359-7