2型糖尿病性骨质疏松骨质量改变研究
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摘要
尽管糖尿病和骨质疏松症是两种不同的慢性代谢性疾病,但糖尿病患者由于血糖异常、胰岛素缺乏或不足、降糖药物应用等诸多因素,经常会影响骨量与骨质量,导致骨质疏松。因此,糖尿病性骨质疏松症(diabetic osteoporosis,DOP)已经被认定为糖尿病的慢性并发症之一。我国2型糖尿病患者众多,影响较之1型糖尿病更为广泛。多项临床研究显示,2型糖尿病性骨质疏松症、骨折风险增高的原因并非是骨密度的减少,而是多种原因导致的骨质量改变,主要包括骨结构与骨质材料属性等。本文就近年来2型糖尿病性骨质疏松骨质量改变相关的研究进展进行综述。
Although diabetes mellitus( DM) and osteoporosis are two different metabolic diseases,the risk of fragility fractures is increased in DM patients,due to the impact of dysglycemia,shortage of insulin secretion,useage of hypoglycemic drugs et al on both bone quality and quantity. Therefore the conception of diabetic osteoporosis( DOP) was proposed,and defined as another important complication of DM. As in China,type 2 DM( T2 DM) has more significant influence on public health than T1 DM. Previous researches had demonstrated that the underlying mechanisms of T2 DM DOP couldn' t be explained by BMD,since BMD in T2 DM is often normal or even slightly elevated as compared to agematched control population. Therefore,alternation of bone material strength( BMS) and sone microstructure in T2 DM dttract much more attention and many advances were achieved recently. The aim of the present review is to summarize theadvance mechanism of T2 DM DOP due to changes of bone quality.
Although diabetes mellitus( DM) and osteoporosis are two different metabolic diseases,the risk of fragility fractures is increased in DM patients,due to the impact of dysglycemia,shortage of insulin secretion,useage of hypoglycemic drugs et al on both bone quality and quantity. Therefore the conception of diabetic osteoporosis( DOP) was proposed,and defined as another important complication of DM. As in China,type 2 DM( T2 DM) has more significant influence on public health than T1 DM. Previous researches had demonstrated that the underlying mechanisms of T2 DM DOP couldn' t be explained by BMD,since BMD in T2 DM is often normal or even slightly elevated as compared to agematched control population. Therefore,alternation of bone material strength( BMS) and sone microstructure in T2 DM dttract much more attention and many advances were achieved recently. The aim of the present review is to summarize theadvance mechanism of T2 DM DOP due to changes of bone quality.
引文
[1]夏维波.应重视糖尿病性骨质疏松症[J].中华糖尿病杂志,2016,8:1-4.
[2] Portal-Nunez S,Ardura JA,Lozano D. Adverse effects of diabetes mellitus on the skeleton of aging mice[J].J Gerontol A Biol Sci Med Sci,2016,71:290-299.
[3] Janghorbani M,Van Dam RM,Willett WC,et al.Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture[J]. Am J Epidemiol, 2007,166:495-505.
[4] Schwartz AV,Vittinghoff E,Bauer DC,et al. Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes[J]. JAMA,2011,305:2184-2192.
[5] Furst JR,Bandeira LC,Fan WW,et al. Advanced Glycation Endproducts and Bone Material Strength in Type 2 Diabetes[J]. J Clin Endocrinol Metab,2016,101:2502-2510.
[6]刘广鹏. MicroCT原理及应用[J].组织工程与重建外科,2006,2:228-229.
[7] Kerckhofs G,Durand M,Vangoitsenhoven R,et al.Changes in bone macro-and microstructure in diabetic obese mice revealed by high resolution microfocus Xray computed tomography[J]. Sci Rep, 2016,6:35517.
[8]夏维波,林董.高分辨外周骨定量CT的临床应用[J].中华骨质疏松和骨矿盐疾病杂志,2016,9:400-413.
[9] Geusens P,Chapurlat R,Schett G,et al. High-resolution in vivo imaging of bone and joints:a window to microarchitecture[J]. Nat Rev Rheumatol, 2014,10:304-313.
[10] Liu XS,Cohen A,Shane E,et al. Bone density,geometry,microstructure, and stiffness:Relationships between peripheral and central skeletal sites assessed by DXA, HR-pQCT, and c QCT in premenopausal women[J]. J Bone Miner Res, 2010, 25:2229-2238.
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[12] Farr JN,Drake MT,Amin S,et al. In vivo assessment of bone quality in postmenopausal women with type 2diabetes[J]. J Bone Miner Res,2014,29:787-795.
[13] Shu A,Yin MT,Stein E,et al. Bone structure and turnover in type 2 diabetes mellitus[J]. Osteoporos Int,2012,23:635-641.
[14] Yu EW,Putman MS,Derrico N,et al. Defects in cortical microarchitecture among African-American women with type 2 diabetes[J]. Osteoporos Int,2015,26:673-679.
[15] Razi F,Esmaili M,Esfahani EN,et al. Bone structure and turnover in postmenopausal women with type 2 diabetes mellitus[J]. Menopause,2016,23:280-285.
[16] Patsch JM,Rasul S,Huber FA,et al. Similarities in trabecular hypertrophy with site-specific differences in cortical morphology between men and women with type2 diabetes mellitus[J]. PLoS One, 2017,12:e0174664.
[17] Holzer G,von Skrbensky G,Holzer LA,et al. Hip fractures and the contribution of cortical versus trabecular bone to femoral neck strength[J]. J Bone Miner Res,2009,24:468-474.
[18] Riggs BL,Wahner HW,Dunn WL,et al. Differential changes in bone mineral density of the appendicular and axial skeleton with aging:relationship to spinal osteoporosis[J]. J Clin Invest,1981,67:325-328.
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[21] McCalden RW,McGeough JA,Barker MB, et al.Age-related changes in the tensile properties of cortical bone. The relative importance of changes in porosity,mineralization,and microstructure[J]. J Bone Joint Surg Am,1993,75:1193-1205.
[22] Rockoff SD,Sweet E,Bleustein J. The relative contribution of trabecular and cortical bone to the strength of human lumbar vertebrae[J]. Calcif Tissue Res,1969,3:163-175.
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[24] Burr DB. Cortical bone:a target for fracture prevention?[J]. Lancet,2010,375:1672-1673.
[25] Mabilleau G,Perrot R,Flatt PR,et al. High fat-fed diabetic mice present with profound alterations of the osteocyte network[J]. Bone,2016,90:99-106.
[26] Burghardt AJ,Issever AS,Schwartz AV,et al. Highresolution peripheral quantitative computed tomographic imaging of cortical and trabecular bone microarchitecture in patients with type 2 diabetes mellitus[J]. J Clin Endocrinol Metab,2010,95:5045-5055.
[27] Qing H,Ardeshirpour L,Pajevic PD,et al. Demonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation[J]. J Bone Miner Res2012,27:1018-1029.
[28] Dallas SL,Prideaux M,Bonewald LF. The osteocyte:an endocrine cell and more[J]. Endocr Rev,2013,34:658-690.
[29] Bonewald LF. The amazing osteocyte[J]. J Bone Mineral Res,2011,26:229-238.
[30] Ionova-Martin SS,Wade JM,Tang S,et al. Changes in cortical bone response to high-fat diet from adolescence to adulthood in mice[J]. Osteoporos Int,2011,22:2283-2293.
[31] Tanaka KI,Yamaguchi T,Kanazawa I,et al. Effects of high glucose and advanced glycation end products on the expressions of sclerostin and RANKL as well as apoptosis in osteocyte-like MLO-Y4-A2 cells[J].Biochem Biophy Res Commun,2015,461:193-199.
[32] Harvey NC,Gluer CC,Binkley N,et al. Trabecular bone score(TBS)as a new complementary approach for osteoporosis evaluation in clinical practice[J].Bone,2015,78:216-224.
[33] Farr JN,Khosla S. Determinants of bone strength and quality in diabetes mellitus in humans[J]. Bone,2016,82:28-34.
[34] Kim JH,Choi HJ,Ku EJ,et al. Trabecular bone score as an indicator for skeletal deterioration in diabetes[J]. J Clin Endocrinol Metab,2015,100:475-482.
[35] Nilsson AG,Sundh D,Johansson L,et al. 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]. J Bone Miner Res,2017,32:1062-1071.
[36] Bridges D,Randall C,Hansma PK. A new device for performing reference point indentation without a reference probe[J]. Rev Sci Instrum,2012,83:044301.
[37] Yamamoto M, Yamaguchi T, Yamauchi M, et al.Serum pentosidine levels are positively associated with the presence of vertebral fractures in postmenopausal women with type 2 diabetes[J]. J Clin Endocrinol Metab,2008,93:1013-1019.
[38] Acevedo C,Sylvia M,Schaible E,et al. Contributions of material properties and structure to increased bone fragility for a given bone mass in the UCD-T2DM rat model of type 2 diabetes[J]. J Bone Miner Res,2018,33:1066-1075.
[39] Peng J,Hui K,Hao C,et al. Low bone turnover and reduced angiogenesis in streptozotocin-induced osteoporotic mice[J]. Connect Tissue Res, 2016, 57:277-289.
[40] Shanbhogue VV,Hansen S,Frost M,et al. Compromised cortical bone compartment in type 2 diabetes mellitus patients with microvascular disease[J]. Eur J Endocrinol,2016,174:115-124.
[41] Gennari L,Merlotti D,Valenti R,et al. Circulating sclerostin levels and bone turnover in type 1 and type 2diabetes[J]. J Clin Endocrinol Metab,2012,96:1737-1744.
[42] Towler DA. Commonalities between vasculature and bone:an osseocentric view of arteriosclerosis[J]. Circulation,2017,135:320-322.
[43] Spinetti G,Cordella D,Fortunato O,et al. Global remodeling of the vascular stem cell niche in bone marrow of diabetic patients:implication of the microRNA-155/FOXO3a signaling pathway[J]. Circ Res,2013,112:510-522.
[44] Teraa M,Fledderus JO, Rozbeh RI, et al. Bone marrow microvascular and neuropathic alterations in patients with critical limb ischemia[J]. Circ Res,2014,114:311-314.
[45] Bonnet N. Bone-derived factors:a new gateway to regulate glycemia[J]. Calcif Tissue Int, 2017, 100:174-183.
[46]刘建民.骨骼对糖代谢的调控作用[J].中华糖尿病杂志,2016,1:8-11.
[47] Fulzele K,Riddle RC,Di Girolamo DJ,et al. Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition[J]. Cell,2010,142:309-319.
[48] Ferron M,McKee MD,Levine RL,et al. Intermittent injections of osteocalcin improve glucose metabolism and prevent type 2 diabetes in mice[J]. Bone,2012,50:568-575.
[49] Wei J,Ferron M,Clarke CJ,et al. Bone-specific insulin resistance disrupts whole-body glucose homeostasis via decreased osteocalcin activation[J]. J Clin Invest,2014,124:1-13.
[50] Mansur SA,Mieczkowska A,Flatt PR,et al. A new stable GIP-Oxyntomodulin hybrid peptide improved bone strength both at the organ and tissue levels in genetically-inherited type 2 diabetes mellitus[J]. Bone,2016,87:102-113.
[51] Khorsand B,Nicholson N,Do AV,et al. Regeneration of bone using nanoplex delivery of FGF-2 and BMP-2 genes in diaphyseal long bone radial defects in a diabetic rabbit model[J]. J Control Release,2017,248:53-59.
[52] Schmidt FN,Zimmermann EA,Campbell GM,et al.Assessment of collagen quality associated with non-enzymatic cross-links in human bone using Fourier-transform infrared imaging[J]. Bone, 2017, 97:243-251.
[53] McCarthy AD,Uemura T,Etcheverry SB,et al. Advanced glycation endproducts interefere with integrinmediated osteoblastic attachment to a type-I collagen matrix[J]. Int J Biochem Cell Biol, 2004, 36:840-848.
[54] Saito M,Fujii K,Mori Y,et al. Role of collagen enzymatic and glycation induced cross-links as a determinant of bone quality in spontaneously diabetic WBN/Kob rats[J]. Osteoporos Int,2006,17:1514-1523.
[55] Valcourt U,Merle B,Gineyts E,et al. Non-enzymatic glycation of bone collagen modifies osteoclastic activity and differentiation[J]. J Biol Chem, 2007, 282:5691-5703.
[56] Takagi M,Kasayama S,Yamamoto T,et al. Advanced glycation endproducts stimulate interleukin-6 production by human bone-derived cells[J]. J Bone Miner Res,1997,12:439-446.
[57] Kume S,Kato S,Yamagishi SI,et al. Advanced glycation end-products attenuate human mesenchymal stem cells and prevent cognate differentiation into adipose tissue,cartilage,and bone[J]. J Bone Mineral Res,2005,20:1647-1658.
[58] Phimphilai M,Pothacharoen P,Kongtawelert P,et al.Impaired osteogenic differentiation and enhanced cellular receptor of advanced glycation end products sensitivity in patients with type 2 diabetes[J]. J Bone Miner Metab,2017,35:631-641.
[59] Meng HZ, Zhang WL, Liu F, et al. Advanced glycation end products affect osteoblast proliferation and function by modulating autophagy via the receptor of advanced glycation end products/raf protein/mitogen-activated protein kinase/extracellular signalregulated kinase kinase/extracellular signal-regulated kinase(RAGE/Raf/MEK/ERK)pathway[J]. J Biol Chem,2015,290:28189-28199.
[60] Notsu M,Kanazawa I,Takeno A,et al. Advanced glycation end product 3(AGE3)increases apoptosis and the expression of sclerostin by stimulating TGF-beta expression and secretion in osteocyte-like MLO-Y4-A2cells[J]. Calcif Tissue Int,2017,100:402-411.
[61] Ogawa N,Yamaguchi TF,Yano SF,et al. The combination of high glucose and advanced glycation endproducts(AGEs)inhibits the mineralization of osteoblastic MC3T3-E1 cells through glucose-induced increase in the receptor for AGEs[J]. Horm Metab Res,2007,39:871-875.
[62] Yang L,Meng H,Yang M. Autophagy protects osteoblasts from advanced glycation end products-induced apoptosis through intracellular reactive oxygen species[J]. J Mol Endocrinol,2016,56:291-300.
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[66] Frassetto LA,Sebastian A. How metabolic acidosis and oxidative stress alone and interacting may increase the risk of fracture in diabetic subjects[J]. Med Hypotheses,2012,79:189-192.
[67] Quaini F,Chang TC,Hsu MF,et al. High glucose induces bone marrow-derived mesenchymal stem cell senescence by upregulating autophagy[J]. PLoS One,2015,10:e0126537.
[68] Oei L,Zillikens MC,Dehghan A,et al. High bone mineral density and fracture risk in type 2 diabetes as skeletal complications of inadequate glucose control the Rotterdam study[J]. Diabetes Care, 2013, 36:1619-1628.
[2] Portal-Nunez S,Ardura JA,Lozano D. Adverse effects of diabetes mellitus on the skeleton of aging mice[J].J Gerontol A Biol Sci Med Sci,2016,71:290-299.
[3] Janghorbani M,Van Dam RM,Willett WC,et al.Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture[J]. Am J Epidemiol, 2007,166:495-505.
[4] Schwartz AV,Vittinghoff E,Bauer DC,et al. Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes[J]. JAMA,2011,305:2184-2192.
[5] Furst JR,Bandeira LC,Fan WW,et al. Advanced Glycation Endproducts and Bone Material Strength in Type 2 Diabetes[J]. J Clin Endocrinol Metab,2016,101:2502-2510.
[6]刘广鹏. MicroCT原理及应用[J].组织工程与重建外科,2006,2:228-229.
[7] Kerckhofs G,Durand M,Vangoitsenhoven R,et al.Changes in bone macro-and microstructure in diabetic obese mice revealed by high resolution microfocus Xray computed tomography[J]. Sci Rep, 2016,6:35517.
[8]夏维波,林董.高分辨外周骨定量CT的临床应用[J].中华骨质疏松和骨矿盐疾病杂志,2016,9:400-413.
[9] Geusens P,Chapurlat R,Schett G,et al. High-resolution in vivo imaging of bone and joints:a window to microarchitecture[J]. Nat Rev Rheumatol, 2014,10:304-313.
[10] Liu XS,Cohen A,Shane E,et al. Bone density,geometry,microstructure, and stiffness:Relationships between peripheral and central skeletal sites assessed by DXA, HR-pQCT, and c QCT in premenopausal women[J]. J Bone Miner Res, 2010, 25:2229-2238.
[11] Burghardt AJ,Issever AS,Schwartz AV,et al. Highresolution peripheral quantitative computed tomographic imaging of cortical and trabecular bone microarchitecture in patients with type 2 diabetes mellitus[J]. J Clin Endocrinol Metab,2010,95:5045-5055.
[12] Farr JN,Drake MT,Amin S,et al. In vivo assessment of bone quality in postmenopausal women with type 2diabetes[J]. J Bone Miner Res,2014,29:787-795.
[13] Shu A,Yin MT,Stein E,et al. Bone structure and turnover in type 2 diabetes mellitus[J]. Osteoporos Int,2012,23:635-641.
[14] Yu EW,Putman MS,Derrico N,et al. Defects in cortical microarchitecture among African-American women with type 2 diabetes[J]. Osteoporos Int,2015,26:673-679.
[15] Razi F,Esmaili M,Esfahani EN,et al. Bone structure and turnover in postmenopausal women with type 2 diabetes mellitus[J]. Menopause,2016,23:280-285.
[16] Patsch JM,Rasul S,Huber FA,et al. Similarities in trabecular hypertrophy with site-specific differences in cortical morphology between men and women with type2 diabetes mellitus[J]. PLoS One, 2017,12:e0174664.
[17] Holzer G,von Skrbensky G,Holzer LA,et al. Hip fractures and the contribution of cortical versus trabecular bone to femoral neck strength[J]. J Bone Miner Res,2009,24:468-474.
[18] Riggs BL,Wahner HW,Dunn WL,et al. Differential changes in bone mineral density of the appendicular and axial skeleton with aging:relationship to spinal osteoporosis[J]. J Clin Invest,1981,67:325-328.
[19] Zebaze RM,Ghasem-Zadeh A,Bohte A,et al. Intracortical remodelling and porosity in the distal radius and post-mortem femurs of women:a cross-sectional study[J]. Lancet,2010,375:1729-1736.
[20] Patsch JM,Burghardt AJ,Yap SP,et al. Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures[J]. J Bone Miner Res,2013,28:313-324.
[21] McCalden RW,McGeough JA,Barker MB, et al.Age-related changes in the tensile properties of cortical bone. The relative importance of changes in porosity,mineralization,and microstructure[J]. J Bone Joint Surg Am,1993,75:1193-1205.
[22] Rockoff SD,Sweet E,Bleustein J. The relative contribution of trabecular and cortical bone to the strength of human lumbar vertebrae[J]. Calcif Tissue Res,1969,3:163-175.
[23] Heilmeier U,Cheng K,Pasco C,et al. 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[J]. Osteoporos Int, 2016,27:2791-2802.
[24] Burr DB. Cortical bone:a target for fracture prevention?[J]. Lancet,2010,375:1672-1673.
[25] Mabilleau G,Perrot R,Flatt PR,et al. High fat-fed diabetic mice present with profound alterations of the osteocyte network[J]. Bone,2016,90:99-106.
[26] Burghardt AJ,Issever AS,Schwartz AV,et al. Highresolution peripheral quantitative computed tomographic imaging of cortical and trabecular bone microarchitecture in patients with type 2 diabetes mellitus[J]. J Clin Endocrinol Metab,2010,95:5045-5055.
[27] Qing H,Ardeshirpour L,Pajevic PD,et al. Demonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation[J]. J Bone Miner Res2012,27:1018-1029.
[28] Dallas SL,Prideaux M,Bonewald LF. The osteocyte:an endocrine cell and more[J]. Endocr Rev,2013,34:658-690.
[29] Bonewald LF. The amazing osteocyte[J]. J Bone Mineral Res,2011,26:229-238.
[30] Ionova-Martin SS,Wade JM,Tang S,et al. Changes in cortical bone response to high-fat diet from adolescence to adulthood in mice[J]. Osteoporos Int,2011,22:2283-2293.
[31] Tanaka KI,Yamaguchi T,Kanazawa I,et al. Effects of high glucose and advanced glycation end products on the expressions of sclerostin and RANKL as well as apoptosis in osteocyte-like MLO-Y4-A2 cells[J].Biochem Biophy Res Commun,2015,461:193-199.
[32] Harvey NC,Gluer CC,Binkley N,et al. Trabecular bone score(TBS)as a new complementary approach for osteoporosis evaluation in clinical practice[J].Bone,2015,78:216-224.
[33] Farr JN,Khosla S. Determinants of bone strength and quality in diabetes mellitus in humans[J]. Bone,2016,82:28-34.
[34] Kim JH,Choi HJ,Ku EJ,et al. Trabecular bone score as an indicator for skeletal deterioration in diabetes[J]. J Clin Endocrinol Metab,2015,100:475-482.
[35] Nilsson AG,Sundh D,Johansson L,et al. 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]. J Bone Miner Res,2017,32:1062-1071.
[36] Bridges D,Randall C,Hansma PK. A new device for performing reference point indentation without a reference probe[J]. Rev Sci Instrum,2012,83:044301.
[37] Yamamoto M, Yamaguchi T, Yamauchi M, et al.Serum pentosidine levels are positively associated with the presence of vertebral fractures in postmenopausal women with type 2 diabetes[J]. J Clin Endocrinol Metab,2008,93:1013-1019.
[38] Acevedo C,Sylvia M,Schaible E,et al. Contributions of material properties and structure to increased bone fragility for a given bone mass in the UCD-T2DM rat model of type 2 diabetes[J]. J Bone Miner Res,2018,33:1066-1075.
[39] Peng J,Hui K,Hao C,et al. Low bone turnover and reduced angiogenesis in streptozotocin-induced osteoporotic mice[J]. Connect Tissue Res, 2016, 57:277-289.
[40] Shanbhogue VV,Hansen S,Frost M,et al. Compromised cortical bone compartment in type 2 diabetes mellitus patients with microvascular disease[J]. Eur J Endocrinol,2016,174:115-124.
[41] Gennari L,Merlotti D,Valenti R,et al. Circulating sclerostin levels and bone turnover in type 1 and type 2diabetes[J]. J Clin Endocrinol Metab,2012,96:1737-1744.
[42] Towler DA. Commonalities between vasculature and bone:an osseocentric view of arteriosclerosis[J]. Circulation,2017,135:320-322.
[43] Spinetti G,Cordella D,Fortunato O,et al. Global remodeling of the vascular stem cell niche in bone marrow of diabetic patients:implication of the microRNA-155/FOXO3a signaling pathway[J]. Circ Res,2013,112:510-522.
[44] Teraa M,Fledderus JO, Rozbeh RI, et al. Bone marrow microvascular and neuropathic alterations in patients with critical limb ischemia[J]. Circ Res,2014,114:311-314.
[45] Bonnet N. Bone-derived factors:a new gateway to regulate glycemia[J]. Calcif Tissue Int, 2017, 100:174-183.
[46]刘建民.骨骼对糖代谢的调控作用[J].中华糖尿病杂志,2016,1:8-11.
[47] Fulzele K,Riddle RC,Di Girolamo DJ,et al. Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition[J]. Cell,2010,142:309-319.
[48] Ferron M,McKee MD,Levine RL,et al. Intermittent injections of osteocalcin improve glucose metabolism and prevent type 2 diabetes in mice[J]. Bone,2012,50:568-575.
[49] Wei J,Ferron M,Clarke CJ,et al. Bone-specific insulin resistance disrupts whole-body glucose homeostasis via decreased osteocalcin activation[J]. J Clin Invest,2014,124:1-13.
[50] Mansur SA,Mieczkowska A,Flatt PR,et al. A new stable GIP-Oxyntomodulin hybrid peptide improved bone strength both at the organ and tissue levels in genetically-inherited type 2 diabetes mellitus[J]. Bone,2016,87:102-113.
[51] Khorsand B,Nicholson N,Do AV,et al. Regeneration of bone using nanoplex delivery of FGF-2 and BMP-2 genes in diaphyseal long bone radial defects in a diabetic rabbit model[J]. J Control Release,2017,248:53-59.
[52] Schmidt FN,Zimmermann EA,Campbell GM,et al.Assessment of collagen quality associated with non-enzymatic cross-links in human bone using Fourier-transform infrared imaging[J]. Bone, 2017, 97:243-251.
[53] McCarthy AD,Uemura T,Etcheverry SB,et al. Advanced glycation endproducts interefere with integrinmediated osteoblastic attachment to a type-I collagen matrix[J]. Int J Biochem Cell Biol, 2004, 36:840-848.
[54] Saito M,Fujii K,Mori Y,et al. Role of collagen enzymatic and glycation induced cross-links as a determinant of bone quality in spontaneously diabetic WBN/Kob rats[J]. Osteoporos Int,2006,17:1514-1523.
[55] Valcourt U,Merle B,Gineyts E,et al. Non-enzymatic glycation of bone collagen modifies osteoclastic activity and differentiation[J]. J Biol Chem, 2007, 282:5691-5703.
[56] Takagi M,Kasayama S,Yamamoto T,et al. Advanced glycation endproducts stimulate interleukin-6 production by human bone-derived cells[J]. J Bone Miner Res,1997,12:439-446.
[57] Kume S,Kato S,Yamagishi SI,et al. Advanced glycation end-products attenuate human mesenchymal stem cells and prevent cognate differentiation into adipose tissue,cartilage,and bone[J]. J Bone Mineral Res,2005,20:1647-1658.
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