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DOI: 10.1055/s-0042-117719
Type 2 Diabetes and Aging: A Not so Sweet Scenario for Bone
Publication History
received 21 December 2015
accepted 12 September 2016
Publication Date:
11 October 2016 (online)
Abstract
Type 2 diabetes and fractures are associated with substantial mortality and morbidity in the aging population. Given the normal to high bone mineral density, skeletal fragility in type 2 diabetes is an intriguing topic of ongoing research. An improved understanding of the underlying mechanisms and regulators of bone pathology in diabetes is needed to formulate targeted prevention and intervention strategies in this high risk population. Although the changes in bone induced by aging and disease are divergent, the pathogenetic mechanisms of aging and type 2 diabetes, thus far known, are not mutually exclusive. These mechanisms may provide deeper insight into the quantitative and qualitative deficits to further our knowledge of diabetes-specific bone pathology.
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References
- 1 Centers for Disease Control and Prevention . The State of Aging and Health in America 2013. Available at http://www.cdc.gov/features/agingandhealth/state_of_aging_and_health_in_america_2013.pdf Accessed December 2015
- 2 Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A. Incidence and Economic Burden of Osteoporosis-Related Fractures in the United States, 2005–2025. J Bone Miner Res 2007; 22: 465-475
- 3 Centers for Disease Control and Prevention . National Diabetes Fact Sheet: General Information and National Estimates on Diabetes in the United States, 2011. Atlanta, Georgia, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2011. Available at http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf Accessed December 2015
- 4 International Diabetes Federation . Diabetes Atlas, 5th ed. 2011. International Diabetes Federation [serial online]. Available at http://www.diabetesatlas.org/content/diabetes-and-impaired-glucosetolerance Accessed December 2015
- 5 Lipscombe LL, Jamal SA, Booth GL, Hawker GA. The risk of hip fractures in older individuals with diabetes: a population-based study. Diabetes Care 2007; 30: 835-841
- 6 Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a meta-analysis. Osteoporos Int 2007; 18: 427-444
- 7 Janghorbani M, Van Dam RM, Willett WC, Hu FB. Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol 2007; 166: 495-505
- 8 Volpato S, Leveille SG, Blaum C, Fried LP, Guralnik JM. Risk factors for falls in older disabled women with diabetes: the women’s health and aging study. J Gerontol A Biol Sci Med Sci 2005; 60: 1539-1545
- 9 Schwartz AV, Vittinghoff E, Sellmeyer DE, Feingold KR, de Rekeneire N, Strotmeyer ES, Shorr RI, Vinik AI, Odden MC, Park SW, Faulkner KA, Harris TB. Diabetes-related complications, glycemic control, and falls in older adults. Diabetes Care 2008; 31: 391-396
- 10 Schwartz AV, Sellmeyer DE, Ensrud KE, Cauley JA, Tabor HK, Schreiner PJ, Jamal SA, Black DM, Cummings SR. Older women with diabetes have an increased risk of fracture: a prospective study. J Clin Endocrinol Metab 2001; 86: 32-38
- 11 Strotmeyer ES, Cauley JA, Schwartz AV, Nevitt MC, Resnick HE, Zmuda JM, Bauer DC, Tylavsky FA, de Rekeneire N, Harris TB, Newman AB. Diabetes is associated independently of body composition with BMD and bone volume in older white and black men and women: The Health, Aging, and Body Composition Study. J Bone Miner Res 2004; 19: 1084-1091
- 12 Bonds DE, Larson JC, Schwartz AV, Strotmeyer ES, Robbins J, Rodriguez BL, Johnson KC, Margolis KL. Risk of fracture in women with type 2 diabetes: the Women’s Health Initiative Observational Study. J Clin Endocrinol Metab 2006; 91: 3404-3410
- 13 Szoke E, Shrayyef MZ, Messing S, Woerle HJ, van Haeften TW, Meyer C, Mitrakou A, Pimenta W, Gerich JE. Effect of aging on glucose homeostasis: accelerated deterioration of beta-cell function in individuals with impaired glucose tolerance. Diabetes Care 2008; 31: 539-543
- 14 Chang AM, Halter JB. Aging and insulin secretion. Am J Physiol Endocrinol Metab 2003; 284: E7-E12
- 15 Riggs BL, Khosla S, Melton LJ. Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev 2002; 23: 279-302
- 16 Brown SA, Rosen CJ. Osteoporosis. Med Clin North Am 2003; 87: 1039-1063
- 17 Riggs BL, Melton III LJ, Robb RA, Camp JJ, Atkinson EJ, Peterson JM, Rouleau PA, McCollough CH, Bouxsein ML, Khosla S. A population-based study of age and sex differences in bone volumetric density, size, geometry and structure at different skeletal sites. J Bone Miner Res 2004; 19: 1945-1954
- 18 Riggs BL, Melton LJ, Robb RA, Camp JJ, Atkinson EJ, McDaniel L, Amin S, Rouleau PA, Khosla S. A population-based assessment of rates of bone loss at multiple skeletal sites: evidence for substantial trabecular bone loss in young adult women and men. J Bone Miner Res 2008; 23: 205-214
- 19 Johansson H, Kanis JA, Oden A, McCloskey E, Chapurlat RD, Christiansen C, Cummings SR, Diez-Perez A, Eisman JA, Fujiwara S, Glüer CC, Goltzman D, Hans D, Khaw KT, Krieg MA, Kröger H, Lacroix AZ, Lau E, Leslie WD, Mellström D, Melton 3rd LJ, O’Neill TW, Pasco JA, Prior JC, Reid DM, Rivadeneira F, van Staa T, Yoshimura N, Zillikens MC. A meta-analysis of the association of fracture risk and body mass index in women. J Bone Miner Res 2014; 29: 223-233
- 20 De 2nd L, Van der Klift M, De Laet CE, Van Daele PL, Hofman A, Pols HA. Bone mineral density and fracture risk in type-2 diabetes mellitus: the Rotterdam Study. Osteoporos Int 2005; 16: 1713-1720
- 21 Cummings SR, Black DM, Nevitt MC, Browner W, Cauley J, Ensrud K, Genant HK, Palermo L, Scott J, Vogt TM. Bone density at various sites for prediction of hip fractures. The Study of Osteoporotic Fractures Research Group. Lancet 1993; 341: 72-75
- 22 Orwoll E, Blank JB, Barrett-Connor E, Cauley J, Cummings S, Ensrud K, Lewis C, Cawthon PM, Marcus R, Marshall LM, McGowan J, Phipps K, Sherman S, Stefanick ML, Stone K. Design and baseline characteristics of the osteoporotic fractures in men (MrOS) study–a large observational study of the determinants of fracture in older men. Contemp Clin Trials 2005; 26: 569-585
- 23 Petit MA, Paudel ML, Taylor BC, Hughes JM, Strotmeyer ES, Schwartz AV, Cauley JA, Zmuda JM, Hoffman AR, Ensrud KE. Osteoporotic Fractures in Men (MrOs) Study Group. Bone mass and strength in older men with type 2 diabetes: the Osteoporotic Fractures in Men Study. J Bone Miner Res 2010; 25: 285-291
- 24 Heilmeier U, Carpenter DR, Patsch JM, Harnish R, Joseph GB, Burghardt AJ, Baum T, Schwartz AV, Lang TF, Link TM. Volumetric femoral BMD, bone geometry, and serum sclerostin levels differ between type 2 diabetic postmenopausal women with and without fragility fractures. Osteoporos Int 2015; 26: 1283-1293
- 25 Dalle Carbonare L, Giannini S. Bone microarchitecture as an important determinant of bone strength. J Endocrinol Invest 2004; 27: 99-105
- 26 Laib A, Hauselmann HJ, Ruegsegger P. In vivo high resolution 3D-QCT of the human forearm. Technol. Health Care 1998; 6: 329-337
- 27 Laib A, Ruegsegger P. Calibration of trabecular bone structure measurements of in vivo three-dimensional peripheral quantitative computed tomography with 28-μm-resolution microcomputed tomography. Bone 1999; 24: 35-39
- 28 Ito K, Minka MA, Leunig M, Werlen S, Ganz R. Femoroacetabular impingement and the cam-effect. A MRI-based quantitative anatomical study of the femoral head-neck offset. J Bone Joint Surg Br 2001; 83: 171-176
- 29 Thompson DD. Age changes in bone mineralization, cortical thickness, and haversian canal area. Calcif Tissue Int 1980; 31: 5-11
- 30 Hansen S, Shanbhogue V, Folkestad L, Nielsen MMF, Brixen K. Bone microarchitecture and estimated strength in 499 adult Danish women and men: a cross-sectional, population-based high-resolution peripheral quantitative computed tomographic study on peak bone structure. Calcif Tissue Int 2014; 94: 269-281
- 31 Khosla S, Riggs BL, Atkinson EJ, Oberg AL, McDaniel LJ, Holets M, Peterson JM, Melton 3rd LJ. Effects of sex and age on bone microstructure at the ultradistal radius: a population-based nonin-vasive in vivo assessment. J Bone Miner Res 2006; 21: 124-131
- 32 Macdonald HM, Nishiyama KK, Kang J, Hanley DA, Boyd SK. Age-related patterns of trabecular and cortical bone loss differ between sexes and skeletal sites: a population-based HR-pQCT study. J Bone Miner Res 2011; 26: 50-62
- 33 Parfitt AM, Mathews CH, Villanueva AR, Kleerekoper M, Frame B, Rao DS. Relationships between surface, volume, and thickness of iliac trabecular bone in aging and in osteoporosis. Implications for the microanatomic and cellular mechanisms of bone loss. J Clin Invest 1983; 72: 1396-1409
- 34 Aaron JE, Makins NB, Sagreiya K. The microanatomy of trabecular bone loss in normal aging men and women. Clin Orthop Relat Res 1987; 215: 260-271
- 35 Zebaze RM, Ghasem-Zadeh A, Bohte A, luliano-Burns S, Mirams Price RI, Mackie EJ, Seeman E. Intracortical remodelling and porosity in the distal radius and post-mortem femurs of women: a cross-sectional study. Lancet 2010; 375: 1729-1736
- 36 Burghardt AJ, Issever AS, Schwartz AV, Davis KA, Masharani U, Majumdar S, Link TM. High-resolution peripheral quantitative computed tomographic imaging of cortical and trabecular bone microarchitecture in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 2010; 95: 5045-5055
- 37 Patsch JM, Burghardt AJ, Yap SP, Baum T, Schwartz AV, Joseph GB, Link TM. Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures. J Bone Miner Res 2013; 28: 313-324
- 38 Seeman E, Delmas PD. Bone quality—the material and structural basis of bone strength and fragility. N Engl J Med 2006; 354: 2250-2261
- 39 Farr JN, Drake MT, Amin S, Melton 3rd LJ, McCready LK, Khosla S. In vivo assessment of bone quality in postmenopausal women with type 2 diabetes. J Bone Miner Res 2014; 29: 787-795
- 40 Schwartz AV, Ewing SK, Porzig AM, McCulloch CE, Resnick HE, Hillier TA, Ensrud KE, Black DM, Nevitt MC, Cummings SR, Sellmeyer DE. Diabetes and change in bone mineral density at the hip, calcaneus, spine, and radius in older women. Front Endocrinol (Lausanne) 2013; 4: 62
- 41 Schwartz AV, Sellmeyer DE, Strotmeyer ES, Tylavsky FA, Feingold KR, Resnick HE, Shorr RI, Nevitt MC, Black DM, Cauley JA, Cummings SR, Harris TB. Health ABC Study. Diabetes and bone loss at the hip in older black and white adults. J Bone Miner Res 2005; 20: 596-603
- 42 Gerdhem P, Isaksson A, Akesson K, Obrant KJ. Increased bone density and decreased bone turnover, but no evident alteration of fracture susceptibility in elderly women with diabetes mellitus. Osteoporos Int 2005; 16: 1506-1512
- 43 Dobnig H, Roth M, Piswanger-Sölkner JC, Roth M, Obermayer-Pietsch B, Tiran A, Strele A, Maier E, Maritschnegg P, Sieberer C, Fahrleitner-Pammer A. Type 2 diabetes mellitus in nursing home patients: effects on bone turnover, bone mass, and fracture risk. J Clin Endocrinol Metab 2006; 91: 3355-3363
- 44 Shu A, Yin MT, Stein E, Cremers S, Dworakowski E, Ives R, Rubin MR. Bone structure and turnover in type 2 diabetes mellitus. Osteoporos Int 2011; 23: 635-641
- 45 Yamamoto M, Yamaguchi T, Nawata K, Yamauchi M, Sugimoto T. Decreased PTH levels accompanied by low bone formation are associated with vertebral fractures in postmenopausal women with type 2 diabetes. J Clin Endocrinol Metab 2012; 97: 1277-1284
- 46 Liu C, Wo J, Zhao Q, Wang Y, Wang B, Zhao W. Association between Serum Total Osteocalcin Level and Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Horm Metab Res 2015; 47: 813-819
- 47 Starup-Linde J, Eriksen SA, Lykkeboe S, Handberg A, Vestergaard P. Biochemical markers of bone turnover in diabetes patients–a meta-analysis, and a methodological study on the effects of glucose on bone markers. Osteoporos Int 2014; 25: 1697-1708
- 48 Manavalan JS, Cremers S, Dempster DW, Zhou H, Dworakowski E, Kode A, Kousteni S, Rubin MR. Circulating osteogenic precursor cells in type 2 diabetes mellitus. J Clin Endocrinol Metab 2012; 97: 3240-3250
- 49 Krakauer JC, McKenna MJ, Buderer NF, Rao DS, Whitehouse FW, Parfitt AM. Bone loss and bone turnover in diabetes. Diabetes 1995; 44: 775-782
- 50 Leite Duarte ME, da Silva RD. Histomorphometric analysis of the bone tissue in patients with non-insulin-dependent diabetes (DMNID). Rev Hosp Clin Fac Med Sao Paulo 1996; 51: 7-11
- 51 Amrein K, Dobnig H, Wagner D, Piswanger-Solkner C, Pieber TR, Pilz S, Tomaschitz A, Dimai HP, Fahrleitner-Pammer A. Sclerostin in institutionalized elderly women: associations with quantitative bone ultrasound, bone turnover, fractures and mortality. J. Am. Geriatr. Soc 2014; 62: 1023-1029
- 52 Ardawi MS, Rouzi AA, Al-Sibiani SA, Al-Senani NS, Qari MH, Mousa SA. High serum sclerostin predicts the occurrence of osteoporotic fractures in postmenopausal women: the Center of Excellence for Osteoporosis Research Study. J. Bone Miner. Res 2012; 27: 2592-2602
- 53 Arasu A, Cawthon PM, Lui LY, Do TP, Arora PS, Cauley JA, Ensrud KE, Cummings SR. Study of Osteoporotic Fractures Research Group. Serum sclerostin and risk of hip fracture in older Caucasian women. J Clin Endocrinol Metab 2012; 97: 2027-2032
- 54 Dovjak P, Dorfer S, Foger-Samwald U, Kudlacek S, Marculescu R, Pietschmann P. Serum levels of sclerostin and dickkopf-1: effects of age, gender and fracture status. Gerontology 2014; 60: 493-501
- 55 Gennari L, Merlotti D, Valenti R, Ceccarelli E, Ruvio M, Pietrini MG, Capodarca C, Franci MB, Campagna MS, Calabro A, Cataldo D, Stolakis K, Dotta F, Nuti R. Circulating sclerostin levels and bone turnover in type 1 and type 2 diabetes. J Clin Endocrinol Metab 2012; 97: 1737-1744
- 56 Ardawi MS, Akhbar DH, Alshaikh A, Ahmed MM, Qari MH, Rouzi AA, Ali AY, Abdulrafee AA, Saeda MY. Increased serum sclerostin and decreased serum IGF-1 are associated with vertebral fractures among postmenopausal women with type-2 diabetes. Bone 2013; 56: 355-362
- 57 Lyons TJ, Thorpe SR, Baynes JW. Glycation and autoxidation of proteins in aging and diabetes. In: Ruderman N, Williamson J, Brownlee M. (eds.). Hyperglycemia, Diabetes, and Vascular Disease. New York: Oxford Univ. Press; 1992: 197-217
- 58 Tsilibary EC. Microvascular basement membranes in diabetes mellitus. J Pathol 2003; 200: 537-546
- 59 Almeida M, O’Brien CA. Basic biology of skeletal aging: role of stress response pathways. J Gerontol A Biol Sci Med Sci 2013; 68: 1197-1208
- 60 Manolagas SC. From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr. Rev 2010; 31: 266-300
- 61 Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell 2005; 120: 483-495
- 62 Wanagat J, Dai DF, Rabinovitch P. Mitochondrial oxidative stress and mammalian healthspan. Mech Ageing Dev 2010; 131: 527-535
- 63 Kelley DE, He J, Menshikova EV, Ritov VB. Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes 2002; 51: 2944-2950
- 64 Bai XC, Lu D, Bai J, Zheng H, Ke ZY, Li XM, Luo SQ. Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-κB. Biochem Biophys Res Commun 2004; 314: 197-207
- 65 Garrett IR, Boyce BF, Oreffo RO, Bonewald L, Poser J, Mundy GR. Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo. J Clin Invest 1990; 85: 632-639
- 66 Ambrogini E, Almeida M, Martin-Millan M, Paik JH, Depinho RA, Han L, Goellner J, Weinstein RS, Jilka RL, O’Brien CA, Manolagas SC. FoxO-mediated defense against oxidative stress in osteoblasts is indispensable for skeletal homeostasis in mice. Cell Metab. 2010; 11: 136-146
- 67 Rached MT, Kode A, Xu L, Yoshikawa Y, Paik JH, Depinho RA, Kousteni S. FoxO1 is a positive regulator of bone formation by favoring protein synthesis and resistance to oxidative stress in osteoblasts. Cell Metab. 2010; 11: 147-160
- 68 Tyner SD, Venkatachalam S, Choi J, Jones S, Ghebranious N, Igelmann H, Lu X, Soron G, Cooper B, Brayton C, Park SH, Thompson T, Karsenty G, Bradley A, Donehower LA. p53 mutant mice that display early ageing-associated phenotypes. Nature 2002; 415: 45-53
- 69 Jagger CJ, Lean JM, Davies JT, Chambers TJ. Tumor necrosis factor-alpha mediates osteopenia caused by depletion of antioxidants. Endocrinology 2005; 146: 113-118
- 70 Nojiri H, Saita Y, Morikawa D, Kobayashi K, Tsuda C, Miyazaki T, Saito M, Marumo K, Yonezawa I, Kaneko K, Shirasawa T, Shimizu T. Cytoplasmic superoxide causes bone fragility owing to low-turnover osteoporosis and impaired collagen cross-linking. J Bone Miner Res 2011; 26: 2682-2694
- 71 Stenderup K, Justesen J, Clausen C, Kassem M. Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 2003; 33: 919-926
- 72 Kasper G, Mao L, Geissler S, Draycheva A, Trippens J, Kühnisch J, Tschirschmann M, Kaspar K, Perka C, Duda GN, Klose J. Insights into mesenchymal stem cell aging: involvement of antioxidant defense and actin cytoskeleton. Stem Cells 2009; 27: 1288-1297
- 73 Rosen CJ, Bouxsein ML. Mechanisms of disease: is osteoporosis the obesity of bone?. Nat Clin Pract Rheumatol 2006; 2: 35-43
- 74 Heino TJ, Hentunen TA, Väänänen HK. Conditioned medium from osteocytes stimulates the proliferation of bone marrow mesenchymal stem cells and their differentiation into osteoblasts. Exp Cell Res 2004; 294: 458-468
- 75 Huang SC, Wu TC, Yu HC, Chen MR, Liu CM, Chiang WS, Lin KM. Mechanical strain modulates age-related changes in the proliferation and differentiation of mouse adipose-derived stromal cells. BMC Cell Biol 2010; 11: 18
- 76 Dyer DG, Dunn JA, Thorpe SR, Bailie KE, Lyons TJ, McCance DR, Baynes JW. Accumulation of Maillard reaction products in skin collagen in diabetes and aging. J Clin Invest 1993; 91: 2463-2469
- 77 Brodeur MR, Brissette L, Falstrault L, Ouellet P, Moreau R. Influence of oxidized low-density lipoproteins (LDL) on the viability of osteoblastic cells. Free Radic Biol Med 2008; 44: 506-517
- 78 Klein BY, Rojansky N, Ben-Yehuda A, Abou-Atta I, Abedat S, Friedman G. Cell death in cultured human Saos2 osteoblasts exposed to low-density lipoprotein. J Cell Biochem 2003; 90: 42-58
- 79 Karim L, Vashishth D. Heterogeneous glycation of cancellous bone and its association with bone quality and fragility. PLoS One 2012; 7: e35047
- 80 Valcourt U, Merle B, Gineyts E, Viguet-Carrin S, Delmas PD, Garnero P. Non-enzymatic glycation of bone collagen modifies osteoclastic activity and differentiation. J Biol Chem 2007; 282: 5691-5703
- 81 McCarthy AD, Molinuevo MS, Cortizo AM. Ages and Bone Ageing in Diabetes Mellitus. J. Diabetes Metab 2013; 4: 276
- 82 Tang SY, Allen MR, Phipps R, Burr DB, Vashishth D. Changes in non-enzymatic glycation and its association with altered mechanical properties following 1-year treatment with risedronate or alendronate. Osteoporos Int 2009; 20: 887-894
- 83 Reeve J, Loveridge N. The fragile elderly hip: Mechanisms associated with age-related loss of strength and toughness. Bone 2014; 61: 138-148
- 84 Nalla RK, Stolken JS, Kinney JH, Ritchie RO. Fracture in human cortical bone: local fracture criteria and toughening mechanisms. J Biomech 2005; 38: 1517-1525
- 85 Schaffler MB, Choi K, Milgrom C. Aging and matrix microdamage accumulation in human compact bone. Bone 1995; 17: 521-525
- 86 Zioupos P, Currey JD. Changes in the stiffness, strength and toughness of human cortical bone with age. Bone 1998; 22: 57-66
- 87 Kume S, Kato S, Yamagishi S, Inagaki Y, Ueda S, Arima N, Okawa T, Kojiro M, Nagata K. Advanced glycation end-products attenuate human mesenchymal stem cells and prevent cognate differentiation into adipose tissue, cartilage, and bone. J. Bone Miner Res 2005; 20: 1647-1658
- 88 McCarthy AD, Uemura T, Etcheverry SB, Cortizo AM. Advanced glycation endproducts interefere with integrin-mediated osteoblastic attachment to a type-I collagen matrix. Int J Biochem Cell Biol 2004; 36: 840-848
- 89 Schwartz AV, Garnero P, Hillier TA, Sellmeyer DE, Strotmeyer ES, Feingold KR, Resnick HE, Tylavsky FA, Black DM, Cummings SR, Harris TB, Bauer DC. Pentosidine and increased fracture risk in older adults with type 2 diabetes. Health, Aging, and Body Composition Study. J Clin Endocrinol Metab 2009; 94: 2380-2386
- 90 Ojima A, Matsui T, Nakamura N, Higashimoto Y, Ueda S, Fukami K, Okuda S, Yamagishi S. DNA aptamer raised against advanced glycation end products (ages) improves glycemic control and decreases adipocyte size in fructose-fed rats by suppressing age-rage axis. Horm Metab Res 2015; 47: 253-258
- 91 Bouillon R, Bex M, Van Herck E, Laureys J, Dooms L, Lesaffre E, Ravussin E. Influence of age, sex, and insulin on osteoblast function: osteoblast dysfunction in diabetes mellitus. J Clin Endocrinol Metab 1995; 80: 1194-1202
- 92 Kawai M, Rosen CJ. The IGF-I regulatory system and its impact on skeletal and energy homeostasis. J Cell Biochem 2010; 111: 14-19
- 93 Hayden JM, Mohan S, Baylink DJ. The insulin-like growth factor system and the coupling of formation to resorption. Bone 1995; 17: 93S-98S
- 94 Mohan S, Baylink DJ. Serum insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5 levels in aging and age-associated diseases. Endocrine 1997; 7: 87-91
- 95 Seck T, Scheppach B, Scharla S, Diel I, Blum WF, Bismar H, Schmid G, Krempien B, Ziegler R, Pfeilschifter J. Concentration of insulin-like growth factor (IGF)-I and -II in iliac crest bone matrix from pre- and postmenopausal women: relationship to age, menopause, bone turnover, bone volume, and circulating IGFs. J Clin Endocrinol Metab 1998; 83: 2331-2337
- 96 Garnero P, Sornay-Rendu E, Delmas PD. Low serum IGF-1 and occurrence of osteoporotic fractures in postmenopausal women. Lancet 2000; 355: 898-899
- 97 Yamamoto M, Yamaguchi T, Yamauchi M, Kaji H, Sugimoto T. Diabetic patients have an increased risk of vertebral fractures independent of BMD or diabetic complications. J Bone Miner Res 2009; 24: 702-709
- 98 Drake MT, Khosla S. Male osteoporosis. Endocrinol Metab Clin North Am 2012; 41: 629-641
- 99 Dhindsa S, Prabhakar S, Sethi M, Bandyopadhyay A, Chaudhuri A, Dandona P. Frequent occurrence of hypogonadotropic hypogonadism in Type 2 diabetes. J Clin Endocrinol Metab 2004; 89: 5462-5468
- 100 Asano M, Fukui M, Hosoda M, Shiraishi E, Harusato I, Kadono M, Tanaka M, Hasegawa G, Yoshikawa T, Nakamura N. Bone stiffness in men with type 2 diabetes mellitus. Metabolism 2008; 57: 1691-1695
- 101 Makino N, Maeda T, Sugano M, Satoh S, Watanabe R, Abe N. High serum TNF-alpha level in Type 2 diabetic patients with microangiopathy is associated with eNOS down-regulation and apoptosis in endothelial cells. J Diabetes Complications 2005; 19: 347-355
- 102 Evans WJ, Paolisso G, Abbatecola AM, Corsonello A, Bustacchini S, Strollo F, Lattanzio F. Frailty and muscle metabolism dysregulation in the elderly. Biogerontology 2010; 11: 527-536
- 103 Tanaka KI, Kanazawa I, Sugimoto T. Reduction in endogenous insulin secretion is a risk factor of sarcopenia in men with type 2 diabetes mellitus. Calcif Tissue Int 2015; 97: 385-390
- 104 Strotmeyer ES, Cauley JA, Schwartz AV, de Rekeneire N, Resnick HE, Zmuda JM, Shorr RI, Tylavsky FA, Vinik AI, Harris TB, Newman AB. Health ABC Study. Reduced peripheral nerve function is related to lower hip BMD and calcaneal QUS in older white and black adults: the Health, Aging, and Body Composition Study. J Bone Miner Res 2006; 21: 1803-1810
- 105 Ye Z, Sharp SJ, Burgess S, Scott RA, Imamura F, Langenberg C, Wareham NJ, Forouhi NG. Association between circulating 25-hydroxyvitamin D and incident type 2 diabetes: a mendelian randomisation study. Lancet Diabetes Endocrinol 2015; 3: 35-42
- 106 Strobel F, Reusch J, Penna-Martinez M, Ramos-Lopez E, Klahold E, Klepzig C, Wehrle J, Kahles H, Badenhoop K. Effect of a randomised controlled vitamin D trial on insulin resistance and glucose metabolism in patients with type 2 diabetes mellitus. Horm Metab Res 2014; 46: 54-58
- 107 McNair P, Madsbad S, Christensen MS, Christiansen C, Faber OK, Binder C, Transbøl I. Bone mineral loss in insulin-treated diabetes mellitus: studies on pathogenesis. Acta Endocrinol (Copenh) 1979; 90: 463-472