Abstract
Summary
Fracture risk is increased in type 2 diabetes mellitus (T2DM). The effect of pre-diabetes and T2DM on bone macroarchitecture and strength has not been well investigated. In this study, we show that in women only, both pre-diabetes and T2DM are associated with decreased hip bending strength and mineralization which might lead to skeletal weakness.
Introduction
Older men and women with T2DM are at increased risk for fracture despite normal bone mineral density (BMD). The discordance between bone quantity and skeletal fragility has driven investigation into additional determinants of fracture resistance in T2DM. Additionally, the effect of pre-diabetes on bone strength has not been well described. The aim of this study was to determine differences in bone macroarchitecture and strength, measured by hip geometry, in persons with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM.
Methods
We performed cross-sectional analyses of older (age >55 years) men (n = 472) and women (n = 473) participating in the Baltimore Longitudinal Study of Aging (BLSA) classified as NGT, IGT, or T2DM based on oral glucose tolerance testing. Bone strength measures included the hip geometry parameters of section modulus (Z), cross-sectional area (CSA), and buckling ratio (BR). Sex-stratified analyses were conducted using adjusted stepwise regression models.
Results
In women, IGT and T2DM were negatively associated with hip geometry parameters including mineralization in cross section (CSA, ß −0.076 and −0.073, respectively; both p < 0.05) and hip bending strength (Z, ß −0.097 and −0.09, respectively; both p < 0.05); conversely, IGT and T2DM were associated with improved compressive strength (BR, ß −0.31 and −0.29, respectively; both p < 0.05). There was no significant association between glycemic status and hip geometry in men.
Conclusions
In women only, both IGT and T2DM were inversely associated with bone macroarchitecture and measures of bone mineralization and bending strength. The same association between worsening glycemic status and bone strength was not observed in men. These data suggest a differential effect of sex on hip geometry with evolving glucose intolerance.
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References
Looker AC, Dawson-Hughes B, Tosteson AN, Johansson H, Kanis JA, Melton LJ 3rd (2010) Hip fracture risk in older US adults by treatment eligibility status based on new National Osteoporosis Foundation guidance. Osteoporos Int 22(2):541–549
Tosteson AN, Gottlieb DJ, Radley DC, Fisher ES, Melton LJ 3rd (2007) Excess mortality following hip fracture: the role of underlying health status. Osteoporos Int 18(11):1463–1472
Leibson CL, Tosteson AN, Gabriel SE, Ransom JE, Melton LJ (2002) Mortality, disability, and nursing home use for persons with and without hip fracture: a population-based study. J Am Geriatr Soc 50(10):1644–1650
Shaw JE, Sicree RA, Zimmet PZ (2010) Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 87(1):4–14
Cowie CC, Rust KF, Byrd-Holt DD et al (2006) Prevalence of diabetes and impaired fasting glucose in adults in the U.S. population: national health and nutrition examination survey 1999–2002. Diabetes Care 29(6):1263–1268
Strotmeyer ES, Cauley JA, Schwartz AV et al (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(14):1612–1617
de Liefde II, 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(12):1713–1720
Schwartz AV, Sellmeyer DE, Ensrud KE et al (2001) Older women with diabetes have an increased risk of fracture: a prospective study. J Clin Endocrinol Metab 86(1):32–38
Bonds DE, Larson JC, Schwartz AV et al (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
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
Melton LJ 3rd, 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
Seeman E, Delmas PD (2006) Bone quality—the material and structural basis of bone strength and fragility. N Engl J Med 354(21):2250–2261
Bouxsein ML (2003) Bone quality: where do we go from here? Osteoporos Int 14(Suppl 5):S118–S127
Brownbill RA, Ilich JZ (2003) Hip geometry and its role in fracture: what do we know so far? Curr Osteoporos Rep 1(1):25–31
Bonnick SL (2007) HSA: beyond BMD with DXA. Bone 41(1 Suppl 1):S9–S12
Lauretani F, Bandinelli S, Griswold ME et al (2008) Longitudinal changes in BMD and bone geometry in a population-based study. J Bone Miner Res 23(3):400–408
Donnelly E (2011) Methods for assessing bone quality: a review. Clin Orthop Relat Res 469(8):2128–2138
Beck TJ, Ruff CB, Warden KE, Scott WW Jr, Rao GU (1990) Predicting femoral neck strength from bone mineral data. A structural approach. Investig Radiol 25(1):6–18
Viegas M, Costa C, Lopes A, Griz L, Medeiro MA, Bandeira F (2011) Prevalence of osteoporosis and vertebral fractures in postmenopausal women with type 2 diabetes mellitus and their relationship with duration of the disease and chronic complications. J Diabet Complicat 25(4):216–221
Metter EJ, Windham BG, Maggio M et al (2008) Glucose and insulin measurements from the oral glucose tolerance test and mortality prediction. Diabetes Care 31(5):1026–1030
American Diabetes Association (2010) Standards of medical care in diabetes—2010. Diabetes Care 33(Suppl 1):S11–S61
Beck TJ, Ruff CB, Scott WW Jr, Plato CC, Tobin JD, Quan CA (1992) Sex differences in geometry of the femoral neck with aging: a structural analysis of bone mineral data. Calcif Tissue Int 50(1):24–29
Moseley KF (2012) Type 2 diabetes and bone fractures. Curr Opin Endocrinol Diabetes Obes 19(2):128–135
Schwartz AV, Sellmeyer DE (2007) Diabetes, fracture, and bone fragility. Curr Osteoporos Rep 5(3):105–111
Forsen L, Meyer HE, Midthjell K, Edna TH (1999) Diabetes mellitus and the incidence of hip fracture: results from the Nord-Trondelag Health Survey. Diabetologia 42(8):920–925
Cortes-Sancho R, Perez-Castrillon JL, Martin-Escudero JC, Iglesias S, Alvarez-Manzanares P, Ramos R (2004) Type 2 diabetes mellitus as a risk factor for hip fracture. J Am Geriatr Soc 52(10):1778–1779
Nicodemus KK, Folsom AR, Iowa Women’s Health Study (2001) Type 1 and type 2 diabetes and incident hip fractures in postmenopausal women. Diabetes Care 24(7):1192–1197
Michaelsson K, Holmberg L, Mallmin H et al (1995) Diet and hip fracture risk: a case–control study. Study Group of the Multiple Risk Survey on Swedish Women for Eating Assessment. Int J Epidemiol 24(4):771–782
Patsch JM, Burghardt AJ, Yap SP et al (2013) Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures. J Bone Miner Res 28(2):313–324
Farr JN, Drake MT, Amin S, Melton LJ 3rd, McCready LK, Khosla S (2013) In vivo assessment of bone quality in postmenopausal women with type 2 diabetes. J Bone Miner Res 29(4):787–795
Schwartz AV, Sellmeyer DE (2008) Effect of thiazolidinediones on skeletal health in women with type 2 diabetes. Expert Opin Drug Saf 7(1):69–78
Adami S (2009) Bone health in diabetes: considerations for clinical management. Curr Med Res Opin 25(5):1057–1072
Ishii S, Cauley JA, Crandall CJ et al (2012) Diabetes and femoral neck strength: findings from the hip strength across the menopausal transition study. J Clin Endocrinol Metab 97(1):190–197
Garg R, Chen Z, Beck T et al (2012) Hip geometry in diabetic women: implications for fracture risk. Metabolism 61(12):1756–1762
Srikanthan P, Crandall CJ, Miller-Martinez D et al (2013) Insulin resistance and bone strength. Findings from the study of midlife in the United States. J Bone Miner Res 29(4):796–803
Beck TJ, Petit MA, Wu G, LeBoff MS, Cauley JA, Chen Z (2009) Does obesity really make the femur stronger? BMD, geometry, and fracture incidence in the women's health initiative-observational study. J Bone Miner Res 24(8):1369–1379
Moseley KF, Dobrosielski DA, Stewart KJ, Sellmeyer DE, Jan De Beur SM (2011) Lean mass predicts hip geometry in men and women with non-insulin-requiring type 2 diabetes mellitus. J Clin Densitom 14(3):332–339
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(6):1619–1628
Acknowledgments
This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging, and the National Institute of Diabetes and Digestive and Kidney Diseases, K23DK093720. It was also supported by the Legato Research Scholar Awards in Gender-Specific Medicine, Foundation for Gender-Specific Medicine, Inc.
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L. Ferrucci and D. E. Sellmeyer contributed equally to this work.
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Moseley, K.F., Chia, C.W., Simonsick, E.M. et al. Sex-specific differences in progressive glucose intolerance and hip geometry: the Baltimore Longitudinal Study of Aging. Osteoporos Int 26, 1555–1562 (2015). https://doi.org/10.1007/s00198-015-3027-z
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DOI: https://doi.org/10.1007/s00198-015-3027-z