Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures

The primary goal of this study was to assess peripheral bone microarchitecture and strength in postmenopausal women with type 2 diabetes with fragility fractures (DMFx) and to compare them with postmenopausal women with type 2 diabetics without fractures (DM). Secondary goals were to assess differences in nondiabetic postmenopausal women with fragility fractures (Fx) and nondiabetic postmenopausal women without fragility fractures (Co), and in DM and Co women. Eighty women (mean age 61.3 ± 5.7 years) were recruited into these four groups (DMFx, DM, Fx, and Co; n = 20 per group). Participants underwent dual‐energy X‐ray absorptiometry (DXA) and high‐resolution peripheral quantitative computed tomography (HR‐pQCT) of the ultradistal and distal radius and tibia. In the HR‐pQCT images volumetric bone mineral density and cortical and trabecular structure measures, including cortical porosity, were calculated. Bone strength was estimated using micro–finite element analysis (µFEA). Differential strength estimates were obtained with and without open cortical pores. At the ultradistal and distal tibia, DMFx had greater intracortical pore volume (+52.6%, p = 0.009; +95.4%, p = 0.020), relative porosity (+58.1%, p = 0.005; +87.9%, p = 0.011) and endocortical bone surface (+10.9%, p = 0.031; +11.5%, p = 0.019) than DM. At the distal radius DMFx had 4.7‐fold greater relative porosity (p < 0.0001) than DM. At the ultradistal radius, intracortical pore volume was significantly higher in DMFx than DM (+67.8%, p = 0.018). DMFx also displayed larger trabecular heterogeneity (ultradistal radius: +36.8%, p = 0.035), and lower total and cortical BMD (ultradistal tibia: −12.6%, p = 0.031; −6.8%, p = 0.011) than DM. DMFx exhibited significantly higher pore‐related deficits in stiffness, failure load, and cortical load fraction at the ultradistal and distal tibia, and the distal radius than DM. Comparing nondiabetic Fx and Co, we only found a nonsignificant trend with increase in pore volume (+38.9%, p = 0.060) at the ultradistal radius. The results of our study suggest that severe deficits in cortical bone quality are responsible for fragility fractures in postmenopausal diabetic women. © 2013 American Society for Bone and Mineral Research

[1]  P. Vestergaard,et al.  Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a meta-analysis , 2007, Osteoporosis International.

[2]  P. Zysset,et al.  Validation of an anatomy specific finite element model of Colles' fracture. , 2008, Journal of biomechanics.

[3]  Ego Seeman,et al.  Intracortical remodelling and porosity in the distal radius and post-mortem femurs of women: a cross-sectional study , 2010, The Lancet.

[4]  S. Cummings,et al.  Older women with diabetes have an increased risk of fracture: a prospective study. , 2001, The Journal of clinical endocrinology and metabolism.

[5]  A. Hofman,et al.  Bone mineral density and fracture risk in type-2 diabetes mellitus: the Rotterdam Study. , 2005, Osteoporosis International.

[6]  Heather M. Macdonald,et al.  Age‐related patterns of trabecular and cortical bone loss differ between sexes and skeletal sites: A population‐based HR‐pQCT study , 2011, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[7]  Walter C Willett,et al.  Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. , 2007, American journal of epidemiology.

[8]  JB. Pialat,et al.  Visual grading of motion induced image degradation in high resolution peripheral computed tomography: impact of image quality on measures of bone density and micro-architecture. , 2012, Bone.

[9]  P Rüegsegger,et al.  Comparison of structure extraction methods for in vivo trabecular bone measurements. , 1999, Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society.

[10]  X. Guo,et al.  Abnormal microarchitecture and stiffness in postmenopausal women with ankle fractures. , 2011, The Journal of clinical endocrinology and metabolism.

[11]  Steven K Boyd,et al.  Bone strength at the distal radius can be estimated from high-resolution peripheral quantitative computed tomography and the finite element method. , 2008, Bone.

[12]  X. Guo,et al.  High-Resolution Peripheral Quantitative Computed Tomography Can Assess Microstructural and Mechanical Properties of Human Distal Tibial Bone , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[13]  S. Cummings,et al.  Older women with diabetes have an increased risk of fracture: a prospective study. , 2001, The Journal of clinical endocrinology and metabolism.

[14]  Thomas M. Link,et al.  The Effects of Geometric and Threshold Definitions on Cortical Bone Metrics Assessed by In Vivo High-Resolution Peripheral Quantitative Computed Tomography , 2007, Calcified Tissue International.

[15]  Ralph Müller,et al.  Contribution of In Vivo Structural Measurements and Load/Strength Ratios to the Determination of Forearm Fracture Risk in Postmenopausal Women , 2007, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[16]  P. Rüegsegger,et al.  In vivo high resolution 3D-QCT of the human forearm. , 1998, Technology and health care : official journal of the European Society for Engineering and Medicine.

[17]  R. Huiskes,et al.  Direct mechanics assessment of elastic symmetries and properties of trabecular bone architecture. , 1996, Journal of biomechanics.

[18]  P. Pietschmann,et al.  Serum osteocalcin levels in diabetes mellitus: analysis of the type of diabetes and microvascular complications , 1988, Diabetologia.

[19]  Claus Christiansen,et al.  Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. , 1994, World Health Organization technical report series.

[20]  M. Nevitt,et al.  Vertebral fracture assessment using a semiquantitative technique , 1993, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[21]  Sharmila Majumdar,et al.  Reproducibility of direct quantitative measures of cortical bone microarchitecture of the distal radius and tibia by HR-pQCT. , 2010, Bone.

[22]  S. Robinovitch,et al.  Prediction of upper extremity impact forces during falls on the outstretched hand. , 1998, Journal of biomechanics.

[23]  Steven K Boyd,et al.  Automatic segmentation of cortical and trabecular compartments based on a dual threshold technique for in vivo micro-CT bone analysis. , 2007, Bone.

[24]  A. Sebastian,et al.  How metabolic acidosis and oxidative stress alone and interacting may increase the risk of fracture in diabetic subjects. , 2012, Medical hypotheses.

[25]  E. Vittinghoff,et al.  Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. , 2011, JAMA.

[26]  S. Yamagishi.  Role of advanced glycation end products (AGEs) in osteoporosis in diabetes. , 2011, Current drug targets.

[27]  Sharmila Majumdar,et al.  Age- and Gender-Related Differences in the Geometric Properties and Biomechanical Significance of Intracortical Porosity in the Distal Radius and Tibia , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[28]  S. Cremers,et al.  Bone structure and turnover in type 2 diabetes mellitus , 2012, Osteoporosis International.

[29]  M. Bouxsein,et al.  A bone structural basis for fracture risk in diabetes. , 2008, The Journal of clinical endocrinology and metabolism.

[30]  Felix Eckstein,et al.  Computational finite element bone mechanics accurately predicts mechanical competence in the human radius of an elderly population. , 2011, Bone.

[31]  B. van Rietbergen,et al.  Bone micro-architecture and determinants of strength in the radius and tibia: age-related changes in a population-based study of normal adults measured with high-resolution pQCT , 2009, Osteoporosis International.

[32]  A. Schwartz,et al.  Diabetes, fracture, and bone fragility , 2007, Current osteoporosis reports.

[33]  Marion Kee,et al.  Analysis , 2004, Machine Translation.

[34]  S. Majumdar,et al.  High-resolution peripheral quantitative computed tomographic imaging of cortical and trabecular bone microarchitecture in patients with type 2 diabetes mellitus. , 2010, Journal of Clinical Endocrinology and Metabolism.

[35]  Steven K Boyd,et al.  Postmenopausal women with osteopenia have higher cortical porosity and thinner cortices at the distal radius and tibia than women with normal aBMD: An in vivo HR‐pQCT study , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[36]  P. Rüegsegger,et al.  Calibration of trabecular bone structure measurements of in vivo three-dimensional peripheral quantitative computed tomography with 28-microm-resolution microcomputed tomography. , 1999, Bone.

[37]  Emily Stein,et al.  Differences in bone microarchitecture between postmenopausal Chinese‐American and white women , 2011, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[38]  J. A. Garcia-Salcedo,et al.  Circulating levels of sclerostin are increased in patients with type 2 diabetes mellitus. , 2012, The Journal of clinical endocrinology and metabolism.

[39]  G. H. van Lenthe,et al.  Assessing forearm fracture risk in postmenopausal women , 2010, Osteoporosis International.

[40]  P. Rüegsegger,et al.  A new method for the model‐independent assessment of thickness in three‐dimensional images , 1997 .

[41]  Laurence Vico,et al.  High‐Resolution pQCT Analysis at the Distal Radius and Tibia Discriminates Patients With Recent Wrist and Femoral Neck Fractures , 2008, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[42]  M. Bouxsein,et al.  In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography. , 2005, The Journal of clinical endocrinology and metabolism.

[43]  P Rüegsegger,et al.  Three-dimensional finite element modelling of non-invasively assessed trabecular bone structures. , 1995, Medical engineering & physics.

[44]  Pamela J Schreiner,et al.  Older women with diabetes have a higher risk of falls: a prospective study. , 2002, Diabetes care.

[45]  R. Ferber,et al.  Bone quality and muscle strength in female athletes with lower limb stress fractures. , 2011, Medicine and science in sports and exercise.

[46]  Ann L Oberg,et al.  Effects of Sex and Age on Bone Microstructure at the Ultradistal Radius: A Population‐Based Noninvasive In Vivo Assessment , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[47]  P. Delmas,et al.  Alterations of Cortical and Trabecular Architecture Are Associated With Fractures in Postmenopausal Women, Partially Independent of Decreased BMD Measured by DXA: The OFELY Study , 2007, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.