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Volumetric femoral BMD, bone geometry, and serum sclerostin levels differ between type 2 diabetic postmenopausal women with and without fragility fractures

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Abstract

Summary

While type 2 diabetes (T2D) is associated with higher skeletal fragility, specific risk stratification remains incompletely understood. We found volumetric bone mineral density, geometry, and serum sclerostin differences between low-fracture risk and high-fracture risk T2D women. These features might help identify T2D individuals at high fracture risk in the future.

Introduction

Diabetic bone disease, an increasingly recognized complication of type 2 diabetes mellitus (T2D), is associated with high skeletal fragility. Exactly which T2D individuals are at higher risk for fracture, however, remains incompletely understood. Here, we analyzed volumetric bone mineral density (vBMD), geometry, and serum sclerostin levels in two specific T2D subsets with different fracture risk profiles. We examined a T2D group with prior history of fragility fractures (DMFx, assigned high-risk group) and a fracture-free T2D group (DM, assigned low-risk group) and compared their results to nondiabetic controls with (Fx) and without fragility fractures (Co).

Methods

Eighty postmenopausal women (n = 20 per group) underwent quantitative computed tomography (QCT) to compute vBMD and bone geometry of the proximal femur. Additionally, serum sclerostin, vitamin D, parathyroid hormone (PTH), HbA1c, and glomerular filtration rate (GFR) levels were measured. Statistical analyses employed linear regression models.

Results

DMFx subjects exhibited up to 33 % lower femoral neck vBMD than DM subjects across all femoral sites (−19 % ≤ ΔvBMD ≤ −33 %, 0.008 ≤ p ≤0.021). Additionally, DMFx subjects showed significantly thinner cortices (−6 %, p = 0.046) and a trend toward larger bone volume (+10 %, p = 0.055) relative to DM women and higher serum sclerostin levels when compared to DM (+31.4 %, p = 0.013), Fx (+25.2 %, p = 0.033), and control (+22.4 %, p = 0.028) subjects.

Conclusion

Our data suggest that volumetric bone parameters by QCT and serum sclerostin levels can identify T2D individuals at high risk of fracture and might therefore show promise as clinical tools for fracture risk assessment in T2D. However, future research is needed to establish diabetes-specific QCT- and sclerostin-reference databases.

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Acknowledgments

This study was supported by the National Institutes of Health grants RC1 AR058405 to TML and R01 AR060700 to AJB and the Erwin Schroedinger grant (J-3079 to JMP). We thank Thelma Munoz and Melissa Guan for their help in recruiting and consenting the patients. We also would like to thank Elzbieta Dworakowski and Serge Cremers (Columbia University) for the analysis of serum sclerostin levels which was supported by the National Center for Advancing Translational Sciences, National Institutes of Health through grant number UL1 TR000040 (PI Henry Ginsberg).

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Authors and Affiliations

  1. Musculoskeletal Quantitative Imaging Research Group, Department of Radiology & Biomedical Imaging, University of California San Francisco, 185 Berry Street, Lobby 6, Suite 350, San Francisco, CA, 94158, USA

    U. Heilmeier, J. M. Patsch, R. Harnish, G. B. Joseph, A. J. Burghardt, T. Baum, T. F. Lang & T. M. Link

  2. Department of Mechanical Engineering, University of Colorado Denver, 1200 Larimer Street, Denver, CO, 80217-3364, USA

    D. R. Carpenter

  3. Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria

    J. M. Patsch

  4. Department of Epidemiology and Biostatistics, University of California San Francisco, 185 Berry Street, San Francisco, CA, 94158, USA

    A. V. Schwartz

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  1. U. Heilmeier
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  2. D. R. Carpenter
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  7. T. Baum
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  8. A. V. Schwartz
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  9. T. F. Lang
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Correspondence to U. Heilmeier.

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Heilmeier, U., Carpenter, D.R., Patsch, J.M. et al. Volumetric femoral BMD, bone geometry, and serum sclerostin levels differ between type 2 diabetic postmenopausal women with and without fragility fractures. Osteoporos Int 26, 1283–1293 (2015). https://doi.org/10.1007/s00198-014-2988-7

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