Individuals with type 2 diabetes mellitus show dimorphic and heterogeneous patterns of loss in femoral bone quality

Wölfel, Eva M.<sup>1</sup>; Jähn-Rickert, Katharina<sup>1</sup>; Schmidt, Felix N.<sup>1</sup>; Wulff, Birgit<sup>2</sup>; Mushumba, Herbert<sup>2</sup>; Sroga, Grazyna E.<sup>3</sup>; Püschel, Klaus<sup>2</sup>; Milovanovic, Petar<sup>1,4</sup>; Amling, Michael<sup>1</sup>; Campbell, Graeme M.<sup>1</sup>; Vashishth, Deepak<sup>3</sup>; Busse, Björn<sup>1</sup>

Affiliations

¹Department of Osteology and Biomechanics, University Medical Center Hamburg‐Eppendorf, Hamburg, Germany

²Department of Forensic Medicine, University Medical Center Hamburg‐Eppendorf, Hamburg, Germany

³Center for Biotechnology and Interdisciplinary Studies, Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA

⁴Laboratory for Anthropology and Skeletal Biology, Institute of Anatomy, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

Abstract and keywords

Type 2 diabetes mellitus (T2DM), a metabolic disease on the rise, is associated with substantial increase in bone fracture risk. Because individuals with T2DM have normal or high bone mineral density (BMD), osteodensitometric measurements of BMD do not predict fracture risk with T2DM. Here, we aim to identify the underlying mechanism of the diabetes-induced fracture risk using a high-resolution multi-scale analysis of human cortical bone with special emphasis on osseous cellular activity. Specifically, we show increased cortical porosity in a subgroup of T2DM individuals accompanied by changed mineralization patterns and glycoxidative damage to bone protein, caused by non-enzymatic glycation of bone by reducing sugar. Furthermore, the high porosity T2DM subgroup presents with higher regional mineralization heterogeneity and lower mineral maturity, whereas in the T2DM subgroup regional higher mineral-to-matrix ratio was observed. Both T2DM groups show significantly higher carboxymethyl-lysine accumulation. Our results show a dimorphic pattern of cortical bone reorganization in individuals afflicted with T2DM and hence provide new insight into the diabetic bone disease leading to increased fracture risk.

Keywords: Type 2 diabetes mellitus; Micro-CT;Cortical bone; Histomorphometry; bone quality

Links

DOI: 10.1016/j.bone.2020.115556

PubMed: 32730921

WoS: 000572849900010

History

Received: 2020-03-23

Revised: 2020-07-09

Accepted: 2020-07-09

Online: 2020-07-28

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Cited By (8)

Year	Entry
2022	Stephen SJ, Bailey S, D'Erminio DN, Krishnamoorthy D, Iatridis JC, Vashishth D. Bone matrix quality in a developing high-fat diet mouse model is altered by RAGE deletion. Bone. September 2022;162:116470.
2022	Wölfel EM, Fiedler IAK, Dragoun Kolibova S, Krug J, Lin M-C, Yazigi B, Siebels AK, Mushumba H, Wulff B, Ondruschka B, Püschel K, Glüer CC, Jähn-Rickert K, Busse B. Human tibial cortical bone with high porosity in type 2 diabetes mellitus is accompanied by distinctive bone material properties. Bone. December 2022;165:116546.
2023	Wang B, Vashishth D. Advanced glycation and glycoxidation end products in bone. Bone. November 2023;176:116880.
2022	Dhaliwal R, Ewing SK, Vashishth D, Semba RD, Schwartz AV. Greater carboxy-methyl-lysine is associated with increased fracture risk in type 2 diabetes. J Bone Miner Res. February 2022;37(2):265-272.
2022	Wölfel EM, Schmidt FN, vom Scheidt A, Siebels AK, Wulff B, Mushumba H, Ondruschka B, Püschel K, Scheijen J, Schalkwijk CG, Vettorazzi E, Jähn-Rickert K, Gludovatz B, Schaible E, Amling M, Rauner M, Hofbauer LC, Zimmermann EA, Busse B. Dimorphic mechanisms of fragility in diabetes mellitus: the role of reduced collagen fibril deformation. J Bone Miner Res. November 2022;37(11):2259-2276.
2023	Lekkala S, Sacher SE, Taylor EA, Williams RM, Moseley KF, Donnelly E. Increased advanced glycation endproducts, stiffness, and hardness in iliac crest bone from postmenopausal women with type 2 diabetes mellitus on insulin. J Bone Miner Res. February 2023;38(2):261-277.
2021	Jia S, Gong H, Cen H, Shi P, Zhang R, Li Z, Bi X. Influence of non-enzymatic glycation on the mechanical properties of cortical bone. J Mech Behav Biomed Mater. July 1, 2021;119:104553.
2021	Sacher S. Characterization of Trabecular Morphology, Microdamage Accumulation, and Collagen Crosslinking in Bone Tissue from Individuals With Type II Diabetes Mellitus [Master's thesis]. Ithaca, NY: Cornell University; May 2021.