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Bone tissue composition in post-menopausal women varies with glycemic control from normal glucose tolerance to type 2 diabetes mellitus. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Hunt, H. B., Miller, N. A., Hemmerling, K. J., Koga, M. n., Lopez, K. A., Taylor, E. A., Sellmeyer, D. E., Moseley, K. F., Donnelly, E. n. 2020

Abstract

The risk of fragility fracture increases for people with type 2 diabetes mellitus (T2DM), even after controlling for bone mineral density, body mass index, visual impairment, and falls. We hypothesize that progressive glycemic derangement alters micro-scale bone tissue composition. We used Fourier-transform infrared (FTIR) imaging to analyze the composition of iliac crest biopsies from cohorts of post-menopausal women characterized by oral glucose tolerance testing: normal glucose tolerance (NGT; n=35, age=65±7, HbA1c=5.8±0.3%), impaired glucose tolerance (IGT; n=26, age=64±5, HbA1c=6.0±0.4%), and overt T2DM on insulin (n=25, age=64±6, HbA1c=9.13±0.6). The distributions of cortical bone mineral content had greater mean values (+7%) and were narrower (-10%) in T2DM vs. NGT groups (p<0.05). The distributions of acid phosphate, an indicator of new mineral, were narrower in cortical T2DM vs. NGT and IGT groups (-14% and -14%, respectively) and in trabecular NGT and IGT vs. T2DM groups (-11% and -10%, respectively) (all p<0.05). The distributions of crystallinity were wider in cortical NGT vs. T2DM groups (+16%) and in trabecular NGT vs. T2DM groups (+14%) (all p<0.05). Additionally, bone turnover was lower in T2DM vs. NGT groups (P1NP: -25%, CTx: -30%, ucOC: -24%). Serum pentosidine was similar across groups. The FTIR compositional and biochemical marker values of the IGT group typically fell between the NGT and T2DM group values, though the differences were not always statistically significant. In summary, worsening glycemic control was associated with greater mineral content and narrower distributions of acid phosphate, an indicator of new mineral, which together are consistent with observations of lower turnover; however, wider distributions of mineral crystallinity were also observed. A more mineralized, less heterogeneous tissue may affect tissue-level mechanical properties, and in turn degrade macroscale skeletal integrity. In conclusion, these data are the first evidence of progressive alteration of bone tissue composition with worsening glycemic control in humans.

View details for DOI 10.1002/jbmr.4186

View details for PubMedID 32970898