Bone Tissue Composition in Postmenopausal Women Varies With Glycemic Control From Normal Glucose Tolerance to Type 2 Diabetes Mellitus

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 microscale bone tissue composition. We used Fourier‐transform infrared (FTIR) imaging to analyze the composition of iliac crest biopsies from cohorts of postmenopausal women characterized by oral glucose tolerance testing: normal glucose tolerance (NGT; n = 35, age = 65 ± 7 years, HbA1c = 5.8 ± 0.3%), impaired glucose tolerance (IGT; n = 26, age = 64 ± 5 years, HbA1c = 6.0 ± 0.4%), and overt T2DM on insulin (n = 25, age = 64 ± 6 years, HbA1c = 9.13 ± 0.6). The distributions of cortical bone mineral content had greater mean values (+7%) and were narrower (−10%) in T2DM versus NGT groups (p < 0.05). The distributions of acid phosphate, an indicator of new mineral, were narrower in cortical T2DM versus NGT and IGT groups (−14% and −14%, respectively) and in trabecular NGT and IGT versus T2DM groups (−11% and −10%, respectively) (all p < 0.05). The distributions of crystallinity were wider in cortical NGT versus T2DM groups (+16%) and in trabecular NGT versus T2DM groups (+14%) (all p < 0.05). Additionally, bone turnover was lower in T2DM versus 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, although 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. © 2020 American Society for Bone and Mineral Research (ASBMR).

Histological Assessment of Cortical Bone Changes in Diabetic Rats

“…In fact, this mineral deposit was abnormal mineralization, possibly resulting in reduced bone absorption and bone strength. Hunt et al reported that mineral crystallinity was observed in patients with diabetes by FTIR (Hunt et al, 2021). This mineral crystallinity may be related to the mineral deposit found in this study.…”

“…The few studies on histological assessments of bone in DM have only included human samples obtained by biopsy or through autopsy. Recently, Hunt et al reported that worsening glycemic control was associated with greater mineral content and narrower distributions of acid phosphate using Fourier-transform infrared (FTIR) for the samples obtained by biopsy (Hunt et al, 2021). However, the actual histological mechanism of bone quality deterioration in DM is largely unknown (Jiang and Xia, 2018).…”

Fracture risk assessment in diabetes mellitus

“…Third, long-term hyperglycemia leads to the accumulation of advanced glycation end products (AGEs). Besides inhibiting the proliferation and differentiation of osteoblasts, AGEs accumulated in the body can not only promote oxidative stress and produce nonenzymatic crosslinking with type I collagen (the two best-characterized AGEs related to collagen are pentosidine and N-carboxymethyllysine) but also damage bone matrix and increase bone stiffness, increasing the chances of fractures (102,103). Although some studies indicated that serum or urinary levels of pentosidine correlated with the risk of vertebral fracture in T2DM (104, 105), the feasibility of predicting fracture risk needs to be further confirmed.…”

Effect of verapamil on bone mass, microstructure and mechanical properties in type 2 diabetes mellitus rats

“…Some scholars have studied the effects of elevated blood glucose in T2DM on advanced glycation end products (AGEs), mineral content and collagen. Elevated blood glucose in T2DM increases AGEs and mineral content [ 8 – 10 ]; hyperglycemia in T2DM leads to increased bone mineral content and average maturity of collagen [ 8 ]. Changes in bone microstructure and material properties (such as bone mineral and collagen) in patients with T2DM can lead to the decrease of bone quality and strength [ 6 ].…”