Department of Materials Science and Engineering, Cornell University, Ithaca, NY, USA.
Sibley School of Mechanical Engineering, Cornell University, Ithaca, NY, USA.
J Bone Miner Res. 2021 Feb;36(2):334-346. doi: 10.1002/jbmr.4186. Epub 2020 Oct 29.
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).
2 型糖尿病（T2DM）患者发生脆性骨折的风险增加，即使在控制骨密度、体重指数、视力障碍和跌倒后也是如此。我们假设渐进性血糖紊乱会改变微尺度骨组织的组成。我们使用傅里叶变换红外（FTIR）成像分析了口服葡萄糖耐量试验（OGTT）特征的绝经后妇女的髂嵴活检的组成：正常糖耐量（NGT；n = 35，年龄 = 65 ± 7 岁，HbA1c = 5.8 ± 0.3%）、糖耐量受损（IGT；n = 26，年龄 = 64 ± 5 岁，HbA1c = 6.0 ± 0.4%）和显性 T2DM 胰岛素治疗（n = 25，年龄 = 64 ± 6 岁，HbA1c = 9.13 ± 0.6）。皮质骨矿物质含量的分布有更高的平均值（+7%）和更窄的范围（-10%）在 T2DM 与 NGT 组之间（p < 0.05）。新矿化的酸性磷酸盐的分布在皮质 T2DM 与 NGT 和 IGT 组（-14%和-14%）以及小梁 NGT 和 IGT 与 T2DM 组（-11%和-10%）更窄（均 p < 0.05）。皮质 NGT 与 T2DM 组（+16%）和小梁 NGT 与 T2DM 组（+14%）的结晶度分布更宽（均 p < 0.05）。T2DM 与 NGT 组相比，骨转换率更低（P1NP：-25%，CTX：-30%，ucOC：-24%）。各组血清戊糖含量相似。IGT 组的 FTIR 组成和生化标志物值通常介于 NGT 和 T2DM 组值之间，尽管差异并不总是具有统计学意义。总之，血糖控制恶化与矿物质含量增加和酸性磷酸盐分布变窄有关，酸性磷酸盐是新矿化的指标，这与骨转换率降低的观察结果一致；然而，也观察到矿物质结晶度分布变宽。更矿化、更不均匀的组织可能会影响组织水平的机械性能，并进而破坏大尺度骨骼的完整性。总之，这些数据首次证明了在人类中，随着血糖控制的恶化，骨组织组成逐渐发生变化。
