Nonenzymatic Glycation and Degree of Mineralization Are Higher in Bone From Fractured Patients With Type 1 Diabetes Mellitus

Abstract

Objective Low-energy fractures are frequent complications in Type 1 Diabetes Mellitus patients (T1DM). Modifications of bone intrinsic composition might be a potential cause of fragility observed in diabetic subjects. Advanced Glycation End-products (AGEs) were found in numerous connective tissues from T1DM patients. However, whether AGEs are present at high levels in bone matrix from diabetic subjects is unknown. Moreover, whether elevated AGEs in the bone matrix impair mineralization has not been addressed in humans. The purposes of this study were 1) to determine whether bone matrix from fracturing and non-fracturing T1DM contained more AGEs than bone from healthy patients (CTL), and 2) to compare the degree of mineralization of bone and hardness between fracturing and non-fracturing T1DM versus CTL. Design and methods We analyzed iliac crest bone biopsies from 5 fracturing (Type 1 Diabetes Mellitus) T1DM patients, 5 non-fracturing T1DM patients and 5 healthy subjects, all age- and sex-matched. AGEs (Pentosidine) in bone matrix was measured by high performance liquid chromatography separately in trabecular and cortical bone. The degree of mineralization of bone (DMB) was assessed by digitized microradiography, and mechanical properties by micro- and nanohardness tests. Results Trabecular bone from fracturing T1DM exhibited significantly higher levels of Pentosidine than CTL (p=0.04) and was more mineralized than non-fracturing T1DM (p=0.04) and CTL (p=0.04). Trabecular bone was not significantly different in pentosidine between non-fracturing T1DM and CTL. Cortical bone from non-fracturing T1DM was not significantly different from CTL. Positive correlations were found between HbA1c and Pentosidine (r′=0.79, p<0.003), and between HbA1c and DMB (r′=0.64, p<0.02). Conclusion Both modifications could lead to less flexible bone (reduced modulus of elasticity), and a tendency toward low-energy fractures in T1DM patients.

Interaction between bone and glucose metabolism [Review]

“…Also, we reported a cross-sectional study showing that serum pentosidine levels were significantly and positively associated with prevalent vertebral fracture in postmenopausal women with T2DM [17]. In addition, a recent clinical study using bone biopsy in patients with T1DM showed that pentosidine content in trabecular was significantly and positively associated with HbA1c levels, and increased in T1DM patients with fracture [18]. Therefore, accumulation of pentosidine collagen cross-links in bone may be major cause of BMD-independent bone fragility in patients with DM.…”

MECHANISMS IN ENDOCRINOLOGY: Mechanisms and evaluation of bone fragility in type 1 diabetes mellitus

“…A recent reanalysis of these biopsies further indicates an increased degree of bone mineralization and non-enzymatic collagen crosslinks in diabetes subjects, particularly those with fractures, which would be consistent with a lower bone turnover. Moreover, these parameters were positively correlated with HbA1C, indicating that poor glycemic control has consequences on material bone properties (85).…”

Features of bone metabolism in diabetes mellitus

“…Кроме того, ранее в кросс-секционном исследовании было дока-зано, что уровни пентазидина в сыворотке достоверно и положительно ассоциируются с распространенными при СД2 переломами позвоночника у женщин в постме-нопаузе [9]. Недавнее клиническое исследование, в ко-тором проводилась биопсия кости у пациентов с СД1 показало, что содержание пентозидина в трабекулах было достоверно и положительно связано с уровнем HbA 1c , и было увеличено у СД1 пациентов с перелома-ми [10].…”