Shen Ivana, Usala Rachel L, Mohseni Mahshid, Bouxsein Mary L, Mitchell Deborah M, Scheller Erica L
Division of Bone and Mineral Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Clin Endocrinol Metab. 2025 Apr 22;110(5):e1555-e1565. doi: 10.1210/clinem/dgae511.
Neuropathy and fracture are prevalent complications of type 1 diabetes (T1D). Although correlated in the clinical literature, it remains unknown whether neuropathy contributes to the initiation of bone loss at the earliest stages of disease.
We performed a single-center, cross-sectional study to quantify parameters of nerve and bone health in adolescent girls with T1D (n = 21) and associated controls (n = 12). Groups were well matched for age, height, strength, and physical activity.
By high-resolution peripheral quantitative computed tomograpy, participants with T1D had lower trabecular bone volume fraction at the distal radius (-14.6%, P-adj = .095) and the tibia (-12.8%, P-adj = .017) and decreased trabecular thickness (-8.3% radius, P-adj = .007; -7.5% tibia, P-adj = .034) after adjustment for body size. In the tibia only, cortical bone mineral density was increased by 8.6% (P-adj = .024) and porosity was decreased by 52.9% with T1D (P-adj = .012). There were no significant differences in bone density by dual-energy x-ray absorptiometry. Participants with T1D also had lower circulating levels of osteocalcin (-30%, P = .057), and type I collagen cross-linked C-telopeptide (-36%, P = .035), suggesting low bone formation and turnover in T1D. Based on the Michigan Neuropathy Screening Instrument, 9.5% of those with T1D had clinical evidence of diabetic peripheral neuropathy. However, consideration of neuropathy status failed to explain the widespread T1D-associated changes in bone.
Our study defines early deficits in trabecular bone microarchitecture, decreased cortical porosity in the tibia, and suppression of biomarkers of bone turnover in adolescent girls with T1D, prior to the onset of symptomatic peripheral neuropathy. These findings inform our understanding of the rapid progression of skeletal disease in young girls with T1D and suggests that early detection and management strategies may help to prevent fracture and related comorbidities later in life.
神经病变和骨折是1型糖尿病（T1D）的常见并发症。尽管在临床文献中有相关性，但神经病变是否在疾病的最早阶段就导致骨质流失仍不清楚。
我们进行了一项单中心横断面研究，以量化患有T1D的青春期女孩（n = 21）和相关对照组（n = 12）的神经和骨骼健康参数。两组在年龄、身高、力量和身体活动方面匹配良好。
通过高分辨率外周定量计算机断层扫描，在调整身体大小后，患有T1D的参与者桡骨远端的骨小梁体积分数较低（-14.6%，校正P值 = 0.095），胫骨的骨小梁体积分数较低（-12.8%，校正P值 = 0.017），骨小梁厚度降低（桡骨-8.3%，校正P值 = 0.007；胫骨-7.5%，校正P值 = 0.034）。仅在胫骨中，患有T1D的参与者皮质骨矿物质密度增加了8.6%（校正P值 = 0.024），孔隙率降低了52.9%（校正P值 = 0.012）。通过双能X线吸收法测量的骨密度没有显著差异。患有T1D的参与者骨钙素的循环水平也较低（-30%，P = 0.057），I型胶原交联C末端肽水平较低（-36%，P = 0.035），表明T1D患者的骨形成和骨转换较低。根据密歇根神经病变筛查工具，9.5%的T1D患者有糖尿病性周围神经病变的临床证据。然而，考虑神经病变状态并不能解释与T1D相关的广泛的骨骼变化。
我们的研究确定了患有T1D的青春期女孩在出现症状性周围神经病变之前，骨小梁微结构的早期缺陷、胫骨皮质孔隙率降低以及骨转换生物标志物的抑制。这些发现有助于我们理解患有T1D的年轻女孩骨骼疾病的快速进展，并表明早期检测和管理策略可能有助于预防晚年的骨折和相关合并症。
