Lei Wang Shin, Rodrick Eugene B, Belcher Staci L, Kelly Andrea, Kindler Joseph M
Department of Nutritional Sciences, The University of Georgia, Athens, GA, USA.
Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
J Clin Transl Endocrinol. 2023 Feb 6;31:100314. doi: 10.1016/j.jcte.2023.100314. eCollection 2023 Mar.
Studies in adults indicate that macronutrient ingestion yields an acute anti-resorptive effect on bone, reflected by decreases in C-terminal telopeptide (CTX), a biomarker of bone resorption, and that gut-derived incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), facilitate this response. There remain knowledge gaps relating to other biomarkers of bone turnover, and whether gut-bone cross-talk is operative during the years surrounding peak bone strength attainment. This study first, describes changes in bone resorption during oral glucose tolerance testing (OGTT), and second, tests relationships between changes in incretins and bone biomarkers during OGTT and bone micro-structure.
We conducted a cross-sectional study in 10 healthy emerging adults ages 18-25 years. During a multi-sample 2-hour 75 g OGTT, glucose, insulin, GIP, GLP-1, CTX, bone-specific alkaline phosphatase (BSAP), osteocalcin, osteoprotegerin (OPG), receptor activator of nuclear factor kappa-β ligand (RANKL), sclerostin, and parathyroid hormone (PTH) were assayed at mins 0, 30, 60, and 120. Incremental areas under the curve (iAUC) were computed from mins 0-30 and mins 0-120. Tibia bone micro-structure was assessed using second generation high resolution peripheral quantitative computed tomography.
During OGTT, glucose, insulin, GIP, and GLP-1 increased significantly. CTX at min 30, 60, and 120 was significantly lower than min 0, with a maximum decrease of about 53 % by min 120. Glucose-iAUC inversely correlated with CTX-iAUC (rho = -0.91, P < 0.001), and GLP-1-iAUC positively correlated with BSAP-iAUC (rho = 0.83, P = 0.005), RANKL-iAUC (rho = 0.86, P = 0.007), and cortical volumetric bone mineral density (rho = 0.93, P < 0.001).
Glucose ingestion yields an anti-resorptive effect on bone metabolism during the years surrounding peak bone strength. Cross-talk between the gut and bone during this pivotal life stage requires further attention.
针对成年人的研究表明，常量营养素摄入对骨骼产生急性抗吸收作用，这可通过骨吸收生物标志物C端肽（CTX）的降低反映出来，并且肠道源性肠促胰岛素激素、葡萄糖依赖性促胰岛素多肽（GIP）和胰高血糖素样肽-1（GLP-1）促进了这种反应。关于骨转换的其他生物标志物以及在达到峰值骨强度前后数年肠道与骨骼之间的相互作用是否存在，仍存在知识空白。本研究首先描述口服葡萄糖耐量试验（OGTT）期间骨吸收的变化，其次测试OGTT期间肠促胰岛素变化与骨生物标志物以及骨微结构之间的关系。
我们对10名年龄在18至25岁的健康青年成年人进行了一项横断面研究。在为期2小时的75克OGTT多样本测试期间，在第0、30、60和120分钟时测定葡萄糖、胰岛素、GIP、GLP-1、CTX、骨特异性碱性磷酸酶（BSAP）、骨钙素、骨保护素（OPG）、核因子κ-β受体激活剂配体（RANKL）、硬化蛋白和甲状旁腺激素（PTH）。计算第0至30分钟和第0至120分钟的曲线下增量面积（iAUC）。使用第二代高分辨率外周定量计算机断层扫描评估胫骨骨微结构。
在OGTT期间，葡萄糖、胰岛素、GIP和GLP-1显著增加。第30、60和120分钟时的CTX显著低于第0分钟，到第120分钟时最大降幅约为53%。葡萄糖-iAUC与CTX-iAUC呈负相关（rho = -0.91，P < 0.001），GLP-1-iAUC与BSAP-iAUC呈正相关（rho = 0.83，P = 0.005）、与RANKL-iAUC呈正相关（rho = 0.86，P = 0.007）以及与皮质骨体积骨密度呈正相关（rho = 0.93，P < 0.001）。
在达到峰值骨强度前后数年，摄入葡萄糖对骨代谢产生抗吸收作用。在这个关键生命阶段肠道与骨骼之间的相互作用需要进一步关注。
