Bone resorption follows a circadian rhythm, with a marked reduction in circulating markers of resorption (such as carboxy-terminal telopeptide region of collagen type I in serum) in the postprandial period. Several gut hormones, including glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP1) and GLP2, have been linked to this effect in humans and rodent models. These hormones are secreted from enteroendocrine cells in the gastrointestinal tract in response to a variety of stimuli and effect a wide range of physiological processes within and outside the gut. Single GLP1, dual GLP1–GIP or GLP1–glucagon and triple GLP1–GIP–glucagon receptor agonists have been developed for the treatment of type 2 diabetes mellitus and obesity. In addition, single GIP, GLP1 and GLP2 analogues have been investigated in preclinical studies as novel therapeutics to improve bone strength in bone fragility disorders. Dual GIP–GLP2 analogues have been developed that show therapeutic promise for bone fragility in preclinical studies and seem to exert considerable activity at the bone material level. This Review summarizes the evidence of the action of gut hormones on bone homeostasis and physiology.

骨吸收遵循昼夜节律，餐后吸收的循环标志物（例如血清中 I 型胶原蛋白的羧基末端端肽区域）显着减少。多种肠道激素，包括葡萄糖依赖性促胰岛素多肽 (GIP)、胰高血糖素样肽 1 (GLP1) 和 GLP2，在人类和啮齿动物模型中与这种效应有关。这些激素由胃肠道的肠内分泌细胞响应各种刺激而分泌，并影响肠道内外的广泛生理过程。单GLP1、双GLP1-GIP或GLP1-胰高血糖素和三重GLP1-GIP-胰高血糖素受体激动剂已被开发用于治疗2型糖尿病和肥胖症。此外，单一 GIP、GLP1 和 GLP2 类似物已在临床前研究中作为改善骨脆性疾病的骨强度的新疗法进行了研究。双 GIP-GLP2 类似物已被开发出来，在临床前研究中显示出治疗骨脆性的前景，并且似乎在骨材料水平上发挥了相当大的活​​性。本综述总结了肠道激素对骨稳态和生理学作用的证据。