Basic, translational and clinical research over the past few decades has provided new understanding on the mechanisms by which activation of the receptor of parathyroid hormone (parathyroid hormone 1 receptor (PTH1R)) regulates bone physiology and pathophysiology. A fundamental change in the field emerged upon the recognition that osteocytes, which are permanent residents of bone and the most abundant cells in bone, are targets of the actions of natural and synthetic ligands of PTH1R (parathyroid hormone and abaloparatide, respectively), and that these cells drive essential actions related to bone remodelling. Among the numerous genes regulated by PTH1R in osteocytes, SOST (which encodes sclerostin, the WNT signalling antagonist and inhibitor of bone formation) has a critical role in bone homeostasis and changes in its expression are associated with several bone pathologies. The bone fragility syndrome induced by diabetes mellitus is accompanied by increased osteocyte apoptosis and changes in the expression of osteocytic genes, including SOST. This Review will discuss advances in our knowledge of the role of osteocytes in PTH1R signalling and the new opportunities to restore bone health in diabetes mellitus by targeting the osteocytic PTH1R–sclerostin axis.

过去几十年的基础、转化和临床研究为甲状旁腺激素受体（甲状旁腺激素 1 受体 （PTH1R））激活调节骨骼生理学和病理生理学的机制提供了新的理解。当人们认识到骨细胞是骨骼的永久居民和骨骼中最丰富的细胞，是 PTH1R 的天然和合成配体（分别为甲状旁腺激素和阿巴帕肽）作用的目标，并且这些细胞驱动与骨重塑相关的基本作用时，该领域的根本性变化出现了。在骨细胞中受 PTH1R 调控的众多基因中，SOST（编码硬化蛋白，WNT 信号拮抗剂和骨形成抑制剂）在骨稳态中起关键作用，其表达的变化与多种骨病理有关。糖尿病诱导的骨脆性综合征伴有骨细胞凋亡增加和骨细胞基因（包括 SOST）表达的变化。本综述将讨论我们对骨细胞在 PTH1R 信号传导中的作用的认识进展，以及通过靶向骨细胞 PTH1R-硬化蛋白轴来恢复糖尿病骨骼健康的新机会。