Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114.
Cold Spring Harb Perspect Med. 2018 Aug 1;8(8):a031237. doi: 10.1101/cshperspect.a031237.
Parathyroid hormone (PTH) exerts profound effects on skeletal homeostasis through multiple cellular and molecular mechanisms. Continuous hyperparathyroidism causes net loss of bone mass, despite accelerating bone formation by osteoblasts. Intermittent treatment with PTH analogs represents the only Food and Drug Administration (FDA)-approved bone anabolic osteoporosis treatment strategy. Functional PTH receptors are present on cells of the osteoblast lineage, ranging from early skeletal stem cells to matrix-embedded osteocytes. In addition, bone remodeling by osteoclasts liberates latent growth factors present within bone matrix. Here, we will provide an overview of the multiple cellular and molecular mechanisms through which PTH influences bone homeostasis. Notably, net skeletal effects of continuous versus intermittent can differ significantly. Where possible, we will highlight mechanisms through which continuous hyperparathyroidism leads to bone loss, and through which intermittent hyperparathyroidism boosts bone mass. Given the therapeutic usage of intermittent PTH (iPTH) treatment for osteoporosis, particular attention will be paid toward mechanisms underlying the bone anabolic effects of once daily PTH administration.
甲状旁腺激素（PTH）通过多种细胞和分子机制对骨骼稳态发挥深远影响。尽管成骨细胞加速了骨形成，但持续的甲状旁腺功能亢进仍会导致净骨量丢失。PTH 类似物的间歇性治疗是唯一获得美国食品和药物管理局（FDA）批准的骨合成代谢骨质疏松症治疗策略。功能性 PTH 受体存在于成骨细胞谱系的细胞上，范围从早期骨骼干细胞到基质嵌入的成骨细胞。此外，破骨细胞的骨重塑会释放存在于骨基质中的潜在生长因子。在这里，我们将概述 PTH 影响骨骼稳态的多种细胞和分子机制。值得注意的是，连续与间歇的净骨骼效应可能有很大差异。在可能的情况下，我们将重点介绍连续甲状旁腺功能亢进导致骨丢失的机制，以及间歇甲状旁腺功能亢进如何促进骨量增加。鉴于间歇性 PTH（iPTH）治疗骨质疏松症的治疗用途，将特别关注每日一次 PTH 给药的骨合成代谢作用的机制。
