Disuse osteoporosis describes a state of bone loss due to local skeletal unloading or systemic immobilization. This review will discuss advances in the field that have shed light on clinical observations, mechanistic insights and options for the treatment of disuse osteoporosis. Clinical settings of disuse osteoporosis include spinal cord injury, other neurological and neuromuscular disorders, immobilization after fractures and bed rest (real or modeled). Furthermore, spaceflight-induced bone loss represents a well-known adaptive process to microgravity. Clinical studies have outlined that immobilization leads to immediate bone loss in both the trabecular and cortical compartments accompanied by relatively increased bone resorption and decreased bone formation. The fact that the low bone formation state has been linked to high levels of the osteocyte-secreted protein sclerostin is one of the many findings that has brought matrix-embedded, mechanosensitive osteocytes into focus in the search for mechanistic principles. Previous basic research has primarily involved rodent models based on tail suspension, spaceflight and other immobilization methods, which have underlined the importance of osteocytes in the pathogenesis of disuse osteoporosis. Furthermore, molecular-based in vitro and in vivo approaches have revealed that osteocytes sense mechanical loading through mechanosensors that translate extracellular mechanical signals to intracellular biochemical signals and regulate gene expression. Osteocytic mechanosensors include the osteocyte cytoskeleton and dendritic processes within the lacuno-canalicular system (LCS), ion channels (e.g., Piezo1), extracellular matrix, primary cilia, focal adhesions (integrin-based) and hemichannels and gap junctions (connexin-based). Overall, disuse represents one of the major factors contributing to immediate bone loss and osteoporosis, and alterations in osteocytic pathways appear crucial to the bone loss associated with unloading.

废用性骨质疏松症描述了由于局部骨骼卸载或全身固定导致的骨质流失状态。本综述将讨论该领域的进展，这些进展揭示了临床观察、机制见解和治疗废用性骨质疏松症的选择。废用性骨质疏松症的临床情况包括脊髓损伤、其他神经和神经肌肉疾病、骨折后的固定和卧床休息（真实或模拟）。此外，太空飞行引起的骨质流失代表了众所周知的微重力适应过程。临床研究表明，固定会导致骨小梁和皮质隔室立即出现骨丢失，并伴有相对增加的骨吸收和减少的骨形成。低骨形成状态与高水平的骨细胞分泌蛋白 sclerostin 相关这一事实是众多发现之一，这些发现使基质嵌入、机械敏感的骨细胞成为寻找机械原理的焦点。以往的基础研究主要涉及基于尾部悬吊、航天等固定方法的啮齿动物模型，这些都强调了骨细胞在废用性骨质疏松症发病机制中的重要性。此外，基于分子的体外和体内方法表明，骨细胞通过机械传感器感知机械负荷，机械传感器将细胞外机械信号转化为细胞内生化信号并调节基因表达。骨细胞机械传感器包括腔隙-小管系统 (LCS)、离子通道（例如 Piezo1）、细胞外基质、初级纤毛、粘着斑（基于整合素）和半通道和间隙连接（基于连接蛋白）内的骨细胞骨架和树突状过程. 总体而言，废用是导致即刻骨质流失和骨质疏松症的主要因素之一，而骨细胞通路的改变似乎对与卸载相关的骨质流失至关重要。