Osteoporosis is a systemic disease that results in loss of bone density and increased fracture risk, particularly in the vertebrae and the hip. This condition and associated morbidity and mortality increase with population ageing. Long noncoding (lnc) RNAs are transcripts longer than 200 nucleotides that are not translated into proteins, but play important regulatory roles in transcriptional and post-transcriptional regulation. Their contribution to disease onset and development is increasingly recognized. Herein, we present an integrative revision on the studies that implicate lncRNAs in osteoporosis and that support their potential use as therapeutic tools. Firstly, current evidence on lncRNAs involvement in cellular and molecular mechanisms linked to osteoporosis and its major complication, fragility fractures, is reviewed. We analyze evidence of their roles in osteogenesis, osteoclastogenesis, and bone fracture healing events from human and animal model studies. Secondly, the potential of lncRNAs alterations at genetic and transcriptomic level are discussed as osteoporosis risk factors and as new circulating biomarkers for diagnosis. Finally, we conclude debating the possibilities, persisting difficulties, and future prospects of using lncRNAs in the treatment of osteoporosis.

骨质疏松症是一种全身性疾病，会导致骨密度下降和骨折风险增加，特别是在椎骨和髋部。这种情况以及相关的发病率和死亡率随着人口老龄化而增加。长非编码 (lnc) RNA 是长度超过 200 个核苷酸的转录物，不会翻译成蛋白质，但在转录和转录后调控中发挥重要的调控作用。它们对疾病发生和发展的贡献日益得到认可。在此，我们对涉及 lncRNA 与骨质疏松症的研究进行了综合修订，并支持它们作为治疗工具的潜在用途。首先，回顾了 lncRNA 参与骨质疏松症及其主要并发症脆性骨折相关细胞和分子机制的现有证据。我们从人类和动物模型研究中分析了它们在成骨、破骨细胞生成和骨折愈合事件中作用的证据。其次，讨论了 lncRNA 在遗传和转录组水平上改变作为骨质疏松症危险因素和新的循环诊断生物标志物的潜力。最后，我们总结了使用 lncRNA 治疗骨质疏松症的可能性、持续存在的困难和未来前景。