Fluoride and Bone Health: Mechanisms and Its Dose-Dependent Effects

氟化物作为人体必需的微量元素能够促进成骨细胞的增殖、功能的增强及骨基质的矿化，从而有助于骨密度的提高，但过量氟化物摄入则可能对骨骼健康产生负面影响，主要表现为骨骼结构异常。因此，氟化物对骨骼的影响具有明显的剂量依赖性。已有研究表明，氟化物通过多种细胞信号通路作用于成骨细胞，其中，钙感受器(CaSR)和丝裂原活化蛋白激酶(MAPK)信号通路在氟化物调控成骨细胞功能和骨形成过程中的作用尤为重要。本文综述了氟化物通过多种机制作用于成骨细胞，探讨CaSR/MAPK信号通路在氟化物促进骨形成作用的研究进展及氟化物对成骨作用的剂量依赖性效应。通过本系统回顾氟化物的生物学作用，为其在临床和公共卫生中的应用提供理论基础，同时也为氟的安全摄入和骨健康的维护提供参考。Fluoride, an essential trace element for the human body, is beneficial to bone health when consumed in appropriate amounts. It can promote the proliferation of osteoblasts, enhance their function, and facilitate the mineralization of the bone matrix, thereby contributing to increased bone density. However, excessive fluoride intake may have compromised effects on bone health, mainly leading to the abnormalities of the bone structure. Therefore, the impact of fluoride on bones exhibits a clear dose-dependent manner. Previous studies have demonstrated that fluoride exerts its effects on osteoblasts through various cellular signaling pathways, among which the calcium-sensing receptor (CaSR) and mitogen-activated protein kinase (MAPK) signaling pathways play particularly important roles in regulating osteoblast function and bone formation. This review summarizes the mechanisms by which fluoride influences osteoblasts, with a focus on the role of the CaSR/MAPK signaling pathway in promoting bone formation. Additionally, the dose-dependent effects of fluoride are discussed. By systematically reviewing the biological effects of fluoride, this study provides a theoretical foundation for its application in clinical and public health settings, while also offering guidance on safe fluoride intake and bone health maintenance.