Marie P J, De Vernejoul M C, Lomri A
Unité 349 INSERM, Lariboisière Hospital, Paris.
J Bone Miner Res. 1992 Jan;7(1):103-13. doi: 10.1002/jbmr.5650070115.
In this study we evaluated whether the fluoride-induced increased bone formation in osteoporosis is mediated by stimulation of bone cell proliferation and/or differentiation. We analyzed the kinetics of DNA synthesis and the phenotypic features of osteoblastic cells isolated from the trabecular bone surface in relationship to histomorphometric indices of bone formation evaluated on the same bone biopsy in 12 osteoporotic patients treated with fluoride. Osteoblastic cells isolated from patients with a higher than normal bone formation rate, increased mean wall thickness of trabecular bone packets, and high trabecular bone volume after fluoride therapy displayed a higher than normal rate of DNA synthesis in vitro. The peak of [3H]thymidine incorporation into DNA, the maximal DNA synthesis, and the area under the growth curve of osteoblastic cells isolated from these patients were higher than the values in normal bone cells obtained from age-matched controls. By contrast, in vitro parameters of osteoblastic cell proliferation were not different from normal in fluoride-treated osteoporosis patients in whom bone formation was not increased, although the duration of treatment and bone fluoride content were not different. Parameters of bone cell proliferation in vitro were increased in correlation with the mean wall thickness, and the latter correlated with the trabecular bone volume, indicating that the augmentation of bone formation and bone volume induced by fluoride was paralleled by an increased proliferation of osteoblastic cells. Basal osteocalcin production (corrected for cell protein) and alkaline phosphatase activity in vitro were comparable, and the response to 1,25-dihydroxyvitamin D3 (10 nmol/liter, 48 h) was not different in normal osteoblastic cells and in cells from fluoride-treated osteoporosis patients whether they had high or normal bone formation. The results show that the fluoride-induced increased bone formation in osteoporotic patients is associated with an increased in vitro proliferative capacity of osteoblastic cells lining the trabecular bone surface, whereas parameters of osteoblast differentiation are not affected. The data also suggest that induction of a higher than normal bone cell proliferation is prerequisite for the stimulation of bone formation by fluoride.
在本研究中，我们评估了氟化物诱导的骨质疏松症中骨形成增加是否由骨细胞增殖和/或分化的刺激介导。我们分析了从12例接受氟化物治疗的骨质疏松症患者的小梁骨表面分离的成骨细胞的DNA合成动力学和表型特征，并将其与在同一骨活检中评估的骨形成组织形态计量学指标相关联。从氟化物治疗后骨形成率高于正常、小梁骨包壁平均厚度增加和小梁骨体积高的患者中分离出的成骨细胞在体外显示出高于正常的DNA合成率。从这些患者中分离出的成骨细胞中，[3H]胸苷掺入DNA的峰值、最大DNA合成以及生长曲线下的面积均高于从年龄匹配对照获得的正常骨细胞中的值。相比之下，在骨形成未增加的氟化物治疗的骨质疏松症患者中，体外成骨细胞增殖参数与正常情况无差异，尽管治疗持续时间和骨氟含量并无不同。体外骨细胞增殖参数与平均壁厚度相关增加，而平均壁厚度又与小梁骨体积相关，这表明氟化物诱导的骨形成和骨体积增加与成骨细胞增殖增加平行。体外基础骨钙素产生（校正细胞蛋白）和碱性磷酸酶活性相当，正常成骨细胞和氟化物治疗的骨质疏松症患者的细胞（无论骨形成高或正常）对1,25 - 二羟维生素D3（10 nmol/升，48小时）的反应无差异。结果表明，氟化物诱导的骨质疏松症患者骨形成增加与小梁骨表面衬里的成骨细胞体外增殖能力增加有关，而成骨细胞分化参数未受影响。数据还表明，诱导高于正常的骨细胞增殖是氟化物刺激骨形成的先决条件。
