THE EFFECTS OF INHIBITORS OF OSTEOCLASTC BONE RESORPTION IN GIANT CELL TUMOR

双膦酸盐抑制骨吸收，并且在骨转换增加的疾病如佩吉特病和恶性肿瘤的高钙血症中治疗有效。它们的作用机制尚不清楚。提出的机制包括抑制破骨细胞从前体细胞形成和对成熟破骨细胞的抑制或毒性作用。我们已经开发了一种新的体外模型来研究破骨细胞的存活，并在本文中，可以解释两个观察到的破骨细胞数量减少和骨吸收的成熟破骨细胞，即双膦酸盐诱导programd细胞死亡（凋亡）。三种双膦酸盐导致破骨细胞比例增加4至24倍，显示出体外细胞凋亡的特征形态。在这三种化合物中，利塞膦酸钠是体内最有效的骨吸收抑制剂，是体外破骨细胞凋亡的最强诱导剂。因此，破骨细胞凋亡可能是双膦酸盐减少破骨细胞数量和活性的主要机制，诱导细胞凋亡可能是新的抗破骨细胞药物的治疗目标。

Bisphosphonates inhibit bone resorption and are therapeutically effective in diseases of increased bone turnover, such as Paget's disease and hypercalcemia of malignancy. The mechanisms by which they act remain unclear. Proposed mechanisms include inhibition of osteoclast formation from precursors and inhibitory or toxic effect on mature osteoclasts. We have developed a new in vitro model to study osteoclast survival and in this paper that may explain both the observed reduction in osteoclast numbers and in bone resorption by mature osteoclasts, namely that bisphosphonates induce programd cell death (apoptosis). Three bisphosphonates caused a 4- to 24-fold increase in the proportion of osteoclasts showing the characteristic morphology of apoptosis in vitro. Of the three compounds, risedronate, the most potent inhibitor of bone resorption in vivo, was the strongest inducer of osteoclast apoptosis in vitro. Osteoclast apoptosis may therefore be a major mechanism whereby bisphosphonates reduce osteoclast numbers and activity, and induction of apoptosis could be a therapeutic goal for new antiosteoclast drugs.