We compared the effects of a nitrogen-containing bisphosphonate (N-BP), zoledronic acid (ZA), and an anti-mouse RANKL antibody (anti-mRANKL Ab) on the bone tissue pathology of a transgenic mouse model of human fibrous dysplasia (FD). For comparison, we also reviewed the histological samples of a child with McCune–Albright syndrome (MAS) treated with Pamidronate for 3 years. EF1α-Gsα^R201C mice with FD-like lesions in the tail vertebrae were treated with either 0.2 mg/kg of ZA at day 0, 7, and 14 or with 300 μg/mouse of anti-mRANKL Ab at day 0 and 21. All mice were monitored by Faxitron and histological analysis was performed at day 42. ZA did not affect the progression of the radiographic phenotype in EF1α-Gsα^R201C mice. FD-like lesions in the ZA group showed the persistence of osteoclasts, easily detectable osteoclast apoptotic activity and numerous “giant osteoclasts”. In contrast, in the anti-mRANKL Ab-treated mice, osteoclasts were markedly reduced/absent, the radiographic phenotype reverted and the FD-like lesions were extensively replaced by newly formed bone. Numerous “giant osteoclasts” were also detected in the samples of the child with MAS. This study supports the hypothesis that osteoclasts per se, independently of their resorptive activity, are essential for development and expansion of FD lesions.

我们比较了含氮的双膦酸酯（N-BP），唑来膦酸（ZA）和抗小鼠RANKL抗体（anti-mRANKL Ab）对人纤维发育不良的转基因小鼠模型的骨组织病理学的影响（ FD）。为了进行比较，我们还回顾了接受帕米膦酸治疗3年的McCune-Albright综合征（MAS）儿童的组织学样本。在第^0、7和14天用0.2 mg / kg ZA或在第0和21天用300μg/小鼠抗mRANKL Ab治疗EF1α- ^GsαR201C小鼠的^尾椎有FD样病变。通过Faxitron监测小鼠并在第42天进行组织学分析^。ZA不会影响EF1α- ^GsαR201C的放射学表型进展老鼠。ZA组的FD样病变表现出破骨细胞的持久性，易于检测的破骨细胞凋亡活性和大量“巨破骨细胞”。相比之下，在抗mRANKL Ab治疗的小鼠中，破骨细胞明显减少/缺失，射线照相表型恢复，FD样病变被新形成的骨广泛替代。在患有MAS的儿童样本中也检测到大量“巨破骨细胞”。该研究支持以下假设：破骨细胞本身，无论其吸收活性如何，对于FD病变的发展和扩展都是必不可少的。