This study examined the ability of local alendronate (ALN) administration to control β‐tricalcium phosphate (β‐TCP) resorption as well as the induction of bone formation by recombinant human bone morphogenetic protein‐2 (rhBMP‐2). A 15‐mm critical‐sized bone defect was created in the diaphysis of rabbit ulnae. Nine female rabbits (4 to 5 months‐old) were divided into 3 groups. Group 1 (n = 6 ulnae) animals received implants consisting of β‐TCP granules and 25 μg of rhBMP‐2 in 6.5% collagen gel. Group 2 (6 ulnae) and Group 3 (6 ulnae) animals received the same implants, but with 10⁻⁶ M and 10⁻³ M ALN‐treated TCP granules, respectively. Two weeks postsurgery, tartrate‐resistant acid phosphatase‐positive cell counts, new bone formation, and residual β‐TCP were evaluated. This study showed that a high dose of ALN strongly reduced osteoclastic resorption of β‐TCP induced by rhBMP‐2, resulting in decreased bone formation. In contrast, a low dose of ALN slightly reduced the bone resorptive effect but increased bone formation. These results suggest that osteoclast‐mediated resorption plays an important role in bone formation and a coupling‐like phenomenon could occur in the β‐TCP‐implanted area, and that administration of a low dose of ALN may solve clinical bone resorptive problems induced by rhBMP‐2.

中文翻译：

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阿仑膦酸盐的局部应用控制重组人骨形态发生蛋白-2 诱导的骨形成和 β-磷酸三钙吸收。

本研究检查了局部阿仑膦酸盐 (ALN) 给药控制 β-磷酸三钙 (β-TCP) 吸收以及重组人骨形态发生蛋白-2 (rhBMP-2) 诱导骨形成的能力。在兔尺骨骨干中产生了一个 15 毫米的临界尺寸骨缺损。9 只雌性兔（4 至 5 个月大）分为 3 组。第 1 组（n = 6 尺骨）动物接受由 β-TCP 颗粒和 25 μg rhBMP-2 6.5% 胶原凝胶组成的植入物。第 2 组（6 尺骨）和第 3 组（6 尺骨）动物接受相同的植入物，但具有 10 ^-6 M 和 10 ^-3分别为 M ALN 处理的 TCP 颗粒。术后两周，对抗酒石酸酸性磷酸酶阳性细胞计数、新骨形成和残留 β-TCP 进行了评估。该研究表明，高剂量的 ALN 强烈降低了由 rhBMP-2 诱导的 β-TCP 的破骨细胞吸收，导致骨形成减少。相比之下，低剂量的 ALN 略微降低了骨吸收作用，但增加了骨形成。这些结果表明，破骨细胞介导的骨吸收在骨形成中起重要作用，β-TCP 植入区可能发生耦合样现象，低剂量 ALN 的给药可能会解决由 rhBMP 引起的临床骨吸收问题。 ‐2.