Bisphosphonate-induced jawbone necrosis : studies for its mechanism, prevention, and treatment

双膦酸盐（BPs）被广泛用作抗骨吸收药物，含氮BPs（NBPs）比不含氮BPs（non-NBPs）具有更强的抗骨吸收作用。然而，NBPs有炎症和坏死的副作用，包括颌骨坏死。我们发现非nbps的依地膦酸盐和氯膦酸盐没有这样的副作用。相反，它们可以预防或减少nbp的副作用。在此项目期间，我们积累了许多关于NBPs副作用和非NBPs保护作用的机制以及它们联合对骨骼的影响的研究结果。此外，我们注意到非NBPs具有强效镇痛作用（缺乏NBPs且独立于其抗骨吸收作用）。基于这些发现，我们建议(i)依地膦酸盐和氯膦酸盐可以分别作为NBP的替代药物和与NBP的联合药物，以及（ii）它们作为骨质疏松症的安全药物需要重新评估。

Bisphosphonates(BPs)are widely used as anti-bone-resorptive drugs, and nitrogen-containing BPs(NBPs)are much more powerful than non-nitrogen-containing BPs(non-NBPs). However, NBPs have inflammatory and necrotic side effects including jawbone necrosis. We have discovered that the non-NBPs etidronate and clodronate lack such side effects. On the contrary, they can prevent or reduce the NBPs'side effects. During the period of this project, we could accumulate many findings concerning the mechanisms underlying the NBPs'side effects and non-NBPs' protective effects and the effects of their combination on bone. In addition, we noted that the non-NBPs have a potent analgesic effect(lacked in NBPs and independent of their anti-bone-resorptive effects). Based on these findings, we propose that(i)etidronate and clodronate can be used as a substitution drug to NBPs and a combination drug with an NBP, respectively, and(ii)they warrant reappraisal as safe drugs for osteoporosis.