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

双膦酸盐(BPS)是一种广泛应用的抗骨吸收药物，其中含氮双膦(NBPS)的药效远高于不含氮的双膦(Non-nBPS)。然而，NBPS有炎症和坏死性副作用，包括颌骨坏死。我们发现，非nbps的依替磷酸和氯屈膦没有这样的副作用。相反，它们可以预防或减少NBPS的副作用。在本项目期间，我们可以积累许多关于NBPS副作用和非NBPS保护作用的潜在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NPPS有很强的止痛作用(缺乏NBPS并且独立于它们的抗骨吸收作用)。基于这些发现，我们建议(I)依替膦酸盐和氯屈膦酸盐可分别作为NBP的替代药物和与NBP的联合用药，以及(Ii)它们值得重新评估为治疗骨质疏松的安全药物。

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.