所有的双膦酸盐都一样吗?

All the bisphosphonate are same?

双膦酸盐是一类广泛应用于治疗骨代谢性疾病的化合物,这类化合物均含有共同的P-C-P的骨架结构,R侧链基团影响双膦酸盐的羟磷灰石结合活性及对破骨细胞的作用,所以各种双膦酸盐的不同特殊结构决定其抗骨吸收的效力。R侧链基团中的氮原子增强双膦酸盐抑制焦膦酸法尼酯合成的活性,促进破骨细胞凋亡。双膦酸盐结构的差异揭示了临床使用过程中它们的抗骨吸收活性和作用持续时间的差异,这种结构-功能的关系反映在临床观察结果中。许多大型临床试验发现各种双膦酸盐疗效的区别,如骨折干预试验(FIT)、利塞膦酸预防椎体骨折研究(VERT)和伊班膦酸预防椎体骨折研究(BONE)等,临床研究的数据显示利塞膦酸和阿仑膦酸具有降低椎体和非椎体骨折风险的能力,而伊班膦酸仅降低椎体骨折风险,对髋部和非椎体骨折的作用无足够的数据支持。不同双膦酸盐抗骨折作用的效力应该通过以骨折为研究终点的头对头试验证实。

Bisphosphonates are a chemical class of compounds in widespread use for the management of disorders of bone metabolism. The members of this drug class share a common P-C-P backbone structure, which act as a ＂bone hook＂ and is essential for binding to bydroxyapatite and exert differential actions within osteoclasts. The unique structure of each bisphosphoate determines its efficacy and relative utility in treating specific disorders of bone resorption. The R side group predominantly determines the antiresorptive potency of the bisphophonates and has some effect on binding. The presence of nitrogen groups within the R side group is associated with the ability of an individual bisphosphonate to inhibit farnesyl pyrophosphate （FPP） synthase, a major enzyme in the mevalonate pathway. Structural differences among bisphophonates explain the observed differences in mineral binding and antiresorptive potency and may in turn account for some of the clinical differences that have been seen in potency, duration of effect, and antifracture efficacy among members of this drug class. These structure-function variations may account for the differences observed in the outcomes of clinical efficacy trials, particularly in antifracture effects. Several major trial have contributed to our current understanding of the impact of bisphophonates in osteoporosis, including the Fracture Intervention Trial （FIT）, the Vertebral Efficacy with Risedronate Therapy trial （VERT）, and the Oral Ibandronate Osteoporosis Vertebral Fracture in North America and Europe （BONE）. Clinical trial data, have shown that risedronate and alcndronate reduce the risk of vertebral and nonvertebral fractures as early as 6 months （risedronate） and 12 months （alendronate）. In contrast to risedronate and alendronate, ibandronate only reduces the risk of vertebral fractures, with no evidence for its efficacy in hip and nonvertebral fracture reduction. The antifracture efficacy of different bisphophonates ideally should be compared via head-to-head comparisons in fracture endpoint trials.