Russell R G G, Watts N B, Ebetino F H, Rogers M J
Nuffield Department of Orthopaedic Surgery, Oxford University Institute of Musculoskeletal Sciences (The Botnar Research Centre), Nuffield Orthopaedic Centre, Headington, Oxford OX3 7LD, UK.
Osteoporos Int. 2008 Jun;19(6):733-59. doi: 10.1007/s00198-007-0540-8.
Bisphosphonates (BPs) are well established as the leading drugs for the treatment of osteoporosis. There is new knowledge about how they work. The differences that exist among individual BPs in terms of mineral binding and biochemical actions may explain differences in their clinical behavior and effectiveness.
The classical pharmacological effects of bisphosphonates (BPs) appear to be the result of two key properties: their affinity for bone mineral and their inhibitory effects on osteoclasts.
There is new information about both properties. Mineral binding affinities differ among the clinically used BPs and may influence their differential distribution within bone, their biological potency, and their duration of action. The antiresorptive effects of the nitrogen-containing BPs (including alendronate, risedronate, ibandronate, and zoledronate) appear to result from their inhibition of the enzyme farnesyl pyrophosphate synthase (FPPS) in osteoclasts. FPPS is a key enzyme in the mevalonate pathway, which generates isoprenoid lipids utilized for the post-translational modification of small GTP-binding proteins that are essential for osteoclast function. Effects on other cellular targets, such as osteocytes, may also be important. BPs share several common properties as a drug class. However, as with other families of drugs, there are obvious chemical, biochemical, and pharmacological differences among the individual BPs. Each BP has a unique profile that may help to explain potential clinical differences among them, in terms of their speed and duration of action, and effects on fracture reduction.
双膦酸盐类药物（BPs）是治疗骨质疏松症的主要药物，这一点已得到充分证实。关于它们的作用机制有了新的认识。不同双膦酸盐类药物在矿物质结合和生化作用方面存在差异，这可能解释了它们临床行为和疗效的差异。
双膦酸盐类药物（BPs）的经典药理作用似乎是由两个关键特性导致的：它们对骨矿物质的亲和力以及对破骨细胞的抑制作用。
关于这两个特性都有了新的信息。临床使用的双膦酸盐类药物在矿物质结合亲和力方面存在差异，这可能会影响它们在骨内的分布差异、生物学效力以及作用持续时间。含氮双膦酸盐类药物（包括阿仑膦酸盐、利塞膦酸盐、伊班膦酸盐和唑来膦酸盐）的抗吸收作用似乎是由于它们抑制了破骨细胞中的法尼基焦磷酸合酶（FPPS）。FPPS是甲羟戊酸途径中的关键酶，该途径产生类异戊二烯脂质，用于小GTP结合蛋白的翻译后修饰，而这些小GTP结合蛋白对破骨细胞功能至关重要。对其他细胞靶点（如骨细胞）的影响可能也很重要。双膦酸盐类药物作为一类药物具有几个共同特性。然而，与其他药物家族一样，不同双膦酸盐类药物在化学、生化和药理方面存在明显差异。每种双膦酸盐类药物都有独特的特性，这可能有助于解释它们在作用速度和持续时间以及对骨折减少的影响方面潜在的临床差异。
