Bisphosphonate binding affinity affects drug distribution in both intracortical and trabecular bone of rabbits.
Bisphosphonate binding affinity affects drug distribution in both intracortical and trabecular bone of rabbits.
复制标题
双膦酸盐结合亲和力影响药物在兔子皮质内和小梁骨中的分布。
DOI：
10.1007/s00223-012-9570-0
复制
发表时间：
2012
影响因子：
4.2
通讯作者：
Allen,MatthewR
中科院分区：
文献类型：
--
作者：
Turek,John;Ebetino,FHal;Lundy,MarkW;Sun,Shuting;Kashemirov,BorisA;McKenna,CharlesE;Gallant,MaximeA;Plotkin,LilianI;Bellido,Teresita;Duan,Xuchen;Triffitt,JamesT;Russell,RGrahamG;Burr,DavidB;Allen,MatthewR
已提出双膦酸盐与骨矿物质结合亲和力的差异，以确定其在骨内的定位和作用持续时间。本研究的主要目的是检验矿物质结合亲和力影响皮质骨和松质骨内基本多细胞单位（BMU）水平双膦酸盐分布的假设。为了实现这一目标，同时注射与不同荧光团结合的低亲和力和高亲和力双膦酸盐类似物的睾丸成熟雌性家兔（n= 8）。使用共聚焦显微镜评估肋骨、胫骨和椎骨中的骨骼分布。对于高亲和力化合物，新形成肋骨骨单位的骨水泥线内或椎体小梁中半骨单位的反转线内所含骨细胞与骨水泥/反转线外的骨细胞之间的染色强度比大于低亲和力化合物。这表明，与高亲和力化合物相比，低亲和力化合物更均匀地分布在骨水泥/反转线上，高亲和力化合物主要集中在表面附近。这些数据来自经历类似于人类的皮质内重塑的动物模型，表明双膦酸盐对骨的亲和力决定了药物在皮质骨和松质骨中的作用范围。
Differences in the binding affinities of bisphosphonates for bone mineral have been proposed to determine their localizations and duration of action within bone. The main objective of this study was to test the hypothesis that mineral binding affinity affects bisphosphonate distribution at the basic multicellular unit (BMU) level within both cortical and cancellous bone. To accomplish this objective, skeletally mature female rabbits (n= 8) were injected simultaneously with both low- and high-affinity bisphosphonate analogs bound to different fluorophores. Skeletal distribution was assessed in the rib, tibia, and vertebra using confocal microscopy. The staining intensity ratio between osteocytes contained within the cement line of newly formed rib osteons or within the reversal line of hemiosteons in vertebral trabeculae compared to osteocytes outside the cement/reversal line was greater for the high-affinity compared to the low-affinity compound. This indicates that the low-affinity compound distributes more equally across the cement/reversal line compared to a high-affinity compound, which concentrates mostly near surfaces. These data, from an animal model that undergoes intracortical remodeling similar to humans, demonstrate that the affinity of bisphosphonates for the bone determines the reach of the drugs in both cortical and cancellous bone.