课件：骨质疏松指南解读解析.ppt

随着人类寿命延长和老龄化社会的到来，骨质疏松症已成为人类重要的健康问题 * 发生一次脆性骨折后，发生再次骨折的风险明显增加。 * 骨质疏松症是一个多因素疾病，在诊断原发性骨质疏松症之前一定要重视排除其他影响骨代谢的疾病，以免漏诊或误诊 * 为骨组织本身的代谢产物，分为骨形成标志物和骨吸收标志物，前者代表成骨细胞活动及骨形成时的代谢产物，后者代表破骨细胞活动及骨吸收时的代谢产物。在正常人不同年龄段或各种代谢性骨病时，骨转换标志物会发生不同程度的变化，因此这些指标的测定有利于判断骨转换类型，骨丢失速率以及疗效监测等。 * * MA-* Functional Domains of Bisphosphonates Bisphosphonates have several functional domains and different molecular structures. As a class, all bisphosphonates work by binding their phosphonate groups to hydroxyapatite. All approved bisphosphonates have and OH group in R1; this creates a triple hook and enhances binding to bone. Varying the R2 substituents can result in differences in antiresorptive potency of several orders of magnitude. Pamidronate and alendronate have an R2 side chain that contains a basic primary nitrogen atom in an alkyl chain and have greater antiresorptive potency than either etidronate or clodronate. Ibandronate has a more highly substituted nitrogen moiety in R2 and shows greater antiresorptive potency than pamidronate or alendronate. The most potent antiresorptive bisphosphonates are risedronate and zoledronic acid, which both contain a nitrogen atom within a heterocyclic ring in the R2 position. Enhancements in antiresorptive potency resulting from differences in the R2 groups appear to be particularly linked to inhibition of the farnesyl pyrophosphate synthase enzyme within the mevalonate pathway in osteoclasts. Reference Nancollas GH, Tang R, Phipps RJ, et al. Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone. 2006;38:617-627. MA-* Action of Bisphosphonates Depends on Mineral Binding and Effects on Osteoclasts MA-* Zoledronic Acid Has a High Binding Affinity for Hydroxyapatite In Vitro The results of a study by Nancollas and colleagues suggest that zoledronic acid has a higher binding affinity for both pure hydroxyapatite and octacalcium phosphate in vitro than clodronate, etidronate, risedronate, ibandronate, or a