Rauch Frank, Travers Rose, Plotkin Horacio, Glorieux Francis H
Genetics Unit, Shriners Hospital for Children, and McGill University, Montréal, Québec, Canada.
J Clin Invest. 2002 Nov;110(9):1293-9. doi: 10.1172/JCI15952.
Cyclical pamidronate infusions increase bone mass in children suffering from osteogenesis imperfecta. The histological basis for these effects remains unknown. Therefore, we compared parameters of iliac bone histomorphometry from 45 patients before and after 2.4 +/- 0.6 years of pamidronate treatment (age at the time of the first biopsy, 1.4-17.5 years; 23 girls). Although biopsy size did not change significantly (P = 0.30), cortical width increased by 88%. Cancellous bone volume increased by 46%. This was due to a higher trabecular number, whereas trabecular thickness remained stable. Bone surface-based indicators of cancellous bone remodeling decreased by 26-75%. There was no evidence for a mineralization defect in any of the patients. These results suggest that, in the growing skeleton, pamidronate has a twofold effect. In remodeling, bone resorption and formation are coupled and consequently both processes are inhibited. However, osteoclasts and osteoblasts are active on different surfaces (and are thus uncoupled) during modeling of cortical bone. Therefore resorption is selectively targeted, and continuing bone formation can increase cortical width.
周期性输注帕米膦酸盐可增加成骨不全患儿的骨量。这些作用的组织学基础尚不清楚。因此，我们比较了45例患者在接受2.4±0.6年帕米膦酸盐治疗前后的髂骨组织形态计量学参数（首次活检时年龄为1.4 - 17.5岁；23例女孩）。尽管活检样本大小无显著变化（P = 0.30），但皮质骨宽度增加了88%。松质骨体积增加了46%。这是由于小梁数量增加，而小梁厚度保持稳定。基于骨表面的松质骨重塑指标下降了26% - 75%。未发现任何患者存在矿化缺陷。这些结果表明，在生长中的骨骼中，帕米膦酸盐具有双重作用。在重塑过程中，骨吸收和骨形成是偶联的，因此两个过程均受到抑制。然而，在皮质骨建模过程中，破骨细胞和成骨细胞在不同表面活跃（因此是解偶联的）。因此，吸收被选择性地靶向，持续的骨形成可增加皮质骨宽度。
