Chavassieux Pascale, Meunier Pierre J, Roux Jean Paul, Portero-Muzy Nathalie, Pierre Marlène, Chapurlat Roland
INSERM UMR 1033 and Université de Lyon, Lyon, France.
J Bone Miner Res. 2014 Mar;29(3):618-28. doi: 10.1002/jbmr.2074.
Preclinical studies indicate that strontium ranelate (SrRan) induces opposite effects on bone osteoblasts and osteoclasts, suggesting that SrRan may have a dual action on both formation and resorption. By contrast, alendronate (ALN) is a potent antiresorptive agent. In this multicenter, international, double-blind, controlled study conducted in 387 postmenopausal women with osteoporosis, transiliac bone biopsies were performed at baseline and after 6 or 12 months of treatment with either SrRan 2 g per day (n = 256) or alendronate 70 mg per week (n = 131). No deleterious effect on mineralization of SrRan or ALN was observed. In the intention-to-treat (ITT) population (268 patients with paired biopsy specimens), changes in static and dynamic bone formation parameters were always significantly higher with ALN compared with SrRan at month 6 (M6) and month 12 (M12). Static parameters of formation were maintained between baseline and the last value with SrRan, except for osteoblast surfaces, which decreased at M6. Significant decreases in the dynamic parameters of formation (mineralizing surface, bone formation rate, adjusted apposition rate, activation frequency) were noted at M6 and M12 in SrRan. Compared with ALN, the bone formation parameters at M6 and M12 were always significantly higher (p < 0.001) with SrRan. ALN, but not SrRan, decreased resorption parameters. Compared with the baseline paired biopsy specimens, wall thickness was significantly decreased at M6 but not at M12 and cancellous bone structure parameters (trabecular bone volume, trabecular thickness, trabecular number, number of nodes/tissue volume) were significantly decreased at M12 with SrRan; none of these changes were significantly different from ALN. In conclusion, this large controlled paired biopsy study over 1 year shows that the bone formation remains higher with a lower diminution of the bone remodeling with SrRan versus ALN. From these results, SrRan did not show a significant anabolic action on bone remodeling.
临床前研究表明，雷奈酸锶（SrRan）对骨成骨细胞和破骨细胞具有相反的作用，这表明SrRan可能对骨形成和骨吸收都有双重作用。相比之下，阿仑膦酸盐（ALN）是一种有效的抗骨吸收药物。在这项针对387名绝经后骨质疏松妇女进行的多中心、国际性、双盲、对照研究中，在基线时以及用每天2克SrRan（n = 256）或每周70毫克阿仑膦酸盐（n = 131）治疗6或12个月后进行了经髂骨活检。未观察到SrRan或ALN对矿化有有害影响。在意向性治疗（ITT）人群（268例有配对活检标本的患者）中，在第6个月（M6）和第12个月（M12）时，与SrRan相比，ALN的静态和动态骨形成参数变化始终显著更高。用SrRan时，除了成骨细胞表面在M6时下降外，形成的静态参数在基线和最后值之间保持不变。在SrRan组中，在M6和M12时观察到形成的动态参数（矿化表面、骨形成率、调整后的沉积率、激活频率）显著下降。与ALN相比，SrRan在M6和M12时的骨形成参数始终显著更高（p < 0.001）。ALN降低了骨吸收参数，但SrRan没有。与基线配对活检标本相比，SrRan组在M6时骨壁厚度显著降低，但在M12时没有，并且在M12时松质骨结构参数（骨小梁体积、骨小梁厚度、骨小梁数量、节点/组织体积数量）显著降低；这些变化与ALN组均无显著差异。总之，这项为期1年的大型对照配对活检研究表明，与ALN相比，SrRan组骨形成更高，骨重塑减少更低。从这些结果来看，SrRan在骨重塑方面未显示出显著的合成代谢作用。
