Arlot Monique E, Jiang Yebin, Genant Harry K, Zhao Jenny, Burt-Pichat Brigitte, Roux Jean-Paul, Delmas Pierre D, Meunier Pierre J
INSERM, Université Lyon 1, Lyon, France.
J Bone Miner Res. 2008 Feb;23(2):215-22. doi: 10.1359/jbmr.071012.
Strontium ranelate is a new anti-osteoporotic treatment. On bone biopsies collected from humans receiving long-term treatment over 5 yr, it has been shown that strontium ranelate has good bone safety and better results than placebo on 3D microarchitecture. Hence, these effects may explain the decreased fracture rate.
Strontium ranelate's mode of action involving dissociation of bone formation and resorption was shown in preclinical studies and could explain its antifracture efficacy in humans.
One hundred forty-one transiliac bone biopsies were obtained from 133 postmenopausal osteoporotic women: 49 biopsies after 1-5 yr of 2 g/d strontium ranelate and 92 biopsies at baseline or after 1-5 yr of placebo.
Histomorphometry provided a 2D demonstration of the bone safety of strontium ranelate, with significantly higher mineral apposition rate (MAR) in cancellous bone (+9% versus control, p = 0.019) and borderline higher in cortical bone (+10%, p = 0.056). Osteoblast surfaces were significantly higher (+38% versus control, p = 0.047). 3D analysis of 3-yr biopsies with treatment (20 biopsies) and placebo (21 biopsies) using microCT showed significant changes in microarchitecture with, in the strontium ranelate group, higher cortical thickness (+18%, p = 0.008) and trabecular number (+14%, p = 0.05), and lower structure model index (-22%, p = 0.01) and trabecular separation (-16%, p = 0.04), with no change in cortical porosity. The changes in 3D microarchitecture may enhance bone biomechanical competence and explain the decreased fracture rate with strontium ranelate.
雷奈酸锶是一种新型抗骨质疏松治疗药物。在对接受超过5年长期治疗的人类进行的骨活检中,已表明雷奈酸锶具有良好的骨安全性,并且在三维微结构方面比安慰剂效果更好。因此,这些作用可能解释了骨折率的降低。
临床前研究显示雷奈酸锶的作用模式涉及骨形成和骨吸收的解离,这可以解释其在人类中的抗骨折疗效。
从133名绝经后骨质疏松女性中获取了141份髂骨活检样本:49份活检样本是在每日服用2克雷奈酸锶1 - 5年后取得的,92份活检样本是在基线时或服用安慰剂1 - 5年后取得的。
组织形态计量学提供了雷奈酸锶骨安全性的二维证明,松质骨中的矿物质沉积率(MAR)显著更高(与对照组相比增加9%,p = 0.019),皮质骨中的MAR略高(增加10%,p = 0.056)。成骨细胞表面显著更高(与对照组相比增加38%,p = 0.047)。使用显微CT对3年治疗组(20份活检样本)和安慰剂组(21份活检样本)的活检样本进行三维分析显示,微结构有显著变化,在雷奈酸锶组中,皮质厚度更高(增加18%,p = 0.008)和小梁数量更多(增加14%,p = 0.05),结构模型指数更低(降低22%,p = 0.01)和小梁间距更小(降低16%,p = 0.04),皮质孔隙率无变化。三维微结构的变化可能增强骨生物力学性能,并解释雷奈酸锶降低骨折率的原因。