INSERM, UMR1033, F-69372, Lyon, France.
J Bone Miner Res. 2012 Apr;27(4):825-34. doi: 10.1002/jbmr.1501.
In the treatment of postmenopausal osteoporosis (PMOP), the use of alendronate (ALN) leads to a decrease in the risk of vertebral and nonvertebral fractures. To explore the possible adverse effects of prolonged ALN therapy, we studied the effects of 8 ± 2 years (6-10 years) of ALN treatment on the iliac cortical bone mineral and collagen quality and micromechanical properties; by design, our study examined these parameters, independent of the degree of mineralization. From six ALN-treated and five age-matched untreated PMOP women, 153 bone structural units have been chosen according their degree of mineralization to obtain the same distribution in each group. In those bone structural units, Fourier transform infrared spectroscopy, quantitative microradiography, and nanoindentation were used to assess bone quality. Irrespective of the degree of mineralization, ALN treatment was associated with higher collagen maturity (+7%, p < 0.001, c.v. = 13% and 16% in treated and untreated women, respectively) and lower mineral crystallinity than that observed in the untreated PMOP group (-2%, p < 0.0001, c.v. = 3% in both groups). Bone matrix from ALN-treated women also had lower elastic modulus (-12%, p < 0.0001, c.v. = 14% in both groups) and, contact hardness (-6%, p < 0.05, c.v. = 14% in both groups) than that of untreated women. Crystallinity (which reflects the size and perfection of crystals) was associated with both elastic modulus and contact hardness in treated women exclusively (r = 0.43 and r = 0.54, p < 0.0001, respectively), even after adjustment for the amount of mineral. We infer that long-term ALN treatment compromises micromechanical properties of the bone matrix as assessed ex vivo. The strength deficits are in part related to difference in crystallinity, irrespective of the mineral amount and mineral maturity. These novel findings at local levels of bone structure will have to be taken into account in the study of the pathophysiology of bone fragilities associated with prolonged ALN treatment.
在治疗绝经后骨质疏松症 (PMOP) 时，使用阿仑膦酸钠 (ALN) 可降低椎体和非椎体骨折的风险。为了探索长期 ALN 治疗可能产生的不良影响，我们研究了 8±2 年（6-10 年） ALN 治疗对髂骨皮质骨矿物质和胶原质量以及微力学特性的影响；根据设计，我们的研究检查了这些参数，而不考虑矿化程度。从六位接受 ALN 治疗和五位年龄匹配的未接受治疗的 PMOP 女性中，根据矿化程度选择了 153 个骨结构单元，以使每个组别的分布相同。在这些骨结构单元中，使用傅立叶变换红外光谱、定量微射线照相术和纳米压痕法评估骨质量。无论矿化程度如何，ALN 治疗与更高的胶原成熟度相关（+7%，p<0.001，在治疗和未治疗的女性中分别为 c.v. = 13%和 16%），并且与未治疗的 PMOP 组相比，矿物质结晶度更低（-2%，p<0.0001，c.v. = 3%）。来自 ALN 治疗女性的骨基质还具有更低的弹性模量（-12%，p<0.0001，c.v. = 14%），并且，接触硬度（-6%，p<0.05）低于未治疗的女性。结晶度（反映晶体的大小和完整性）与治疗女性的弹性模量和接触硬度均相关（r=0.43 和 r=0.54，p<0.0001），即使在调整矿物质含量后也是如此。我们推断，长期 ALN 治疗会损害骨基质的微力学特性，这种损害是可以通过离体评估的。强度缺陷部分与结晶度有关，而与矿物质含量和矿物质成熟度无关。这些在骨结构局部水平的新发现将必须在研究与长期 ALN 治疗相关的骨脆弱性的病理生理学时加以考虑。
