title: Bone micromechanical properties are compromised during long-term alendronate therapy independently of mineralization.
abstract: 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.
authors.affiliation: INSERM, UMR1033, F-69372, Lyon, France. yohannbala@gmail.fr
authors.forename: Yohann
authors.initials: Y
authors.lastname: Bala
authors.forename: Baptiste
authors.initials: B
authors.lastname: Depalle
authors.forename: Delphine
authors.initials: D
authors.lastname: Farlay
authors.forename: Thierry
authors.initials: T
authors.lastname: Douillard
authors.forename: Sylvain
authors.initials: S
authors.lastname: Meille
authors.forename: Helene
authors.initials: H
authors.lastname: Follet
authors.forename: Roland
authors.initials: R
authors.lastname: Chapurlat
authors.forename: Jérôme
authors.initials: J
authors.lastname: Chevalier
authors.forename: Georges
authors.initials: G
authors.lastname: Boivin
mesh_terms: D000368:Aged; D019386:Alendronate / Q000494:pharmacology*; D001696:Biomechanical Phenomena / Q000187:drug effects*; D001706:Biopsy; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D002113:Calcification, Physiologic / Q000187:drug effects*; D005260:Female; D006801:Humans; D017698:Postmenopause / Q000187:drug effects; D011859:Radiography; D012044:Regression Analysis; D017550:Spectroscopy, Fourier Transform Infrared; D013997:Time Factors; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D019386:Alendronate