title: A longitudinal HR-pQCT study of alendronate treatment in postmenopausal women with low bone density: Relations among density, cortical and trabecular microarchitecture, biomechanics, and bone turnover.
abstract: The goal of this study was to characterize longitudinal changes in bone microarchitecture and function in women treated with an established antifracture therapeutic. In this double-blind, placebo-controlled pilot study, 53 early postmenopausal women with low bone density (age = 56 ± 4 years; femoral neck T-score = -1.5 ± 0.6) were monitored by high-resolution peripheral quantitative computed tomography (HR-pQCT) for 24 months following randomization to alendronate (ALN) or placebo (PBO) treatment groups. Subjects underwent annual HR-pQCT imaging of the distal radius and tibia, dual-energy X-ray absorptiometry (DXA), and determination of biochemical markers of bone turnover (BSAP and uNTx). In addition to bone density and microarchitecture assessment, regional analysis, cortical porosity quantification, and micro-finite-element analysis were performed. After 24 months of treatment, at the distal tibia but not the radius, HR-pQCT measures showed significant improvements over baseline in the ALN group, particularly densitometric measures in the cortical and trabecular compartments and endocortical geometry (cortical thickness and area, medullary area) (p < .05). Cortical volumetric bone mineral density (vBMD) in the tibia alone showed a significant difference between treatment groups after 24 months (p < .05); however, regionally, significant differences in Tb.vBMD, Tb.N, and Ct.Th were found for the lateral quadrant of the radius (p < .05). Spearman correlation analysis revealed that the biomechanical response to ALN in the radius and tibia was specifically associated with changes in trabecular microarchitecture (|ρ| = 0.51 to 0.80, p < .05), whereas PBO progression of bone loss was associated with a broad range of changes in density, geometry, and microarchitecture (|ρ| = 0.56 to 0.89, p < .05). Baseline cortical geometry and porosity measures best predicted ALN-induced change in biomechanics at both sites (ρ > 0.48, p < .05). These findings suggest a more pronounced response to ALN in the tibia than in the radius, driven by trabecular and endocortical changes.
authors.affiliation: Musculoskeletal Quantitative Imaging Research Group, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA. andrew.burghardt@ucsf.edu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Burghardt
authors.forename: Galateia J
authors.initials: GJ
authors.lastname: Kazakia
authors.forename: Miki
authors.initials: M
authors.lastname: Sode
authors.forename: Anne E
authors.initials: AE
authors.lastname: de Papp
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Link
authors.forename: Sharmila
authors.initials: S
authors.lastname: Majumdar
mesh_terms: D015502:Absorptiometry, Photon; D019386:Alendronate / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000000981:diagnostic imaging* / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D017698:Postmenopause / Q000187:drug effects*; D011884:Radius / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D018709:Statistics, Nonparametric; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D019386:Alendronate