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.

Author(s): Burghardt AJ, Kazakia GJ, Sode M, de Papp AE, Link TM, Majumdar S

Affiliation(s): Musculoskeletal Quantitative Imaging Research Group, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA. andrew.burghardt@ucsf.edu

Publication date & source: 2010-12, J Bone Miner Res., 25(12):2558-71. Epub 2010 Jun 18.

Publication type: Randomized Controlled Trial; Research Support, N.I.H., Extramural

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 (|rho| = 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 (|rho| = 0.56 to 0.89, p < .05). Baseline cortical geometry and porosity measures best predicted ALN-induced change in biomechanics at both sites (rho > 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. Copyright (c) 2010 American Society for Bone and Mineral Research.