Identification of Hip BMD Loss and Fracture Risk Markers Through Population-Based Serum Proteomics

作者：Carrie M. Nielson, Jack Wiedrick, Jian Shen, Jon Jacobs, Erin Baker, Aaron Baraff, Paul Piehowski, Christine G. Lee, Arie Baratt, Vladislav Petyuk, Shannon K. McWeeney, Jeong Youn Lim, Douglas C. Bauer, Nancy E. Lane, Peggy M. Cawthon, Richard Smith, Jodi Lapidus, Eric Orwoll · 发表于：Journal of Bone and Mineral Research · 年份：2017 · DOI：10.1002/jbmr.3125 · 被引用次数：58 · 研究领域：Advanced Proteomics Techniques and Applications、Bone Metabolism and Diseases、Clusterin in disease pathology

ABSTRACT Serum proteomics analysis may lead to the discovery of novel osteoporosis biomarkers. The Osteoporotic Fractures in Men (MrOS) study comprises men ≥65 years old in the US who have had repeated BMD measures and have been followed for incident fracture. High-throughput quantitative proteomic analysis was performed on baseline fasting serum samples from non-Hispanic white men using a multidimensional approach coupling liquid chromatography, ion-mobility separation, and mass spectrometry (LC-IMS-MS). We followed the participants for a mean of 4.6 years for changes in femoral neck bone mineral density (BMD) and for incident hip fracture. Change in BMD was determined from mixed effects regression models taking age and weight into account. Participants were categorized into three groups: BMD maintenance (no decline; estimated change ≥0 g/cm2, n = 453); expected loss (estimated change 0 to 1 SD below the estimated mean change, –0.034 g/cm2 for femoral neck, n = 1184); and accelerated loss (estimated change ≥1 SD below mean change, n = 237). Differential abundance values of 3946 peptides were summarized by meta-analysis to determine differential abundance of each of 339 corresponding proteins for accelerated BMD loss versus maintenance. Using this meta-analytic standardized fold change at cutoffs of ≥1.1 or ≤0.9 (p < 0.10), 20 proteins were associated with accelerated BMD loss. Associations of those 20 proteins with incident hip fracture were tested using Cox proportio...