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

Carrie M. Nielson, Jack Wiedrick, Jian Shen, Jon Jacobs, Erin S. Baker, Aaron Baraff, Paul Piehowski, Christine G. Lee, Arie Baratt, Vladislav Petyuk, Shannon Mcweeney, Jeong Youn Lim, Douglas C. Bauer, Nancy E Lane, Peggy M. Cawthon, Richard D. Smith, Jodi Lapidus, Eric S. Orwoll

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 ≥0g/cm2, n=453); expected loss (estimated change 0 to 1 SD below the estimated mean change, -0.034g/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 proportional hazards models with age and BMI adjustment in 2473 men. Five proteins were associated with incident hip fracture (HR between 1.29 and 1.41 per SD increase in estimated protein abundance). Some proteins have been previously associated with fracture risk (eg, CD14 and SHBG), whereas others have roles in cellular senescence and aging (B2MG and TIMP1) and complement activation and innate immunity (CO7, CO9, CFAD). These findings may inform development of biomarkers for future research in bone biology and fracture prediction.

Original languageEnglish (US)
JournalJournal of Bone and Mineral Research
DOIs
StateAccepted/In press - 2017

Fingerprint

Pelvic Bones
Proteomics
Bone Density
Hip Fractures
Serum
Population
Proteins
Cell Aging
Femur Neck
Biomarkers
Maintenance
Social Adjustment
Osteoporotic Fractures
Complement Activation
Bone Fractures
Proportional Hazards Models
Innate Immunity
Liquid Chromatography
Osteoporosis
Meta-Analysis

Keywords

  • Biochemical markers of bone turnover
  • General population studies
  • Osteoporosis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Nielson, C. M., Wiedrick, J., Shen, J., Jacobs, J., Baker, E. S., Baraff, A., ... Orwoll, E. S. (Accepted/In press). Identification of Hip BMD Loss and Fracture Risk Markers Through Population-Based Serum Proteomics. Journal of Bone and Mineral Research. https://doi.org/10.1002/jbmr.3125

Identification of Hip BMD Loss and Fracture Risk Markers Through Population-Based Serum Proteomics. / Nielson, Carrie M.; Wiedrick, Jack; Shen, Jian; Jacobs, Jon; Baker, Erin S.; Baraff, Aaron; Piehowski, Paul; Lee, Christine G.; Baratt, Arie; Petyuk, Vladislav; Mcweeney, Shannon; Lim, Jeong Youn; Bauer, Douglas C.; Lane, Nancy E; Cawthon, Peggy M.; Smith, Richard D.; Lapidus, Jodi; Orwoll, Eric S.

In: Journal of Bone and Mineral Research, 2017.

Research output: Contribution to journalArticle

Nielson, CM, Wiedrick, J, Shen, J, Jacobs, J, Baker, ES, Baraff, A, Piehowski, P, Lee, CG, Baratt, A, Petyuk, V, Mcweeney, S, Lim, JY, Bauer, DC, Lane, NE, Cawthon, PM, Smith, RD, Lapidus, J & Orwoll, ES 2017, 'Identification of Hip BMD Loss and Fracture Risk Markers Through Population-Based Serum Proteomics', Journal of Bone and Mineral Research. https://doi.org/10.1002/jbmr.3125
Nielson, Carrie M. ; Wiedrick, Jack ; Shen, Jian ; Jacobs, Jon ; Baker, Erin S. ; Baraff, Aaron ; Piehowski, Paul ; Lee, Christine G. ; Baratt, Arie ; Petyuk, Vladislav ; Mcweeney, Shannon ; Lim, Jeong Youn ; Bauer, Douglas C. ; Lane, Nancy E ; Cawthon, Peggy M. ; Smith, Richard D. ; Lapidus, Jodi ; Orwoll, Eric S. / Identification of Hip BMD Loss and Fracture Risk Markers Through Population-Based Serum Proteomics. In: Journal of Bone and Mineral Research. 2017.
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AU - Lee, Christine G.

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