An updated overview of the search for biomarkers of osteoporosis based on human proteomics

Abstract

Osteoporosis is a chronic metabolic disease that increases bone fragility and, leads to severe osteoporotic fractures. In recent years, the use of high-throughput omics to explore physiological and pathological biomarkers related to bone metabolism has gained popularity. In this review, we first briefly review the technical approaches of proteomics. Additionally, we summarize the relevant literature in the last decade to provide a comprehensive overview of advances in human proteomics related to osteoporosis. We describe the specific roles of various proteins related to human bone metabolism, highlighting their potential as biomarkers for risk assessment, early diagnosis and disease course monitoring in osteoporosis. Finally, we outline the main challenges currently faced by human proteomics in the field of osteoporosis and offer suggestions to address these challenges, to inspire the search for novel osteoporosis biomarkers and a foundation for their clinical translation. In conclusion, proteomics is a powerful tool for discovering osteoporosis-related biomarkers, which can not only provide risk assessment, early diagnosis and disease course monitoring, but also reveal the underlying mechanisms of disease and provide key information for personalized treatment.

The translational potential of this article: This review provides an insightful summary of recent human-based studies on osteoporosis-associated proteomics, which can aid the search for novel osteoporosis biomarkers based on human proteomics and the clinical translation of research results.

Keywords: Biomarkers; Bone mineral density; Osteoporosis; Proteomics.

Graphical abstract

Fig. 1

Schematic illustration of human proteomics sample sources. Figure created with the help of https://www.biorender.com.

Fig. 2

Schematic representation of the workflow for the proteomic approach in osteoporosis. Figure created with the help of https://www.biorender.com.

Fig. 3

An overview of proteomics techniques. Figure created with the help of https://www.biorender.com.

Fig. 4

Proteome-wide profiling reveals dysregulated molecular features and accelerated aging in osteoporosis by prospective study (A) Overview of the study cohort and design. (B) Prospective associations between serum proteins with osteoporosis and BMD. (C) Prospective associations of PRS with osteoporosis and BMD. (D) The prospective associations between biological age scores and osteoporosis risk [18]. Copyright 2023, John Wiley and Sons.

Fig. 5

Human bone tissue and serum-based screening for biomarkers of osteoporosis with iron accumulation (A) Workflow for quantitative mass spectrometry profiling. (B) Quantitative proteomics analysis of human bone from osteoporosis patients with iron accumulation. ∗∗P < 0.01. (C) Serum protein levels of physical exam volunteers were tested by ELISA kits. (D) Graphed summary of four core proteins [63]. Copyright 2022, Frontiers.