Large scale proteomic analyses of HR-pQCT-derived bone loss at the radius and tibia in older men

Although bone loss progresses rapidly in older adults, its biological drivers are poorly understood, and effective biomarkers are not available. We used large-scale discovery proteomics to identify serum proteins associated with bone loss, and to develop predictive signatures, in older men (mean age 84 yr). Rates of distal radial and tibial bone loss were assessed with high-resolution peripheral quantitative computed tomography (HR-pQCT) over ~6 yr, and ~ 7 K serum proteins were measured with aptamer-based assays (SomaLogic). Using stringent statistical criteria, 22 proteins were found to be associated with incident bone loss. Higher levels of FSH were most consistently and robustly linked to greater loss. Several other biological pathways were associated with change in bone, including inflammation and endocrine influences. Protein associations with radial and tibial loss were broadly similar, but with distinct patterns. A 22-protein signature was strongly related to bone loss and was considerably more predictive of change than other bone remodeling markers. These data are among the first to examine the serum proteins associated with longitudinal bone loss, and they implicate several underlying biological processes that might be related. The distinct protein patterns associated with loss at radial and tibial sites suggest the nature of those events may be site specific. Serum protein signatures may provide value in predicting those with more rapid bone loss.