Serum biomarkers that predict lean mass loss over bed rest in older adults: An exploratory study

Abstract

Background: Lean mass (LM) loss during extended bed rest contributes to long term functional decline in older adults. Identifying blood biomarkers that predict a hospitalized individual's risk of losing LM could allow for timely intervention.

Methods: LM from 19 healthy subjects (age 60-76 y, 4 males, 15 females), who were confined to 10 days of complete bed rest, was measured pre- and post-bed rest. One hundred eighty-seven biomarkers from pre-bed rest fasted serum samples were obtained from all evaluable subjects (n = 18), analyzed using multiplexed immunoassay array and pooled. Decision tree analysis was used to identify pre-bed rest markers that predict LM loss over bed rest.

Results: Sixty-three markers were excluded due to being below assay detection limits. One pair of markers, Tissue inhibitor of metalloprotease-1 (TIMP1) and tenascin C (TNC), were found to correlate with percent change in total LM over bed rest: [R² = 0.71, all subjects; R² = 0.76, females]. Subjects with pre-bed rest TIMP1 ≥ 141 ng/ml had the highest loss of total LM over bed rest, whereas subjects with pre-bed rest TIMP1 < 141 and TNC ≥ 461 ng/ml maintained total LM over bed rest. An additional marker set was found to correlate with percent change in leg LM loss over bed rest: matrix metalloprotease-3 (MMP3) and apolipoprotein A2 (APOA2) [R² = 0.59, females]. Females with pre-bed rest MMP3 < 6.93 ng/ml had the highest loss of leg LM over bed rest. Whereas females with pre-bed rest MMP3 ≥ 6.93 and ApoA2 < 276 ng/ml, maintained leg lean mass at the end of bed rest.

Conclusions: Panels of blood biomarkers associated with the muscle extracellular matrix may predict the likelihood for LM loss over extended bed rest.

Keywords: Bed rest; Biomarkers; DEXA; Hospitalization; Immobilization; Lean mass.