Immobilization by 21-days of bed rest causes changes in biomarkers of cartilage homeostasis in healthy individuals

Osteoarthr Cartil Open. 2025 Feb 28;7(2):100597. doi: 10.1016/j.ocarto.2025.100597. eCollection 2025 Jun.

Abstract

Objective: To investigate the effects of 21 days bed rest immobilization (with and without exercise and nutrition intervention) on serum concentrations of cartilage homeostasis biomarkers in healthy individuals.

Design: Twelve male volunteers (age 34.2 ​± ​8.3 years; BMI 22.4 ​± ​1.7 ​kg/m2) participated in 6 days of baseline data collection (BDC), 21 days of 6° head-down-tilt (HDT) bed rest (CON) ​+ ​interventions HDT ​+ ​resistive vibration exercise (RVE; 2 times/week; 25 ​min) and HDT ​+ ​RVE ​+ ​nutrition (NeX; 0.6 ​g/kg body weight/day whey protein and 90 ​mmol KHCO3/day bicarbonate supplementation), and 6 days of recovery (R) in a cross-over designed study. The starting HDT condition was randomized (CON-RVE-NeX, RVE-NeX-CON, NeX-CON-RVE). Blood samples were collected before, during and after HDT. Serum concentrations of COMP, MMP-3, MMP-9, YKL-40 and resistin were analyzed.

Results: The main effect of time was significant for all biomarkers tested (p ​< ​0.001). While COMP (-36 ​% at HDT5, p ​< ​0.001) and MMP-3 (-36 ​% at HDT21, p ​< ​0.001) decreased during HDT bed rest, MMP-9 (+18 ​% at HDT5, p ​< ​0.001) and resistin (+13 ​% at HDT21, p ​< ​0.001) increased during HDT bed rest. Interestingly, during recovery, YKL-40 levels increased (+13 ​% at R1, p ​= ​0.022), while MMP-9 levels decreased (-19 ​% at R6, p ​= ​0.035). We identified correlations between COMP and MMP-3 (rrm ​= ​0.58, p ​< ​0.001) as well as between MMP-9 and resistin (rrm ​= ​0.58, p ​< ​0.001).

Conclusions: Immobilization affects serum concentrations of cartilage homeostasis biomarkers suggesting changes in cartilage metabolism that do not completely recover during re-ambulation. Both interventions had only minimal effects.

Keywords: Bed rest; Cartilage biomarkers; Cartilage homeostasis; Immobilization; MNX-Study; Non-collagenous biomarkers.