Longitudinal 18F-NaF PET/MR and CT Assessment of CKD-Related Osteosarcopenia and Bone–Muscle Crosstalk in Rats

Background Chronic kidney disease (CKD) drives sarcopenia and disrupts bone-muscle crosstalk, contributing to frailty and excess mortality. However, longitudinal, non-invasive molecular imaging biomarkers capable of tracking these interconnected alterations remain lacking. This study aimed to characterize the temporal progression of muscle-bone pathology using a multimodal imaging framework. Male Sprague-Dawley rats underwent 5/6 nephrectomy (CKD, n = 6) or sham surgery (n = 6). Over 20 weeks, animals were longitudinally monitored using integrated ¹⁸F-NaF PET/MR and micro-CT, alongside functional gait assessment. Terminal histology (H&E, Masson’s trichrome, and α-SMA immunostaining) was performed to quantify muscle degeneration and bone marrow angiogenesis. Pairwise correlations were analyzed to delineate the relationships between imaging metrics and pathological features. Results CKD rats exhibited progressive hindlimb weakness detected by gait analysis from week 12 (P < 0.01). In skeletal muscle, gastrocnemius T2 relaxation times were significantly prolonged (indicating edema), accompanied by micro-CT-documented atrophy and decreased histologic cross-sectional area. In bone, ¹⁸F-NaF PET demonstrated markedly elevated uptake in the tibia (SUV: ~6.09 vs. 3.18 in sham, P < 0.01) and fibula, which was corroborated by increased bone marrow microvascular density on histology. Correlation analysis revealed strong inverse relationships between T2 values and muscle structural parameters (r = − 0.78, P < 0.01) and a positive association between T2 values and ¹⁸F-NaF uptake (r = 0.71, P < 0.05). Notably, skeletal ¹⁸F-NaF uptake showed a robust linkage with marrow vessel density (r = 0.72, P < 0.01), underscoring the coordinated nature of vascular-mediated muscle-bone deterioration. Conclusions Longitudinal multimodal imaging effectively captures the temporal cascade of sarcopenia and aberrant bone remodeling in CKD. Specifically, integrated ¹⁸F-NaF PET/MR and CT sensitively reflect uremia-driven bone-muscle crosstalk, likely mediated by microvascular remodeling. These findings establish a robust preclinical framework and highlight ¹⁸F-NaF PET/MR as a promising translational biomarker for monitoring CKD-associated frailty.