THE AGING JOINT: QUANTITATIVE [18F]NAF PET-MR IMAGING OF CELLULAR & MOLECULAR CHANGES IN BONE, CARTILAGE AND MUSCLE ACROSS THE LIFESPAN

Abstract

INTRODUCTION

Osteoarthritis (OA) is increasingly recognized as a whole-joint disease, affecting cartilage, subchondral bone and periarticular muscles. While structural changes throughout the lifespan have been investigated in prior work, few studies have explored early cellular and molecular changes, such as bone metabolism, cartilage matrix composition, and muscle quality. In this study, we simultaneously assessed bone metabolic activity, cartilage microstructure, and muscle morphometry and composition in vivo, and examined their associations with key OA risk factors including age, body mass index (BMI), and sex.

OBJECTIVE

To characterize cellular and molecular features of bone, cartilage, and muscle in asymptomatic adults, and determine how these metrics vary with key OA risk factors of age, BMI, and sex.

METHODS

Forty-five asymptomatic subjects (23-79 years old, 22 female) with no history of knee injury or symptomatic arthritis underwent bilateral knee imaging on a 3T GE PET-MRI scanner (Figure 1). Quantitative DESS MR images (TEs 6 and 30.4 ms) were used to compute mean cartilage T2 relaxation time and thickness in femoral, tibial and patellar subregions, which were segmented using a previously validated automated pipeline. Dynamic [¹⁸F]NaF PET scans were acquired before and after a stair-climbing exercise (2.5mCi dose/injection) and were used to quantify Standardized Uptake Value measures (SUVmean, SUVmax) and their exercise-induced change: ΔSUVmean, ΔSUVmax. Iterative Decomposition of water and fat with Echo Assymetry and Least squares estimation (IDEAL) scans of the bilateral thighs were also acquired. The quadriceps, hamstrings, and hip adductors were segmented using an automated pipeline (MuscleMap) and muscle volume (normalized to BMI), fat fraction, and lean muscle mass were calculated for each muscle. Statistical analysis included a linear mixed effects model for each tissue outcome (cartilage, bone, and muscle metrics), where sex (male vs. female), age (years) and BMI (kg/m²) were included as fixed-effect predictors, and random intercepts for subject and for side nested within subject (to account for the paired left/right measures) captured within‐individual correlation. Significance threshold was set at p < 0.05 for this analysis.

RESULTS

Table 1 shows results from the linear mixed effects model.

1) Higher BMI was associated with markedly greater baseline (SUVmean and SUVmax) and post‐exercise bone tracer uptake (ΔSUVmean and ΔSUVmax), indicating increased bone turnover in individuals with higher body mass. Age was linked specifically to higher maximum uptake measures (SUVmax and ΔSUVmax), suggesting that focal sites of remodeling intensify with aging even if the overall mean uptake remains relatively stable.

2) In cartilage, T2 relaxation times rose progressively across whole, deep, and superficial layers as participants grew older, while cartilage thickness was consistently lower in female subjects. Deep T2 also showed a positive association with BMI.

3) Muscle composition also shifted with age and adiposity: intramuscular fat fraction increased in individuals who are older and had higher BMI; overall muscle volume declined with advancing age; and lean muscle mass was significantly lower in women and continued to decrease over the lifespan.

CONCLUSION

This comprehensive in vivo assessment suggests that age and BMI are associated with increased subchondral bone activity, cartilage matrix degeneration, and muscle deterioration, with sex-specific differences in cartilage thickness and muscle mass. These coordinated changes under established OA risk factors highlight the need for integrated, whole-joint analyses to develop composite biomarkers and multi-targeted treatments. Future work will incorporate longitudinal imaging, larger cohorts, additional knee tissues (e.g., menisci), and exploration of cross-tissue interactions.