Age-related bone mass and body composition dynamics in female cynomolgus monkeys: dual-energy X-ray absorptiometry insights for osteoporosis etiology.

Background: Osteoporosis, characterized by reduced bone mass and increased fracture risk, is a major global health burden. Nonhuman primates, particularly female cynomolgus monkeys, are critical preclinical models due to their skeletal and hormonal similarity to humans. Dual-energy X-ray absorptiometry (DXA) is the gold standard for measuring bone mineral density (BMD) and body composition. However, data on age-related changes in these metrics in cynomolgus monkeys are inconsistent, and the relationship between body composition and BMD remains debated and understudied in this model. The objectives of this study were to delineate the age-dependent trends in bone mass and body composition and to evaluate the impact of body composition on bone mass. This study aims to furnish a data reference for experiments involving bone mass and body composition in cynomolgus monkeys as a disease model. Methods: A cohort of 112 healthy female cynomolgus monkeys was stratified into four age-based groups. DXA scans were conducted to ascertain total body bone mass, subcranial bone mass, spine BMD (BMDs), central region-of-interest bone mineral density (BMDCROI), and body composition metrics. A generalized additive model (GAM) was utilized for non-linear regression analysis of the aging trends in bone mass and body composition parameters. Spearman's rank correlation and multiple linear regression analyses were conducted to investigate the interplay between body composition and bone mass. Results: In female cynomolgus monkeys ≤10 years of age, bone mass parameters showed a significant increase with age. Beyond the age of 10 years, BMDs remained stable with age, while total body BMD (BMDTB) and subcranial BMD exhibited a slight increasing trend in advanced age. A relative decline in BMDCROI was observed in the elderly cohort, with a higher cumulative bone loss rate compared to BMDs (-10.0% vs. 1.8%). BMDTB demonstrated a strong positive correlation with subcranial BMD, with correlation coefficients ranging from 0.947 to 0.990 (P<0.001). Similarly, total body bone mineral content (BMCTB) was highly correlated with subcranial BMC, with correlation coefficients ranging from 0.961 to 0.996 (P<0.001). In the correlation analysis of bone mass and body composition in female cynomolgus monkeys prior to peak age (≤10 years old), both lean mass (LM) and fat mass (FM) positively influenced BMD, with LM contributing more significantly. Post-peak age (>10 years), FM had a more pronounced effect on total body bone mass. Conclusions: The bone mass and body composition data of female cynomolgus monkeys across different age groups serve as a valuable reference for studies employing female cynomolgus monkeys as animal models. BMDCROI is a sensitive indicator for detecting spinal bone mass loss, minimizing the confounding effects of osteoarthritis (OA). The variable contributions of LM and FM to bone mass in female cynomolgus monkeys at different ages offer significant insights for investigating the etiological factors of osteoporosis.