The paradox of obesity: denser bones with disturbed bone remodeling in premenopausal women

Obesity is a multifactorial disease characterized by excessive body fat accumulation that adversely affects health. Skeletal alterations may be present in patients living with obesity. Increased mechanical load, low grade inflammatory state, gut dysbiosis and sedentary behavior are obesity-associated factors that influence bone remodeling. The coordinated activity of osteoblasts and osteoclasts is essential for maintaining skeletal homeostasis; however, obesity can disrupt this balance. While studies in rodents indicate that obesity enhances bone resorption and reduces bone formation, leading to osteoporosis, human data remain inconclusive, showing both positive and negative associations between bone mineral density (BMD) and obesity indicators. In such cases, factors such as age and sex are key determinants of these variations. Few studies have addressed how obesity affects the skeleton in premenopausal women, a group that is not confounded by age-related changes. This study investigated the impact of increased adiposity on total, lumbar spine and femoral neck BMD in premenopausal women and examined its association with plasma markers of bone resorption and formation. Despite presenting higher total and regional BMD and increased lean mass, women with obesity showed a musculoskeletal imbalance when bone and lean mass were normalized to fat mass. Moreover, they showed reduced plasma concentrations of bone formation markers (amino-terminal propeptide of type 1 procollagen and Osteocalcin), alongside elevated levels of resorption markers (carboxy-terminal type I collagen telopeptide and RANK-L), indicating impaired bone remodeling. In conclusion, obesity in premenopausal women seems to be associated to an apparent increase in BMD and lean mass that may be misleading, since bone remodeling is compromised; suggesting that greater density could represent structural fragility rather than true skeletal integrity.