Obesity is an alarming disease that favors the upset of other illnesses and enhances mortality. It is spreading fast worldwide may affect more than 1 billion people by 2030. The imbalance between excessive food ingestion and less energy expenditure leads to pathological adipose tissue expansion, characterized by increased production of proinflammatory mediators with harmful interferences in the whole organism. Bone tissue is one of those target tissues in obesity. Bone is a mineralized connective tissue that is constantly renewed to maintain its mechanical properties. Osteoblasts are responsible for extracellular matrix synthesis, while osteoclasts resorb damaged bone, and the osteocytes have a regulatory role in this process, releasing growth factors and other proteins. A balanced activity among these actors is necessary for healthy bone remodeling. In obesity, several mechanisms may trigger incorrect remodeling, increasing bone resorption to the detriment of bone formation rates. Thus, excessive weight gain may represent higher bone fragility and fracture risk. This review highlights recent insights on the central mechanisms related to obesity-associated abnormal bone. Publications from the last ten years have shown that the main molecular mechanisms associated with obesity and bone loss involve: proinflammatory adipokines and osteokines production, oxidative stress, non-coding RNA interference, insulin resistance, and changes in gut microbiota. The data collection unveils new targets for prevention and putative therapeutic tools against unbalancing bone metabolism during obesity.

Background: Obesity poses a significant global health challenge, given its association with the excessive accumulation of adipose tissue (AT) and various systemic disruptions. Within the adipose microenvironment, expansion and enrichment with immune cells trigger the release of inflammatory mediators and growth factors, which can disrupt tissues, including bones. While obesity’s contribution to bone loss is well established, the direct impact of obese AT on osteoblast maturation remains uncertain. This study aimed to explore the influence of the secretomes from obese and lean AT on osteoblast differentiation and activity. Methods: SAOS-2 cells were exposed to the secretomes obtained by culturing human subcutaneous AT from individuals with obesity (OATS) or lean patients, and their effects on osteoblasts were evaluated. Results: In the presence of the OATS, mature osteoblasts underwent dedifferentiation, showing an increased proliferation accompanied by a morphological shift towards a mesenchymal phenotype, with detrimental effects on osteogenic markers and the calcification capacity. Concurrently, the OATS promoted the expression of mesenchymal and adipogenic markers, inducing the formation of cytoplasmic lipid droplets in SAOS-2 cells exposed to an adipogenic differentiation medium. Additionally, TGF-β1 emerged as a key mediator of these effects, as the OATS was enriched with this growth factor. Conclusions: Our findings demonstrate that obese subcutaneous AT promotes the dedifferentiation of osteoblasts and increases the adipogenic profile in these cells.

Obesity is a multifactorial disease characterized by excessive adiposity that influences bone remodeling through increased mechanical loading, chronic low‐grade inflammation, and sedentary behavior. While obesity is linked to structural skeletal changes, its precise impact on bone mineral density (BMD) and bone remodeling in humans remains controversial, particularly in young women. This is particularly relevant because the majority of studies have investigated young women, in whom many of the observed skeletal alterations are attributable to aging rather than obesity per se. This study investigated the impact of increased adiposity on total, lumbar spine, and femoral neck BMD in 54 young Brazilian women with 18–40 years. Body composition and BMD were assessed by DXA, and plasma markers of bone formation and resorption were analyzed. Associations among adiposity, lean mass, BMD, and bone turnover markers were examined. Women with obesity exhibited higher total and regional BMD and greater lean mass than women without obesity. However, adjusting bone and lean mass for fat mass revealed a musculoskeletal imbalance. In addition, obesity was associated with a suppressed bone turnover profile; these women presented lower circulating levels of the formation markers P1NP and osteocalcin, alongside elevated resorption markers CTX‐I and RANK‐L/OPG. Ultimately, these findings demonstrate that bone remodeling is compromised despite an apparent increase in bone mass. Obesity in young Brazilian women is associated with higher BMD and lean mass; however, these findings may mask underlying detrimental alterations in bone remodeling. The observed imbalance between bone formation and resorption demonstrates that increased density does not reflect improved skeletal health, but rather compromised bone quality and structural fragility.