Osteoporosis, conventionally defined as a widespread affliction affecting bone tissue structural integrity and heightening the risk of fractures and mortality (Johnston and Dagar, 2020; Reid and Billington, 2022), has a worldwide prevalence of 19.7% as per a meta-analysis, with Asian populations exhibiting a greater susceptibility compared to their European and American counterparts (Xiao et al., 2022). Notably, in mainland China, the estimated prevalence of osteoporosis among individuals aged 50 years or above is approximately 20.73% for males and 38.05% for females (Wang et al., 2023a). By 2035, osteoporosis-related fractures are predicted to reach 4.83 million per year, incurring an annual cost of roughly $19.92 billion (Si et al., 2015). Therefore, it is imperative to delve into the risk factors of osteoporosis among the Chinese population and implement preventive measures.

Changes in body mass index (BMI) frequently occur among middle-aged and elderly individuals (Yuan et al., 2022). The BMI change leads to alterations in skeletal loading, endocrine environment, and nutritional status, thereby impacting bone mineral density (BMD) (Liu et al., 2018). Animal studies have illustrated that diet-induced weight gain could exacerbate the harmful effects of estrogen deficiency on bone (Ali et al., 2022). Research has indicated that leptin, produced in adipocytes, may directly or indirectly influence osteoblasts and chondrocytes through weight changes (Reid et al., 2018). However, there are still limited population-based studies exploring the association between BMI change and BMD, with inconsistent findings. For instance, Wang and colleagues found the adverse effect of excessive BMI gain on bone loss among Americans (Wang et al., 2023b). Following weight loss intervention, older individuals experienced a continued decline in hip BMD over the year (Kammire et al., 2019). Jia et al. found weight change from obesity to non-obesity was associated with a lower risk of osteoporosis (Jia and Yuan, 2023). Despite such findings, there remains a scarcity of studies investigating the impact of BMI changes on bone loss within the Chinese population.

BMI changes play a crucial role in regulating lipid metabolism. BMI was positively correlated with the very low-density lipoprotein (VLDL) metabolites and negatively associated with high-density lipoprotein (HDL) metabolites (Okekunle et al., 2022). Intervention trials have found alterations in lipidomic biomarkers among those who lose weight (Lin et al., 2023; Romero-Moraleda et al., 2015). In another study, individuals exhibited upregulation of lipid metabolism-related genes after a slight weight increase (Piening et al., 2018). Furthermore, the relationship between lipids and BMD has been extensively investigated. HDL was found to be negatively associated with BMD (Zhang et al., 2020). Mendelian randomization studies also suggested that there may be causal relationships between lipids and BMD (Wu et al., 2023; Yang et al., 2019a; Zheng et al., 2020a). Additionally, lipid parameters and lipid metabolites have already been used to improve the performance of osteoporosis prediction models (Mei et al., 2020; Tang et al., 2021). Given the relationship between BMI change, lipid metabolism, and BMD, it is imperative to delve deeper into the mechanisms through which BMI changes influence bone loss via lipid metabolism.

Therefore, this study aimed to investigate the association between BMI change and osteoporosis and osteopenia among the 55–65-year-old Chinese population using data from the Taizhou Imaging Study (TIS). We utilized the metabolomics data to examine the role of various metabolites in the relationship between BMI change and bone loss. Our research may provide valuable insights into weight management for the prevention of osteoporosis in the Chinese elderly population, shedding light on the mechanisms by which BMI change impacts BMD.