Abstract / Summary
Abstract Objective Type 2 diabetes mellitus (T2DM) compromises bone quality and biomechanical integrity, driven by impaired microstructure, suppressed turnover, and collagen abnormalities. Crucially, this fragility occurs despite normal bone mineral density and may initiate early in the disease, underscoring the need for timely skeletal assessment. Materials and methods Twelve male Sprague-Dawley rats were randomly assigned to either the control or the T2DM group. Within 2 weeks of model confirmation, all underwent dual-energy x-ray absorptiometry, in vivo magnetic resonance imaging of the liver and femur, and blood collection for comprehensive biochemical and lipid profiling. Subsequently, all right femurs were harvested for micro-computed tomography, biomechanical testing, and Masson’s staining. The tibia and fibula were collected for the analysis of bone metabolism markers and advanced glycation end products (AGEs). Results Compared with the control group, T2DM rats exhibited higher body weight from week 10 onward, along with increased fat mass and body fat percentage. Serum total cholesterol, alanine aminotransferase and aspartate aminotransferase levels were elevated. Hepatic proton density fat fraction (PDFF) was higher. No intergroup differences of serum calcium, magnesium and phosphorus, cancellous/cortical bone and biomechanical testing parameters. Femoral collagen fiber organization was impaired in T2DM rats. Procollagen type I N-terminal propeptide was upregulated, while osteocalcin relative mRNA expression was downregulated. Femoral collagen organization was strongly negatively correlated with hepatic PDFF. Conclusion In early-stage T2DM, bone damage follows a temporal sequence (organic before inorganic) and site-specific (pronounced in cancellous bone). These changes parallel systemic metabolic disturbances, and ameliorating adipose and hepatic dysfunction may help restore bone collagen matrix homeostasis. Key Points Question How does the metabolic microenvironment shaped by adipose tissue redistribution affect bone microarchitecture in patients with early-stage T2DM? Findings In early-stage T2DM, bone damage may exhibit a temporal (organic-first) and spatial (cancellous-predominant) pattern, and coexists particularly with abnormal lipid metabolism and hepatic dysfunction. Relevance statement In early-stage T2DM, abnormal lipid metabolism and liver function may serve as a potential indicator of compromised bone quality. Therapeutic interventions aimed at ameliorating adipose and hepatic dysfunction in T2DM may help restore bone collagen matrix homeostasis.