Objective: While type 2 diabetes (T2D) is known to increase the risk of bone fragility and fractures, the specific mechanisms are not fully understood. Previous research has implicated neuropeptides in bone metabolism regulation, but the role of the neuropeptide neurotensin (NT), centrally involved in metabolic and cardiovascular diseases, in this context remained unexplored. The study aimed to investigate the relationship between NT precursor levels (pro-NT) and bone health in women with T2D. Research design and methods: For this longitudinal prospective study, 126 female T2D patients who underwent bone density scans and had pro-NT levels measured, were recruited. Biomarkers of bone metabolism and inflammation were assessed. After a year, bone mineral density (BMD) was re-evaluated in 49 patients. Results: 32% of the participants had osteopenia/osteoporosis at baseline and had higher pro-NT levels compared to those with normal BMD (200.8±113.7 vs 161.6±108.8 pg/ml; p=0.013). Pro-NT inversely correlated with BMD and T-score at femur level (p<0.01) and associated with degraded bone architecture, estimated by the DXA-derived index Trabecular Bone Score (p=0.02), and with biomarkers of bone turnover/inflammation (OPN, P1NP, TNF-alfa IL-1 beta). Baseline pro-NT predicted further BMD reduction at the 12-month follow-up, independently of potential confounders (p=0.023). Conclusions: Elevated pro-NT levels are associated with impaired bone mineralization and BMD decline over time in women with T2D. The findings highlight the potential significance of pro-NT as a diagnostic tool for identifying T2D patients at a higher risk of osteopenia and osteoporosis, indicating a possible connection between this neuropeptide and bone metabolism in diabetes.