Prevalence of low bone mineral density and associated plasma metabolite alterations in thalassemia

While metabolomics offers insights into metabolic diseases, plasma metabolites in thalassemia patients with low bone mineral density (BMD) have not been explored. This cross-sectional study investigated plasma metabolite alterations in thalassemia patients with low BMD compared to those with normal BMD and healthy controls at Chiang Mai University's Hematology Clinic. Eighty thalassemia patients and 40 age- and sex-matched controls were enrolled. BMD was measured at two skeletal sites, the lumbar spine (L1-L4) and hip, using dual-energy X-ray absorptiometry. Targeted plasma metabolomics and bone turnover markers (β-CTX-I, total PINP) were assessed. Low BMD was defined as a Z-score ≤ - 2 at any site, and its prevalence among thalassemia patients was 47.5%. Compared to those with normal BMD, thalassemia patients with low BMD showed elevated glutamate, arachidonic acid, and medium- to long-chain acylcarnitines, but reduced glutamine levels. Phosphatidylinositol and lysophosphatidylinositol were also increased. β-CTX-I and total PINP levels did not differ between thalassemia groups. A predictive model using key metabolites (glutamine, arachidonic acid, asparagine, lysoPI (18:0), myristoylcarnitine) showed fair discriminatory ability for low BMD (AUC 0.762, p = 0.007). Thalassemia with low BMD is associated with glutamate-glutamine metabolism disruptions, impaired fatty acid oxidation, and elevated phosphatidylinositol levels.