α- and β-Thalassemia Show Distinct Bone Microarchitectural Phenotypes in Southeast Asian Adults: Associations with Marrow Expansion Phenotype

Bone disease is well recognized in β-thalassemia, but bone microarchitecture in α-thalassemia remains poorly characterized. We prospectively studied 86 adults with thalassemia at a tertiary center in northeast Thailand: 16 with α-thalassemia and 70 with β-thalassemia. Lumbar spine (LS) and femoral neck bone mineral density (BMD) and trabecular bone score (TBS) were measured using the same DXA platform. A prespecified Marrow Expansion Phenotype Score (MEPS; 0–3), comprising thalassemic facies, scoliosis, and hepatomegaly, served as an exploratory marker of chronic ineffective erythropoiesis. Sequential linear regression assessed attenuation of genotype effects after adjustment for transfusion-dependent thalassemia status and MEPS. Compared with β-thalassemia, α-thalassemia was associated with higher LS BMD (0.822 ± 0.130 vs. 0.754 ± 0.117 g/cm²; p = 0.039), higher LS Z-score (−1.27 ± 0.65 vs. −1.99 ± 0.99; p = 0.009), and a trend toward higher TBS (1.318 ± 0.102 vs. 1.255 ± 0.128; p = 0.071). Low LS Z-score (<−2) was less frequent in α-thalassemia (12.5% vs. 45.7%; p = 0.021). Mean MEPS was lower (0.88 ± 0.62 vs. 1.84 ± 0.88; p < 0.001). Genotype associations with TBS, LS BMD, and LS Z-score persisted after adjustment for transfusion status but were attenuated and no longer significant after MEPS adjustment. Ferritin adjustment did not materially change the estimates but cannot exclude effects of total iron burden. Adults with α-thalassemia had better lumbar bone density and microarchitecture than those with β-thalassemia. Attenuation after MEPS adjustment is consistent with, but does not prove, a role for marrow-expansion phenotype. Formal mediation was not performed. Given the small α-thalassemia group, these findings are exploratory and require replication.