Metabolic Bone Disorder in Thalassemia

Wen-Pin YangTaiwan Speaker Metabolic Bone Disorder in ThalassemiaIntroduction: Thalassemia-associated osteoporosis (TAO) is a prevalent and debilitating complication in adult patients with β-thalassemia major (β-TM), despite advancements in transfusion and chelation therapies. Given the complexity of its pathogenesis, TAO presents a unique challenge to endocrinologists, requiring a nuanced understanding of the interplay between ineffective erythropoiesis, iron overload, and the endocrine axis. Pathogenesis & Endocrine Involvement: The aetiology of TAO is multifactorial. Chronic ineffective erythropoiesis leads to bone marrow expansion, causing mechanical disruption of the trabecular microarchitecture. Simultaneously, systemic iron overload (hemosiderosis) exerts direct toxicity on osteoblasts and induces secondary endocrine failures. Clinical evidence demonstrates that BMD in β-TM patients is significantly correlated with multiple endocrine parameters: it is negatively associated with TSH, HbA1c, iPTH, and FGF23 levels, while positively correlating with testosterone and IGF-1. Pituitary and thyroid hemosiderosis are major drivers of impaired peak bone mass accrual and accelerated bone loss. Diagnostic Considerations: While Dual-energy X-ray absorptiometry (DXA) remains the standard for monitoring, its accuracy is often limited by scoliosis, vertebral deformities, and marrow expansion. Complementary tools, such as bone turnover markers (CTX and P1NP) and opportunistic QCT, are essential for a comprehensive skeletal assessment and for identifying patients at high risk for fragility fractures. Therapeutic Strategies: Management requires a multidisciplinary approach beyond optimizing iron chelation and Vitamin D status. Antiresorptive agents, particularly Zoledronate and Denosumab, are effective in increasing BMD and reducing bone pain. However, in severe cases with prevalent fractures, anabolic therapy with Teriparatide has demonstrated superior efficacy, with significant BMD gains in both the lumbar spine and femoral neck. This presentation will emphasize the "sequential therapy" model—initiating with anabolic agents followed by antiresorptives—to maximize and maintain skeletal recovery. Conclusion: TAO requires lifelong vigilance and a tailored treatment plan. Early intervention targeting endocrine deficiencies and the strategic application of sequential pharmacological therapies are vital to preventing fractures and improving the quality of life for this aging population.