Iron Overload Associated Endocrine Dysfunction Leading to Lower Bone Mineral Density in Thalassemia Major

Abstract

Context: Patients with thalassemia major (TM) have a lower bone mineral density (BMD) and higher risk of fracture than the general population. The possible mechanisms include anemia, iron overload, malnutrition, and hormonal deficiency, but these have not been thoroughly investigated.

Objective: To identify major mineral and hormonal factors related to BMD in adult TM patients to provide human evidence for the proposed mechanisms.

Design: Retrospective study.

Setting: Referral center.

Patients: Twenty-nine patients with β-TM, aged 23 to 44 years who were followed-up during 2017 to 2018 were enrolled.

Outcome measurements: Endocrine profiles, including thyroid, parathyroid, and pituitary function, glucose, vitamin D, calcium, phosphate, and fibroblast growth factor 23 (FGF23) were obtained. The relationships among the above parameters, body height, fractures, and BMD were analyzed.

Results: Abnormal BMD was observed in 42.9% of women and 23.1% of men. The mean final heights of women and men were 3.7 cm and 7.3 cm lower than the mean expected values, respectively. Fracture history was recorded in 26.7% of women and 35.7% of men. BMD was negatively correlated with parathyroid hormone, FGF23, thyrotropin, and glycated hemoglobin (HbA1c) levels, and positively correlated with testosterone, IGF-1, and corticotropin levels (all P < .05). Moreover, hypothyroidism was associated with lower BMD in both the lumbar spine (P = .024) and the femoral neck (P = .004). Patients with hypothyroidism had a higher percentage of abnormal BMD (P = .016).

Conclusion: Hypothyroidism, higher HbA1c, and lower adrenocorticotropin were predictors of abnormal BMD in patients with β-TM. Whether the correction of these factors improves BMD warrants further research.

Trial registration: ClinicalTrials.gov NCT03951818.

Keywords: bone mineral density; corticotropin; hemoglobin A1c; pituitary; thalassemia major; thyroid.