Mineral and Hormonal Dysfunction Associated With Lower BMD in Thalassemia Major

Hemotransfusion in treatment of anemia, 3D illustration showing two populations of red blood cells, small hypochromic red blood cells and normal. A small lymphocyte is drawn for size comparison
Hypothyroidism, hyperglycemia, and low adrenocorticotrophic hormone levels are associated with lower bone mass in patients with thalassemia major.

Hypothyroidism, hyperglycemia, and low adrenocorticotrophic hormone (ACTH) levels are associated with lower bone mass in patients with thalassemia major, according to study results published in The Journal of Clinical Endocrinology & Metabolism.

The major mechanisms of endocrine dysfunction that lead to decreased bone mineral density (BMD) and increased risk for fracture in patients with thalassemia major remain poorly understood. Researchers aimed to identify the mineral and hormonal factors associated with low BMD in adults with β-thalassemia major in a retrospective study of patients who received treatment at the National Taiwan University Hospital (ClinicalTrials.gov Identifier: NCT03951818).

Medical history was obtained for 29 patients (51.7% women), including bone-associated biochemical markers such as serum calcium, phosphorus, intact parathyroid hormone, vitamin D, and fibroblast growth factor 23 levels. Pituitary function and thyroid hormone levels were used as a proxy for endocrine function. BMD was measured using dual-energy x-ray absorptiometry. Expected height was calculated for each individual based on parental height from patient records.

The mean observed height across all patients was lower than expected (women, -3.7 cm; men, -7.3 cm). Abnormal BMD, defined as a z score ≥2 standard deviations away from normal BMD, was observed in 42.9% of women and 23.1% of men. In addition, 26.7% of women and 35.7% of men had a history of fracture. Vitamin D deficiency (women, 100%; men, 81.8%), hypogonadism (women, 60%; men, 57.1%), and growth hormone deficiency (women, 75%; men, 57.1%) were highly prevalent in the study group.

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Several factors were associated with either femoral neck or lumbar spine BMD, but only thyroid status and lower ACTH levels correlated with BMD at both sites (P <.05). Along with thyroid status (P =.016) and ACTH levels (P =.005), glycated hemoglobin levels (P =.039) were significantly different in patients with normal vs abnormal BMD. When included in a multivariate regression model adjusted for ferritin level, age, and sex, however, hypothyroidism was the only factor significantly associated with lower femoral neck BMD (P =.034). Patients with hypothyroidism had lower BMD at both the lumbar spine (P =.024) and femoral neck (P =.004). No association was found with fracture risk.

“Our study is the first study to review the complete endocrine and mineral profiles to identify factors related to the severity of decreased BMD in patients with [thalassemia major],” the researchers noted. “We found that hypothyroidism and hyperglycemia were the most relevant factors of lower bone mass, while ACTH had a protective role.”

The researchers also noted that the interplay between these factors supports the idea that iron overload may be a driver of decreased bone mass in patients with thalassemia major.

“Based on these findings, it is promising to conduct interventional trials in the future that evaluate the effect of treating hypothyroidism or glycemic control on BMD and the risk of fracture in patients with [thalassemia major],” the researchers concluded.

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Yang WP, Chang HH, Li HY, et al. Iron overload associated endocrine dysfunction leading to lower bone mineral density in thalassemia major [published online January 7, 2020]. J Clin Endocrinol Metab. doi:10.1210/clinem/dgz309