Catastrophic Skeletal Fragility in Transfusion-Dependent HbE β-Thalassemia: Endocrine Siderosis and Failure of Anti-Resorptive Therapy
https://doi.org/10.15605/jafes.041.S1
- Author:
Ahmad Syahmi Yusof Zaki
1
;
Nur Izat Muhamad
2
;
Ezelea Elwina Walter Sandosam
2
;
Wan Mohd Izani Wan Mohamed
2
Author Information
1. Faculty of Medicine, University Sultan Zainal Abidin;Department of Internal Medicine, School of Medical Sciences, University Science Malaysia
2. Department of Internal Medicine, School of Medical Sciences, University Science Malaysia
- Publication Type:Journal Article
- MeSH:
Siderosis;
Thalassemia
- From:
Journal of the ASEAN Federation of Endocrine Societies
2026;41(S1):75-76
- CountryPhilippines
- Language:English
-
Abstract:
Introduction:Skeletal disease in transfusion-dependent thalassemia
is commonly attributed to reduced bone mineral density
and managed with anti-resorptive therapy. However,
chronic iron overload can induce progressive endocrine
siderosis, disrupting anabolic pathways essential for bone
homeostasis. This mechanism remains under-recognized
and may underlie treatment failure in severe cases.
Case:We describe a 34-year-old female with transfusiondependent HbE β-thalassemia, post-splenectomy, receiving
regular transfusions and iron chelation, who sustained
multiple pathological fractures following a trivial fall,
including bilateral supracondylar femur fractures and a
distal radius fracture. She had severe systemic iron overload
(ferritin 2,621 ng/mL) complicated by hepatic cirrhosis,
insulin-dependent diabetes, and hypogonadotropic
hypogonadism. Bone mineral density assessment
demonstrated severe osteoporosis (hip T-score −5.4) despite prolonged bisphosphonate therapy, with prior vertebral
compression fracture. Endocrine evaluation revealed multiaxis dysfunction, including gonadal failure and probable
growth hormone deficiency, consistent with pituitary and
peripheral endocrine siderosis.
Conclusion:This case demonstrates that skeletal fragility in transfusiondependent thalassemia reflects an endocrine-driven failure
of bone formation rather than isolated loss of bone mineral
density. Iron overload–induced endocrine siderosis
impairs osteoblast function and suppresses anabolic
signaling, leading to profound skeletal vulnerability. The
progression of osteoporosis despite anti-resorptive therapy
highlights the limitation of conventional approaches and
supports reframing thalassemia-associated bone disease as
an endocrine disorder. Severe osteoporosis should prompt
systematic endocrine evaluation, with early hormonal
replacement and consideration of anabolic therapy to
prevent catastrophic fractures and long-term disability.
- Full text:2026080411121012999EP_A102.pdf
