Thalassemia Bone Disease: A 19-Year Longitudinal Analysis

Abstract

Thalassemia is an inherited disorder of alpha or beta globin chain synthesis leading to ineffective erythropoiesis requiring chronic transfusion therapy in its most severe form. This leads to iron overload, marrow expansion, and hormonal complications, which are implicated in bone deformity and loss of bone mineral density (BMD). In this 19-year retrospective longitudinal study, the relationships between BMD (determined by dual-energy X-ray absorptiometry) and risk factors for osteoporosis in 277 subjects with transfusiondependent thalassemia were examined. The mean age at first review was 23.2 AE 11.9 years and 43.7% were male. Hypogonadism was present in 28.9%. Fractures were confirmed in 11.6% of subjects and were more frequent in males (16.5%) compared with females (7.7%). Lumbar spine (LS), femoral neck (FN), and total body (TB) Z-scores were derived. Patients with transfusion-dependent thalassemia had a significant longitudinal decline in BMD at the FN and TB. In the linear mixed-model analysis of BMD and risk factors for bone loss, FN Z-score was more significantly associated with risk factors compared with the LS and TB. The rate of decline at the FN was 0.02 Z-score per year and was 3.85-fold greater in males. The decline in FN Z-score over the last 5 years (years 15 to 19) was 2.5-fold that of the previous 7 years (years 8 to 14) and coincided with a change in iron chelator therapy from desferrioxamine to deferasirox. Hemoglobin (Hb) levels positively correlated with higher TB and LS Z-scores. In conclusion, the FN is the preferred site for follow-up of BMD. Male patients with b-thalassemia experienced a greater loss of BMD and had a higher prevalence of fractures compared with females. Transfusing patients (particularly males) to a higher Hb target may reduce the decline in BMD. Whether deferasirox is implicated in bone loss warrants further study.

Effects of strontium ranelate on bone mass and bone turnover in women with thalassemia major-related osteoporosis

“…As the longevity of patients with TM increases, osteoporosis is becoming a prominent problem [1,9]. Because osteoporosis is a progressive disease, prevention, early diagnosis and treatment of the established disease are crucial to avoid fractures and preserve quality of life [29].…”

“…The poor bone formation is proven by histomorphometric studies and is mainly caused by iron poisoning in osteoblasts and the reduced function of growth hormone and insulin-like growth factor-1 (IGF-1) axis [1,5,10].…”

“…Considerable morbidity in older subjects with thalassemia major (TM) results from bone disease due to osteoporosis which is often accompanied by disabling pain and fractures [1,2].…”

Bone Disease in Thalassemia: A Molecular and Clinical Overview

“…In cross-sectional studies of thalassemia bone disease, serum ferritin levels were not found to be significantly associated with BMD (49,106). Similarly, there was no significant association between serum ferritin or BMD in a large 19 year longitudinal study of thalassemia bone disease (107). The failure to show a statistically significant association between serum ferritin and BMD in thalassemia may be due to several reasons.…”

Thalassemia 2016: Modern medicine battles an ancient disease

“…Among the areas receiving attention is the chronic bone pain and osteoporosis which can be quite debilitating in adult patients [47]. The pathogenesis is multifactorial, from bone expansion due to hyperactivity of the bone marrow, to hypogonadism [48], and even iron overload is contributory [49]. Recently, an expert panel has published recommendations for surveillance and therapy which are quite welcome, as this area has previously been one of controversy.…”