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Osteoporosis and β-thalassemia major: Role of the IGF-I/IGFBP-III axis

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Abstract

Patients with β-thalassaemia major are susceptible to osteopenia due to several factors which interfere with bone remodeling. It is known that bone metabolism and skeletal consolidation result from a complex sequence of hormonal changes, where the concerted actions of GH, IGFI and sex hormones and their receptors, are responsible for the timing and attainment of skeletal consolidation. IGF-I and the corresponding binding protein (IGFBP-III), markers of bone metabolism and lumbar and femoral neck BMD were measured in 28 adult patients, undergoing hormonal replacement and chelation therapy and a hypertransfusion program, with β-thalassaemia major (12 males with mean age 22.5±3.1 and 16 females with mean age 27.5±8.2), and in 28 healthy volunteers matched for age, anthropometric features and sex to the patients. BMD values, both at lumbar and femoral neck level were significantly lower (p<0.001 and p<0.05) by 18.7 and 4.2% respectively, in patients than in the controls. Markers of bone resorption [pyridinoline (Pyr) 78.1±15.7 vs 47.5±11.2 pmol/μmol urinary creatinine, p<0.001 and deoxypyridinoline (D-Pyr) 21.9±3.5 vs 14.5±5.4 pmol/μmol urinary creatinine, p<0.001] were higher in patients than in controls, whereas the marker of bone formation was slightly lower [osteocalcin (BGP) 3.8±0.6 vs4.6±1.7 pmol/ml, p<0.05]. Plasma levels of IGF-I (21.07±5.12 vs 35.25±8.33 nmol/ml, p<0.001) and IGF binding protein III (IGFBP-III) (1.9±0.4 vs2.5±0.1 mg/ml, p<0.001) were lower in patients than in controls and positively correlated with BMD L2-L4 (r=0.57, p<0.05 and r=0.47, p<0.05 respectively), BMD neck (r=0.40, p<0.05 and r=0.34, p<0.05 respectively) and BGP (r=0.52, p<0.05 and r=0.34, p<0.05 respectively). Our β-thalassaemic patients, in spite of normalizing hemoglobin levels, adequate hormone replacement and chelation therapies, showed osteopenia and an unbalanced bone turnover with an increased resorptive phase and a decreased formation phase probably correlated to low levels of IGF-I and IGFBP-III observed in our study.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Messina, Via Faustina e Tertullo 19, 98100, Messina, Italy

    A. Lasco, N. Morabito, A. Gaudio, A. Crisafulli & N. Frisina

  2. Department of Pediatrics, University of Messina, Messina, Italy

    A. Meo

  3. Department of Radiological Sciences, University of Messina, Messina, Italy

    G. Denuzzo

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  1. A. Lasco
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  2. N. Morabito
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  3. A. Gaudio
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  4. A. Crisafulli
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  5. A. Meo
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  6. G. Denuzzo
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  7. N. Frisina
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Correspondence to A. Lasco.

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Lasco, A., Morabito, N., Gaudio, A. et al. Osteoporosis and β-thalassemia major: Role of the IGF-I/IGFBP-III axis. J Endocrinol Invest 25, 338–344 (2002). https://doi.org/10.1007/BF03344015

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