Osteoporosis and beta-thalassemia major: role of the IGF-I/IGFBP-III axis.
Patients with beta-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, IGF-I 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 beta-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/pmol urinary creatinine, p<0.001 and deoxypyridinoline (D-Pyr) 21.9+/-3.5 vs 14.5+/-5.4 pmol/ micromol 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 vs 4.6+/-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 vs 2.5+/-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 beta-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.
Lasco
A
A
Department of Internal Medicine, University of Messina, Italy. alasco@unime.it
Morabito
N
N
Gaudio
A
A
Crisafulli
A
A
Meo
A
A
Denuzzo
G
G
Frisina
N
N
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism; D003430:Cross-Sectional Studies; D003676:Deferoxamine / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D005260:Female; D005272:Femur Neck / Q000378:metabolism; D020249:Hormone Replacement Therapy; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000627:therapeutic use; D008159:Lumbar Vertebrae / Q000378:metabolism; D008297:Male; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use; D008777:Methyltestosterone / Q000627:therapeutic use; D010024:Osteoporosis / Q000188:drug therapy / Q000503:physiopathology*; D012016:Reference Values; D017086:beta-Thalassemia / Q000188:drug therapy / Q000503:physiopathology*
D015415:Biomarkers; D018972:Insulin-Like Growth Factor Binding Protein 3; D007502:Iron Chelating Agents; D007334:Insulin-Like Growth Factor I; D017258:Medroxyprogesterone Acetate; D003676:Deferoxamine; D008777:Methyltestosterone