title: Chelation therapy and bone metabolism markers in thalassemia major.
abstract: The aim of our study was to investigate the effects of subcutaneous desferrioxamine (DFX) and oral deferiprone (L1) therapy on bone metabolism markers in patients with thalassemia major. We studied 17 patients with thalassemia receiving long-term treatment with desferrioxamine, 20 patients receiving long-term treatment with deferiprone, and 15 healthy age-matched controls. The following investigations were performed: a) intact parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D] as endocrine parameters; b) alkaline phosphatase (ALP), bone alkaline phosphatase (BALP), osteocalcin (OC); c) bone resorption biochemical markers in serum and urine pyridinium crosslinks: hydroxylysyl-pyridinoline (HP) and lysyl-pyridinoline (LP); d) serum levels of cytokines and growth factors: transforming growth factor-beta1 (TGFbeta1), insulin-like growth factor-I (IGF-I), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-a (TNFalpha); e) serum levels of IGF binding protein-3 (IGFBP-3). No significant differences among all studied variables were found in patients with thalassemia treated with desferrioxamine or deferiprone. In contrast, significant differences were found between patients with thalassemia and the control group: intact PTH was significantly lower in patients with thalassemia than in the controls (p < 0.0005), and a significant increase in ALP and BALP (p < 0.0005), but not in OC, was found in the patient group. With regard to bone resorption and remodeling markers, the urinary excretion of pyridinium crosslinks was higher in patients with thalassemia for HP fraction (p < 0.0005) and LP fraction (p = 0.002), as well as TGFbeta (p = 0.001). In contrast, IGF-I and IGFBP-3 were reduced when compared with controls. In conclusion, the study of bone metabolism markers in adult patients with thalassemia reveals a complex behavior with an increase in bone resorption indexes. Bone formation did not appear to be impaired. In particular, TGFbeta1 was higher in patients with thalassemia receiving L1 treatment.
authors.affiliation: Laboratory of Clinical Pathology, Rizzoli Orthopedic Institutes, Bologna, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Pratelli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Verri
authors.forename: Monica
authors.initials: M
authors.lastname: Fortini
authors.forename: Stefano
authors.initials: S
authors.lastname: Marconi
authors.forename: Carola
authors.initials: C
authors.lastname: Zolezzi
authors.forename: Pier Maria
authors.initials: PM
authors.lastname: Fornasari
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Gamberini
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Sanctis
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D001862:Bone Resorption / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism*; D016022:Case-Control Studies; D015913:Chelation Therapy / Q000009:adverse effects / Q000379:methods*; D016207:Cytokines / Q000097:blood; D000077543:Deferiprone; D003676:Deferoxamine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D007502:Iron Chelating Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D015675:Osteocalcin / Q000378:metabolism; D010024:Osteoporosis / Q000209:etiology / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism; D011728:Pyridones / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D012307:Risk Factors; D017262:Siderophores / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism; D017086:beta-Thalassemia / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D007502:Iron Chelating Agents; D010281:Parathyroid Hormone; D011728:Pyridones; D017262:Siderophores; D015675:Osteocalcin; D014807:Vitamin D; D000077543:Deferiprone; C097949:1,25-dihydroxyvitamin D; C104450:25-hydroxyvitamin D; D000469:Alkaline Phosphatase; D003676:Deferoxamine