title: Endocrine function and bone disease during long-term chelation therapy with deferasirox in patients with β-thalassemia major.
abstract: Iron overload in β-thalassemia major (TM) typically results in iron-induced cardiomyopathy, liver disease, and endocrine complications. We examined the incidence and progression of endocrine disorders (hypothyroidism, diabetes, hypoparathyroidism, hypogonadism), growth and pubertal delay, and bone metabolism disease during long-term deferasirox chelation therapy in a real clinical practice setting. We report a multicenter retrospective cohort study of 86 transfusion-dependent patients with TM treated with once daily deferasirox for a median duration of 6.5 years, up to 10 years. No deaths or new cases of hypothyroidism or diabetes occurred. The incidence of new endocrine complications was 7% (P = 0.338, for change of prevalence from baseline to end of study) and included hypogonadism (n = 5) and hypoparathyroidism (n = 1). Among patients with hypothyroidism or diabetes at baseline, no significant change in thyroid parameters or insulin requirements were observed, respectively. Mean lumbar spine bone mineral density increased significantly (P < 0.001) and the number of patients with lumbar spine osteoporosis significantly decreased (P = 0.022) irrespective of bisphosphonate therapy, hormonal replacement therapy, and calcium or vitamin D supplementation. There were no significant differences in the number of pediatric patients below the 5th centile for height between baseline and study completion. Six pregnancies occurred successfully, and four of them were spontaneous without ovarian stimulation. This is the first study evaluating endocrine function during the newest oral chelation therapy with deferasirox. A low rate of new endocrine disorders and a stabilization of those pre-exisisting was observed in a real clinical practice setting.
authors.affiliation: Dipartimento della Donna, del Bambino e di Chirurgia Generale e Specialistica, Second University of Naples, Naples, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Casale
authors.forename: Serena
authors.initials: S
authors.lastname: Citarella
authors.forename: Aldo
authors.initials: A
authors.lastname: Filosa
authors.forename: Elisa
authors.initials: E
authors.lastname: De Michele
authors.forename: Francesco
authors.initials: F
authors.lastname: Palmieri
authors.forename: Alfonso
authors.initials: A
authors.lastname: Ragozzino
authors.forename: Giovanni
authors.initials: G
authors.lastname: Amendola
authors.forename: Umberto
authors.initials: U
authors.lastname: Pugliese
authors.forename: Immacolata
authors.initials: I
authors.lastname: Tartaglione
authors.forename: Filomena
authors.initials: F
authors.lastname: Della Rocca
authors.forename: Patrizia
authors.initials: P
authors.lastname: Cinque
authors.forename: Bruno
authors.initials: B
authors.lastname: Nobili
authors.forename: Silverio
authors.initials: S
authors.lastname: Perrotta
mesh_terms: D000293:Adolescent; D000328:Adult; D001565:Benzoates / Q000627:therapeutic use*; D015519:Bone Density; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000008:administration & dosage; D015913:Chelation Therapy; D002648:Child; D002675:Child, Preschool; D000077588:Deferasirox; D003920:Diabetes Mellitus / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D004164:Diphosphonates / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007006:Hypogonadism / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D007011:Hypoparathyroidism / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D007037:Hypothyroidism / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D019190:Iron Overload / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011628:Puberty, Delayed / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D012189:Retrospective Studies; D014230:Triazoles / Q000627:therapeutic use*; D014807:Vitamin D / Q000008:administration & dosage; D017086:beta-Thalassemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D001565:Benzoates; D004164:Diphosphonates; D007502:Iron Chelating Agents; D014230:Triazoles; D014807:Vitamin D; D002118:Calcium; D000077588:Deferasirox