title: Bone disease in thalassaemia major: recent advances in pathogenesis and clinical aspects.
abstract: Bone is a dynamic organ, constantly changing metabolically and being remodelled through the balanced activity of osteoclast and osteoblast on trabecular surfaces. Osteoporosis represents a continuum, in which multiple pathogenic mechanisms converge to cause loss of bone mass and deterioration of microarchitecture of skeletal structure. In thalassaemia major (TM), progressive 'aging' of bone starts in early childhood, through the gradual development of an imbalance between augmented osteoclastic resorption and insufficient osteoblastic bone formation. Chronic anemia, iron toxicity and endocrine complications, via a complex mechanism, lead to alterations in the RANK/RANKL/OPG system in favor of increased osteoclastic activity and enhanced osteoblastic dysfunction. Hypogonadotrophic hypogonadism and delayed puberty are the most common endocrine complications in patients with TM; they also contribute to osteopenia and osteoporosis, which is present in more than 50% of patients. There are gender differences not only in the prevalence but also in the severity of the osteoporosis syndrome. The anabolic effects of GH and IGF-1 on bone formation are important for the acquisition of bone mass, mainly during childhood and puberty. In TM, GH secretory dysfunction is common and contributes to osteopenia and osteoporosis, along with other endocrinopathies such as hypoparathyroidism and vitamin D deficiency, hypothyroidism and diabetes. Prevention is with no doubt the first step in the management of osteoporosis in TM, with the final goal of preventing bone loss and fractures. The management of patients with TM should start as early as birth in order to minimize the disease complications. Induction of puberty at a proper age with estrogens in girls and testosterone in boys and later treatment of hypogonadism with HRT are vital steps in the prevention of bone disease in TM. Biphosphonates, the well known medication for osteoporosis, have been tried in the treatment of TM-osteoporosis with promising outcomes. Since the origin of bone disease in TM is multifactorial and some of the underlying pathogenic mechanisms are still unclear, further research in this field is needed, which will allow the design of optimal therapeutic measures.
authors.affiliation: Dept. of Paediatrics, Makarios Hospital, Nicosia, Cyprus. nskordis@cytanet.com.cy
authors.forename: Nicos
authors.initials: N
authors.lastname: Skordis
authors.forename: Meropi
authors.initials: M
authors.lastname: Toumba
mesh_terms: D002648:Child; D004700:Endocrine System Diseases / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D010024:Osteoporosis / Q000209:etiology* / Q000503:physiopathology*; D017086:beta-Thalassemia / Q000150:complications* / Q000503:physiopathology*