title: Bone mineral density in prepubertal children with beta-thalassemia: correlation with growth and hormonal data.
abstract: Patients with beta-thalassemia major (beta-thalassemia) frequently have bone disorders of multifactorial etiology. We attempted to analyze the relationship between the bone mineral density ([BMD] measured by dual-photon absorptiometry) and auxanologic parameters, degree of siderosis, function of the growth hormone (GH)/insulin-like growth factor-I (IGF-I)/IGF-binding protein-3 (IGFBP3) axis, calcium-phosphate balance, parathyroid hormone (PTH), and cytokines (interleukin-1beta [IL-1] and tumor necrosis factor-alpha [TNF-alpha]) in 30 prepubertal children with beta-thalassemia major and 15 age-matched children with constitutional short stature (CSS), who have normal glucose tolerance and thyroid function. Children with beta-thalassemia had a significantly decreased BMD and mean BMD% for age and sex (0.75+/-0.24 g/cm2 and 71%+/-10%, respectively) versus children with CSS (1.06+/-0.3 g/cm2 and 92%+/-7%, respectively). Thalassemic patients had significantly lower circulating concentrations of IGF-I and IGFBP3 (49+/-21 ng/mL and 1.2+/-0.25 mg/L, respectively) compared with control children (153+/-42 ng/mL and 2.1+/-0.37 mg/L, respectively). The GH response to provocation by clonidine and glucagon was defective (peak GH < 7 microg/L) in 12 of the 30 thalassemic children. Serum concentrations of IL-1beta and TNF-alpha did not differ among the two study groups. Hypocalcemia was detected in five of the 30 thalassemic patients: hypoparathyroidism was diagnosed in two of the five and rickets in the other three. BMD was highly correlated with the circulating concentrations of IGF-I and IGFBP3, as well as with the auxanologic parameters (age, weight, height, height standard deviation score [HSDS], and body mass index [BMI]). It is suggested that increasing the circulating IGF-I concentration through aggressive nutritional therapy and/or GH/IGF-I therapy with supplementation with vitamin D and/or calcium might improve bone growth and mineralization and prevent the development of osteoporosis and consequent fractures in these patients. Such therapy requires blinded controlled trials.
authors.affiliation: Department of Pediatrics, University of Alexandria Children's Hospital, Loran, Egypt.
authors.forename: A T
authors.initials: AT
authors.lastname: Soliman
authors.forename: N
authors.initials: N
authors.lastname: El Banna
authors.forename: M
authors.initials: M
authors.lastname: Abdel Fattah
authors.forename: M M
authors.initials: MM
authors.lastname: ElZalabani
authors.forename: B M
authors.initials: BM
authors.lastname: Ansari
mesh_terms: D015502:Absorptiometry, Photon; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D000367:Age Factors; D000469:Alkaline Phosphatase / Q000097:blood / Q000187:drug effects; D000886:Anthropometry; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology; D001827:Body Height / Q000187:drug effects / Q000502:physiology; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D015519:Bone Density / Q000187:drug effects / Q000502:physiology*; D001842:Bone and Bones / Q000187:drug effects / Q000502:physiology; D002112:Calcifediol / Q000097:blood; D002118:Calcium / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000494:pharmacology; D005934:Glucagon / Q000008:administration & dosage / Q000494:pharmacology; D006128:Growth / Q000187:drug effects / Q000502:physiology; D013006:Growth Hormone / Q000097:blood / Q000502:physiology; D006728:Hormones / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006996:Hypocalcemia / Q000097:blood / Q000503:physiopathology; D007037:Hypothyroidism / Q000097:blood / Q000503:physiopathology; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000187:drug effects / Q000378:metabolism; D007375:Interleukin-1 / Q000097:blood; D007501:Iron / Q000097:blood; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D011627:Puberty; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D017086:beta-Thalassemia / Q000097:blood / Q000503:physiopathology*
chemical_list: D000959:Antihypertensive Agents; D005765:Gastrointestinal Agents; D006728:Hormones; D018972:Insulin-Like Growth Factor Binding Protein 3; D007375:Interleukin-1; D010281:Parathyroid Hormone; D010710:Phosphates; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I; D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone; D005934:Glucagon; D007501:Iron; D000469:Alkaline Phosphatase; D003000:Clonidine; D002112:Calcifediol; D002118:Calcium; D006854:Hydrocortisone