title: Bone turnover and mineral density in adult thalassemic patients: relationships with growth hormone secretory status and circulating somatomedins.
abstract: Previous evidence supports a role for growth hormone (GH)-insulin-like growth factor (IGF)-I deficiency in the pathophysiology of osteopenia/osteoporosis in adult thalassemia. Moreover, serum IGF-II has never been studied in this clinical condition. Thus, we elected to study the GH secretory status and the levels of circulating somatomedins, correlating these parameters with bone mineral density (BMD) and biochemical markers of bone turnover. A hundred and thirty-nine normal weight adult thalassemic patients (72 men and 67 women) were studied. Lumbar and femoral neck BMD were measured in 106/139 patients. Sixty-eight patients underwent growth hormone releasing hormone plus arginine testing. Measurement of baseline IGF-I and IGF-II was performed in all patients, while osteocalcin, C-terminal telopeptide of type I collagen (CTx), and urinary cross-linked N-telopeptides of type I collagen (NTx) were assayed in 95 of them. Femoral and lumbar osteoporosis/Z score below the expected range for age were documented in 61.3 and in 56.6 % of patients, respectively. Severe GH deficiency (GHD) was demonstrated in 27.9 % of cases, whereas IGF-I SDS was low in 86.3 %. No thalassemic patients displayed circulating levels of IGF-II below the reference range. GH peaks were positively correlated with femoral, but not lumbar, Z score. No correlations were found between GH peaks and osteocalcin, CTx and NTx. GH peaks were positively correlated with IGF-I values, which in their turn displayed a positive correlation with osteocalcin, CTx, and NTx. No correlations emerged between IGF-I values and either femoral or lumbar Z scores. No correlations were found between IGF-II and any of the following parameters: GH peaks, osteocalcin, CTx, NTx, femoral Z score, and lumbar Z score. Our study, besides providing for the first time evidence of a normal IGF-II production in thalassemia, contributes to a better understanding of the involvement of the somatotropin-somatomedin axis in the pathophysiology of bone demineralization in this disease. In particular, the contribution of GHD to femoral osteoporosis appears to be likely mediated by locally produced rather than circulating IGF-I.
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. massimo.scacchi@unimi.it.|Ospedale San Giuseppe IRCCS, Division of Endocrinology and Metabolic Diseases, Istituto Auxologico Italiano, Oggebbio-Piancavallo, Verbania, Italy. massimo.scacchi@unimi.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Scacchi
authors.affiliation: Ospedale San Luca IRCCS, Division of Endocrinology and Metabolic Diseases, Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Leila
authors.initials: L
authors.lastname: Danesi
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Cattaneo
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Sciortino
authors.affiliation: Ospedale San Luca IRCCS, Division of Endocrinology and Metabolic Diseases, Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Radin
authors.affiliation: Ospedale San Luca IRCCS, Division of Endocrinology and Metabolic Diseases, Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Alberto Giacinto
authors.initials: AG
authors.lastname: Ambrogio
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.|Ospedale San Luca IRCCS, Division of Endocrinology and Metabolic Diseases, Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vitale
authors.affiliation: Second Pediatric Clinic, University of Milan, Fondazione Policlinico Mangiagalli Regina Elena, Milan, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: D'Angelo
authors.affiliation: Second Pediatric Clinic, University of Milan, Fondazione Policlinico Mangiagalli Regina Elena, Milan, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Mirra
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Zanaboni
authors.affiliation: Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy.
authors.forename: Marica
authors.initials: M
authors.lastname: Arvigo
authors.affiliation: Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Boschetti
authors.affiliation: Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Ferone
authors.affiliation: Ospedale San Giuseppe IRCCS, Division of Endocrinology and Metabolic Diseases, Istituto Auxologico Italiano, Oggebbio-Piancavallo, Verbania, Italy.|Department of Translational Medicine, Università del Piemonte Orientale "A. Avogadro", Novara, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Marzullo
authors.affiliation: Department of Medicine and Medical Specialties, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Baldini
authors.affiliation: Department of Medicine and Medical Specialties, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Cassinerio
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.|Department of Medicine and Medical Specialties, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Cappellini
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.|Ospedale San Luca IRCCS, Division of Endocrinology and Metabolic Diseases, Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Persani
authors.affiliation: Laboratory of Neuroendocrine Research, Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cavagnini
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000502:physiology*; D016723:Bone Remodeling / Q000502:physiology*; D024042:Collagen Type I / Q000097:blood; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging*; D010455:Peptides / Q000097:blood; D013789:Thalassemia / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013007:Growth Hormone-Releasing Hormone
keywords: Growth hormone; IGF-I; IGF-II; Thalassemia
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