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Bone turnover and mineral density in adult thalassemic patients: relationships with growth hormone secretory status and circulating somatomedins

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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.

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Funding

This study was funded in part by the Italian Ministry of Health (Grant Number RF-2009-1519507).

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Authors and Affiliations

  1. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

    Massimo Scacchi, Agnese Cattaneo, Giovanna Sciortino, Giovanni Vitale, Laura Zanaboni, Maria Domenica Cappellini & Luca Persani

  2. Ospedale San Giuseppe IRCCS, Division of Endocrinology and Metabolic Diseases, Istituto Auxologico Italiano, Oggebbio-Piancavallo, Verbania, Italy

    Massimo Scacchi & Paolo Marzullo

  3. Ospedale San Luca IRCCS, Division of Endocrinology and Metabolic Diseases, Istituto Auxologico Italiano, Milan, Italy

    Leila Danesi, Raffaella Radin, Alberto Giacinto Ambrogio, Giovanni Vitale & Luca Persani

  4. Second Pediatric Clinic, University of Milan, Fondazione Policlinico Mangiagalli Regina Elena, Milan, Italy

    Emanuela D’Angelo & Nadia Mirra

  5. Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy

    Marica Arvigo, Mara Boschetti & Diego Ferone

  6. Department of Translational Medicine, Università del Piemonte Orientale “A. Avogadro”, Novara, Italy

    Paolo Marzullo

  7. Department of Medicine and Medical Specialties, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Marina Baldini, Elena Cassinerio & Maria Domenica Cappellini

  8. Laboratory of Neuroendocrine Research, Istituto Auxologico Italiano, Milan, Italy

    Francesco Cavagnini

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  1. Massimo Scacchi
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Correspondence to Massimo Scacchi.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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This paper is dedicated to the memory of Professor Francesco Minuto.

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Scacchi, M., Danesi, L., Cattaneo, A. et al. Bone turnover and mineral density in adult thalassemic patients: relationships with growth hormone secretory status and circulating somatomedins. Endocrine 53, 551–557 (2016). https://doi.org/10.1007/s12020-016-0865-1

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