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Analysis of Circulating Mediators of Bone Remodeling in Prader–Willi Syndrome

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Abstract

We tested the hypothesis that the levels of bone remodeling mediators may be altered in Prader–Willi syndrome (PWS). We assessed RANKL, OPG, sclerostin, DKK-1 serum levels, and bone metabolism markers in 12 PWS children (7.8 ± 4.3 years), 14 PWS adults (29.5 ± 7.2 years), and 31 healthy controls matched for sex and age. Instrumental parameters of bone mineral density (BMD) were also evaluated. Lumbar spine BMD Z-scores were reduced in PWS children (P < 0.01), reaching osteopenic levels in PWS adults. PWS patients showed lower 25(OH)-vitamin D serum levels than controls (P < 0.001). Osteocalcin was increased in PWS children but reduced in adults respect to controls (P < 0.005 and P < 0.01, respectively). RANKL levels were higher in both pediatric and PWS adults than controls (P < 0.004), while OPG levels were significantly reduced (P < 0.004 and P < 0.006, respectively). Sclerostin levels were increased in children (P < 0.04) but reduced in adults compared to controls (P < 0.01). DKK-1 levels did not show significant difference between patients and controls. In PWS patients, RANKL, OPG, and sclerostin significantly correlated with metabolic and bone instrumental parameters. Consistently, with adjustment for age, multiple linear regression analysis showed that BMD and osteocalcin were the most important predictors for RANKL, OPG, and sclerostin in children, and GH and sex steroid replacement treatment in PWS adults. We demonstrated the involvement of RANKL, OPG, and sclerostin in the altered bone turnover of PWS subjects suggesting these molecules as markers of bone disease and new potential pharmacological targets to improve bone health in PWS.

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Authors and Affiliations

  1. Department of Basic Medical Sciences, Neuroscience and Sense Organs, Section of Human Anatomy and Histology, University of Bari ‘A. Moro’, Bari, Italy

    G. Brunetti

  2. Division of Auxology, Istituto Auxologico Italiano, Research Institute, Verbania, Italy

    G. Grugni

  3. Department of Biomedical Sciences and Human Oncology, Section of Pediatrics, University of Bari ‘A. Moro’, Piazza G. Cesare, 11, 70124, Bari, Italy

    L. Piacente, M. Delvecchio, A. Ventura, P. Giordano, D. Laforgia & M. F. Faienza

  4. Department of Emergency and Organ Transplantation, University of Bari ‘A. Moro’, Bari, Italy

    M. Grano

  5. Neonatal Intensive Care Unit, Di Venere Hospital, Bari, Italy

    G. D’Amato

  6. Autoimmune Endocrine Diseases Unit, Bambino Gesù Hospital, Research Institute, Palidoro (Rome), Italy

    A. Crinò

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  1. G. Brunetti
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  2. G. Grugni
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  9. D. Laforgia
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Correspondence to M. F. Faienza.

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Conflict of interest

G. Brunetti, G. Grugni, L. Piacente, M. Delvecchio, A. Ventura, P. Giordano, M. Grano, G. D’Amato, D. Laforgia, A. Crinò, and M. F. Faienza declare that they have no conflict of interest to disclose.

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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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Written informed consent was obtained from all the legal guardians, and from the patients when applicable, prior to inclusion. All procedures were approved by local institutional review boards.

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Brunetti, G., Grugni, G., Piacente, L. et al. Analysis of Circulating Mediators of Bone Remodeling in Prader–Willi Syndrome. Calcif Tissue Int 102, 635–643 (2018). https://doi.org/10.1007/s00223-017-0376-y

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  • DOI: https://doi.org/10.1007/s00223-017-0376-y

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