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Sclerostin and DKK-1: two important regulators of bone metabolism in HIV-infected youths

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Abstract

Reduced bone mineral density (BMD) and altered bone metabolism are common findings in HIV-infected patients. Increased bone formation has been described both in HIV-infected adults and children. Wnt ligands promote bone formation by stimulating osteoblast differentiation and their survival. Sclerostin and dickkopf factor 1 (DKK-1), Wnt antagonists, are important negative regulators of bone formation. We studied 86 HIV-infected patients whose ages ranged from 5.7 to 27.9 years. Patients were all on antiretroviral therapy, but seven who were naïve to treatment. Bone alkaline phosphatase (BAP), sclerostin, and DKK-1 were measured in serum by enzyme immunoassay. BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine and in the whole skeleton. Biochemical indexes were also measured in 143 healthy controls (age range 4.5–27.4 years). HIV-infected patients had lower than normal BMD (spine P < 0.005, and whole skeleton P < 0.03). BAP measurements were significantly higher in HIV-infected patients than controls (P ≤ 0.05). Sclerostin and DKK-1 concentrations were markedly lower than in controls (P ≤ 0.0006, and P ≤ 0.03, respectively). The serum concentration of both analytes of patients naïve to antiretroviral treatment was not different from that of treated patients. No correlations were found between sclerostin, DKK-1, and bone mineral measurements. Our data confirm the alteration of bone metabolism pathways in HIV-infected individuals. The lower concentration of Wnt antagonists is consistent with the increased bone formation markers.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Laboratory of Pediatric Endocrinology, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, MI, Italy

    Stefano Mora, Maria Puzzovio, Katia Maruca & Silvia Capelli

  2. Department of Pediatrics, L. Sacco Hospital, University of Milan, Milan, Italy

    Vania Giacomet & Pilar Nannini

  3. Department of Pediatrics, Ospedale dei Bambini V. Buzzi, University of Milan, Milan, Italy

    Valentina Fabiano & Gian Vincenzo Zuccotti

  4. Laboratory of Experimental Biochemistry & Molecular Biology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy

    Giovanni Lombardi

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  1. Stefano Mora
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  2. Maria Puzzovio
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  4. Valentina Fabiano
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  9. Gian Vincenzo Zuccotti
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Correspondence to Stefano Mora.

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Mora, S., Puzzovio, M., Giacomet, V. et al. Sclerostin and DKK-1: two important regulators of bone metabolism in HIV-infected youths. Endocrine 49, 783–790 (2015). https://doi.org/10.1007/s12020-015-0527-8

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  • DOI: https://doi.org/10.1007/s12020-015-0527-8

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