title: Sclerostin and DKK-1: two important regulators of bone metabolism in HIV-infected youths.
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.
authors.affiliation: Laboratory of Pediatric Endocrinology, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, MI, Italy, mora.stefano@hsr.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Mora
authors.forename: Maria
authors.initials: M
authors.lastname: Puzzovio
authors.forename: Vania
authors.initials: V
authors.lastname: Giacomet
authors.forename: Valentina
authors.initials: V
authors.lastname: Fabiano
authors.forename: Katia
authors.initials: K
authors.lastname: Maruca
authors.forename: Silvia
authors.initials: S
authors.lastname: Capelli
authors.forename: Pilar
authors.initials: P
authors.lastname: Nannini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lombardi
authors.forename: Gian Vincenzo
authors.initials: GV
authors.lastname: Zuccotti
mesh_terms: D015502:Absorptiometry, Photon; D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D000886:Anthropometry; D023241:Antiretroviral Therapy, Highly Active; D015519:Bone Density; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology*; D001842:Bone and Bones / Q000201:enzymology / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D005819:Genetic Markers / Q000235:genetics / Q000502:physiology*; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006887:Hydroxycholecalciferols / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D005819:Genetic Markers; D006887:Hydroxycholecalciferols; D036341:Intercellular Signaling Peptides and Proteins; D010281:Parathyroid Hormone; C422903:SOST protein, human; D000469:Alkaline Phosphatase