title: Alterations in circulating osteoimmune factors may be responsible for high bone resorption rate in HIV-infected children and adolescents.
abstract: OBJECTIVE
  Bone metabolism derangements have been reported in HIV-infected children and adolescents. Nuclear factor kappa B ligand (RANKL) and osteoprotegerin potently stimulate and inhibit, respectively, osteoclast formation and activity. We investigated the possible role of RANKL and osteoprotegerin on bone metabolism alterations in paediatric patients.
  
  
  METHODS
  A prospective controlled longitudinal study. Measurements were obtained before and 6 months after switching antiretroviral regimen.
  
  
  METHODS
  We studied 27 vertically HIV-infected children and adolescents (aged 4.9-17.3 years) on long-term HAART (70.1 +/- 1.5 months). All patients received lamivudine, stavudine and one protease inhibitor (PI). During follow-up, the PI was replaced with efavirenz and stavudine with tenofovir. We also enrolled 336 healthy children, aged 4.8-17.9 years. Concentrations of bone-specific alkaline phosphatase (BALP), N-terminal telopeptide of type I collagen (NTx), RANKL, and osteoprotegerin were measured at baseline and 6 months after switching.
  
  
  RESULTS
  BALP serum concentrations and NTx urine levels of HIV-infected patients were significantly higher than those of healthy children both at baseline and after 6 months (P < 0.001). Baseline osteoprotegerin and RANKL concentrations of HIV-infected patients were significantly higher than in healthy children (P < 0.0001). Both concentrations decreased after 6 months, and RANKL levels were no longer different to controls. At baseline the RANKL/osteoprotegerin ratio was significantly higher (P = 0.02) in HIV-infected children (0.27 +/- 0.07) compared with healthy children (0.078 +/- 0.01).
  
  
  CONCLUSIONS
  A marked alteration in the RANKL/osteoprotegerin system is present in patients receiving PI-based HAART. Short-term data indicate that replacing stavudine and PI with tenofovir and efavirenz restores the RANKL/osteoprotegerin equilibrium, and may thus lead to a reduction in the bone resorption rate.
authors.affiliation: Laboratory of Pediatric Endocrinology and BoNetwork, San Raffaele Scientific Institute, Milan, Italy. mora.stefano@hsr.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Mora
authors.forename: Ilaria
authors.initials: I
authors.lastname: Zamproni
authors.forename: Laura
authors.initials: L
authors.lastname: Cafarelli
authors.forename: Vania
authors.initials: V
authors.lastname: Giacomet
authors.forename: Paola
authors.initials: P
authors.lastname: Erba
authors.forename: Gianvincenzo
authors.initials: G
authors.lastname: Zuccotti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Viganò
mesh_terms: D000293:Adolescent; D000469:Alkaline Phosphatase / Q000097:blood; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015415:Biomarkers / Q000032:analysis; D015519:Bone Density / Q000502:physiology; D001862:Bone Resorption / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D024042:Collagen Type I / Q000652:urine; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D053244:Osteoprotegerin / Q000097:blood*; D010455:Peptides / Q000652:urine; D011446:Prospective Studies; D053245:RANK Ligand / Q000097:blood*
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D053244:Osteoprotegerin; D010455:Peptides; D053245:RANK Ligand; C052929:collagen type I trimeric cross-linked peptide; D000469:Alkaline Phosphatase