title: Changed bone status in human immunodeficiency virus type 1 (HIV-1) perinatally infected children is related to low serum free IGF-I.
abstract: BACKGROUND
  Adults and children affected by human immunodeficiency virus type-1 (HIV-1) infection show bone demineralization. Little is known about skeletal status using a quantitative high-frequency ultrasound (QUS) technique in these patients.
  
  
  OBJECTIVE
  To evaluate the bone quality and assess the role of the IGF system in the bone metabolism and skeletal status of HIV-1 perinatally infected children.
  
  
  METHODS
  Serum free and total IGF-I, IGFBP-3, serum osteocalcin level, urinary deoxypyridinoline concentration, spontaneous interleukin-6 (IL-6) release and broadband ultrasound attenuation (BUA) were evaluated in 44 prepubertal children who had perinatal HIV-1 infection. The patients were divided into two groups depending on the severity of their clinical condition: group 1 (23 children with no or mild clinical symptoms, mean age 8.0 +/- 2.9 years) and group 2 (21 children with severe clinical symptoms, mean age 8.58 +/- 2.47 years). Fifty-five healthy age- and sex-matched controls were analysed for comparison.
  
  
  RESULTS
  Compared with group 1 and the controls, group 2 patients showed a significantly reduced BUA Z-score (P < 0.001), and significantly reduced concentrations of serum osteocalcin (P < 0.001) and urinary deoxypyridinoline (P < 0.001 and P < 0.05, respectively). Group 2 patients also showed significantly reduced serum free IGF-I (P < 0.001) and total IGF-I (P < 0.05) levels compared with the controls, but not with group 1. No statistically significant differences were found between the three groups with regard to IGFBP-3. Group 2 patients showed significantly higher spontaneous IL-6 release than group 1 patients and controls (P < 0.001). BUA Z-scores displayed a significant correlation with free IGF-I in group 2 (r = 0.96; P < 0.001), group 1 (r = 0.56; P = 0.005) and controls (r = 0.50; P < 0.001).
  
  
  CONCLUSIONS
  Our study shows that only patients affected by perinatal HIV-1 infection with severe clinical manifestations present significant changes in bone quality and bone metabolism. Our data also show that impairment of skeletal status is related to reduction in serum total and free IGF-I. Children with perinatal HIV-1 infection, because of a considerable improvement in life expectancy, seem at great risk of not obtaining an optimal bone mass. A possible therapeutic approach should be considered in these children.
authors.affiliation: Department of Paediatrics, University of Florence, Anna Meyer Children's Hospital, Florence, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Stagi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bindi
authors.forename: Fiorella
authors.initials: F
authors.lastname: Galluzzi
authors.forename: Luisa
authors.initials: L
authors.lastname: Galli
authors.forename: Roberto
authors.initials: R
authors.lastname: Salti
authors.forename: Maurizio
authors.initials: M
authors.lastname: de Martino
mesh_terms: D000596:Amino Acids / Q000652:urine; D000704:Analysis of Variance; D015992:Body Mass Index; D015519:Bone Density; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000503:physiopathology*; D015497:HIV-1; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D015675:Osteocalcin / Q000097:blood
chemical_list: D000596:Amino Acids; D018972:Insulin-Like Growth Factor Binding Protein 3; D015850:Interleukin-6; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; C036020:deoxypyridinoline