Changed bone status in human immunodeficiency virus type 1 (HIV‐1) perinatally infected children is related to low serum free IGF‐I

Abstract

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. 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. 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. 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). 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.