Background:  The discovery of NFkB ligand (RANKL) and osteoprotegerin (OPG) dramatically changed our understanding of the processes underlying regulation of bone resorption. RANKL and OPG potently stimulate and inhibit, respectively, osteoclast formation. Bone metabolism derangement has been described in HIV-infected children. We investigated the possible role of RANKL and OPG on bone metabolism alterations in pediatrics patients.

Methods:  We studied 27 vertically HIV-infected children and adolescents (aged 4.9 to 17.3 years) on long-term HAART (70±8 months). All patients received lamivudine (3TC), stavudine (d4T), and 1 protease inhibitor (PI). Their mean CD4 number was 841±291, mean CD4% was 34±6, and HIV RNA was <50 copies/mL. As a control group, we enrolled 336 healthy children, aged 4.8 to 17.9 years. Serum concentration of bone alkaline phosphatase (BAP), RANKL, and OPG were measured by EIA assays. The concentration of NTx (a bone resorption index) was measured by ELISA assay in timed urine samples. Comparisons between HIV-infected children and healthy children subjects were performed by multivariate analyses, to correct for the confounding effect of sex and age on markers’ concentration.

Results:  Patients and control subjects did not differ for age, sex distribution, and anthropometric measurements. Patients had significantly (p <0.0001) higher concentration of BAP (128±49 U/L) and NTx (374±231 nM BCE/mM Cr), compared to healthy children (104±51 U/L, and 253±139 nM BCE/mM Cr, respectively). Serum concentration of RANKL was 2.1±1.9 pmol/L in HIV, and 0.4±0.7 pmol/L in healthy children (p <0.0001). Patients showed significantly (p <0.0001) higher concentration of OPG (10.3±2.4 U/L), compared to healthy children (5.3±1.4 U/L). The ratio of RANKL/OPG was significantly higher (p = 0.013) in HIV-infected children (0.22±0.27), compared to healthy controls (0.07±0.14).

Conclusions:  The current data confirm the presence of an altered bone metabolism in HIV-infected children and adolescents. The high bone resorption rate seems to be the result of a profound modification of the factors regulating osteoclastogenesis, since the ratio between OPG and RANKL was in favor of the latter. Moreover, in vitro evidence indicates a role of HIV infection and antiviral treatment in the production of RANKL by T cells. Our patients were all on long-term HAART, and thus the high concentration of RANKL observed may be in part due to the use of antiviral drugs.