Objectives: 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. Design: 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). Conclusion: 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.
Alterations in circulating osteoimmune factors may be responsible for high bone resorption rate in HIV-infected children and adolescents / S. Mora, I. Zamproni, L. Cafarelli, V. Giacomet, P. Erba, G.V. Zuccotti, A. Viganò. - In: AIDS. - ISSN 0269-9370. - 21:9(2007), pp. 29-35.
Alterations in circulating osteoimmune factors may be responsible for high bone resorption rate in HIV-infected children and adolescents
L. Cafarelli;V. Giacomet;P. Erba;G.V. Zuccotti;
2007
Abstract
Objectives: 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. Design: 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). Conclusion: 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.
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