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.
OBJECTIVES: Bone metabolism derangements have been reported in HIV-infectedchildren 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-infectedchildren 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-infectedpatients 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-infectedpatients 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-infectedchildren (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.
Authors: Kerunne S Ketlogetswe; Rebeccah McKibben; Lisa P Jacobson; Xuihong Li; Adrian S Dobs; Matthew Budoff; Mallory D Witt; Frank J Palella; Lawrence Kingsley; Joseph B Margolick; Wendy S Post; Todd T Brown Journal: J Acquir Immune Defic Syndr Date: 2015-12-01 Impact factor: 3.731
Authors: James J Jang; Aron I Schwarcz; Daniel A Amaez; Mark Woodward; Jeffrey W Olin; Marla J Keller; Alison D Schecter Journal: J Int AIDS Soc Date: 2010-03-22 Impact factor: 5.396
Authors: Michael T Yin; Dalian Lu; Serge Cremers; Phyllis C Tien; Mardge H Cohen; Qiuhu Shi; Elizabeth Shane; Elizabeth T Golub; Kathryn Anastos Journal: J Acquir Immune Defic Syndr Date: 2010-02 Impact factor: 3.731
Authors: Nathan W Cummins; Anna Klicpera; Amy M Sainski; Gary D Bren; Sundeep Khosla; Jennifer J Westendorf; Andrew D Badley Journal: PLoS One Date: 2011-09-12 Impact factor: 3.240
Authors: Theodoros Kelesidis; Michelle A Kendall; Otto O Yang; Howard Hodis; Judith S Currier Journal: AIDS Res Hum Retroviruses Date: 2013-02-25 Impact factor: 1.723