Prospective evaluation of bone markers, parathormone and 1,25-(OH)2 vitamin D in HIV-positive patients after the initiation of tenofovir/emtricitabine with atazanavir/ritonavir or efavirenz

BMC Infectious Diseases

Research Article

Laura Sighinolfi¹  Eugenia Quiros-Roldan²  Daria Gotti²  Laura Albini²  Alessandra Calabresi²  Ilaria Izzo²  Davide Motta²  Nigritella Brianese²  Emanuele Focಠ Carlo Torti³  Marco Borderi⁴  Bruno Mario Cesana⁵  Davide Gibellini⁶  Alberto Clò⁶  Maria Carla Re⁶  Pasquale Narciso⁷  Rita Bellagamba⁷ 

[1] Infectious Diseases Department, S. Anna Hospital, Ferrara, Italy;Infectious Diseases Department, University of Brescia, Brescia, Italy;Infectious Diseases Department, University of Brescia, Brescia, Italy;Institute of Infectious and Tropical Diseases, University of Brescia, School of Medicine, P.le Spedali Civili, 1, 25123, Brescia, Italy;Infectious Diseases Section, University of Bologna, Bologna, Italy;Medical Statistics and Biometry Section, University of Brescia, Brescia, Italy;Microbiology Section, University of Bologna, Bologna, Italy;National Institute of Infectious Diseases, Rome, Italy;

关键词: HIV;    Antiretroviral therapy;    Bone turnover;    Osteoporosis;    Vitamin D;   

DOI  :  10.1186/1471-2334-12-38

 received in 2011-09-21, accepted in 2012-02-14,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundIncreased risk of fractures and osteoporosis have been associated with the use of antiretroviral drugs. There is a paucity of prospective evaluations of bone markers after the initiation of drugs currently recommended to treat HIV infection and results on the evolution of these markers are conflicting. Lastly, the effect of tenofovir on 1,25-(OH)2 vitamin D is uncertain.MethodsWe performed a prospective study on the evolution of bone markers, parathormone and 1,25-(OH)2 vitamin D before and after standard antiretroviral regimens. This was a sub-study of a trial conducted in antiretroviral-naïve patients randomized to tenofovir + emtricitabine in combination with either atazanavir/ritonavir (ATV/r) or efavirenz (EFV). Follow-up lasted 48 weeks. The following bone markers were analyzed: C-terminal cross-laps (CTx), osteocalcin (OC), osteoprotegerin (OPG), and receptor activator of nuclear factor κB ligand (RANKL). Mixed-factorial analysis of variance with random-coefficient general linear model was used to compare their trends over time and linear multivariable regression was performed with a backward selection method to assess predictors of their variations from baseline to week 48. Trends of parathormone and 1,25-(OH)2 vitamin D were also evaluated.ResultsSeventy-five patients were studied: 33 received EFV and 42 ATV/r. Significant increases were found for all markers except for RANKL. There was a significant direct association between CTx and OC increases. Multivariable analysis showed that higher glomerular filtration rate (estimated through cystatin C clearance) predicted greater OPG increase, while older age, higher HIV RNA at baseline and use of ATV/r predicted greater CTx increase. A significant increase of parathormone accompanied the evolution of the study markers. 1,25-(OH)2 vitamin D remained stable, though a seasonality variation was demonstrated.ConclusionsThese data demonstrate CTx increase (bone resorption marker) corresponding to OC increase (bone formation marker) early upon HAART initiation. Moreover, predictors of bone marker increases have been suggested, possibly indicating that a stricter monitoring of bone health and pro-active interventions are needed in older patients, those with higher HIV RNA, prescribed ATV/r rather than EFV, and with decreased renal function at baseline. Further studies are needed to clarify the mechanisms responsible for up-regulation of bone turnover markers, as well as to understand if and what markers are best correlated or predictive of pathological fractures.

【 授权许可】

Unknown   
© Focà et al; BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.