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

Emanuele Focà, Davide Motta, Marco Borderi, Daria Gotti, Laura Albini, Alessandra Calabresi, Ilaria Izzo, Rita Bellagamba, Pasquale Narciso, Laura Sighinolfi, Alberto Clò, Davide Gibellini, Eugenia Quiros-Roldan, Nigritella Brianese, Bruno M. Cesana, Maria C. Re, Carlo Torti

Research output: Contribution to journalArticle

Abstract

Background: Increased 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.Methods: We 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.Results: Seventy-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.Conclusions: These 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.

Original languageEnglish
Article number38
JournalBMC Infectious Diseases
Volume12
DOIs
Publication statusPublished - Feb 14 2012

Fingerprint

Tenofovir
efavirenz
Ergocalciferols
Ritonavir
Parathyroid Hormone
HIV
Osteocalcin
Bone and Bones
Osteoprotegerin
Linear Models
RNA
Cystatin C
Spontaneous Fractures
Bone Remodeling
Highly Active Antiretroviral Therapy
Bone Resorption
Cytoplasmic and Nuclear Receptors
Glomerular Filtration Rate
Osteogenesis
Pharmaceutical Preparations

Keywords

  • Antiretroviral therapy
  • Bone turnover
  • HIV
  • Osteoporosis
  • Vitamin D

ASJC Scopus subject areas

  • Infectious Diseases

Cite this

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. / Focà, Emanuele; Motta, Davide; Borderi, Marco; Gotti, Daria; Albini, Laura; Calabresi, Alessandra; Izzo, Ilaria; Bellagamba, Rita; Narciso, Pasquale; Sighinolfi, Laura; Clò, Alberto; Gibellini, Davide; Quiros-Roldan, Eugenia; Brianese, Nigritella; Cesana, Bruno M.; Re, Maria C.; Torti, Carlo.

In: BMC Infectious Diseases, Vol. 12, 38, 14.02.2012.

Research output: Contribution to journalArticle

Focà, E, Motta, D, Borderi, M, Gotti, D, Albini, L, Calabresi, A, Izzo, I, Bellagamba, R, Narciso, P, Sighinolfi, L, Clò, A, Gibellini, D, Quiros-Roldan, E, Brianese, N, Cesana, BM, Re, MC & Torti, C 2012, '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, vol. 12, 38. https://doi.org/10.1186/1471-2334-12-38
Focà, Emanuele ; Motta, Davide ; Borderi, Marco ; Gotti, Daria ; Albini, Laura ; Calabresi, Alessandra ; Izzo, Ilaria ; Bellagamba, Rita ; Narciso, Pasquale ; Sighinolfi, Laura ; Clò, Alberto ; Gibellini, Davide ; Quiros-Roldan, Eugenia ; Brianese, Nigritella ; Cesana, Bruno M. ; Re, Maria C. ; Torti, Carlo. / 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. In: BMC Infectious Diseases. 2012 ; Vol. 12.
@article{05b146e1441144ca91b7f944c710ce50,
title = "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",
abstract = "Background: Increased 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.Methods: We 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-na{\"i}ve 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.Results: Seventy-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.Conclusions: These 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.",
keywords = "Antiretroviral therapy, Bone turnover, HIV, Osteoporosis, Vitamin D",
author = "Emanuele Foc{\`a} and Davide Motta and Marco Borderi and Daria Gotti and Laura Albini and Alessandra Calabresi and Ilaria Izzo and Rita Bellagamba and Pasquale Narciso and Laura Sighinolfi and Alberto Cl{\`o} and Davide Gibellini and Eugenia Quiros-Roldan and Nigritella Brianese and Cesana, {Bruno M.} and Re, {Maria C.} and Carlo Torti",
year = "2012",
month = "2",
day = "14",
doi = "10.1186/1471-2334-12-38",
language = "English",
volume = "12",
journal = "BMC Infectious Diseases",
issn = "1471-2334",
publisher = "BioMed Central Ltd.",

}

TY - JOUR

T1 - 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

AU - Focà, Emanuele

AU - Motta, Davide

AU - Borderi, Marco

AU - Gotti, Daria

AU - Albini, Laura

AU - Calabresi, Alessandra

AU - Izzo, Ilaria

AU - Bellagamba, Rita

AU - Narciso, Pasquale

AU - Sighinolfi, Laura

AU - Clò, Alberto

AU - Gibellini, Davide

AU - Quiros-Roldan, Eugenia

AU - Brianese, Nigritella

AU - Cesana, Bruno M.

AU - Re, Maria C.

AU - Torti, Carlo

PY - 2012/2/14

Y1 - 2012/2/14

N2 - Background: Increased 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.Methods: We 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.Results: Seventy-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.Conclusions: These 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.

AB - Background: Increased 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.Methods: We 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.Results: Seventy-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.Conclusions: These 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.

KW - Antiretroviral therapy

KW - Bone turnover

KW - HIV

KW - Osteoporosis

KW - Vitamin D

UR - http://www.scopus.com/inward/record.url?scp=84857013805&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84857013805&partnerID=8YFLogxK

U2 - 10.1186/1471-2334-12-38

DO - 10.1186/1471-2334-12-38

M3 - Article

C2 - 22333484

AN - SCOPUS:84857013805

VL - 12

JO - BMC Infectious Diseases

JF - BMC Infectious Diseases

SN - 1471-2334

M1 - 38

ER -