Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort

Álvaro H Borges; Jennifer Hoy; Eric Florence; Dalibor Sedlacek; Hans-Jürgen Stellbrink; Vilma Uzdaviniene; Janez Tomazic; Panagiotis Gargalianos-Kakolyris; Patrick Schmid; Chloe Orkin; Court Pedersen; Clifford Leen; Christian Pradier; Fiona Mulcahy; Anna Lisa Ridolfo; Therese Staub; Fernando Maltez; Rainer Weber; Leo Flamholc; Galina Kyselyova; Jens D Lundgren; Amanda Mocroft; for EuroSIDA

doi:10.1093/cid/cix167

Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort

Álvaro H Borges, Jennifer Hoy, Eric Florence, Dalibor Sedlacek, Hans-Jürgen Stellbrink, Vilma Uzdaviniene, Janez Tomazic, Panagiotis Gargalianos-Kakolyris, Patrick Schmid, Chloe Orkin, Court Pedersen, Clifford Leen, Christian Pradier, Fiona Mulcahy, Anna Lisa Ridolfo, Therese Staub, Fernando Maltez, Rainer Weber, Leo Flamholc, Galina KyselyovaJens D Lundgren, Amanda Mocroft, for EuroSIDA

Institut for Klinisk Medicin

35 Citationer (Scopus)

Abstract

Background: Antiretrovirals (ARVs) affect bone density and turnover, but their effect on risk of fractures and osteonecrosis of the femoral head is less understood. We investigated if exposure to ARVs increases the risk of both bone outcomes.

Methods: EuroSIDA participants were followed to assess fractures and osteonecrosis. Poisson regression identified clinical, laboratory and demographic predictors of either bone outcome. Ever, current, and cumulative exposures to ARVs were assessed.

Results: During 86118 PYFU among 11820 included persons (median age 41y, 75% male, median baseline CD4 440/mm3, 70.4% virologically suppressed), there were 619 fractures (incidence/1000 PYFU 7.2; 95% CI 6.6-7.7) and 89 osteonecrosis (1.0; 0.8-1.3). Older age, white race, lower BMI, IV drug use, lower baseline CD4, HCV coinfection, prior osteonecrosis, prior fracture, cardiovascular disease, and recent non-AIDS cancer (last 12 months) were associated with fractures. After adjustment, persons who had ever used tenofovir disoproxil fumarate (TDF) (1.40; 1.15-1.70) or who were currently on TDF (1.25; 1.05-1.49) had higher incidence of fractures. There was no association between cumulative exposure to TDF and fractures (1.08/5 y exposure; 0.94-1.25). No other ARV was associated with fractures (all P > .1). Risk of osteonecrosis was associated with white race, lower nadir CD4, prior osteonecrosis, prior fracture, and prior AIDS. After mutual adjustment, no ARV was associated with osteonecrosis.

Conclusions: In human immunodeficiency virus (HIV) infection, host factors, HIV-specific variables, and comorbidities contribute to risk of fractures and osteonecrosis. Exposure to TDF, but not other ARVs, was an independent risk factor for fractures.

Originalsprog	Engelsk
Tidsskrift	Clinical Infectious Diseases
Vol/bind	64
Udgave nummer	10
Sider (fra-til)	1413-1421
ISSN	1058-4838
DOI	https://doi.org/10.1093/cid/cix167
Status	Udgivet - 15 maj 2017

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Borges, Á. H., Hoy, J., Florence, E., Sedlacek, D., Stellbrink, H-J., Uzdaviniene, V., Tomazic, J., Gargalianos-Kakolyris, P., Schmid, P., Orkin, C., Pedersen, C., Leen, C., Pradier, C., Mulcahy, F., Ridolfo, A. L., Staub, T., Maltez, F., Weber, R., Flamholc, L., ... for EuroSIDA (2017). Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort. Clinical Infectious Diseases, 64(10), 1413-1421. https://doi.org/10.1093/cid/cix167

Borges, ÁH, Hoy, J, Florence, E, Sedlacek, D, Stellbrink, H-J, Uzdaviniene, V, Tomazic, J, Gargalianos-Kakolyris, P, Schmid, P, Orkin, C, Pedersen, C, Leen, C, Pradier, C, Mulcahy, F, Ridolfo, AL, Staub, T, Maltez, F, Weber, R, Flamholc, L, Kyselyova, G, Lundgren, JD, Mocroft, A & for EuroSIDA 2017, 'Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort', Clinical Infectious Diseases, bind 64, nr. 10, s. 1413-1421. https://doi.org/10.1093/cid/cix167

@article{37ed967552e245cdb50b62e22c4f07fc,

title = "Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort",

abstract = "Background: Antiretrovirals (ARVs) affect bone density and turnover, but their effect on risk of fractures and osteonecrosis of the femoral head is less understood. We investigated if exposure to ARVs increases the risk of both bone outcomes.Methods: EuroSIDA participants were followed to assess fractures and osteonecrosis. Poisson regression identified clinical, laboratory and demographic predictors of either bone outcome. Ever, current, and cumulative exposures to ARVs were assessed.Results: During 86118 PYFU among 11820 included persons (median age 41y, 75% male, median baseline CD4 440/mm3, 70.4% virologically suppressed), there were 619 fractures (incidence/1000 PYFU 7.2; 95% CI 6.6-7.7) and 89 osteonecrosis (1.0; 0.8-1.3). Older age, white race, lower BMI, IV drug use, lower baseline CD4, HCV coinfection, prior osteonecrosis, prior fracture, cardiovascular disease, and recent non-AIDS cancer (last 12 months) were associated with fractures. After adjustment, persons who had ever used tenofovir disoproxil fumarate (TDF) (1.40; 1.15-1.70) or who were currently on TDF (1.25; 1.05-1.49) had higher incidence of fractures. There was no association between cumulative exposure to TDF and fractures (1.08/5 y exposure; 0.94-1.25). No other ARV was associated with fractures (all P > .1). Risk of osteonecrosis was associated with white race, lower nadir CD4, prior osteonecrosis, prior fracture, and prior AIDS. After mutual adjustment, no ARV was associated with osteonecrosis.Conclusions: In human immunodeficiency virus (HIV) infection, host factors, HIV-specific variables, and comorbidities contribute to risk of fractures and osteonecrosis. Exposure to TDF, but not other ARVs, was an independent risk factor for fractures.",

keywords = "Adult, Anti-HIV Agents/administration & dosage, Bone Density/drug effects, CD4 Lymphocyte Count, Cohort Studies, Coinfection/epidemiology, Data Collection, Europe/epidemiology, Female, Femoral Fractures/epidemiology, Fractures, Bone/epidemiology, HIV Infections/complications, Humans, Male, Middle Aged, Osteonecrosis/epidemiology, Regression Analysis, Risk Factors, Tenofovir/adverse effects",

author = "Borges, {{\'A}lvaro H} and Jennifer Hoy and Eric Florence and Dalibor Sedlacek and Hans-J{\"u}rgen Stellbrink and Vilma Uzdaviniene and Janez Tomazic and Panagiotis Gargalianos-Kakolyris and Patrick Schmid and Chloe Orkin and Court Pedersen and Clifford Leen and Christian Pradier and Fiona Mulcahy and Ridolfo, {Anna Lisa} and Therese Staub and Fernando Maltez and Rainer Weber and Leo Flamholc and Galina Kyselyova and Lundgren, {Jens D} and Amanda Mocroft and {for EuroSIDA}",

year = "2017",

month = may,

day = "15",

doi = "10.1093/cid/cix167",

language = "English",

volume = "64",

pages = "1413--1421",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "10",

}

TY - JOUR

T1 - Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort

AU - Borges, Álvaro H

AU - Hoy, Jennifer

AU - Florence, Eric

AU - Sedlacek, Dalibor

AU - Stellbrink, Hans-Jürgen

AU - Uzdaviniene, Vilma

AU - Tomazic, Janez

AU - Gargalianos-Kakolyris, Panagiotis

AU - Schmid, Patrick

AU - Orkin, Chloe

AU - Pedersen, Court

AU - Leen, Clifford

AU - Pradier, Christian

AU - Mulcahy, Fiona

AU - Ridolfo, Anna Lisa

AU - Staub, Therese

AU - Maltez, Fernando

AU - Weber, Rainer

AU - Flamholc, Leo

AU - Kyselyova, Galina

AU - Lundgren, Jens D

AU - Mocroft, Amanda

AU - for EuroSIDA

PY - 2017/5/15

Y1 - 2017/5/15

N2 - Background: Antiretrovirals (ARVs) affect bone density and turnover, but their effect on risk of fractures and osteonecrosis of the femoral head is less understood. We investigated if exposure to ARVs increases the risk of both bone outcomes.Methods: EuroSIDA participants were followed to assess fractures and osteonecrosis. Poisson regression identified clinical, laboratory and demographic predictors of either bone outcome. Ever, current, and cumulative exposures to ARVs were assessed.Results: During 86118 PYFU among 11820 included persons (median age 41y, 75% male, median baseline CD4 440/mm3, 70.4% virologically suppressed), there were 619 fractures (incidence/1000 PYFU 7.2; 95% CI 6.6-7.7) and 89 osteonecrosis (1.0; 0.8-1.3). Older age, white race, lower BMI, IV drug use, lower baseline CD4, HCV coinfection, prior osteonecrosis, prior fracture, cardiovascular disease, and recent non-AIDS cancer (last 12 months) were associated with fractures. After adjustment, persons who had ever used tenofovir disoproxil fumarate (TDF) (1.40; 1.15-1.70) or who were currently on TDF (1.25; 1.05-1.49) had higher incidence of fractures. There was no association between cumulative exposure to TDF and fractures (1.08/5 y exposure; 0.94-1.25). No other ARV was associated with fractures (all P > .1). Risk of osteonecrosis was associated with white race, lower nadir CD4, prior osteonecrosis, prior fracture, and prior AIDS. After mutual adjustment, no ARV was associated with osteonecrosis.Conclusions: In human immunodeficiency virus (HIV) infection, host factors, HIV-specific variables, and comorbidities contribute to risk of fractures and osteonecrosis. Exposure to TDF, but not other ARVs, was an independent risk factor for fractures.

AB - Background: Antiretrovirals (ARVs) affect bone density and turnover, but their effect on risk of fractures and osteonecrosis of the femoral head is less understood. We investigated if exposure to ARVs increases the risk of both bone outcomes.Methods: EuroSIDA participants were followed to assess fractures and osteonecrosis. Poisson regression identified clinical, laboratory and demographic predictors of either bone outcome. Ever, current, and cumulative exposures to ARVs were assessed.Results: During 86118 PYFU among 11820 included persons (median age 41y, 75% male, median baseline CD4 440/mm3, 70.4% virologically suppressed), there were 619 fractures (incidence/1000 PYFU 7.2; 95% CI 6.6-7.7) and 89 osteonecrosis (1.0; 0.8-1.3). Older age, white race, lower BMI, IV drug use, lower baseline CD4, HCV coinfection, prior osteonecrosis, prior fracture, cardiovascular disease, and recent non-AIDS cancer (last 12 months) were associated with fractures. After adjustment, persons who had ever used tenofovir disoproxil fumarate (TDF) (1.40; 1.15-1.70) or who were currently on TDF (1.25; 1.05-1.49) had higher incidence of fractures. There was no association between cumulative exposure to TDF and fractures (1.08/5 y exposure; 0.94-1.25). No other ARV was associated with fractures (all P > .1). Risk of osteonecrosis was associated with white race, lower nadir CD4, prior osteonecrosis, prior fracture, and prior AIDS. After mutual adjustment, no ARV was associated with osteonecrosis.Conclusions: In human immunodeficiency virus (HIV) infection, host factors, HIV-specific variables, and comorbidities contribute to risk of fractures and osteonecrosis. Exposure to TDF, but not other ARVs, was an independent risk factor for fractures.

KW - Adult

KW - Anti-HIV Agents/administration & dosage

KW - Bone Density/drug effects

KW - CD4 Lymphocyte Count

KW - Cohort Studies

KW - Coinfection/epidemiology

KW - Data Collection

KW - Europe/epidemiology

KW - Female

KW - Femoral Fractures/epidemiology

KW - Fractures, Bone/epidemiology

KW - HIV Infections/complications

KW - Humans

KW - Male

KW - Middle Aged

KW - Osteonecrosis/epidemiology

KW - Regression Analysis

KW - Risk Factors

KW - Tenofovir/adverse effects

U2 - 10.1093/cid/cix167

DO - 10.1093/cid/cix167

M3 - Journal article

C2 - 28329090

SN - 1058-4838

VL - 64

SP - 1413

EP - 1421

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 10

ER -

Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort

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