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

Álvaro H Borges, Jennifer F 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

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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.

Original languageEnglish
JournalClinical Infectious Diseases
Volume64
Issue number10
Pages (from-to)1413-1421
ISSN1058-4838
DOIs
Publication statusPublished - 2017

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HIV
Femoral Fractures
Incidence
Virus Diseases
Coinfection
Bone Density
Comorbidity
Acquired Immunodeficiency Syndrome
Pharmaceutical Preparations
Neoplasms

Keywords

  • Journal Article

Cite this

Borges, Á. H., Hoy, J. F., Florence, E., Sedlacek, D., Stellbrink, H-J., Uzdaviniene, V., ... 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, Álvaro H ; Hoy, Jennifer F ; Florence, Eric ; Sedlacek, Dalibor ; Stellbrink, Hans-Jürgen ; Uzdaviniene, Vilma ; Tomazic, Janez ; Gargalianos-Kakolyris, Panagiotis ; Schmid, Patrick ; Orkin, Chloe ; Pedersen, Court ; Leen, Clifford ; Pradier, Christian ; Mulcahy, Fiona ; Ridolfo, Anna Lisa ; Staub, Therese ; Maltez, Fernando ; Weber, Rainer ; Flamholc, Leo ; Kyselyova, Galina ; Lundgren, Jens D ; Mocroft, Amanda ; for EuroSIDA. / Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort. In: Clinical Infectious Diseases. 2017 ; Vol. 64, No. 10. pp. 1413-1421.
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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.",
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Borges, ÁH, Hoy, JF, 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, vol. 64, no. 10, pp. 1413-1421. https://doi.org/10.1093/cid/cix167

Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort. / Borges, Álvaro H; Hoy, Jennifer F; Florence, Eric; Sedlacek, Dalibor; Stellbrink, Hans-Jürgen; Uzdaviniene, Vilma; Tomazic, Janez; Gargalianos-Kakolyris, Panagiotis; Schmid, Patrick; Orkin, Chloe; Pedersen, Court; Leen, Clifford; Pradier, Christian; Mulcahy, Fiona; Ridolfo, Anna Lisa; Staub, Therese; Maltez, Fernando; Weber, Rainer; Flamholc, Leo; Kyselyova, Galina; Lundgren, Jens D; Mocroft, Amanda; for EuroSIDA.

In: Clinical Infectious Diseases, Vol. 64, No. 10, 2017, p. 1413-1421.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

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

AU - Borges, Álvaro H

AU - Hoy, Jennifer F

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

Y1 - 2017

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 - Journal Article

U2 - 10.1093/cid/cix167

DO - 10.1093/cid/cix167

M3 - Journal article

C2 - 28329090

VL - 64

SP - 1413

EP - 1421

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 10

ER -

Borges ÁH, Hoy JF, Florence E, Sedlacek D, Stellbrink H-J, Uzdaviniene V et al. Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort. Clinical Infectious Diseases. 2017;64(10):1413-1421. https://doi.org/10.1093/cid/cix167