Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort.
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.
Centre of Excellence for Health, Immunity and Infections (CHIP), Department of Infectious Diseases, Rigshospitalet, and.|Institute for Clinical Medicine, University of Copenhagen, Denmark.
Álvaro H
ÁH
Borges
Department of Infectious Diseases, The Alfred Hospital and Monash University, Melbourne, Australia.
Jennifer
J
Hoy
Institute of Tropical Medicine, Antwerp, Belgium.
Eric
E
Florence
Charles University Hospital Plzen, Czech Republic.
Dalibor
D
Sedlacek
Infektionsmedizinisches Centrum Hamburg (ICH) Study Center, Innere Medizin, Hamburg, Germany.
Hans-Jürgen
HJ
Stellbrink
Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania.
Vilma
V
Uzdaviniene
University Medical Centre Ljubljana, Clinic of Infectious Diseases Ljubljana, Medical Faculty, University of Ljubljana, Slovenia.
Janez
J
Tomazic
The General Hospital of Athens "G. Gennimatas" First Department Of Medicine - Infectious Diseases Unit, Athens, Greece.
Panagiotis
P
Gargalianos-Kakolyris
Division of Infectious Diseases, Cantonal Hospital St. Gallen, Switzerland.
Patrick
P
Schmid
Barts and The Royal London Hospital NHS Trust, London, United Kingdom.
Chloe
C
Orkin
Odense Universitetshospital, Forskningsenheden, Denmark.
Court
C
Pedersen
Western General Hospital, Edinburgh, United Kingdom.
Clifford
C
Leen
CHU Nice Hopital de l' Archet 1, Nice, France.
Christian
C
Pradier
St. James' Hospital, Dublin, Ireland.
Fiona
F
Mulcahy
Ospedale L. Sacco, Milan, Italy.
Anna Lisa
AL
Ridolfo
Centre Hospitalier de Luxembourg, Luxemborg.
Therese
T
Staub
Hospital Curry Cabral, Lisbon, Portugal.
Fernando
F
Maltez
University Hospital Zürich, Switzerland.
Rainer
R
Weber
Skåne University Hospital, Malmö, Sweden.
Leo
L
Flamholc
Crimean Republican AIDS Centre, Simferopol, Ukraine; and.
Galina
G
Kyselyova
Centre of Excellence for Health, Immunity and Infections (CHIP), Department of Infectious Diseases, Rigshospitalet, and.
Jens D
JD
Lundgren
Department of Infection and Population Health, University College London, UK.
Amanda
A
Mocroft
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D060085:Coinfection / Q000453:epidemiology; D003625:Data Collection; D005060:Europe / Q000453:epidemiology; D005260:Female; D005264:Femoral Fractures / Q000453:epidemiology / Q000209:etiology / Q000821:virology; D050723:Fractures, Bone / Q000453:epidemiology / Q000208:ethnology / Q000209:etiology* / Q000821:virology; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010020:Osteonecrosis / Q000453:epidemiology / Q000209:etiology* / Q000821:virology; D012044:Regression Analysis; D012307:Risk Factors; D000068698:Tenofovir / Q000009:adverse effects / Q000627:therapeutic use
D019380:Anti-HIV Agents; D000068698:Tenofovir
HIV.; avascular necrosis; bone; fractures; osteonecrosis