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Fractures Related to Tenofovir

A Case/Noncase Study in the European Pharmacovigilance Database

García, Montserrat G. PharmD1,*; Larrinaga-Torrontegui, Unai MD2; Eduardo Martinez, Eduardo MD3; Lertxundi, Unax PharmD4; Palacios-Zabalza, Itziar PharmD5; Aguirre, Carmelo PhD, MD1,6

doi: 10.1097/MJT.0000000000000718
Brief Report

Background: There is no clear consensus on the relationship between tenofovir (TDF) and fracture risk because the studies published so far present contradictory findings.

Study Question: Our objective was to detect, from the European pharmacovigilance database (EudraVigilance), a signal of fracture risk during TDF exposure in patients infected with HIV.

Methods: Herein, we analyze all the cases of fractures suspected to be related to TDF recorded in EudraVigilance between 2001 and November 10, 2016. A case/noncase method was used to assess the association between fractures and TDF, calculating proportional reporting ratios (PRRs) and their 95% confidence intervals (CIs) as a measure of disproportionality. According to the Medical Dictionary for Regulatory Activities (MedDRA) terminology, osteoporotic fractures are included in High Level Group Term (HLGT) “Fractures” and traumatic fractures in HLGT “Bone and joint injuries,” so, we selected cases included in both HLGTs. The noncases used as controls were all the remaining adverse drug reaction reports recorded in EudraVigilance during the same period.

Results: There were 68,113 cases of fractures in the 4,776,472 reports recorded in EudraVigilance during the study period. TDF was involved in 181 cases. The median latency period until the appearance of fracture was 995 days. TDF was present as the only suspect drug in 140 cases. The PRR of TDF and fractures was 1.11 (95% CI, 0.96–1.28). Nevertheless, disproportionality was observed for some types of fractures: osteoporotic fractures (PRR 17.24; 95% CI, 9.90–30.01), bone fissure (PRR 16.60; 95% CI, 6.11–45.10), and pathological fracture (PRR 4.40; 95% CI, 2.77–7.00).

Conclusions: Our findings do not show a disproportionality for fractures in patients treated with TDF, although disproportionality was found for some types of fractures, mainly osteoporotic fractures.

1Basque Country Pharmacovigilance Unit, Galdakao-Usansolo Hospital, Galdakao, Spain;

2Preventive Medicine Service, Cruces University Hospital, Barakaldo, Spain;

3Infectious Diseases Unit, Galdakao-Usansolo Hospital, Galdakao, Spain;

4Pharmacy Service, Araba´s Mental Health Network, Vitoria-Gasteiz, Spain;

5Pharmacy Service, Galdakao-Usansolo Hospital, Galdakao, Spain; and

6Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country, Leioa, Spain.

Address for correspondence: Montserrat G. García, PharmD, Basque Country Pharmacovigilance Unit, Galdakao-Usansolo Hospital, Barrio Labeaga 46A, 48960 Galdakao, Bizkaia, Spain. E-mail:

The authors have no conflicts of interest to declare.

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