Fractures Related to Tenofovir: A Case/Noncase Study in the European Pharmacovigilance Database.

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.