Journal of Pharmacovigilance

Abstract

Assessing Risks of Impaired Healing and Osteomyelitis Associated with Bisphosphonates Using FDA Adverse Event Reporting System (FAERS)

Amie Cai, Ana Hincapie, Kevin Dong, Wendy Chaing, Tibebe Woldemariam, Xiaodong Feng, Kevin Yamashiro and Bin Guan

Objective: Bisphosphonates are the leading class of drugs to prevent and treat osteoporosis. Numerous cases of bisphosphonates related to bone necrosis and bone fractures have been reported. In this study the risks of impaired healing and osteomyelitis associated with bisphosphonates were assessed using case reports submitted to the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

Methods: Using FAERS the adverse events reports from the first quarter of 2004 to the second quarter of 2012 associated with bisphosphonates and non-bisphosphonates anti-osteoporosis drugs were generated and evaluated. Standardized pharmacovigilance tools were applied to detect the signal of impaired healing and osteoporosis.

Results: Among 14493 total reported events of impaired healing in FAERS, 49% of the cases were associated with use of bisphophonates. Substantial and pharmacovigilantly significant signals of impaired healing (PRR=13.39) and osteomyelitis (PRR=7.06) were detected. There was less risk of impaired healing (PRR=4.8) and osteomyelitis (PRR=1.61) associated with ibandronate (PRR=4.80) compared to other bisphosphonates. Interestingly weak but significant signals of impaired healing (PRR=3.40) and osteomyelitis (PRR=2.38) were also detected for denosumab. There were no significant risks of impaired healing (PRR=1.85) and osteomyelitis (PRR=0.25) associated with teriparatide.

Conclusion: This study for the first time signals an increasing risk of impaired healing and osteomyelitis associated with bisphosphonates using FAERS. It has significant implication for patient safety in pharmacy practice. Considering the limitation of FAERS, such as under reporting, reporting bias and Weber-effect, this study provides goal for future large pharmacoepidemiologic studies.