Bisphosphonates-related tendinopathies and ligament disorders: Cases analysis from the U.S. Food and Drug Administration adverse event reporting system

Fluoroquinolone antibiotics are known to induce serious tendinopathies and ligament disorders (TPLDs) on rare occasion, but it is less well-appreciated whether such adverse reactions result from the use of bisphosphonates (BPs). In this study, we assessed the correlation between TPLDs and the use of BPs via U.S. FDA Adverse Event Reporting System (FAERS) database. Bayesian and nonproportional analyses were applied to data retrieved from the FAERS database from the first quarter of 2004 to the third quarter of 2022. A total of 3202 reported cases of TPLDs were associated with five BPs (alendronate, pamidronate, ibandronate, risedronate, zoledronate), with statistically significant reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC). Alendronate showed the highest association with tendinopathies and ligament disorders (ROR = 16.30, PRR = 15.47, IC = 3.88), while zoledronate had the lowest association (ROR = 2.13, PRR = 2.12, IC = 1.08), which was consistent with the results of top 10 preferred terms (PTs) under the narrow standardized MedDRA queries (SMQs) sorted by frequency of reports. Excluding zoledronate, over half of patients who reported BP-related TPLDs were hospitalized, either briefly or extendedly. This was especially true for alendronate, which showed the highest rate of hospitalization (83.25 %), however, the mortality rate reported by those taking alendronate were significantly lower than those of zoledronate and pamidronate. In addition, the clinical characteristics of BP-related TPLDs was analyzed. It is more common to reported in middle-aged and elderly females, the highest proportion was in 50-69 years old. Except for osteoporosis, osteopenia, and osteoporosis prophylaxis, cancer bone metastasis was also the indication of some BPs. The most often reported concomitant/prior medicines were calcium supplements, another BPs, antitumor agents, and nonsteroidal anti-inflammatory drugs. In conclusion, we provide a comprehensive overview of the correlation and clinical characteristics, and prognosis of BP-related TPLDs deserving continued surveillance and appropriate management.