Musculoskeletal disorders and bisphosphonates: a disproportionality analysis within the Spanish pharmacovigilance database

Abstract Background: several musculoskeletal adverse effects associated with the use of bisphosphonates have been identified, although their frequency, severity and risk factors are still unknown. The aim of our study is to determine the possible causal relationship between the most widely used bisphosphonates in Spain and the occurrence of musculoskeletal adverse events. Material and methods: we conducted a retrospective, observational, analytical, case/non-case study using the database of the Spanish Pharmacovigilance System. The bisphosphonates selected were alendronic acid, ibandronic acid and risedronic acid. The adverse reactions studied according to MedDRA terminology were SOC musculoskeletal and connective tissue disorders and PTs myalgia, arthralgia, bone pain, paresthesia, musculoskeletal pain, musculoskeletal stiffness, arthritis, muscle weakness and pain in an extremity. Results: the ROR values obtained for the SOC were > 1 for all 3 drugs studied. These reactions occur mostly in those over 65 years of age, women and that most of them are classified as serious. For the 9 PTs studied (myalgia, arthralgia, bone pain, paresthesia, musculoskeletal pain, musculoskeletal stiffness, arthritis, muscle weakness and pain in a limb), ROR values > 1 were found for all three drugs, except for the PT paresthesia and PT pain in a limb. Conclusion: musculoskeletal adverse reactions not listed in the official information have been detected. The information provided by this work could recommend for a re-evaluation and update of the benefit-risk ratio of these drugs.