Associations between osteoporosis and drug exposure: A post-marketing study of the World Health Organization pharmacovigilance database (VigiBase®)

Background: Bone remodeling is a complex process, and many conditions (including drug exposure) lead to osteoporosis. Here, we sought to detect new disproportionality signals for drugs associated with osteoporosis. Methods: We performed a disproportionality analysis of the World Health Organization's VigiBase (R) pharmacovigilance database through April 12, 2020. The frequency of reports on osteoporosis for all identified drug classes was compared with that for all other drugs and quoted as the reporting odds ratio (ROR) [95% confidence interval (CI)]. Results: Of the 7,594,968 cases spontaneously recorded to VigiBase (R), 4758 concerned osteoporosis. New disproportionality signals with a pharmacologically plausible mechanism were found for drugs used in neurology (levodopa (ROR [95%CI]: 10.18 [4.33-25.10]), selective serotonin agonists (4.22 [2.34-7.00]) and memantine (4.10 [1.56-8.93])), hematology (romiplostim (4.93 [1.15-21.10])), pulmonology (macitentan (3.02 [1.84-4.90])), ophthalmology (ranibizumab (3.31 [1.00-10.51])) and rheumatology (tofacitinib (3.65 [3.00-4.40])). The robustness of these new results is supported by the significant RORs for the vast majority of drugs already known to induce osteoporosis and/or increase the fracture risk, namely glucocorticoids, gonadotropin-releasing hormone analogs, anti-aromatases, androgen receptor blockers, thyroid hormones, proton pump inhibitors, thiazolidinediones, vitamin K antagonists, loop diuretics, protease inhibitors, nucleoside and nucleotide reverse transcriptase inhibitors, and enzyme-inducing antiepileptics including barbiturates and derivatives, hydantoin derivatives, carboxamide derivatives and fatty acid derivatives. Conclusion: We established up a comprehensive list of drugs potentially associated with osteoporosis and highlighted those with pharmacologically plausible mechanisms leading to bone fragility. Our results might pave the way for additional exploration of these mechanisms.