Suboptimal medication adherence may favor the progression of vertebral fractures in women with post-menopausal osteoporosis under treatment with denosumab: a real-life observational study.

BACKGROUND: Medication adherence is a determinant of therapeutic outcomes in patients with osteoporosis treated with bisphosphonates. In this monocentric study, we evaluated whether the regular drug administration may influence the effectiveness of denosumab in preventing vertebral fractures (VFs) in real-world clinical practice. METHODS: Two-hundred-four women (median age 75 years, range: 54-90) under treatment with denosumab for post-menopausal osteoporosis were longitudinally evaluated for incident radiological VFs and changes in lumbar spine bone mineral density (BMD) in relationship with medication adherence. All patients were persistent with denosumab treatment (i.e., maximum delay in administration of a single denosumab dose: 90 days). Patients were defined adherent to denosumab therapy when the drug was administered every 6 months+/-28 days. RESULTS: One-hundred-seventy-three patients (84.4%) were adherent to denosumab therapy, whereas the remaining 31 patients (15.6%) received in delay one or more denosumab doses (cumulative delay: 52 days, range 29-183). Fourteen patients (6.9%) experienced incident VFs during the follow-up (median duration: 30 months, range: 18-48), in relationship with non- adherence to denosumab therapy (Hazard Ratio 4.44; C.I. 95% 1.01-19.47) and smaller increase in lumbar spine BMD (Hazard Ratio 0.85, C.I. 95% 0.76-0.94). CONCLUSIONS: In post-menopausal women at high risk of fractures, the small delay in the administration of denosumab (i.e., not uncommon in clinical practice) was associated with a significant increase of incidence of VFs. Preservation of standard dosing schedule appears to be an important determinant of denosumab effectiveness in the real-life clinical practice.