LAUSR

Denosumab, a monoclonal antibody against RANKL, is an effective treatment for osteoporosis. Discontinuation of denosumab has been shown to lead in multiple vertebral fractures in some patients due to a severe acceleration of bone resorption (rebound-associated vertebral fractures-RAVFs). Limited data published during the last 2 years highlighted this issue.The aim of this case series is to describe features of the denosumab-associated RAVFs and the characteristics of these patients.Patients from our outpatient rheumatology clinic who were diagnosed with recent vertebral fractures after denosumab discontinuation from January 2019 to December 2019 were included. Diagnosis was based on x-ray and/or magnetic resonance imaging (MRI) of thoracic (T) or lumbar (L) spine. All cases were the result of reduced compliance of the patients to the treatment regimen. A baseline x-ray examination was available in all patients included and was compared in order to exclude prevalent osteoporotic fractures. Demographic and clinical parameters were recorded.Nine patients (8 females) with a mean±SD age of 71.3±11.9 years were included (Table 1). A total of 32 fractures occurred, affecting median 4 (range 1-6) vertebras (Figure 1). The mean±SD duration of denosumab treatment prior to discontinuation was 54.0±30.1 months, while the mean±SD time that RAVFs occurred after the last denosumab injection was 8.8±2.4 (range 7-12) months. The most commonly affected vertebra was L3 (Table1). Most patients (66.7%) did not have any prevalent osteoporotic fracture. Four patients (44.4%) were receiving drugs that affected bone metabolism (mainly corticosteroids and aromatase inhibitors). Only 33.3% of the patients had a history of previous treatment with bisphosphonates.Table 1.Characteristics of RAVFs and patients affected. L: Lumbar, T: Thoracic, SD: Standard DeviationFemales (%)88.9%Age (years) (mean±SD)71.3±11.9Affected vertebras (median, range)4, 1-6Treatment duration (mean±SD) (months)54.0±30.1Time after last injection (mean±SD) (months)8.8±2.4Vertebral fracture site1 3T10 T11 T122L15L25L38L45L55Patients with prevalent osteoporotic fractures (%)33.3Patients receiving drugs affecting bone metabolism (%)44.4Patients with previous treatment with bisphosphonates (%)33.3Figure 1.Multiple vertebral fractures (yellow arrows - T11, T12, L2-L5) in a patient 7.5 months after the last denosumab injection. T: thoracic, L: LumbarDenosumab-associated RAVFs usually occur within 7-12 months after the last denosumab injection and affect multiple vertebras. Most cases are associated with long-term (>2 years) denosumab administration without previous treatment with bisphosphonates. Rheumatologists should be alert of this complication since the reported compliance in patients under denosumab treatment is only 46% (1) and the expected incidence of RAVFs after denosumab discontinuation has been reported to be 10% (2).[1]Durden E, Pinto L, Lopez-Gonzalez L, Juneau P, Barron R. Two-year persistence and compliance with osteoporosis therapies among postmenopausal women in a commercially insured population in the United States. Arch Osteoporos. 2017 Dec;12(1):22.[2]McClung MR, Wagman RB, Miller PD, Wang A, Lewiecki EM. Observations following discontinuation of long-term denosumab therapy. Osteoporos Int. 2017 May;28(5):1723-1732.None declared