Three-year effect of bisphosphonates on bone mineral density after denosumab withdrawal: observations from a real-world study.

Data on long-term treatment regimens for preventing bone mineral density (BMD) loss that occurs after denosumab (Dmab) withdrawal are scarce. Our aim was to evaluate the long-term changes (12-36 months) in BMD and bone turnover markers in a group of postmenopausal women who had been treated with Dmab and received subsequent treatment with bisphosphonates. Secondary objectives were to evaluate factors associated with BMD loss, to compare the BMD change in patients who received oral vs intravenous bisphosphonates, and to assess the frequency of fragility fractures after Dmab discontinuation. The clinical data of 54 patients, 26 of whom had clinical and DXA assessments at 36 months, were analyzed. After 12 months, the mean LS BMD had decreased by 2.8% (±5.0), FN BMD by 1.9% (±5.8), and TH BMD by 1.9% (±3.7). After 36 months, LS BMD had decreased by 3.7% (±6.7), FN BMD by 2.5% (±7.1), and TH BMD by 3.6% (±5.2). C-terminal cross-linked telopeptide of type I collagen significantly increased during the first 12 months after Dmab withdrawal but then decreased at 36 months. BMD loss at 12 months was higher in patients with more than 30 months of Dmab treatment, but this difference was only statistically significant at FN (-3.3% vs -0.3%,  = .252 at LS, -3.3% vs 0.3%,  = .033 at FN, and -2.1% vs 0.9,  = .091 at TH). There were no statistically significant differences regarding the change in BMD at 12 and 36 months between oral and intravenous treatment. Seven patients suffered incidental vertebral fractures (clinical vertebral fractures:  = 6, morphometric fractures:  = 1) three of which were multiple. None of these patients were treated following international or institutional guidelines or recommendations. In summary, our study suggests that bisphosphonates can help maintain BMD for 36 months after Dmab discontinuation.