Alendronate for 6 or 12 months following denosumab discontinuation in women with postmenopausal osteoporosis: A prospective observational study

Abstract

Unopposed denosumab (Dmab) discontinuation is followed by overshoot in bone turnover markers (BTM), rapid bone mineral density (BMD) loss, and elevated risk of multiple vertebral fractures. To preserve BMD gains and mitigate fracture risk it is currently recommended to administer bisphosphonates following Dmab discontinuation. We prospectively evaluate the efficacy of alendronate (ALN) in preventing BTM overshoot and BMD loss in women with postmenopausal osteoporosis (PMO) discontinuing Dmab. This is a 12-month prospective, observational study among patients treated with Dmab 60 mg every 6 months and achieved osteopenia at the lumbar spine (LS) and femoral neck (FN). Six months after the last Dmab injection participants received oral ALN 70 mg weekly for 6 months followed by 6 months without therapy (Group 1) or for 12 months (Group 2). The primary endpoint was the percent change in LS-BMD from baseline to month 12. Eighty women (39 Group 1, 41 Group 2) who had received 2–22 Dmab injections (mean 9.8) completed the study. Median age was 67 years; 27.5% had prevalent fractures and 59% had prior anti-osteoporotic therapy. At month 12, LS-BMD declined significantly in the overall cohort [−5.9% (8.2%), p < 0.001], with no difference between groups (Group 1: −6.8% vs Group 2: −5.0%, p = 0.50). FN-BMD decreased (−3.5%, p < 0.001), and similarly in both groups. Serum procollagen type 1 N-terminal propeptide (P1NP), C-terminal telopeptide of type 1 collagen (CTX), and tartrate-resistant acid phosphatase isoform 5b increased significantly; P1NP and CTX were significantly higher in Group 1 at month 12. One patient sustained multiple vertebral fractures (1.25%). In conclusion, alendronate did not consistently attenuate BMD loss and BTM rebound after denosumab discontinuation in women with PMO, with 6 months being as effective as 12 months of treatment. Importantly, both regimens were associated with low incidence of multiple vertebral fractures.