Abstract
Discontinuation of denosumab is associated with the increase of bone turnover markers to above-baseline levels (so-called rebound in bone turnover) and rapid bone loss. Several studies have reported vertebral fractures (VFs), particularly multiple spontaneous clinical VFs (MSCVFs), occurring after discontinuation of denosumab. There is currently no recommendation for the management of VFs including MSCVFs. Presently, romosozumab is the strongest anti-osteoporotic agent that inhibits sclerostin and rapidly increases bone mass, but it is uncertain that romosozumab is an effective treatment choice to treat VFs occurring after discontinuation of denosumab. Herein we reported a novel case of a 60-year-old woman who was treated with romosozumab after discontinuation of denosumab and subsequently suffered MSCVFs under romosozumab treatment. She had a history of two osteoporotic VFs (T6 and T8) and received five doses of 60 mg denosumab every 6 months following the osteoporosis diagnosis. As per the patient's convenience, the sixth denosumab injection was postponed. To improve the persistent low bone mass in the lumbar spine (T-score −3.8), 210 mg romosozumab was administered monthly after 9 months following the last denosumab injection. At the first romosozumab injection, she had no clinical symptoms such as low back pain, but her bone formation and resorption marker levels elevated compared with those treated with denosumab. After three doses of romosozumab, spontaneous severe low back pain occurred, and time-course radiographs revealed five new VFs (T12, L2, L3, L4, and L5). Romosozumab administration had no suppressive effect on bone resorption during the rebound in bone turnover after discontinuation of denosumab. This case suggests that romosozumab is not effective in preventing VFs or MSCVFs after denosumab discontinuation.
Highlights
Bisphosphonates remain in the skeletal bone even after their discontinuation because of their high affinity to skeletal bone (Meier et al, 2017)
Discontinuation of denosumab has been known to be associated with the increase of bone turnover markers to above-baseline levels and rapid bone loss (Bone et al, 2011; Popp et al, 2018), and recent reports have demonstrated vertebral fractures (VFs), multiple spontaneous clinical VFs (MSCVFs), occurring after discontinuation of denosumab (Anastasilakis et al, 2017; Tripto-Shkolnik et al, 2018; Lamy et al, 2019)
Romosozumab is the strongest anti-osteoporotic agent that rapidly increases bone mass when compared with other agents, but it is uncertain that romosozumab is an effective treatment choice to treat VFs or MSCVFs occurring after discontinuation of denosumab
Summary
Bisphosphonates remain in the skeletal bone even after their discontinuation because of their high affinity to skeletal bone (Meier et al, 2017). The clinical benefit of other anti-osteoporosis agents, except bisphosphonates, diminishes over time following discontinuation. A bone anabolic agent such as teriparatide seems to be an effective treatment choice to treat VFs occurring after discontinuation of denosumab. In a randomized controlled trial that compared romosozumab with placebo, treatment with romosozumab for 12 months showed a dramatic increase in bone mass and significant reduction of the risk of new VFs and clinical fractures among postmenopausal women with osteoporosis Treatment with romosozumab is reported to significantly increase bone mass among women with postmenopausal osteoporosis transitioning from alendronate treatment (Langdahl et al, 2017). Romosozumab is the strongest anti-osteoporotic agent that rapidly increases bone mass when compared with other agents, but it is uncertain that romosozumab is an effective treatment choice to treat VFs or MSCVFs occurring after discontinuation of denosumab. To the best of our knowledge, this is the first reported case of a 60year-old woman who was treated with romosozumab after discontinuation of denosumab and subsequently suffered MSCVFs under romosozumab treatment
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