ArticleArchives of osteoporosis2026
Revisiting the activate depress free and repeat (ADFR) paradigm: Clinical use of cyclic romosozumab.
Article in Archives of osteoporosis, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
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Abstract
Osteoporosis treatment does not normalize BMD. We hypothesized cyclic romosozumab dosing might provide greater BMD increases. Cyclic therapy (six romosozumab monthly doses then one denosumab dose) produced broadly similar BMD increases as previously reported for 12 romosozumab doses. A second cycle further increased spine and hip BMD but with a blunted response. PURPOSE: Evaluating novel osteoporosis medication approaches to maximize BMD is reasonable. A bone remodeling-based cyclic approach, i.e., activate, depress, free and repeat (ADFR), has been proposed. We hypothesized that short course romosozumab followed by denosumab represents an appropriate cycle. This exploratory retrospective case series reports six months of romosozumab treatment then one denosumab dose, followed by a second identical cycle.
methodsWomen at very high fracture risk were offered cyclic therapy. DXA was obtained at baseline, 1 and 2 years. Data from 41 women treated for 1, and 18 for 2 years are reported. Percent BMD change from baseline was evaluated by ANOVA.
resultsPatient mean (SD) age and BMI were 68.8 (6.6) years and 25.6 (5.0) kg/m
conclusionAt one year, six monthly romosozumab doses then one denosumab dose substantially increased BMD. A second cycle further increased LS and TH BMD, but the response was blunted perhaps reflecting persistent turnover suppression by denosumab. Evaluation of novel romosozumab dosing approaches is indicated.
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