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This multicentre, prospective cohort study measured the effect of romosozumab for 12 months on bone mineral density, taking into account prior therapies. Prior antiresorptive therapy blunted the BMD response to romosozumab, and the duration was correlated with BMD changes at both the lumbar spine and total hip. INTRODUCTION: In Switzerland, romosozumab is administered to high-risk osteoporosis patients. Our study aimed to assess the effect of romosozumab on bone mineral density (BMD), taking into account prior therapies. METHODS: This multicentre, prospective cohort study measured the effect of romosozumab for 12 months in patients in a nationwide Swiss osteoporosis registry. BMD and bone turnover marker (P1NP and CTX) changes were measured and compared between pre-treated and treatment naïve patients. RESULTS: Ninety-nine patients (92 women and 7 men, median age 71 years [65, 76]) were enrolled from January 2021 to December 2023. Among them, 22 had no prior treatment before romosozumab, while 77 had previous therapy (including 23 with a history of prior teriparatide therapy), with a median duration of 6 years [4, 11] of cumulative antiresorptive treatment. Over 12 months, romosozumab led to BMD changes of 10.3% [7.5, 15.5] at the lumbar spine, 3.1% [1.1, 5.8] at the total hip and 3.1% [0.5, 5.3] at the femoral neck, indicating notable variability. Significantly lower BMD responses were observed in pre-treated patients, with the duration of prior antiresorptive therapy inversely associated with BMD increases at the lumbar spine and hip. Other predictors of BMD changes at the total hip included baseline T-scores at the hip, body mass index and baseline CTX level, while the BMD response at the lumbar spine was associated with the lumbar spine T-score at baseline, age and baseline CTX level. CONCLUSION: Prior antiresorptive therapy blunted the BMD response to romosozumab, and the duration was correlated with BMD changes at both the lumbar spine and total hip.
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Different Perspectives of Drug Holiday and Combination Therapies When Treating Osteoporosis Abstract. Sequential and combined therapy for osteoporosis is challenging because of the many options, and difficult because robust fracture data are not available, especially for combination therapies, mostly because the studies are too small. The principle of sequential and combined therapy for osteoporosis is that osteoanabolic therapy (teriparatide [TPTD]), whether sequential or combined, leads to an increase in bone mineral density (BMD), especially in the lumbar spine. The only exception is the sequence of TPTD after denosumab (Dmab), which leads to a loss (transient) of BMD in both the lumbar spine and the hip; for this reason, this sequence should be avoided at all costs. A second principle is that the stronger and longer the antiresorptive pretreatment was, the more delayed and reduced the effect of osteoanabolic therapy (TPTD). A third principle is the need for antiresorptive retreatment after therapies with TPTD and Dmab or their combination to prevent vertebral fractures (Dmab) and maintain bone density (TPTD). An effect of osteoanabolic therapy with TPTD on BMD of the hip is expected only in combination with antiresorptive therapy (bisphosphonates, Dmab). If the antiresorptive therapy is not continued, there is a transient loss in the first months of osteoanabolic monotherapy, the more so the stronger the antiresorptive pretreatment was.