INTRODUCTION: Procollagen type I N-terminal propeptide (P1NP), a bone formation marker, reportedly predicts bone mineral density (BMD) response to teriparatide treatment in treatment-naive patients with osteoporosis. Results from a randomized, phase 3, open-label, active-controlled trial- STRUCTURE-showed that in patients previously treated with bisphosphonates, romosozumab led to gains in hip BMD, which were not observed with teriparatide. This post hoc analysis investigated the comparative utility of early changes in P1NP in predicting BMD response in patients who participated in the STRUCTURE trial, which enrolled patients who switched treatment frombisphosphonates to romosozumab/teriparatide. MATERIALS AND METHODS:Postmenopausal women (aged 55-90 years) with osteoporosis who had previously taken bisphosphonates were randomized to receive open-label subcutaneous romosozumab (210 mg once monthly; n = 218) or teriparatide (20 µg once daily; n = 218) for 12 months. BMD was assessed by dual-energy X-ray absorptiometry at the proximal femur and lumbar spine (LS) at baseline and months 6 and 12. To assess the utility of P1NP, the positive predictive value of increase from baseline in P1NP of > 10 µg/L at month 1 and achievement of various thresholds of percent change from baseline in BMD at month 12 were evaluated. RESULTS: Overall, 95% (191/202) of patients in the romosozumab group and 91% (183/201) in the teriparatide group demonstrated an increase in P1NP of > 10 µg/L from baseline at month 1. Among these patients, 18% and 3% of romosozumab-treated patients versus 60% and 12% of teriparatide-treated patients showed no increase from baseline (i.e., ≤ 0%) in total hip and LS BMD, respectively, at month 12. These data indicate that in patients switching from bisphosphonates to a bone-forming therapy, increases in P1NP do not help predict the hip BMD response. Although most patients treated with either teriparatide or romosozumab showed an increase in P1NP, the majority of patients on romosozumab showed an increase in hip BMD, while more than half of the patients on teriparatide did not. Teriparatide therapy did not increase total hip BMD in the majority of patients who transitioned from bisphosphonates to teriparatide. CONCLUSIONS: Thus, increases in P1NP were not predictive of BMD response in the teriparatide group because in approximately 60% of the patients who were administered teriparatide, the hip BMD decreased independent of the change in P1NP levels.
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INTRODUCTION: Procollagen type I N-terminal propeptide (P1NP), a bone formation marker, reportedly predicts bone mineral density (BMD) response to teriparatide treatment in treatment-naive patients with osteoporosis. Results from a randomized, phase 3, open-label, active-controlled trial- STRUCTURE-showed that in patients previously treated with bisphosphonates, romosozumab led to gains in hip BMD, which were not observed with teriparatide. This post hoc analysis investigated the comparative utility of early changes in P1NP in predicting BMD response in patients who participated in the STRUCTURE trial, which enrolled patients who switched treatment from bisphosphonates to romosozumab/teriparatide. MATERIALS AND METHODS: Postmenopausal women (aged 55-90 years) with osteoporosis who had previously taken bisphosphonates were randomized to receive open-label subcutaneous romosozumab (210 mg once monthly; n = 218) or teriparatide (20 µg once daily; n = 218) for 12 months. BMD was assessed by dual-energy X-ray absorptiometry at the proximal femur and lumbar spine (LS) at baseline and months 6 and 12. To assess the utility of P1NP, the positive predictive value of increase from baseline in P1NP of > 10 µg/L at month 1 and achievement of various thresholds of percent change from baseline in BMD at month 12 were evaluated. RESULTS: Overall, 95% (191/202) of patients in the romosozumab group and 91% (183/201) in the teriparatide group demonstrated an increase in P1NP of > 10 µg/L from baseline at month 1. Among these patients, 18% and 3% of romosozumab-treated patients versus 60% and 12% of teriparatide-treated patients showed no increase from baseline (i.e., ≤ 0%) in total hip and LS BMD, respectively, at month 12. These data indicate that in patients switching from bisphosphonates to a bone-forming therapy, increases in P1NP do not help predict the hip BMD response. Although most patients treated with either teriparatide or romosozumab showed an increase in P1NP, the majority of patients on romosozumab showed an increase in hip BMD, while more than half of the patients on teriparatide did not. Teriparatide therapy did not increase total hip BMD in the majority of patients who transitioned from bisphosphonates to teriparatide. CONCLUSIONS: Thus, increases in P1NP were not predictive of BMD response in the teriparatide group because in approximately 60% of the patients who were administered teriparatide, the hip BMD decreased independent of the change in P1NP levels.
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