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.
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.
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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BMD bone mineral density, BTM bone turnover marker, CTX C-telopeptide of type 1 collagen, DXA dual-energy X-ray absorptiometry, FN femoral neck, LS lumbar spine, P1NP procollagen type I N-terminal propeptide, QD once a day, QM once a month, SC subcutaneous, TH total hip.
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All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work, and have given their approval for this version to be published. Medical writing support was provided by Avinash Thakur and Frances Gambling of Cactus Communications and was funded by AABP. Qualified researchers may request data from Amgen clinical studies. Complete details are available at: https://wwwext.amgen.com/science/clinical-trials/clinical-data-transparency-practices/.
Amgen Inc., and UCB Pharma sponsored this study. All costs associated with the development of this manuscript, including medical writing, were funded by Amgen Inc., Astellas, and UCB Pharma.
Conflict of interest
Rajani Dinavahi, Cassandra E. Milmont, and Andreas Grauer are employees of Amgen Inc., USA, and report holding stocks of Amgen Inc. Etsuro Hamaya, Toshiyasu Hirama, and Yoichi Nakamura are employees of Amgen Astellas BioPharma K.K., Japan. Additionally, Etsuro Hamaya and Toshiyasu Hirama report holding stocks of Amgen Inc. Cesar Libanati is an employee of UCB Pharma, Belgium, and reports holding stocks of UCB Pharma. Junichi Takada and Akimitsu Miyauchi have nothing to disclose.
This study was done in accordance with International Conference on Harmonization Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. An independent ethics committee or institutional review board at each site approved the protocol, informed consent form, and all protocol amendments.
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Takada, J., Dinavahi, R., Miyauchi, A. et al. Relationship between P1NP, a biochemical marker of bone turnover, and bone mineral density in patients transitioned from alendronate to romosozumab or teriparatide: a post hoc analysis of the STRUCTURE trial. J Bone Miner Metab 38, 310–315 (2020). https://doi.org/10.1007/s00774-019-01057-1