Verlauf der Knochendichte und der Knochenumbaumarker unter der Therapie mit Romosozumab
by Johannes Dösereck
Date of Examination:2025-07-02
Date of issue:2025-05-20
Advisor:Prof. Dr. Heide Siggelkow
Referee:Prof. Dr. Heide Siggelkow
Referee:PD Dr. Daniel Hoffmann
Persistent Address:
http://dx.doi.org/10.53846/goediss-11270
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Abstract
English
As a result of demographic changes and the associated increase in life expectancy, pharmacological treatment of osteoporosis will continue to gain importance in the coming years. Currently, the monoclonal antibody romosozumab represents the most effective form of therapy for women with postmenopausal osteoporosis. In the two pivotal approval studies (FRAME and ARCH), increases in bone mineral density (BMD) at the lumbar spine by 13,3% and 13,7%, and at the total hip by 6,8% and 6,2%, respectively, were demonstrated. In this study, data from 68 female patients who were treated with romosozumab for postmenopausal osteoporosis at the Endokrinologikum Göttingen were retrospectively analyzed. A significant increase in BMD was observed at the lumbar spine by 22,2% and at the total left hip by 11,1% (p<0,001). Thus, this real-world clinical study showed a greater increase in BMD than the approval studies. When comparing the patient populations, it became apparent that our patients had the lowest baseline BMD at the lumbar spine (T-score: -3,6 SD) and, along with the ARCH patients, the lowest BMD at the total left hip (T-score: -2,8 SD) before therapy. Additionally, our patients were 6,2 years younger than those in the FRAME study and had more vertebral fractures (60,3% vs. 18,7%), suggesting a sicker cohort compared to the FRAME study. Compared to the ARCH study, our patients were also 9,7 years younger but had fewer vertebral fractures (ARCH study: 96,2%). While the participants in the approval studies did not receive prior treatment, 69,1% of the patients in our study had undergone prior therapy for 4,8 years. Among them, patients with previous teriparatide treatment had the greatest BMD increase, while those previously treated with denosumab showed the least improvement. We found that patients experienced a similar BMD increase regardless of the presence of secondary risk factors. Furthermore, it was observed that baseline BAP concentrations correlated with the BMD increase at the total left hip (r=0,4; p<0,05). Patients in our study also had a higher calcium intake than those in the approval studies. It is therefore conceivable that the higher baseline BAP levels and increased calcium intake contributed to the greater BMD increase. Additionally, the younger age of our patients may have played a role in this improved outcome. Analysis of bone turnover markers revealed a significant increase in the bone formation markers P1NP (p<0,01), osteocalcin (p<0,05), and BAP (p<0,001) after one month of therapy. These markers fell below baseline levels after six to nine months, clearly demonstrating the initial osteoanabolic effect of romosozumab. The antiresorptive effect of romosozumab was reflected by the course of the bone resorption marker CTX, whose concentration decreased after initiation of romosozumab therapy. Moreover, baseline levels of remodeling markers provided insights into the type of prior treatment. During romosozumab therapy, only one patient sustained a traumatic—i.e., non-osteoporotic—fracture.
Keywords: Romosozumab; bone mineral density; bone turnover markers
