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Impact of denosumab on cardiovascular calcification in patients with secondary hyperparathyroidism undergoing dialysis: a pilot study

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Abstract

Summary

The receptor activator of nuclear factor-kappa B ligand (RANKL)/RANK/osteoprotegerin system is dysregulated in hyperparathyroid bone diseases. The introduction of denosumab preceding elective surgery as an alternative option when surgery is not possible immediately.

Introduction

The effects of denosumab on vascular calcification in patients with chronic renal failure and low bone mass have been a subject of interest. Therefore, this investigation aimed to determine the short-term changes in vascular calcification after denosumab treatment using a serial electrocardiography-gated computed tomography (CT) to measure coronary artery calcification (CAC) in patients with secondary hyperparathyroidism (SHPT) and low bone mass.

Methods

This 6-month study enrolled patients with SHPT and low bone mass (T-score < − 2.5) owing to dialysis. The 2 groups administered denosumab at a dose of 60 mg (denosumab group), and conventional treatment (control group) had 21 patients each. All patients underwent CT scans at baseline and at the follow-up examination at 6 months to determine the bone mineral density and CAC.

Results

The control group demonstrated a significant increase in Agatston scores (187.79 ± 72.27) (P = 0.004). However, no significant change was noted in the denosumab group (P = 0.41). In the denosumab group, only the baseline serum alkaline phosphatase levels correlated negatively with changes in the CAC score (P = 0.01); the baseline alkaline phosphatase levels were the deciding biomarkers for non-responsive CAC scores by Berry Criteria after denosumab treatment (P = 0.02). The denosumab group demonstrated significantly increased bone mineral density in the femoral neck and lumbar spine (P < 0.01).

Conclusion

The findings provide evidence that denosumab may suppress the progression of CAC and also regress osseous calcification in severe cases of high bone turnover.

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Data availability

The datasets used, analyzed, or both during the current study are available from the corresponding author upon reasonable request.

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Acknowledgments

The authors would like to thank the participating nephrology and radiology departments and their personnel, all members of the Kaohsiung Veterans General Hospital who have been instrumental to the data collection, and data entry staff, who make the study possible. The authors are indebted to the Department of Medical Education and Research and Research Center of Medical Informatics at Kaohsiung Veterans General Hospital for assistance with data analysis.

Funding

This study was funded by an operating grant (VGHKS 104-69, 105-80, and 107-117) from Kaohsiung Veterans General Hospital and the Ministry of Science and Technology (MOST 108-2314-B-010-019-MY3).

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Correspondence to M.-T. Wu.

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Conflicts of interest

Chien-Liang Chen, Nai-Ching Chen, Fu-Zong Wu, and Ming-Ting Wu declare that they have no conflict of interest.

Ethical approval

Ethical approval for this pilot study was provided by the independent ethics committee of the Kaohsiung Veterans General Hospital (VGHKS18-CT-19), and written informed consent was obtained from all patients. This study is registered with the ISRCTN registry, number ISRCTN92563400.

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Chen, CL., Chen, NC., Wu, FZ. et al. Impact of denosumab on cardiovascular calcification in patients with secondary hyperparathyroidism undergoing dialysis: a pilot study. Osteoporos Int 31, 1507–1516 (2020). https://doi.org/10.1007/s00198-020-05391-3

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  • DOI: https://doi.org/10.1007/s00198-020-05391-3

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