Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2020; 26(33): 4960-4971
Published online Sep 7, 2020. doi: 10.3748/wjg.v26.i33.4960
Effects of denosumab treatment in chronic liver disease patients with osteoporosis
Chisato Saeki, Mitsuru Saito, Tsunekazu Oikawa, Masanori Nakano, Yuichi Torisu, Masayuki Saruta, Akihito Tsubota
Chisato Saeki, Tsunekazu Oikawa, Masanori Nakano, Yuichi Torisu, Masayuki Saruta, Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo 1058461, Japan
Mitsuru Saito, Department of Orthopaedic Surgery, The Jikei University School of Medicine, Tokyo 1058461, Japan
Akihito Tsubota, Core Research Facilities, Research Center for Medical Science, The Jikei University School of Medicine, Tokyo 1058461, Japan
Author contributions: Saeki C and Saito M participated in the conception and design of the study; Saeki C, Oikawa T, Nakano M, and Torisu Y performed the acquisition, analysis, and interpretation of the data; Saeki C and Tsubota A drafted the manuscript; Saito M, Saruta M, and Tsubota A interpreted the data and revised the manuscript; Tsubota A substantively revised and completed the manuscript; all authors read and approved the manuscript.
Institutional review board statement: This project was approved by the ethics committee of the Jikei University School of Medicine (approval No. 28-194) and Fuji City General Hospital (approval No. 162).
Informed consent statement: All the participants gave their written informed consent.
Conflict-of-interest statement: The authors declare no conflict of interests.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Chisato Saeki, MD, PhD, Doctor, Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo 1058461, Japan. chisato@jikei.ac.jp
Received: May 19, 2020
Peer-review started: May 19, 2020
First decision: July 29, 2020
Revised: August 3, 2020
Accepted: August 26, 2020
Article in press: August 26, 2020
Published online: September 7, 2020
Processing time: 108 Days and 3 Hours
Abstract
BACKGROUND

Effective treatment of osteoporosis is essential for improving morbidity and health-related quality of life in chronic liver disease (CLD) patients. Denosumab has been shown to increase bone mineral density (BMD) and decrease the risk of osteoporotic fracture in the general population. However, there are few reports evaluating the efficacy of denosumab in CLD patients.

AIM

To investigated the effects and safety of denosumab in CLD patients with osteoporosis.

METHODS

Sixty CLD patients with osteoporosis were subcutaneously administered denosumab once every 6 mo. The study period for evaluating efficacy and safety was 12 mo. Changes from baseline in BMD at the lumbar spine, femoral neck, and total hip were evaluated at 12 mo of denosumab treatment. Bone turnover and quality were assessed by measuring serum tartrate-resistant acid phosphatase-5b (bone resorption marker), serum total procollagen type I N-terminal propeptide (bone formation maker), and plasma pentosidine (bone quality marker).

RESULTS

Among the 405 CLD patients, 138 (34.1%) patients were diagnosed with osteoporosis; among these, 78 patients met the exclusion criteria and thus 60 patients were finally included in the present study. The median percentage changes from baseline to 12 mo of denosumab treatment in BMD at the lumbar spine, femoral neck, and total hip were +4.44%, +3.71%, and +4.03%, respectively. Denosumab significantly improved BMD, regardless of sex, patient age, and presence of liver cirrhosis. Serum tartrate-resistant acid phosphatase-5b and procollagen type I N-terminal propeptide levels constantly and significantly declined after denosumab treatment (P < 0.001). Plasma pentosidine levels were also significantly lower at 12 mo of treatment (P = 0.010). No patients experienced fractures and moderate-to-severe adverse events, except for transient hypocalcemia.

CONCLUSION

Denosumab treatment was safe and increased BMD, suppressed bone turnover, and improved bone quality marker levels in CLD patients with osteoporosis, irrespective of differences in baseline characteristics.

Keywords: Chronic liver disease, Denosumab, Osteoporosis, Bone mineral density, Bone turnover, Bone quality

Core tip: Osteoporosis is a common complication that causes fragility fractures and reduces health-related quality of life in patients with chronic liver disease. Denosumab treatment significantly increased bone mineral density at the lumbar spine, femoral neck, and total hip; suppressed bone turnover markers; and improved a bone quality marker at 12 mo, regardless of differences in baseline characteristics. No patients experienced fractures and adverse events, except for transient hypocalcemia. Denosumab treatment is safe and beneficial treatment option for osteoporosis in chronic liver disease patients.