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
ARTICLE HIGHLIGHTS
Research background

Chronic liver disease (CLD) patients are frequently complicated by osteoporosis, which causes fragility fractures and reduces health-related quality of life. Denosumab, a fully human anti-receptor activator of nuclear factor kappa-B ligand antibody, has been shown to be effective for osteoporosis and reduce the risk of osteoporotic fracture in the general population. However, the efficacy and safety of denosumab in CLD patients remains unknown.

Research motivation

Adherence to osteoporosis medication is a crucial problem, given that we frequently encounter poor adherence to prescribed osteoporosis medications in a real-world clinical setting, which can result in an increased risk of osteoporotic fractures. Denosumab treatment, subcutaneously administered once every 6 mo, is expected to improve medication adherence compared to weekly oral drugs. Recently, denosumab treatment is suggested to improve health-related quality of life in patients with osteoporosis. Therefore, denosumab has been the focus of public attention as an attractive treatment for osteoporosis.

Research objectives

The primary objective was to investigate the effect of denosumab on bone mineral density (BMD) and its safety in CLD patients with osteoporosis. The secondary objective was to assess the effect of denosumab on bone quality.

Research methods

We screened 405 CLD patients for osteoporosis and diagnosed osteoporosis in 138 (34.1%) patients. Among these patients with osteoporosis, 60 were finally included in the present study. Denosumab was administered once every 6 mo. Changes from baseline in BMD at the lumbar spine, femoral neck, and total hip were evaluated at 12 mo of denosumab treatment. Changes in bone turnover and quality were assessed by measurement of 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).

Research results

BMD values at the lumbar spine (+4.44%), femoral neck (+3.71%), and total hip (+4.03%) were significantly improved at 12 mo of treatment, regardless of differences in baseline characteristics. Denosumab treatment significantly suppressed bone turnover markers and improved a bone quality marker at 12 mo. No patients experienced fractures and adverse events, except for transient hypocalcemia.

Research conclusions

Denosumab treatment is effective and safe even in CLD patients with osteoporosis. Thus, denosumab is a beneficial treatment option for osteoporosis in CLD patients.

Research perspectives

This study opened up new possibilities for osteoporosis treatment in CLD patients. Specifically, it is noteworthy that denosumab treatment improved a bone quality marker along with BMD. A large-scale, randomized controlled study is needed to confirm the long-term effects of denosumab.