CT-derived vertebral bone mineral density is a useful biomarker to predict COVID-19 outcome

Shuhei Azekawa; Tomoki Maetani; Shotaro Chubachi; Takanori Asakura; Naoya Tanabe; Yusuke Shiraishi; Ho Namkoong; Hiromu Tanaka; Takashi Shimada; Takahiro Fukushima; Shiro Otake; Kensuke Nakagawara; Mayuko Watase; Hideki Terai; Mamoru Sasaki; Soichiro Ueda; Yukari Kato; Norihiro Harada; Shoji Suzuki; Shuichi Yoshida; Hiroki Tateno; Yoshitake Yamada; Masahiro Jinzaki; Toyohiro Hirai; Yukinori Okada; Ryuji Koike; Makoto Ishii; Akinori Kimura; Seiya Imoto; Satoru Miyano; Seishi Ogawa; Takanori Kanai; Koichi Fukunaga

doi:10.1016/j.bone.2024.117095

CT-derived vertebral bone mineral density is a useful biomarker to predict COVID-19 outcome

Bone. 2024 Apr 8:184:117095. doi: 10.1016/j.bone.2024.117095. Online ahead of print.

Authors

Shuhei Azekawa¹, Tomoki Maetani², Shotaro Chubachi³, Takanori Asakura⁴, Naoya Tanabe², Yusuke Shiraishi², Ho Namkoong⁵, Hiromu Tanaka¹, Takashi Shimada¹, Takahiro Fukushima¹, Shiro Otake¹, Kensuke Nakagawara¹, Mayuko Watase¹, Hideki Terai¹, Mamoru Sasaki⁶, Soichiro Ueda⁶, Yukari Kato⁷, Norihiro Harada⁷, Shoji Suzuki⁸, Shuichi Yoshida⁸, Hiroki Tateno⁸, Yoshitake Yamada⁹, Masahiro Jinzaki⁹, Toyohiro Hirai¹⁰, Yukinori Okada¹¹, Ryuji Koike¹², Makoto Ishii¹³, Akinori Kimura¹⁴, Seiya Imoto¹⁵, Satoru Miyano¹⁶, Seishi Ogawa¹⁷, Takanori Kanai¹⁸, Koichi Fukunaga¹

Affiliations

¹ Division of Pulmonary Medicine, Department of Medicine, Keio University, School of Medicine, Tokyo, Japan.
² Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
³ Division of Pulmonary Medicine, Department of Medicine, Keio University, School of Medicine, Tokyo, Japan. Electronic address: bachibachi472000@z6.keio.jp.
⁴ Division of Pulmonary Medicine, Department of Medicine, Keio University, School of Medicine, Tokyo, Japan; Department of Clinical Medicine (Laboratory of Bioregulatory Medicine), Kitasato University School of Pharmacy, Tokyo, Japan; Department of Respiratory Medicine, Kitasato University Kitasato Institute Hospital, Tokyo, Japan. Electronic address: takanori.asakura@keio.jp.
⁵ Division of Pulmonary Medicine, Department of Medicine, Keio University, School of Medicine, Tokyo, Japan; Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan.
⁶ Internal Medicine, JCHO (Japan Community Health Care Organization) Saitama Medical Center, Saitama, Japan.
⁷ Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan.
⁸ Department of Pulmonary Medicine, Saitama City Hospital, Saitama, Japan.
⁹ Department of Radiology, Keio University School of Medicine, Tokyo, Japan.
¹⁰ Department of Respiratory Medicine, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
¹¹ Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan; Department of Genome Informatics, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan; Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
¹² Health Science Research and Development Center, Tokyo Medical and Dental University, Tokyo, Japan.
¹³ Division of Pulmonary Medicine, Department of Medicine, Keio University, School of Medicine, Tokyo, Japan; Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
¹⁴ Institute of Research, Tokyo Medical and Dental University, Tokyo, Japan.
¹⁵ Division of Health Medical Intelligence, Human Genome Center, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
¹⁶ M&D Data Science Center, Tokyo Medical and Dental University, Tokyo, Japan.
¹⁷ Department of Pathology and Tumor Biology, Kyoto University, Kyoto, Japan; Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan.
¹⁸ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.

PMID: 38599262
DOI: 10.1016/j.bone.2024.117095

Abstract

The low vertebral bone computed tomography (CT) Hounsfield unit values measured on CT scans reflect low bone mineral density (BMD) and are known as diagnostic indicators for osteoporosis. The potential prognostic significance of low BMD defined by vertebral bone CT values for the coronavirus disease 2019 (COVID-19) remains unclear. This study aimed to assess the impact of BMD on the clinical outcome in Japanese patients with COVID-19 and evaluate the association between BMD and critical outcomes, such as high-flow nasal cannula, non-invasive and invasive positive pressure ventilation, extracorporeal membrane oxygenation, or death. We examined the effects of COVID-19 severity on the change of BMD over time. This multicenter retrospective cohort study enrolled 1132 inpatients with COVID-19 from the Japan COVID-19 Task Force database between February 2020 and September 2022. The bone CT values of the 4th, 7th, and 10th thoracic vertebrae were measured from chest CT images. The average of these values was defined as BMD. Furthermore, a comparative analysis was conducted between the BMD on admission and its value 3 months later. The low BMD group had a higher proportion of critical outcomes than did the high BMD group. In a subanalysis stratifying patients by epidemic wave according to onset time, critical outcomes were higher in the low BMD group in the 1st-4th waves. Multivariable logistic analysis of previously reported factors associated with COVID-19 severity revealed that low BMD, chronic kidney disease, and diabetes were independently associated with critical outcomes. At 3 months post-infection, patients with oxygen demand during hospitalization showed markedly decreased BMD than did those on admission. Low BMD in patients with COVID-19 may help predict severe disease after the disease onset. BMD may decrease over time in patients with severe COVID-19, and the impact on sequelae symptoms should be investigated in the future.

Keywords: Biomarkers; Bone density; Post-acute COVID-19 syndrome; SARS-CoV-2; X-ray computed tomography.