Affiliation:
1. Department of Spine Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, China
2. Institute of Orthopedic Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, China
Abstract
Osteoporosis is common in postmenopausal women but is often asymptomatic until a fracture occurs, highlighting the importance of early screening and preventive interventions. This study aimed to develop molecular subtype risk stratification of postmenopausal osteoporosis and analyze the immune infiltration microenvironment. Microarray data for osteoporosis were downloaded and analyzed. Logistic and least absolute shrinkage and selection operator (LASSO) regression analyses were used to construct the molecular risk model. Circulating blood samples were collected from 10 enrolled participants to validate the key differentially expressed genes, and consistent clustering based on the expression profiles of candidate genes was performed to obtain molecular subtypes. Three key genes, CTNNB1, MITF, and TNFSF11, were obtained as variables and used to construct the risk model. External experimental validation showed substantial differences in the three key genes between patients with osteoporosis and the controls (p < 0.05). Three subtypes were obtained based on dimensionality reduction clustering results. Cluster 3 had significantly more patients with low bone mineral density (BMD), whereas Cluster 2 had significantly more patients with high BMD (p < 0.05). This study introduced a novel molecular risk model and subtype classification system, which is an evidence-based screening strategy that will guide the active prevention, early diagnosis, and treatment of osteoporosis in high-risk postmenopausal women.
Funder
National Natural Science Foundation of China
Key project of the Natural Science Basic Research Plan of Shaanxi Province
Strengthening Basic Disciplines Plan of Innovation Ability in Xi’an
Subject
General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
Reference42 articles.
1. Osteoporosis;Compston;Lancet,2019
2. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: Synopsis of a WHO report. WHO study group;Kanis;Osteoporos. Int.,1994
3. Reduced loosening rate and loss of correction following posterior stabilization with or without PMMA augmentation of pedicle screws in vertebral fractures in the elderly;Meier;Eur. J. Trauma Emerg. Surg.,2013
4. Wang, L., Yu, W., Yin, X., Cui, L., Tang, S., Jiang, N., Cui, L., Zhao, N., Lin, Q., and Chen, L. (2021). Prevalence of osteoporosis and fracture in China: The China Osteoporosis Prevalence Study. JAMA Netw. Open, 4.
5. Incident vertebral fractures and mortality in older women: A prospective study;Kado;Osteoporos. Int.,2003