Metabolomic Insights into Amino Acid Signatures and Pathways Associated with Osteoporosis in Iranian Elderly Population

Hojat Dehghanbanadaki¹Azeen Soltani^2,3Ziba Majidi⁴Mostafa Rezaei-Tavirani⁵Gita Shafiee⁶Afshin Ostovar⁷Fatemeh Bandarian¹Niloufar Najjar¹Bagher Larijani⁸Iraj Nabipour⁹Patricia Khashayar¹⁰Noushin Fahimfar^7*Farideh Razi^1,11*

• ¹Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran, Tehran, Alborz, Iran
• ²School of Medicine, Tehran University of Medical Sciences, Tehran, Alborz, Iran
• ³Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran., Tehran, Alborz, Iran
• ⁴Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Alborz, Iran
• ⁵Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Tehran, Alborz, Iran
• ⁶Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Alborz, Iran
• ⁷Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran., Tehran, Alborz, Iran
• ⁸Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran., Tehran, Alborz, Iran
• ⁹The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran., Bushehr, Bushehr, Iran
• ¹⁰International Institute for Biosensing, University of Minnesota, Minneapolis, USA, Minneapolis, Minnesota, United States
• ¹¹Tehran University of Medical Sciences, Tehran, Iran

Background: Osteoporosis poses a serious health risk to the elderly, particularly in developing countries like Iran. We aimed to determine the 20-amino acids-signatures and pathways associated with osteoporosis in the Iranian elderly population.We analyzed the data from the Bushehr Elderly Health Program (BEHP). In the BEHP cohort, participants aged 50 and older in Bushehr, Iran were selected using a multistage stratified random sampling approach. We used logistic regression, pathway enrichment, and pathway impact analysis to determine the metabolites and pathways altered in osteoporosis. AUC-ROC curve analysis assessed the clinical significance of metabolites in differentiating between osteoporosis and control groups.Results: This study included 1916 participants (1097 women and 819 men). In women, glycine, citrulline, serine, and aspartic acid were associated with 27%, 25%, 23%, and 21% higher risk of osteoporosis. In men, tyrosine, leucine, valine, and lysine were related with a 24%, 22%, 22%, and 22% reduction in the risk of osteoporosis, respectively. The most impactful altered metabolite pathway among the osteoporotic individuals was "phenylalanine, tyrosine and tryptophan biosynthesis" in both genders. In women, citrulline had an AUC of 0.63 for distinguishing between individuals with osteoporosis and healthy controls. In men, valine, leucine, and tyrosine showed AUC values of 0.62, 0.61, and 0.61, respectively.Osteoporosis is associated with altered serum amino acids levels in both men and women. The condition is associated with several altered metabolic pathways, with "phenylalanine, tyrosine, and tryptophan biosynthesis" being the most important one. These metabolite signatures and pathways could be targeted for the prevention and management of osteoporosis in older adults.