Metabolomic Insights Into Amino Acid Signatures and Pathways Associated With Osteoporosis in Iranian Elderly Population Publisher



Dehghanbanadaki H¹ ; Soltani A^{2, 3} ; Majidi Z⁴ ; Rezaeitavirani M⁵ ; Shafiee G⁶ ; Ostovar A⁷ ; Bandarian F¹ ; Najjar N¹ ; Larijani B⁸ ; Nabipour I⁹ ; Khashayar P¹⁰ ; Fahimfar N⁷ ; Razi F¹ Show Affiliations
Source: Frontiers in Medicine Published:2025

Abstract

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. Methods: 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 (1,097 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. Conclusion: 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. Copyright © 2025 Dehghanbanadaki, Soltani, Majidi, Rezaei-Tavirani, Shafiee, Ostovar, Bandarian, Najjar, Larijani, Nabipour, Khashayar, Fahimfar and Razi.