Sclerostin as a Genetic Determinant of Trabecular Bone Score in Postmenopausal Women: The Bushehr Elderly Health (BEH) Program

Abstract

Background: Sclerostin, a protein encoded by the SOST gene, is an important genetic risk factor for osteoporosis in postmenopausal women. This study was conducted on the Iranian postmenopausal women, to investigate the association between this gene and the Trabecular Bone Score (TBS) as a novel index used for assessing osteoporosis. Methods: The present study, conducted in 2024, was performed on 1071 women aged 60 years and older who participated in the Bushehr Elderly Health (BEH) program. The associations between seven independent Single Nucleotide Polymorphisms (SNPs) within the SOST gene and mean TBS of L1 to L4 were examined using the additive, dominant, and recessive models. Genetic risk scores (GRS) were calculated for each postmenopausal woman based on the coefficient regressions derived from the additive and dominant models. The relationship between the GRS quartiles and TBS was evaluated using a linear regression model. Results: After adjusting for age and Body Mass Index (BMI), the associations between the rs2023794-C and TBS were significant in the additive (β = 0.03, P= 4.7×10-5, PFDR= 0.0003) and dominant (β = 0.032, P= 5×10-5, PFDR= 0.0003) models. The GRS derived from both additive and dominant models were related to TBS (P<0.05). For the additive model GRS, TBS showed an average increase of 0.022 score for the fourth quartile in comparison with the first quartile, adjusted for age, BMI, type 2 diabetes mellitus (T2DM), and smoking status (P=0.001). Conclusion: SOST gene is associated with TBS and may have implications for personalized medicine. Targeting sclerostin through SOST could offer a therapeutic approach in managing osteoporosis in high-risk postmenopausal women.