Exploring the anti-osteoporotic potential of simvastatin and metformin: a comprehensive Mendelian randomization and animal experiment investigation  

作　　者：Hui Zhou Jin Zhang Pei-Pei He Yu Gou Xun Sun He-Tong Li 

机构地区：[1]Department of Pediatric Surgery,Shenzhen Baoan Women’s and Children’s Hospital,Shenzhen 518133,China [2]Department of Orthopedic Surgery,Shenzhen Hospital,Southern Medical University,Shenzhen 518000,China [3]Department of Orthopedic Surgery,Tianjin Hospital,Tianjin University,Tianjin 300211,China.

出　　处：《Biomedical Engineering Communications》2024年第4期29-38,共10页生物医学工程通讯

基　　金：funded by the Applied Basic Research Foundation of Tianjin(22JCQNJC00230);the Beijing-Tianjin-Hebei Basic Research Cooperation Project(23JCZXJC00050/J230007);the Tianjin Health and Technology Project(TJWJ2024QN056)。

摘　　要：Background:Both simvastatin and metformin have demonstrated potential efficacy in osteoporosis(OP)treatment.However,there is a lack of systematic studies comparing their anti-osteoporotic effects.This study aims to compare the effects of simvastatin and metformin on OP through Mendelian randomization(MR)studies and animal experiments.Methods:Initially,we will analyze the causal impact of simvastatin or metformin treatment on OP prevalence and three common clinical OP diagnostic markers(bone mineral density(BMD),serum osteocalcin(OCN),and tartrate-resistant acid phosphatase(TRAP)levels)using genome-wide association study(GWAS)summary statistics.Additionally,we established animal models to further analyze and compare the anti-osteoporosis effects of simvastatin and metformin.8 male C57BL/6J mice(3-month-old)and 24 male C57BL/6J mice(18-month-old)were treated with simvastatin or metformin for 12 weeks.OP pathology was assessed using histology,immunohistochemistry,biomechanical tests,micro-computed tomography,and osteogenic differentiation assays.Results:In the MR analysis,metformin treatment was significantly associated with lower OP prevalence(OR(95%CI)=0.933(0.902–0.965),β=-0.0694,P<0.001)and higher BMD(OR(95%CI)=3.719(1.750–7.908),β=1.3136,P<0.001).In the animal experiment,both drugs increased bone mass,improved bone microstructure,and promoted osteoblast differentiation.However,metformin appeared more effective in several aspects.It significantly inhibited bone marrow adipocyte and osteoclast differentiation in aged mice compared to simvastatin.Additionally,metformin better promoted the expression of osteoprotegerin(OPG)and collagen type I(Col-I)in bone tissue and maintained the structure and biomechanical properties of cancellous bone.Conclusion:Both drugs significantly preserved bone homeostasis.Particularly,compared with simvastatin,metformin exhibited superior effects in inhibiting adipogenesis,enhancing the OPG/RANKL pathway,and promoting cancellous bone reconstruction.Metformin may serve as a valuabl

关 键 词：senile osteoporosis Mendelian randomization animal study SIMVASTATIN METFORMIN 

分 类 号：X70[环境科学与工程—环境工程]