Research progress in the relationships between homocysteine and osteoporosis

JIANG Shangkun; YANG Lan; LI Lijun; LI Xinhua

doi:10.3969/j.issn.1674-3806.2026.02.08

Abstract：Osteoporosis(OP)is a globally prevalent skeletal disease that imposes a substantial health and economic burden on society.Homocysteine(Hcy),as a metabolic intermediate of sulfur-containing amino acids,has been confirmed as an independent risk factor for cardiovascular and cerebrovascular diseases when its plasma levels are elevated-a condition known as hyperhomocysteinemia(HHcy).In recent years,some researches have found that HHcy is closely associated with decreased bone mineral density,increased fracture risk and disordered bone metabolism.However,its mechanism of action and clinical significance remain controversial.This paper systematically reviews the research progress in the relationships between Hcy and OP.Firstly,it sorts out epidemiological evidence to clarify the complex relationships between Hcy levels and bone mineral density as well as fracture risk,and summarizes the effects of genetic polymorphisms(e.g.,the MTHFR gene)and the levels of B vitamins on these relationships.Secondly,it deeply explores the molecular and cellular biological mechanisms,focusing on the core role of Hcy in disrupting bone metabolic balance via inducing oxidative stress and inflammatory responses,and interfering with specific signaling pathways.Finally,it evaluates the potential and challenges of reducing Hcy levels and preventing and treating OP through nutritional interventions(e.g.,supplement with folic acid and vitamin B12)and pharmacological interventions.This review aims to provide a comprehensive perspective for a deeper understanding of the role of Hcy in the pathogenesis of OP and offers a theoretical basis for studying new prevention and treatment strategies for OP.