As a bone-confined chronic degenerative disorder, the progression of osteoporosis is characterized by abnormal crosstalk between osteoblasts and osteoclasts, leading to an imbalance of bone remodeling in adults. Several studies reported that arachidonic acid ester 12 lipoxygenase (ALOX12) acts as a regulator in bone genesis by participating in the activation of the peroxisome proliferatoractivated receptor g (PPARG) pathway through its reaction product. A positive correlation between ALOX12 gene polymorphism and bone mineral density (BMD) has also been verified, indicating that serum Se deficiency was accompanied by some ALOX12 variation, contributing to the peak BMD and the development of osteoporosis. Another multidomain enzyme involved in DNA methylation, cystathionine beta-synthase (CBS), regulates the conversion of homocysteine into glutathione. Mutations in CBS lead to the production of more sulfur end-products from the methylation cycle. The newborn CBS-knockout (KO) mice who received treatment with recombinant poly ethylene glycol human truncated CBS (PEG-CBS) were rescued from osteoporosis-like symptoms. In patients with osteoporosis, the expression of CBS was found to be downregulated in femur tissues, leading to a lower BMD. These findings support the idea that DNA methylation-related enzymes, including ALOX12 and CBS, are important for the occurrence of osteoporosis. However, the specificities in these 2 genes of osteoporosis human samples are largely unclear. Thus, we aimed to explore the impact of the DNA methylation level on select candidate genes in osteoporosis. These results will be of great help in optimizing treatments and for the early diagnosis of osteoporosis, complying with the principles of precision medicine.