Objectives: Studies have shown that people with diabetes have a high risk of osteoporosis and fractures. The effect of diabetic medications on bone disease cannot be ignored. This meta-analysis aimed to compare the effects of two types of glucose-lowering drugs, metformin and thiazolidinediones (TZD), on bone mineral density and bone metabolism in patients with diabetes mellitus. Methods: This systematic review and meta-analysis were prospectively registered on PROSPERO, and the registration number is CRD42022320884. Embase, PubMed, and Cochrane Library databases were searched to identify clinical trials comparing the effects of metformin and thiazolidinediones on bone metabolism in patients with diabetes. The literature was screened by inclusion and exclusion criteria. Two assessors independently assessed the quality of the identified studies and extracted relevant data. Results: Seven studies involving 1656 patients were finally included. Our results showed that the metformin group had a 2.77% (SMD = 2.77, 95%CI [2.11, 3.43]; p < 0.00001) higher bone mineral density (BMD) than the thiazolidinedione group until 52 weeks; however, between 52 and 76 weeks, the metformin group had a 0.83% (SMD = −0.83, 95%CI: [−3.56, −0.45]; p = 0.01) lower BMD. The C-terminal telopeptide of type I collagen (CTX) and procollagen type I N-terminal propeptide (PINP) were decreased by 18.46% (MD = −18.46, 95%CI: [−27.98, −8.94], p = 0.0001) and 9.94% (MD = −9.94, 95%CI: [−16.92, −2.96], p = 0.005) in the metformin group compared with the TZD group.

Extrachromosomal circular DNA (eccDNA) was once thought to mainly exist in tumour cells, although it was later shown to be ubiquitous in healthy tissues as well. However, the characteristics and properties of eccDNA in healthy tissue or non-cancer tissue are not well understood. This study first analyses the properties, possible formation mechanisms and potential functions of eccDNA in osteoporotic or normal bone tissue. We used circle-seq to demonstrate the expression spectrum of the eccDNA in the bone tissue. A bioinformatics analysis was performed for the differentially expressed eccDNA, and it enriched the Hippo signalling pathway, PI3K-Akt signalling pathway, Ras signal-ling pathway and other signalling pathways that are closely related to osteoporosis (OP). Then, we used real-time polymerase chain reaction and Sanger sequencing to assess human bone marrow mesenchymal stem cells and obtained the base sequence of the eccDNA cyclization site. Overall, eccDNAs in bone tissue are common and may play a significant role in pathways connected to age-related osteoporosis progression.