Objective:To systematically evaluate the risks of osteonecrosis of the jaw induced by bone-modifying agents (BMAs) in breast cancer patients with bone metastasis.Methods:Randomized controlled trials (RCTs) of BMAs in the treatment of breast cancer bone metastasis, in which osteonecrosis of the jaw were evaluated as one of adverse outcome indicators, were collected by searching relevant databases at home and abroad (up to June 25, 2024). Cochrane risk of bias tool was used to evaluate the quality of the included studies. R software (version 4.2.3) was used to conduct Bayesian network meta-analysis, drawing the network evidence plot, the league map of pairwise comparison, and the surface under the cumulative ranking curve for the risks of osteonecrosis of the jaw induced by BMAs in breast cancer patients with bone metastasis, and ranking the risks of osteonecrosis of the jaw caused by different BMAs. The effect sizes of osteonecrosis of the jaw were expressed by hazard risk ( HR) and its 95% confidence interval ( CI). Results:A total of 12 RCTs were included in the analysis, involving 26 047 patients. BMAs were used in 18 503 patients, including zoledronic acid (in 6 202 patients), ibandronate (in 4 817 patients), clodronate (in 3 897 patients), and denosumab (in 3 587 patients); 7 544 patients were treated with placebo or not be intervened. Among 26 047 patients, 272 occurred osteonecrosis of the jaw. The incidence of osteonecrosis of the jaw was 1.44% (267/18 503) in BMA treated patients and 0.07% (5/7 544) in placebo/non-intervention patients, respectively. The results of the network meta-analysis showed that the HR (95% CI) of osteonecrosis of the jaw caused by denosumab, zoledronic acid, ibandronate and clodronate in breast cancer patients with bone metastases were 18.12 (10.03-35.75), 11.42 (6.03-22.86), 5.92 (2.78-13.22) and 2.73 (0.99-7.20), respectively, compared with the patients in the placebo or non-intervention group. Compared with zoledronic acid or denosumab, ibandronate and clodronate had lower risks of inducing osteonecrosis of the jaw. There was no statistically significant difference in the risk of inducing osteonecrosis of the jaw by denosumab and zoledronic acid. Conclusions:Denosumab and zoledronic acid have a higher risk of inducing osteonecrosis of the jaw. Among BMAs, clodronate and ibandronate should be preferred in treatment of breast cancer patients with bone metastasis who have risk factors of osteonecrosis of the jaw.

Objective:To systematically evaluate the risks of osteonecrosis of the jaw induced by bone-modifying agents (BMAs) in breast cancer patients with bone metastasis.Methods:Randomized controlled trials (RCTs) of BMAs in the treatment of breast cancer bone metastasis, in which osteonecrosis of the jaw were evaluated as one of adverse outcome indicators, were collected by searching relevant databases at home and abroad (up to June 25, 2024). Cochrane risk of bias tool was used to evaluate the quality of the included studies. R software (version 4.2.3) was used to conduct Bayesian network meta-analysis, drawing the network evidence plot, the league map of pairwise comparison, and the surface under the cumulative ranking curve for the risks of osteonecrosis of the jaw induced by BMAs in breast cancer patients with bone metastasis, and ranking the risks of osteonecrosis of the jaw caused by different BMAs. The effect sizes of osteonecrosis of the jaw were expressed by hazard risk ( HR) and its 95% confidence interval ( CI). Results:A total of 12 RCTs were included in the analysis, involving 26 047 patients. BMAs were used in 18 503 patients, including zoledronic acid (in 6 202 patients), ibandronate (in 4 817 patients), clodronate (in 3 897 patients), and denosumab (in 3 587 patients); 7 544 patients were treated with placebo or not be intervened. Among 26 047 patients, 272 occurred osteonecrosis of the jaw. The incidence of osteonecrosis of the jaw was 1.44% (267/18 503) in BMA treated patients and 0.07% (5/7 544) in placebo/non-intervention patients, respectively. The results of the network meta-analysis showed that the HR (95% CI) of osteonecrosis of the jaw caused by denosumab, zoledronic acid, ibandronate and clodronate in breast cancer patients with bone metastases were 18.12 (10.03-35.75), 11.42 (6.03-22.86), 5.92 (2.78-13.22) and 2.73 (0.99-7.20), respectively, compared with the patients in the placebo or non-intervention group. Compared with zoledronic acid or denosumab, ibandronate and clodronate had lower risks of inducing osteonecrosis of the jaw. There was no statistically significant difference in the risk of inducing osteonecrosis of the jaw by denosumab and zoledronic acid. Conclusions:Denosumab and zoledronic acid have a higher risk of inducing osteonecrosis of the jaw. Among BMAs, clodronate and ibandronate should be preferred in treatment of breast cancer patients with bone metastasis who have risk factors of osteonecrosis of the jaw.

Objective To evaluate cardiovascular benefits in patients with type 2 diabetes mellitus treated with the marketed 11 sodium-glucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like polypeptide-1 (GLP-1) receptor agonism by Bayesian network meta-analysis system. Methods MEDLINE, Embase and Cochrane Library were searched from the establishment of the database to 18 July 2020. The endpoint of the study was adverse cardiovascular events. The effect measures were hazard ratios (HR) and 95% credible intervals (CI). Results Compared with placebo, empagliflozin, canagliflozin, dapagliflozin, albiglutide, dulaglutide, exenatide, liraglutide, semaglutide reduced the risk of major adverse cardiovascular events in patients with type 2 diabetes with HR and 95% CI ranging between 0.75(0.60-0.95)~0.90(0.82-0.99); The risk of heart failure was reduced by empagliflozin, canagliflozin, dapagliflozin and ertugliflozin, with HR and 95%CI ranging between 0.64(0.49-0.82)~0.74(0.65-0.85); Empagliflozin, canagliflozin, dapagliflozin, exenatide, liraglutide and oral semaglutide reduced the incidence of all-cause mortality with HR and 95%CI ranging between 0.52(0.33-0.84)~0.89(0.80-0.99); Empagliflozin, canagliflozin, liraglutide and oral semaglutide can reduce the risk of cardiovascular death events, with HR and 95% CI ranging between 0.54(0.30-0.95)~0.83(0.71-0.96) . Conclusion The order of the cardiovascular benefits of SGLT-2 inhibitors or GLP-1 receptor agonists in patients with type 2 diabetes mellitus complicated with atherosclerotic cardiovascular disease are canagliflozin (the best), empagliflozin, dulaglutide, liraglutide; for patients with type 2 diabetes and heart failure. The order of the cardiovascular benefits for patients with type 2 diabetes and heart failure are empagliflozin, canagliflozin, ertugliflozin, and dapagliflozin.

Type 2 diabetes is a high risk factor for atherosclerotic cardiovascular disease. Studies have found that SGLT-2 inhibitor and GLP-1 receptor agonists have cardiovascular protective effects in patients with type 2 diabetes and cardiovascular disease. Therefore, from the aspects of cardiovascular safety test and its Meta-analysis and net-like Meta-analysis, the research progress of cardiovascular safety of SGLT-2 inhibitors and GLP-1 receptor agonists is summarized.

Objective To investigate the overall incidence and risk of hypertension in the treatment of cancer patients who receive anlotinib and compare the differences between anlotinib and other VEGFR inhibitors. Methods Pubmed, Embase, Cochrane Library, ASCO, CNKI, Wangfang, VIP and CBM databases were searched. Eligible studies were phase II and III prospective clinical trials on cancer patients who received anlotinib and had the hypertension data available. Meta-analysis for the incidence and risk of anlotinib was performed by using R software (version 3.6.0). SPSS software (version 26.0) was used to compare the difference between anlotinib and other VEGFR inhibitors. Results A total of 1387 cancer patients from 13 clinical trials were included in the Meta-analysis. The overall incidences of all grade and high grade hypertension in cancer patients who received anlotinib were about 47.1% (95%CI: 37.7%−56.6%) and 10.6% (95%CI: 7.4%−14.2%). The use of anlotinib was associated with significantly increased risk of all grade (RR=5.58, 95%CI: 2.29−13.60, P<0.01) and high grade hypertension (RR=27.78, 95%CI: 3.56−216.86, P<0.01). In addition, the incidence of high grade hypertension associated with anlotinib was similar to axitinib (RR=0.79, 95%CI: 0.61−1.02, P=0.066) and cabozantinib (RR=0.87, 95%CI: 0.67−1.13, P=0.290). The incidences of rest of other VEGFR inhibitors were lower than that of anlotinib. Conclusions There is a high incidence and significant risk of developing hypertension in cancer patients receiving anlotinib. Adequate monitoring and timely treatment of hypertension is recommended.

Objective To review and analysis the clinical manifestations, occurrence rules, treatment and outcomes of adverse drug reactions caused by anlotinib in order to provide reference for safety and reasonable use of anlotinib in clinical practice. Methods The cases reports of anlotinib were searched in Web of Science, Pubmed, Wiley Online Library, CNKI, Wanfang and VIP. The basic patient information, adverse reaction time, characters, treatment, outcomes and involved systems or organs were collected and analyzed. Results A total of 20 cases were collected, 10 females and 10 males, with a median age of 63.5(36～76 years old). Adverse drug reactions mostly occurred within 2 months after the medication. 52 cases occurred in total, involving 9 systems/organs, of which blood and lymphatic system disorders (all were hypertension) were the most common (21.2%). Conclusion After the administration of anlotinib, the incidence rate of adverse reactions in the cardiovascular system is relatively high. The medication process should be closely monitored, and attention should be paid to monitoring the potential adverse reactions mentioned in the instructions.