Both osteoporosis and cardiovascular disease (CVD) share similar pathways in pathophysiology and are intercorrelated with increased morbidity and mortality in elderly women. Although denosumab and raloxifene are the current guideline-based pharmacological treatments, their impacts on cardiovascular protection are yet to be examined. This study aimed to compare mortality rate and cardiovascular events between denosumab and raloxifene in osteoporotic women. Risks of CVD development and all-cause mortality were estimated using Cox proportional hazard regression. A total of 7972 (3986 in each group) women were recruited between January 2003 and December 2018. No significant difference between denosumab and raloxifene was observed in composite CVDs, myocardial infarction, or congestive heart failure. However, comparison of the propensity score matched cohorts revealed that patients with proportion of days covered (PDC) ≥60% had lower incidence of ischemic stroke in the denosumab group than that in the raloxifene group (aHR 0.68; 95% CI 0.47–0.98; p = 0.0399). In addition, all-cause mortality was lower in the denosumab group than in the raloxifene group (aHR 0.59; 95% CI 0.48–0.72; p = 0.001), except in patients aged <65 y/o in this cohort study. We concluded that denosumab is superior to raloxifene in lowering risks of all-cause mortality and certain ischemic strokes in osteoporotic women.

Background: Peritoneal dialysis (PD) is an established kidney replacement therapy, but long-term exposure to bioincompatible dialysate, uremic toxins, recurrent peritonitis, glucose degradation products, oxidative stress, and sterile inflammation progressively remodels the peritoneal membrane and contributes to peritoneal fibrosis (PF). This review summarizes the molecular basis of PF in PD and evaluates the therapeutic rationale for incretin-based interventions beyond weight loss and glycemic control. Methods: This narrative review synthesizes mechanistic, translational, and clinically relevant literature on PD-associated PF, with emphasis on DPP-4 biology, GLP-1 receptor agonism, inflammatory and oxidative signaling, angiogenesis, mesothelial-to-mesenchymal transition, glycemic management in PD, and selected author-conducted translational studies interpreted alongside independent evidence. Results: Available evidence supports a model in which DPP-4 activation, altered GLP-1/GLP-1R signaling, TGF-β/Smad3-driven mesothelial transition, NF-κB/MyD88 inflammation, ROS-mediated oxidative stress, angiogenesis, apoptosis, and cytoskeletal remodeling converge to impair peritoneal membrane integrity. DPP-4 inhibition, exendin-4, and dulaglutide attenuated these pathways in experimental models, while GLP-1 receptor agonists have established metabolic benefits in appropriate diabetic and obese populations. Conclusions: Direct clinical evidence that incretin-based therapies prevent or treat peritoneal fibrosis in humans undergoing PD is currently lacking. Therefore, peritoneal membrane protection, reduced ultrafiltration failure, and improved technique survival should be regarded as investigational, hypothesis-generating possibilities that require prospective clinical validation.