Data on the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on fracture risk are conflicting. Here, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effects of DPP-4 inhibitors. Electronic databases were searched for relevant published articles, and unpublished studies presented at ClinicalTrials.gov were searched for relevant clinical data. Eligible studies included prospective randomized trials evaluating DPP-4 inhibitors versus placebo or other anti-diabetic medications in patients with type 2 diabetes. Study quality was determined using Jadad scores. Statistical analyses were performed to calculate the risk ratios (RRs) and 95% confidence intervals (CIs) using fixed-effects models. There were 62 eligible RCTs with 62,206 participants, including 33,452 patients treated with DPP-4 inhibitors. The number of fractures was 364 in the exposed group and 358 in the control group. The overall risk of fracture did not differ between patients exposed to DPP-4 inhibitors and controls (RR, 0.95; 95% CI, 0.83–1.10; P = 0.50). The results were consistent across subgroups defined by type of DPP-4 inhibitor, type of control, and length of follow-up. The study showed that DPP-4 inhibitor use does not modify the risk of bone fracture compared with placebo or other anti-diabetic medications in patients with type 2 diabetes.

Huangqi Sanxian decoction (HQSXD) is routinely used for the treatment of osteoporosis in the Chinese traditional healthcare system. However, the targets and mechanism underlying the effect of HQSXD on osteoporosis have not been documented. In the present study, seropharmacology and proteomic approaches (two-dimensional gel electrophoresis combined with mass spectrometry) were used to investigate the effects and possible target proteins of HQSXD on osteoblast. We found that HQSXD-treated rat serum significantly enhanced osteoblast proliferation, differentiation, and mineralization. In HQSXD-S-treated osteoblasts, there were increases in the expression of N-formyl peptide receptor 2 and heparan sulfate (glucosamine) 3-O-sulfotransferase 3A1 and reduction in the expression of alpha-spectrin, prohibitin, and transcription elongation factor B (SIII), polypeptide 1. The identified proteins are associated with cell proliferation, differentiation, signal transcription, and cell growth. These findings might provide valuable insights into the mechanism of antiosteoporotic effect affected by HQSXD treatment in osteoblasts.

Chronic inflammatory liver conditions, such as nonalcoholic fatty liver disease (NAFLD), are frequently exacerbated by oxidative stress, rendering the neutralization of reactive oxygen species (ROS) crucial for their amelioration. Oral administration of nanoparticles (NPs) presents an optimal strategy for NAFLD management due to its convenience. This research aimed to overcome the poor water solubility and low bioavailability of icariin (ICA) by engineering an oral nanosystem, ICA-loaded poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA) NPs with chitosan (CS) and mannose surface modification (ICA-NPs), to augment ICA's antioxidant potency against NAFLD. Methods involved comprehensive in vitro characterization of ICA-NPs (including dispersibility, biocompatibility, HepG2 targeting, and ROS scavenging capabilities) and in vivo studies in high-fat diet (HFD)-induced NAFLD mice, assessing liver accumulation, ROS scavenging, and antiobesity effects across multiple experimental groups. Results demonstrated that this targeted oral NP system significantly amplified ICA's therapeutic impact, leading to substantial reductions in body weight, diminished white adipose tissue accumulation, decreased hepatic lipid content, improved hepatic function, and a notable suppression of ROS in the livers of NAFLD-afflicted mice. In conclusion, by harnessing the precision of targeted delivery, this oral nanosystem not only enhances ICA's therapeutic efficacy but also establishes a safe and effective platform for the oral administration of herbal remedies for liver conditions, suggesting a promising avenue for advancing herbal medicine in liver disease treatment.