Clinical efficacy and safety of drug interventions for primary and secondary prevention of osteoporotic fractures in postmenopausal women: Network meta-analysis followed by factor and cluster analysis.

We aimed to evaluate the comparative efficacy and safety of drugs respectively for primary prevention and secondary prevention of osteoporotic fractures in postmenopausal women (PMW), and to further identify the optimal intervention(s) respectively for the two groups when efficacy and safety both considered. We searched three databases. Bayesian network meta-analyses were conducted for two efficacy outcomes (vertebral fractures and nonvertebral fractures) and two safety outcomes (tolerability and acceptability) respectively in primary prevention group and secondary prevention group. We synthesized hazard ratios (HRs) and 95% confidence intervals (CIs) for nonvertebral fractures, and risk ratios (RRs) for three others. Factor and cluster analyses on surface under the cumulative ranking curve (SUCRA) values were conducted to identify the best intervention(s) with efficacy and safety both considered. The study protocol has been registered in PROSPERO. We included 57 randomized trials involving fifteen anti-osteoporotic interventions and 106320 PMW. For primary prevention, only zoledronate (once per 18 months) reduced both vertebral (RR 0.46, 95% CI 0.28-0.74) and nonvertebral (HR 0.66, 95% CI 0.51-0.85) fractures. For secondary prevention, abaloparatide, alendronate, denosumab, lasofoxifene, risedronate, romosozumab, teriparatide, and zoledronate (once per 12 months) reduced both vertebral (RRs: from 0.17 to 0.62) and nonvertebral (HRs: from 0.54 to 0.81) fractures. PTH (1-84) and abaloparatide increased withdrawal risk. Romosozumab, teriparatide, denosumab and risedronate, with the greatest composite scores, constituted the optimal cluster having both superior efficacy and superior safety. Zoledronate used at 5 mg per 18 months, with the similar safety as placebo, is the only drug intervention which has been shown to significantly reduce both vertebral and nonvertebral fractures for primary prevention of osteoporotic fractures in PMW; while romosozumab, teriparatide, denosumab, and risedronate are the optimal treatments for secondary prevention when efficacy and safety both considered. A limitation is that safety outcomes failed to consider the severity of adverse effects

SS-31 Protects Liver from Ischemia-Reperfusion Injury via Modulating Macrophage Polarization

Ischemia-reperfusion injury (IRI) is a common complication in liver surgeries. It is a focus to discover effective treatments to reduce ischemia-reperfusion injury. Previous studies show that oxidative stress and inflammation response contribute to the liver damage during IRI. SS-31 is an innovated mitochondrial-targeted antioxidant peptide shown to scavenge reactive oxygen species and decrease oxidative stress, but the protective effects of SS-31 against hepatic IRI are not well understood. The aim of our study is to investigate whether SS-31 could protect the liver from damages induced by IRI and understand the protective mechanism. The results showed that SS-31 treatment can significantly attenuate liver injury during IRI, proved by HE staining, serum ALT/AST, and TUNEL staining which can assess the degree of liver damage. Meanwhile, we find that oxidative stress and inflammation were significantly suppressed after SS-31 administration. Furthermore, the mechanism revealed that SS-31 can directly decrease ROS production and regulate STAT1/STAT3 signaling in macrophages, thus inhibiting macrophage M1 polarization. The proinflammation cytokines are then significantly reduced, which suppress inflammation response in the liver. Taken together, our study discovered that SS-31 can regulate macrophage polarization through ROS scavenging and STAT1/STAT3 signaling to ameliorate liver injury; the protective effects against hepatic IRI suggest that SS-31 may be an appropriate treatment for liver IRI in the clinic