The Research on Spinopelvic Parameters and Clinical Outcomes of OLIF and TLIF in the Treatment of Complex Degenerative Lumbar Spondylolisthesis.

PURPOSE: To investigate the improvement of spinopelvic parameters and therapeutic efficacy in the treatment of complex degenerative lumbar spondylolisthesis (CDLS) after OLIF and TLIF. METHODS: From January 2018 to December 2020, 71 patients with CDLS underwent OLIF or TLIF at the same hospital: 31 in the OLIF group and 40 in the TLIF group. The spinopelvic parameters, perioperative data and clinical outcomes were elected and compared between the two groups. RESULTS: There were no statistic differences in demographic, perioperative complication rates and preoperative spinopelvic parameters between the two groups. OLIF group showed lower serum C-reactive protein (CRP) in the early postoperative stage, shorter length of stay (LOS), less estimated blood loss (EBL) and larger slippage correction rate (SCR, 88.05 vs 62.37%) (all P＜0.05). There was no significant difference in the VAS and ODI scores before operation and three and six months after surgery, but OLIF group was better in the long-term with VAS and ODI (1.7/13.2vs 2.3/16.5). And it was significantly different in the lumbar lordosis angle (LLA), segmental lordosis angle (SLA), pelvic tilt (PT), sacral slope (SS)( 46.0°/9.3°/18.2°/35.9° vs 40.4°/7.2°/23.9°/31.1°) and sagittal vertical axis (SVA, 21.6 vs 31.7mm) after surgery between OLIF and TLIF groups (all P＜0.05). CONCLUSION: In the therapy of CDLS, OLIF can better reduce PT, LASD and SVA, and increase LLA and SS, showing advantages over TLIF in improving and maintaining spinopelvic parameters. Although there was no difference in complication rates between OLIF and TLIF, OLIF was more minimally invasive, had less tissue damage, had faster recovery, and had better long-term outcomes.

A clinical-stage Nrf2 activator suppresses osteoclast differentiation via the iron-ornithine axis.

Activating Nrf2 by small molecules is a promising strategy to treat postmenopausal osteoporosis. However, there is currently no Nrf2 activator approved for treating chronic diseases, and the downstream mechanism underlying the regulation of Nrf2 on osteoclast differentiation remains unclear. Here, we found that bitopertin, a clinical-stage glycine uptake inhibitor, suppresses osteoclast differentiation and ameliorates ovariectomy-induced bone loss by activating Nrf2. Mechanistically, bitopertin interacts with the Keap1 Kelch domain and decreases Keap1-Nrf2 binding, leading to reduced Nrf2 ubiquitination and degradation. Bitopertin is associated with less adverse events than clinically approved Nrf2 activators in both mice and human subjects. Furthermore, Nrf2 transcriptionally activates ferroportin-coding gene Slc40a1 to reduce intracellular iron levels in osteoclasts. Loss of Nrf2 or iron supplementation upregulates ornithine-metabolizing enzyme Odc1, which decreases ornithine levels and thereby promotes osteoclast differentiation. Collectively, our findings identify a novel clinical-stage Nrf2 activator and propose a novel Nrf2-iron-ornithine metabolic axis in osteoclasts.