Eldecalcitol protected osteocytes against ferroptosis of D-gal-induced senescent MLO-Y4 cells and ovariectomized mice.

BACKGROUND: Active vitamin D analog eldecalcitol is clinically applied in treatment of postmenopausal osteoporosis. This study aims to determine the role of eldecalcitol in the protection of osteocytes from senescence and the associated ferroptosis. METHODS: The MLO-Y4 osteocytes were exposed to D-gal inducing senescence. The ovariectomized (OVX) mice treated with D-gal using as an aging inducer were intraperitoneally injected with eldecalcitol. The multiplexed confocal imaging, fluorescence in situ hybridization and transmission electron microscopy were applied in assessing osteocytic properties. Immunochemical staining and immunoblotting were carried out to detect abundance and expression of molecules. RESULTS: The ablation of vitamin D receptor led to a reduction in amounts of osteocytes, a loss of dendrites, an increase in mRNA expression of SASP factors and in protein expression of senescent factors, as well as changes in mRNA expression of ferroptosis-related genes (PTGS2 & RGS4). Eldecalcitol reversed senescent phenotypes of MLO-Y4 cells shown by improving cell morphology and density, decreasing ß-gal-positive cell accumulation, and down-regulating protein expression (P16, P21 & P53). Eldecalcitol reduced intracellular ROS and MDA productions, elevated JC-1 aggregates, and up-regulated expression of Nrf2 and GPX4. Eldecalcitol exhibited osteopreserve effects in D-gal-induced aging OVX mice. The confocal imaging displayed its improvement on osteocytic network organization. Eldecalcitol decreased the numbers of senescent osteocytes at tibial diaphysis by SADS assay and attenuated mRNA expression of SASP factors as well as down-regulated protein expression of senescence-related factors and restored levels of ferroptotic biomarkers in osteocytes-enriched bone fraction. It reduced 4-HNE staining area, stimulated Nrf2-positive staining, and promoted nuclear translocation of Nrf2 in osteocytes of mice as well as inhibited and promoted protein expression of 4-HNE and Nrf2, respectively, in osteocytes-enriched bone fraction. CONCLUSIONS: The present study revealed the ameliorative effects of eldecalcitol on senescence and the associated ferroptosis of osteocytes, contributing to its preservation against osteoporosis of D-gal-induced senescent ovariectomized mice.

Total Hip Arthroplasty with Robotic Arm Assistance for Precise Cup Positioning: A Case-Control Study.

OBJECTIVE: To determine whether more precise cup positioning can be achieved with robot-assisted total hip arthroplasty (THA) as compared to conventional THA. METHODS: In this study, between July 2019 and May 2021, 93 patients aged 23-75 years with osteonecrosis of the femoral head (ONFH) and adult developmental dysplasia of hip who underwent first hip surgery were included in the study. They were randomly assigned to either the robotic-assisted THA group (n = 45) or the conventional THA group (n = 48). After the operation, all patients were given routine rapid rehabilitation guidance. The duration of operation was recorded to estimate the learning curve through cumulative summation analysis. We compared the demographics, duration of operation, cup positioning, leg length discrepancy, hip offset, and Harris Hip Score between robot-assisted THA and manual THA. Precision in the positioning of the acetabular prosthesis using the MAKO system was also compared between the two groups. RESULTS: The mean duration of operation for the robot-assisted THA group was 91.37 ± 17.34 min (range: 63 to 135 min), which was significantly higher than that for the conventional THA group. When the number of procedures was increased to 13, the duration of operation in the robot-assisted group decreased significantly and gradually became stable. In terms of duration of operation, robot-assisted THA was associated with a learning curve of 13 cases. The mean amount of bleeding in the robot-assisted THA group was not significantly different from that in conventional THA group (328 ± 210 ml vs 315 ± 205 ml) (p = 0.741). There was no significant difference in the proportion of prostheses located within Lewinnek's safe zone between robot-assisted THA group and conventional THA group (69.81% vs 64.41%). The leg length discrepancy (LLD) was significantly smaller in the robot-assisted THA group than in the conventional THA group (p < 0.001), but both were within acceptable limits (10 mm). The inclination and anteversion angles of the acetabular prosthesis planned before operations were correlated with the actual measurement (r = 0.857 p < 0.001, r = 0.830, p < 0.001). After surgery, none of the patients experienced hip dislocation, aseptic loosening, or periprosthetic infection during the 3 months of follow-up. CONCLUSION: The proportion of acetabular prostheses in the Lewinnek's safety zone was higher and the extent of LLD was significantly lower in the robot-assisted THA group, as compared to the same metrics in the conventional THA group. The MAKO robot improved the accuracy of implant placement in THA.