Objective: A prospective, multicenter, randomized controlled trial was conducted to explore the short-term effect of a new robotic-assisted total knee arthroplasty (TKA) system, and the clinical and radiographic effectiveness between the robotic-assisted system and conventional TKA were compared and analyzed. Materials and Methods: Overall, 144 patients were randomly divided into two groups, wherein 72 patients underwent TKA using the robotic‑assisted system and 72 underwent conventional TKA. The demographic data and radiographic parameters of the patients were collected. The factors influencing postoperative hip–knee–ankle (HKA) angle deviation were determined by multiple linear regression. Clinical outcomes including postoperative Knee Society score, 10-cm visual analog scale, and range of motion (ROM) and radiographic results including the deviation value of coronal tibial component angle, coronal femoral component angle (CFCA), sagittal tibial component angle, sagittal femoral component angle (SFCA), and HKA angle as well as the rate of outliers in each angle were observed and compared between the two groups. Results: The preoperative demographic data and imaging parameters, including Knee Society score, ROM, sex, surgical side, age, BMI, preoperative HKA angle, preoperative HKA angle deviation, and visual analog scale, showed no significant differences between groups. The robotic‑assisted system group (RAS group) showed a postoperative malalignment of 3.2% for a mechanical axis higher than 3° and the conventional techniques group (CON group) showed a postoperative malalignment of 41.0% for a mechanical axis higher than 3°; the difference was statistically significant (P<0.001). According to the results of multiple linear regression analysis, when the preoperative HKA angle deviation increased by 1°, the postoperative HKA angle deviation increased by 0.134° (β=0.134 min; 95% CI: 0.045–0.222). Therefore, patients were divided into a slight lower extremity alignment deviation group (preoperative HKA angle deviation <6°) and severe lower extremity alignment deviation group (preoperative HKA angle deviation ≥6°). For the patients with preoperatively slight lower extremity alignment deviation, the rate of postoperative HKA angle outlier in the RAS group was better than that in the CON group, and the operation duration in the RAS group was significantly longer than that in the CON group (P<0.05). In the patients with a preoperative HKA angle deviation ≥6°, the rate of postoperative HKA angle and CFCA outliers in the RAS group was better than that in the CON group; the operation duration in the RAS group was significantly longer than that in the CON group, and the HKA angle deviation and CFCA deviation in the RAS group were significantly lower than those in the CON group (P0.05). Conclusion: This new robotic-assisted TKA system is safe and effective. The authors found that preoperative HKA angle deviation affects the postoperative HKA angle deviation. The robotic-assisted system has similar results to those reported by the traditional method with regard to restoring the mechanical axis of the leg and improving prosthesis alignment and clinical outcomes in patients with slight lower extremity alignment deviations preoperatively. For patients with severe preoperative lower extremity alignment deviations, the effectiveness in terms of the improvement in mechanical axis of the leg and prosthesis alignment were better with the robotic-assisted system, whereas the effectiveness of clinical outcomes was similar. A larger sample size and longer follow-up period are needed to determine whether the improved mechanical axis of the leg and prosthesis alignment observed with the robotic-assisted system can achieve better long-term radiographic and clinical outcomes.

Background: Osteoporosis is a disease threatening the health of millions of individuals. Melatonin is found to be a potential anti-osteoporosis drug. However, whether melatonin plays a role against osteoporosis at different stages of the menopause and the underlying mechanisms are unknown. Methods: Ovariectomy was utilized as a model of perimenopausal and postmenopausal osteoporosis. A total of 100 mg/kg melatonin, or solvent alone, was added to the drinking water of the rats over 8 weeks. Perimenopausal rats immediately received intervention following ovariectomy while postmenopausal rats received intervention 8 weeks after ovariectomy. All rats underwent overdose anesthesia following intervention after which blood samples and femurs were collected for further analysis. Rat femurs were scanned using micro-CT and examined histologically. The serum levels of melatonin and osteogenic biochemical markers were measured and the expression of osteogenesis-associated genes (Runx2, Sp7) were quantified by real-time quantitative PCR. Alkaline phosphatase (ALP) activity and the gene expression (Col1a1, Runx2, Alpl, and Bglap) were measured after bone marrow mesenchymal stem cells (BMSCs) were osteogenically induced, both with and without melatonin in vitro. ALP staining and Alizarin Red S staining were used to identify osteogenesis. Results: Analysis by micro-CT and histological staining demonstrated that bone mass decreased and bone microarchitecture deteriorated over time after ovariectomy. Intervention with melatonin increased bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats. Serum levels of ALP continuously increased after ovariectomy while osteocalcin levels initially rose, then decreased. Melatonin increased the serum levels of ALP and osteocalcin and mRNA expression levels of Runx2 and Sp7 in normal and postmenopausal rats, the opposite of the markers in perimenopausal rats. In vitro study demonstrated that 100 μmol/L melatonin increased the mRNA expression of Col1a1, Runx2, and Alpl three and/or seven days after intervention, and Alpl and Bglap 14 d after intervention. Melatonin increased ALP activity and the extent of ALP and matrix mineralization in the late stage of osteogenesis. Conclusions: Bone mass continuously decreased after ovariectomy, while melatonin increased bone mass and ameliorated bone metabolism in normal, perimenopausal, and postmenopausal osteoporotic rats due to the induction of osteogenic differentiation in BMSCs.

Background: Tissue engineering scaffolds are porous and can be loaded with growth factors to promote osteogenesis and bone repair, which can solve the problem of clinical bone defects. The direct loading of growth factors on scaffolds is hindered by the disadvantages of low loading capacities, and uncontrollable burst release. Zeolitic imidazolate framework-8 (ZIF-8) has osteoinductive activity and drug-loading potential and can be loaded with growth factors to achieve sustained release. In this study, we aimed to establish a sustained release system of composite scaffolds loaded with growth factors to achieve the goal of slow controlled release and effective bone repair. Methods: ZIF‑8 nanoparticles loaded with bone morphogenetic protein-2 (BMP-2) were incorporated into poly-(lactide-co-glycolide)/mesoporous bioactive glass (PLGA/MBG) porous scaffolds by a 3D-printing method. The surface morphology, chemical properties and BMP-2 release of the prepared scaffold were investigated. The osteoblast adhesion, proliferation, spreading, and osteogenic differentiation in vitro and the bone repair ability in vivo of the PLGA/MBG/ZIF-8/BMP-2 (PMZB) scaffold were evaluated, and compared with those of PLGA/MBG (PM) and PLGA/MBG/ZIF-8 (PMZ) scaffolds. Results: The results showed that the PMZB scaffold exhibited a slow and continuous BMP-2 release pattern, enhanced osteoblast adhesion, proliferation, spreading and osteogenic differentiation in vitro, and promoted new bone formation and bone repair in vivo. Conclusion: The PLGA/MBG/ZIF-8/BMP-2 porous scaffold could continuously and slowly release BMP-2, enhance osteogenic activity, and promote new bone formation and bone repair at bone defects. The PMZB scaffold can be used as a bone graft material to repair bone defect at non-weight-bearing sites.

The newly described inflammatory burden index (IBI) reflects a patient’s inflammatory burden. This study aimed to estimate the association between IBI, osteoarthritis (OA), and all-cause mortality in patients with OA. We extracted the data of adults from the National Health and Nutrition Examination Survey database between 1999 and 2018. After using appropriate survey weights to correct for sample bias, we conducted multivariate logistic regression analyses to explore the association between IBI and OA across three models: in the unadjusted model, partially adjusted model (adjusting age, sex, race, education level, marital status, PIR, BMI, smoking status, drinking status, stroke, CVD, DM, and hypertension) and fully adjusted model (which included additional variables: HBA1C, ALT, AST, BUN, TC, and HDL). And the odds ratios (OR) and 95% confidence intervals (CI) were calculated. Similarly, using comparable survey weights and covariates adjustments, we employed Cox proportional hazards regression analysis to investigate the association between IBI and all-cause mortality in the other 3 models. The Cox proportional hazards regression models were fitted to calculate the hazard ratios (HR) and 95% CI of the association between IBI and all-cause mortality. A restricted cubic spline (RCS) was used to explore the nonlinear relationships between association effects. Subgroup analysis was performed to validate the reliability of their effects. In total, 22,343 eligible participants were included. Multiple logistic regression models revealed that participants with the highest IBI had 2.54 times (95%CI, 2.23, 2.90)) higher risk of OA than those with the lowest IBI in Model 1, whereas the OR was 1.21 (95%CI, 1.03, 1.42) in Model 2 and 1.23 (95%CI,1.05, 1.45) in Model 3. Multiple Cox regression models showed participants with the highest IBI had 186% (95%CI, 1.50, 2.31) times risk of developing all-cause death than those with the lowest IBI in Model 1. This trend remained stable in Models 2 (HR,1.54; 95%CI,1.22, 1.95) and 3 (HR, 1.41; 95%CI, 1.10, 1.80). The RCS revealed a significant positive association between IBI and OA risk. With respect to the association between IBI and all-cause mortality, a slight decrease in mortality was observed from the lowest quartile to the second quartile of IBI, and the mortality risk increased with increasing IBI. Subgroup analyses showed that age, cardiovascular disease, and hypertension were pivotal in the association of IBI with all-cause mortality, whereas the association of IBI with OA remained stable after stratification by other factors such as sex, race, education level, marital, smoking, and drinking status, hypertension, and most serological indices. This study provides evidence of a positive association between IBI, OA, and all-cause mortality. IBI may be a promising signature for assessing the inflammatory burden in patients with OA, which, in turn, is conducive to precise references for high-risk population recognition, anti-inflammatory guidance, and reducing mortality intervention.

Core decompression (CD) with the elimination of osteonecrotic bone is the most common strategy for treating early-stage nontraumatic osteonecrosis of the femoral head (ONFH). Adjuvant treatments are widely used in combination with CD as suitable methods of therapy. Existing augmentations have to be fabricated in advance. Here, we report a novel injectable glycerin-modified polycaprolactone (GPCL) that can adapt to the shape of the CD cavity. GPCL shows great flowability at 52.6 °C. After solidification, its compressive modulus was 120 kPa at body temperature (37 °C). This excellent characteristic enables the polymer to provide mechanical support in vivo. In addition, GPCL acts as a carrier of the therapeutic agent zoledronic acid (ZA), demonstrating sustained release into the CD region. ZA-loaded GPCL was injected into ONFH lesions to treat early-stage nontraumatic cases. Compared to that in the CD group, CD+ZA-loaded GPCL injection preserved bone density and increased the collagen level in the femoral head. At the interface between the GPCL and CD tunnel wall, osteogenesis was significantly promoted. In addition, morphological evaluations revealed that the femoral heads in the CD+ZA-GPCL group exhibited improved pressure resistance. These results suggest a strategy effective to preserve the bone density of the femoral head, thus decreasing the possibility of femoral head collapse. This novel injectable polymer has, therefore, considerable potential in clinical applications.