Chenyi Ye

Decreased Bone Mineral Density Is an Independent Predictor for the Development of Atherosclerosis: A Systematic Review and Meta-Analysis.

Background There is conflicting evidence regarding the association between decreased bone mineral density (BMD) and atherosclerosis. To this end, we performed a systematic review and meta-analysis to clarify the association. Methods To identify relevant studies, PubMed, Embase, and the Cochrane Library were systematically searched up to November 2015. All observational and comparative studies directly investigating the relationship between decreased BMD and clinical consequences of atherosclerotic vascular abnormalities, including carotid artery calcification (CAC), cardiovascular disease (CAD), and coronary artery disease (CAD) were obtained, without limitation of language or publication year. Results A total of 25 studies involving 10,299 patients were included. The incidence of atherosclerotic vascular abnormalities was significantly increased in low BMD patients, compared to patients with normal BMD (OR, 1.81, 95% CI [1.01, 2.19], p<0.00001)). Similar results were also observed for postmenopausal women (OR, 2.23, 95% CI [1.72, 2.89], p<0.00001). Subgroup analyses of osteopenia, osteoporosis, and normal BMD also revealed that the combined ORs for the incidence of atherosclerotic vascular abnormalities increased as BMD decreased. Of note, after adjusting for age, sex, body mass index (BMI) and other vascular risk factors, decreased BMD remained significantly associated with the incidence of atherosclerotic vascular abnormalities (OR, 2.96, 95% CI [2.25, 3.88], p < 0.00001). Conclusions Based on the results of this study, decreased BMD is an independent predictor for the development of atherosclerosis in elderly individuals. Moreover, the risk of atherosclerotic vascular abnormalities increased as BMD decreased. Future studies focusing on individuals with different severities of atherosclerosis and comorbidities are of interest.

Local delivery of HMGB1 in gelatin sponge scaffolds combined with mesenchymal stem cell sheets to accelerate fracture healing

Fracture nonunion and delayed union continue to pose challenges for orthopedic surgeons. In the present study, we combined HMGB1 gelatin sponges with MSC sheets to promote bone healing after surgical treatment of rat tibial fractures. The HMGB1 gelatin sponge scaffolds supported the expansion of mesenchymal stem cells (MSCs) and promoted the osteogenic differentiation of MSCs and MSC sheets. Lentiviral vectors were then used to overexpress HMGB1 in MSCs. The results indicated that HMGB1 promotes the osteogenic differentiation of MSCs through the STAT3 pathway. Both siRNA and a STAT3 inhibitor downregulated STAT3, further confirming that HMGB1 induces the osteogenic differentiation of MSCs partly via the STAT3 signal pathway. In a rat tibial osteotomy model, we demonstrated the ability of HMGB1 gelatin sponge scaffolds to increase bone formation. The addition of MSC sheets further enhanced fracture healing. These findings support the use of HMGB1-loaded gelatin sponge scaffolds combined with MSC sheets to enhance fracture healing after surgical intervention.

Icariin Promotes Tendon-Bone Healing during Repair of Rotator Cuff Tears: A Biomechanical and Histological Study

To investigate whether the systematic administration of icariin (ICA) promotes tendon-bone healing after rotator cuff reconstruction in vivo, a total of 64 male Sprague Dawley rats were used in a rotator cuff injury model and underwent rotator cuff reconstruction (bone tunnel suture fixation). Rats from the ICA group (n = 32) were gavage-fed daily with ICA at 0.125 mg/g, while rats in the control group (n = 32) received saline only. Micro-computed tomography, biomechanical tests, serum ELISA (calcium; Ca, alkaline phosphatase; AP, osteocalcin; OCN) and histological examinations (Safranin O and Fast Green staining, type I, II and III collagen (Col1, Col2, and Col3), CD31, and vascular endothelial growth factor (VEGF)) were analyzed two and four weeks after surgery. In the ICA group, the serum levels of AP and OCN were higher than in the control group. More Col1-, Col2-, CD31-, and VEGF-positive cells, together with a greater degree of osteogenesis, were detected in the ICA group compared with the control group. During mechanical testing, the ICA group showed a significantly higher ultimate failure load than the control group at both two and four weeks. Our results indicate that the systematic administration of ICA could promote angiogenesis and tendon-bone healing after rotator cuff reconstruction, with superior mechanical strength compared with the controls. Treatment for rotator cuff injury using systematically-administered ICA could be a promising strategy.

Influence of the Infrapatellar Fat Pad Resection during Total Knee Arthroplasty: A Systematic Review and Meta-Analysis

Background To enhance surgical exposure, resection of the infrapatellar fat pad (IPFP) is usually a routine procedure in total knee arthroplasty (TKA). However, there is conflicting evidence regarding whether IPFP resection during TKA impairs clinical outcome. We performed a systematic review and meta-analysis to clarify the influence of IPFP resection on primary TKA. Methods Embase, PubMed, and the Cochrane Library were systematically searched up to August 2016 to identify relevant studies. All clinical studies comparing IPFP resection (IPFP-R) and IPFP preservation (IPFP-P) in patients undergoing primary TKA were obtained. The meta-analysis was performed with Revman 5.3 and STATA 12.0 software. The weighted mean was estimated by using random effects (RE) models with 95% CIs, heterogeneity was assessed using the H statistic and the inconsistency index (I2). Results Seven studies involving 2,734 patients (3,258 knees) were included. IPFP resection trended to increase the incidence of postoperative anterior knee pain within 2 months postoperatively, compared with patients in whom the IPFP was preserved (odds ratio [OR]s 2.12[0.95, 4.73], p = 0.07). An increased incidence of anterior knee pain was observed in the IPFP resection group > 12 months postoperatively, but the difference was not significant (OR, 3.69 [0.81, 16.82], p = 0.07). In addition, a trend towards more shortening of the patellar tendon was also observed in the IPFP-R group. No significant results were found regarding postoperative knee function. Conclusion These results suggest that preserving the IPFP may be superior to IPFP resection in patients undergoing primary TKA, due to the relatively lower rate of anterior knee pain after short-term follow-up.

Arthroplasty versus Internal Fixation for Displaced Intracapsular Femoral Neck Fracture in the Elderly: Systematic Review and Meta-analysis of Short- and Long-term Effectiveness.

Background:There is conflicting evidence as to whether the femoral head should be preserved or replaced in elderly patients with displaced intracapsular femoral neck fractures. In this article, we performed a systematic review and meta-analysis to compare the short- and long-term effectiveness of arthroplasty (AR) and internal fixation (IF). Methods:PubMed, Embase, and the Cochrane Library were searched systematically up to January 2016. All randomized controlled trials directly comparing the effectiveness of AR and IF for displaced intracapsular fracture were retrieved with no limitation on language or publication year. Results:In total, eight prospective randomized studies involving 2206 patients were included. The results of our study showed that patients in the AR group reported significantly lower complication (risk ratio: 0.56, 95% confidence interval [CI] = 0.38–0.80), re-operation (risk ratio: 0.17, 95% CI = 0.13–0.22), revision rates (risk ratio: 0.11, 95% CI: 0.08–0.16), and better function compared with their IF counterparts, and they were less likely to suffer postoperative pain. No statistically significant differences for the rates of mortality, infection, and/or deep vein thrombosis between AR and IF were found. Conclusions:Based on our analysis, we recommend that AR should be used as the primary treatment for displaced intracapsular femoral neck fractures in the elderly. However, IF may be appropriate for those who are very frail.

Results of a Second-generation Constrained Condylar Prosthesis in Complex Primary and Revision Total Knee Arthroplasty: A Mean 5.5-Year Follow-up

Background:The application of second-generation constrained condylar knee (CCK) prostheses has not been widely studied. This retrospective study was carried out to evaluate the clinical and radiographic outcomes of a second-generation CCK prosthesis for complex primary or revision total knee arthroplasty (TKA). Methods:In total, 51 consecutive TKAs (47 patients) were performed between June 2003 and June 2013 using second-generation modular CCK prostheses. The follow-up was conducted at 3rd day, 1st, 6th, and 12th months postoperatively and later annually. Anteroposterior (AP), lateral, skyline, and long-standing AP radiographs of the affected knees were taken. The Hospital for Special Surgery (HSS) Knee Score, the Knee Society Knee Score (KSKS), the Knee Society Function Score (KSFS), and range of motion (ROM) were also recorded. Heteroscedastic two-tailed Students t-tests were used to compare the HSS score and the Knee Society score between primary and revision TKAs. A value of P < 0.05 was considered statistically significant. Results:Four knees (two patients) were lost to follow-up, and 47 knees (31 primary TKAs and 16 revision TKAs) had a mean follow-up time of 5.5 years. The mean HSS score improved from 51.1 ± 15.0 preoperatively to 85.3 ± 8.4 points at the final follow-up (P < 0.05). Similar results were observed in terms of the KSKS and KSFS, which improved from 26.0 ± 13.0 to 80.0 ± 12.2 and from 40.0 ± 15.0 to 85.0 ± 9.3 points, respectively (P < 0.05). No significant difference in the HSS, KSKS, KSFS, or ROM was found between primary and revision TKAs (P > 0.05). Two complications were observed in the revision TKA group (one intraoperative distal femur fracture and one recurrence of infection) while one complication (infection) was observed in the primary TKA group. No prosthesis loosening, joint dislocation, patella problems, tibial fracture, or nerve injury were observed. Radiolucent lines were observed in 4% of the knees without progressive osteolysis. Conclusions:Second-generation modular CCK prostheses are a safe and practical treatment for both primary and revision knees that cannot be balanced. However, further studies focusing on different types of constrained prostheses are required to validate these results.

IGFBP7 regulates the osteogenic differentiation of bone marrow–derived mesenchymal stem cells via Wnt/β-catenin signaling pathway

Insulin‐like growth factor‐binding protein 7 (IGFBP7), a low‐affinity IGF binder, may play an important role in bone metabolism. However, its function in osteogenic differentiation of human bone marrow‐derived mesenchymal stem cells (BMSCs) remains unclear. Therefore, we investigated its effects on osteogenic differentiation. Overexpression of IGFBP7 enhanced the expression of osteo‐specific genes and proteins, and IGFBP7 knockdown decreased osteogenesis‐specific markers. More mineral deposits and higher alkaline phosphatase activity were observed after the up‐regulation of IGFBP7. Moreover, β‐catenin levels were up‐regulated by the overexpression of IGFBP7 or the addition of extracellular IGFBP7 protein and were reduced by the depletion of IGFBP7. The increase in osteogenic differentiation due to the overexpression of IGFBP7 was partially decreased by specific Wnt/β‐catenin signaling inhibitors. Using a rat tibial osteotomy model, a sheet of IGFBP7–overexpressing BMSCs improved bone healing, as demonstrated by imaging, biomechanical, and histologic analyses. Taken together, these findings indicate that IGFBP7 regulates the osteogenic differentiation of BMSCs partly via the Wnt/ β‐catenin signaling pathway.— Zhang, W., Chen, E., Chen, M., Ye, C., Qi, Y., Ding, Q., Li, H., Xue, D., Gao, X., Pan, Z. IGFBP7 regulates the osteogenic differentiation of bone marrow‐derived mesenchymal stem cells via Wnt/β‐catenin signaling pathway. FASEB J. 32, 2280–2291 (2018). www.fasebj.org

Suprapatellar versus infrapatellar approach for tibia intramedullary nailing: A meta-analysis

OBJECTIVE This meta-analysis was performed to determine the efficacy of suprapatellar versus infrapatellar approach for tibia intramedullary nailing (IMN). METHODS A systematic search was performed in PubMed, Embase, Cochrane library, CNKI and Wanfang. Cochrane collaborations tool and the Newcastle-Ottawa scale were used to evaluate literature qualities. Meta-analysis was performed using RevMan 5.3 software. RESULTS Eight studies were eligible, including two randomized controlled trials (RCTs) and six retrospective cohort trials. There were no significant differences between suprapatellar and infrapatellar approaches in operation time, coronal plane alignment, and incidence of postoperative deep infection, nonunion and secondary operation. However, suprapatellar nailing achieved a significant shorter fluoroscopy time, less VAS pain score, better sagittal plane alignment and lower incidence of angular malalignment. Though pooled results indicated no significant difference in terms of final follow-up knee functional score, the RCT subgroup analysis showed that a higher knee functional score existed in suprapatellar group. CONCLUSIONS For tibia IMN, suprapatellar approach might be superior to infrapatellar approach with shorter fluoroscopy time, less knee pain, better knee function recovery, and more accurate fracture reduction. Meanwhile, no increased risk of postoperative complications was identified. More RCTs are required for further research.

PTH[1-34] improves the effects of core decompression in early-stage steroid-associated osteonecrosis model by enhancing bone repair and revascularization

Steroid-associated osteonecrosis (SAON) might induce bone collapse and subsequently lead to joint arthroplasty. Core decompression (CD) is regarded as an effective therapy for early-stage SAON, but the prognosis is unsatisfactory due to incomplete bone repair. Parathyroid hormone[1–34] (PTH[1–34]) has demonstrated positive efficacy in promoting bone formation. We therefore evaluated the effects of PTH on improving the effects of CD in Early-Stage SAON. Distal femoral CD was performed two weeks after osteonecrosis induction or vehicle injection, with ten of the ON-induced rabbits being subjected to six-week PTH[1–34] treatment and the others, including ON-induced and non-induced rabbits, being treated with vehicle. MRI confirmed that intermittent PTH administration improved SAON after CD therapy. Micro-CT showed increased bone formation within the tunnel. Bone repair was enhanced with decreased empty osteocyte lacunae and necrosis foci area, resulting in enhanced peak load and stiffness of the tunnel. Additionally, PTH enlarged the mean diameter of vessels in the marrow and increased the number of vessels within the tunnels, as well as elevated the expression of BMP-2, RUNX2, IGF-1, bFGF and VEGF, together with serum OCN and VEGF levels. Therefore, PTH[1–34] enhances the efficacy of CD on osteogenesis and neovascularization, thus promoting bone and blood vessels repair in the SAON model.

Platelet-derived growth factor-BB attenuates titanium-particle-induced osteolysis in vivo

Abstract Inflammation and osteoclastogenesis play critical roles in wear-particle-induced periprosthetic osteolysis (WPO). Platelet-derived growth factor-BB (PDGF-BB) could promote osteogenesis and inhibit inflammatory response. The aim of this study was to investigate the impact of PDGF-BB on WPO. Mice were divided into four groups, namely, sham, vehicle, low-, and high-dose PDGF-BB groups. Mice in the rhPDGF-BB groups were treated with PDGF-BB at 0.25 or 1 mg/ml/kg/day. Mice in the sham and vehicle groups received PBS daily. Two weeks after surgery, calvariae were harvested. Immunohistochemical analysis and μ-CT showed that PDGF-BB significantly reduced osteoclast formation and bone resorption. ELISA showed that rhPDGF-BB decreased the secretion of TNF-α, IL-1β, and IL-6. Western blotting revealed that rhPDGF-BB stimulated the expression of osteocalcin and osteoprotegerin. Furthermore, more VEGF and CD31 proteins were observed due to PDGF-BB by immunofluorescence. In conclusion, these findings suggest that rhPDGF-BB represents a potential treatment for WPO.