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The current study evaluated the efficacy and safety of a denosumab biosimilar, QL1206 (60 mg), compared to placebo in postmenopausal Chinese women with osteoporosis and high fracture risk. At 31 study centers in China, a total of 455 postmenopausal women with osteoporosis and high fracture risk were randomly assigned to receive QL1206 (60 mg subcutaneously every 6 months) or placebo. From baseline to the 12-month follow-up, the participants who received QL1206 showed significantly increased bone mineral density (BMD) values (mean difference and 95% CI) in the lumbar spine: 4.780% (3.880%, 5.681%), total hip :3.930% (3.136%, 4.725%), femoral neck 2.733% (1.877%, 3.589%) and trochanter: 4.058% (2.791%, 5.325%) compared with the participants who received the placebo. In addition, QL1206 injection significantly decreased the serum levels of C-terminal crosslinked telopeptides of type 1 collagen (CTX): -77.352% (-87.080%, -66.844%), and N-terminal procollagen of type l collagen (P1NP): -50.867% (-57.184%, -45.217%) compared with the placebo over the period from baseline to 12 months. No new or unexpected adverse events were observed. We concluded that compared with placebo, QL1206 effectively increased the BMD of the lumbar spine, total hip, femoral neck and trochanter in postmenopausal Chinese women with osteoporosis and rapidly decreased bone turnover markers. This study demonstrated that QL1206 has beneficial effects on postmenopausal Chinese women with osteoporosis and high fracture risk.

Background: Previous studies have demonstrated that long non-coding RNA maternally expressed gene 3 (MEG3) emerged as a key regulator in development and tumorigenesis. This study aims to investigate the function and mechanism of MEG3 in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and explores the use of MEG3 in skull defects bone repairing. Methods: Endogenous expression of MEG3 during BMSCs osteogenic differentiation was detected by quantitative real-time polymerase chain reaction (qPCR). MEG3 was knockdown in BMSCs by lentiviral transduction. The proliferation, osteogenic-related genes and proteins expression of MEG3 knockdown BMSCs were assessed by Cell Counting Kit-8 (CCK-8) assay, qPCR, alizarin red and alkaline phosphatase staining. Western blot was used to detect β-catenin expression in MEG3 knockdown BMSCs. Dickkopf 1 (DKK1) was used to block wnt/β-catenin pathway. The osteogenic-related genes and proteins expression of MEG3 knockdown BMSCs after wnt/β-catenin inhibition were assessed by qPCR, alizarin red and alkaline phosphatase staining. MEG3 knockdown BMSCs scaffold with PHMG were implanted in a critical-sized skull defects of rat model. Micro-computed tomography(micro-CT), hematoxylin and eosin staining and immunohistochemistry were performed to evaluate the bone repairing. Results: Endogenous expression of MEG3 was increased during osteogenic differentiation of BMSCs. Downregulation of MEG3 could promote osteogenic differentiation of BMSCs in vitro. Notably, a further mechanism study revealed that MEG3 knockdown could activate Wnt/β-catenin signaling pathway in BMSCs. Wnt/β-catenin inhibition would impair MEG3-induced osteogenic differentiation of BMSCs. By using poly (3-hydroxybutyrate-co-3-hydroxyhexanoate, PHBHHx)-mesoporous bioactive glass (PHMG) scaffold with MEG3 knockdown BMSCs, we found that downregulation of MEG3 in BMSCs could accelerate bone repairing in a critical-sized skull defects rat model. Conclusions: Our study reveals the important role of MEG3 during osteogenic differentiation and bone regeneration. Thus, MEG3 engineered BMSCs may be effective potential therapeutic targets for skull defects.

Background: Previous studies have demonstrated long non-coding RNA maternally expressed gene 3 (MEG3) emerged as a key regulator in development and tumorigenesis. However, whether MEG3 participate in osteogenic differentiation and bone regeneration remains unclear. This study aims to investigate the function and mechanism of MEG3 in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and explores the use of MEG3 in skull defects bone repairing. Methods: Endogenous expression of MEG3 during BMSCs osteogenic differentiation were detected by qPCR. MEG3 was knockdown in BMSCs by lentivirus. The proliferation, osteogenic-related genes and proteins expression were assessed by the CCK-8, PCR, alizarin red and alkaline phosphatase staining in MEG3 knockdown BMSCs. Western blot was used to detected β-catenin expression in MEG3 knockdown BMSCs. DKK1 was used to block wnt/β-catenin pathway, the osteogenic-related genes and proteins expression were assessed by PCR, alizarin red and alkaline phosphatase staining in MEG3 knockdown BMSCs. MEG3 knockdown BMSCs scaffold with PHMG were implanted in a critical-sized skull defects of rat model, micro-CT, hematoxylin and eosin staining, and immunohistochemistry were performed to evaluate the bone repairing. Results: MEG3 was increased during osteogenic differentiation of BMSCs. Downregulation of MEG3 could promote osteogenic differentiation of BMSCs in vitro. Notably, a further mechanism study revealed MEG3 knockdown could activate Wnt/β-catenin signaling pathway in BMSCs. Wnt/β-catenin inhibition would impair MEG3-induced osteogenic differentiation of BMSCs. By using PHMG scaffold with MEG3 knockdown BMSCs, we found that downregulation of MEG3 in BMSCs could accelerated bone repairing in a critical-sized skull defects rat model. Conclusions: Our study reveals the important role of MEG3 during osteogenic differentiation and bone regeneration. Thus, MEG3 engineered BMSCs may be effective potential therapeutic targets for skull defects.

To compare clinical results of treating femoral head necrosis staged Ficat III or IV with total hip arthroplasty (THA) between mini invasive direct anterior approach (DAA) and posterolateral approach.From January 2008 to December 2009, 48 patients with femoral head necrosis staged Ficat III or IV treated with THA were compared and analyzed. There were 21 patients in mini invasive direct anterior approach group including 11 males and 10 females with an average age of (65.2±4.3) years old;while there were 27 patients in posterolateral approach group including 16 males and 11 females with an average age of (63.6±4.0) years old. Operative time, blood loss during operation, bed rest time and complications of two groups were observed and compared. Acetabular abduction and stem shaft angle were measured 1 month after operation and compared between two groups. Postoperative Harris Hip scoring and VAS scoring were applied for evaluating hip function and pain at 1, 6 months and 5 years after operation respectively.All patients were followed up for 48 to 73 months with an average of 60.4 months. Operative time, blood loss in DAA group was (78.30±5.08) min, (351.30±21.46) ml, respectively, in posterolateral approach group was (75.61±10.60) min, (362.20±26.15) ml, and no significant differences between two groups. Bed rest time in DAA group was (2.05±1.10) days, better than that of in posterolateral approach which was (3.30±1.35) days. No significant differences were found between two groups in acetabular abduction and stem shaft angle at 1 month after operation. There was no significant differences between two groups in HHS and VAS score at 1, 6 months and 5 years after operation. There was 1 case with injury of ascending branch of the lateral circumflex femoral artery, 1 case with great trochanter fracture and 1 case with superficial infection in DAA group, 1 case with dislocation in posterolateral group. No prosthesis loosening occurred in two groups.Both DAA and posterolateral approach are effective in treating femoral head necrosis staged Ficat III or IV, and could obtain excellent outcomes. However, DAA seemed to has disadvantage in learing curve compared posteriolateral approach in complex cases.

There are many in vitro experiments showing that particulate bioactive glasses have a broad and certain antibacterial effect, but there is no report about this antibacterial effect in vivo so far. The aim of this study is to examine the efficacy of particulate Bioglass in reducing the rate of infection with Staphylococcus aureus after the fixation of open tibial fractures in rabbits. The test in vivo was carried out with male rabbits split into two groups infected with Staphylococcus aureus at the right tibial fracture sites fixed with plate and screw, either with or without bioactive glass respectively. Culture results show that six of ten rabbits from the control group had a positive culture for the strain of Staphylococcus aureus ATCC25923, compared with six of the nine rabbits from the Bioglass group. The median radiographic score is 4.5 points for the rabbits from the control group and 4 points for the rabbits from the Bioglass group. The median histopathological score was 2.5 points for the rabbits in the control group and 3 points for the rabbits in the Bioglass group. In conclusion, this study showed no significant difference between the rates of infection of two groups. Particulate Bioglass did not reduce the rate of infection with Staphylococcus aureus after the fixation of open tibial fractures in rabbits.