[Mesoporous silica nanoparticles for bone tissue engineering].

As a new potential bone graft material, tissue engineered bone effectively compensates for the defects of today's bone repair materials. Meanwhile, mesoporous silica nanomaterials(MSNs) have been widely recognized due to their large specific surface area, good biocompatibility, and capability of further processing and modification. They have promising application prospects in bone tissue engineering. For the basic scientific research results that have been carried out in the early stage, the basic characteristics of mesoporous silica nano biomaterials and their application advantages, research status and development prospects in bone tissue engineering are reviewed. As for the research status, there are two aspects--as a carrier or as a component of engineering scaffolds. For the first aspect, different kinds of loaded drugs and different loading methods are reviewed. For the second, microstructure and mechanical properties of various complex scaffolds containing MSNs and the molecular and cellular behavior of seeded cells on these scaffolds are reviewed. The research of MSNs in bone cements and metal ions doped MSNs in bone tissue engineering are also included. The future development of MSNs in bone tissue engineering is also discussed.

LDC000067 suppresses RANKL-induced osteoclastogenesis in vitro and prevents LPS-induced osteolysis in vivo.

Bone homeostasis requires a dynamic balance between osteogenesis and osteoclastogenesis, and osteolytic disorders are mainly attributed to aberrant osteoclastogenesis and bone resorption. Accumulating evidence has demonstrated that cyclin-dependent kinase 9 (CDK9) regulates some inflammatory diseases without affecting the cell cycle. Whether the specific inhibitor of CDK9, LDC000067 (abbreviated as LDC067), helps to prevent from osteolytic disorders has not been fully elucidated. Interestingly, this study demonstrated that LDC067 inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and bone resorption in vitro, and suppressed the expression of osteoclast-related marker genes such as cathepsin K (CTSK), tartrate-resistant acid phosphatase (TRAP), dendrite cell-specific transmembrane protein (DC-STAMP), V-ATPase D2, calcitonin receptor (CTR) and nuclear factor of activated T cells cytoplasmic 1 (NFATc1). The bone protective effects of LDC067 can be partly explained by its suppression of nuclear factor-kappa B (NF-κB)-mediated NFATc1 activation via AKT signalling pathway. In keeping with the results obtained in vitro, inhibition of CDK9 with LDC067 was observed to delay subchondral osteolysis and substantially ameliorate LPS-induced osteolysis in murine calvaria. Collectively, these results highlight the positive effects of LDC067 in preventing osteolytic disorders and indicate that this CDK9 inhibitor may a promising therapeutic agent.

Efficacy and Safety of Zhuanggu Joint Capsules in Combination with Celecoxib in Knee Osteoarthritis: A Multi-center, Randomized, Double-blind, Double-dummy, and Parallel Controlled Trial.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic joint disease that manifests as knee pain as well as different degrees of lower limb swelling, stiffness, and movement disorders. The therapeutic goal is to alleviate or eliminate pain, correct deformities, improve or restore joint functions, and improve the quality of life. This study aimed to evaluate the efficacy and safety of Zhuanggu joint capsules combined with celecoxib and the benefit of treatment with Zhuanggu alone for KOA. METHODS: This multi-center, randomized, double-blind, double-dummy, parallel controlled trial, started from December 2011 to May 2014, was carried out in 6 cities, including Beijing, Shanghai, Chongqing, Changchun, Chengdu, and Nanjing. A total of 432 patients with KOA were divided into three groups (144 cases in each group). The groups were treated, respectively, with Zhuanggu joint capsules combined with celecoxib capsule simulants, Zhuanggu joint capsules combined with celecoxib capsules, and celecoxib capsules combined with Zhuanggu joint capsule simulants for 4 weeks consecutively. The improvement of Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and the decreased rates in each dimension of WOMAC were evaluated before and after the treatment. Intergroup and intragroup comparisons of quantitative indices were performed. Statistically significant differences were evaluated with pairwise comparisons using Chi-square test (or Fisher's exact test) and an inspection level of α = 0.0167. RESULTS: Four weeks after treatment, the total efficacies of Zhuanggu group, combination group, and celecoxib group were 65%, 80%, and 64%, respectively, with statistically significant differences among the three groups (P = 0.005). Intergroup pairwise comparisons showed that the total efficacy of the combination group was significantly higher than that of the Zhuanggu (P = 0.005) and celecoxib (P = 0.003) groups. The difference between the latter two groups was not statistically significant (P > 0.0167). Four weeks after discontinuation, the efficacies of the three groups were 78%, 95%, and 65%, respectively, with statistically significant differences (P < 0.0001). Intergroup pairwise comparisons revealed that the efficacy of the combination group was significantly better than that of the Zhuanggu and the celecoxib groups (P < 0.0001). The difference between the latter two groups was not statistically significant (P > 0.0167). The incidences of adverse events in Zhuanggu group, combination group, and celecoxib group were 8.5%, 8.5%, and 11.1%, respectively, with insignificant differences (P > 0.05). CONCLUSIONS: Zhuanggu joint capsules alone or combined with celecoxib showed clinical efficacy in the treatment of KOA. The safety of Zhuanggu joint capsules alone or combined with celecoxib was acceptable. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IPR-15007267; http://www.medresman.org/uc/project/projectedit.aspx?proj=1364.

[Comparison of the effect of total hip arthroplasty through mini invasive direct anterior approach during learning curve period and posterolateral approach for the treatment of femoral head necrosis].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Failure of internal fixation on displaced femoral neck fractures in adults under fifty-five years old].

OBJECTIVE: To investigate the failure of internal fixation on displaced femoral neck fractures in adults under fifty-five years old retrospectively inorder to pay more attention to the treatment of these fractures. METHODS: From Junary 2007 to June 2010,18 failed cases of internal fixation on displaced femoral neck fractures in adults under fifty-five years old were treated,there were 13 males and 5 females with an average age of (48.0 +/- 6.0) years old ranging from 27 to 55. Among them, 17 patients were treated with cannulated screws and 1 patient was treated with intramedullary nail; 16 patients were diagnosed as osteonecrosis and 2 patients as osteonecrosis associated with nonunion. RESULTS: The average time from internal fixation to failure was 23 months (ranged, 8 to 32 months). The quality of fracture reduction in Garden index was poor. The Harris Hip Score was (56.0 +/- 12.5) (ranged,33 to 80). Eight cases of osteonecrosis and 2 cases of nonunion combinated osteonecrosis were received total hip arthroplasty. Hip resurfacing arthroplasty were performed for other 5 osteonecrosis. Because of no evident clinical symptoms,the other 3 cases received conservative treatment. The patients with total hip arthroplasty and hip resurfacing arthroplasty were followed-up for 34 months ranging from 12 to 53 months. After operation,the Harris score was (94.0 +/- 3.0) ranged 89 to 96. CONCLUSION: Osteonecrosis is a common complication after internal fixation on displaced femoral neck fracture in adults under fifty-five years old. More attention should be paid to the treatment of displaced femoral neck fracture in those patients.