The efficacy of autologous matrix-induced chondrogenesis (AMIC) for osteochondral lesions of the talus in the mid-long term: a systematic review and meta-analysis.

PURPOSE: The objective of this study was to provide a comprehensive review of the existing literature regarding the treatment of osteochondral lesions of the talus (OLT) using autologous matrix-induced chondrogenesis (AMIC), while also discussing the mid-long term functional outcomes, complications, and surgical failure rate. METHODS: We searched Embase, PubMed, and Web of Science for studies on OLT treated with AMIC with an average follow-up of at least 2 years. Publication information, patient data, functional scores, surgical failure rate, and complications were extracted. RESULTS: A total of 15 studies were screened and included, with 12 case series selected for meta-analysis and 3 non-randomized controlled studies chosen for descriptive analysis. The improvements in the Visual Analog Scale (VAS), the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot, and Tegner scores at the last follow-up were (SMD = - 2.825, 95% CI - 3.343 to - 2.306, P < 0.001), (SMD = 2.73, 95% CI 1.60 to 3.86, P < 0.001), (SMD = 0.85, 95% CI 0.5 to 1.2, P < 0.001) respectively compared to preoperative values. The surgery failure rate was 11% (95% CI 8-15%), with a total of 12 patients experiencing complications. CONCLUSION: The use of AMIC demonstrates a positive impact on pain management, functional improvement, and mobility enhancement in patients with OLT. It is worth noting that the choice of stent for AMIC, patient age, and OLT size can influence the ultimate clinical outcomes. This study provides evidences supporting the safety and efficacy of AMIC as a viable treatment option in real-world medical practice.

The protective effects of orexin-A in alleviating cell senescence against interleukin-1ß (IL-1ß) in chondrocytes.

Osteoarthritis (OA) is one of the most important causes of global disability, and dysfunction of chondrocytes is an important risk factor. The treatment of OA is still a challenge. Orexin-A is a hypothalamic peptide, and its effects in OA are unknown. In this study, we found that exposure to interleukin-1ß (IL-1ß) reduced the expression of orexin-2R, the receptor of orexin-A in TC-28a2 chondrocytes. Importantly, the senescence-associated ß-galactosidase (SA-ß-gal) staining assay demonstrated that orexin-A treatment ameliorates IL-1ß-induced cellular senescence. Importantly, the presence of IL-1ß significantly reduced the telomerase activity of TC-28a2 chondrocytes, which was rescued by orexin-A. We also found that orexin-A prevented IL-1ß-induced increase in the levels of Acetyl-p53 and the expression of p21. It is shown that orexin-A mitigates IL-1ß-induced reduction of sirtuin 3 (SIRT3). Silencing of SIRT3 abolished the protective effects of orexin-A against IL-1ß-induced cellular senescence. These results imply that orexin-A might serve as a promising therapeutic agent for OA.

Finite Element Analysis of Six Internal Fixations in the Treatment of Pauwels Type III Femoral Neck Fracture.

OBJECTIVE: The current investigation sought to utilize finite element analysis to replicate the biomechanical effects of different fixation methods, with the objective of establishing a theoretical framework for the optimal choice of modalities in managing Pauwels type III femoral neck fractures. METHODS: The Pauwels type III fracture configuration, characterized by angles of 70°, was simulated in conjunction with six distinct internal fixation methods, including cannulated compression screw (CCS), dynamic hip screw (DHS), DHS with de-rotational screw (DS), CCS with medial buttress plate (MBP), proximal femoral nail anti-rotation (PFNA), and femoral neck system (FNS). These models were developed and refined using Geomagic and SolidWorks software. Subsequently, finite element analysis was conducted utilizing Ansys software, incorporating axial loading, torsional loading, yield loading and cyclic loading. RESULTS: Under axial loading conditions, the peak stress values for internal fixation and the femur were found to be highest for CCS (454.4; 215.4 MPa) and CCS + MBP (797.2; 284.2 MPa), respectively. The corresponding maximum and minimum displacements for internal fixation were recorded as 6.65 mm for CCS and 6.44 mm for CCS + MBP. When subjected to torsional loading, the peak stress values for internal fixation were highest for CCS + MBP (153.6 MPa) and DHS + DS (72.8 MPa), while for the femur, the maximum and minimum peak stress values were observed for CCS + MBP (119.3 MPa) and FNS (17.6 MPa), respectively. Furthermore, the maximum and minimum displacements for internal fixation were measured as 0.249 mm for CCS + MBP and 0.205 mm for PFNA. Additionally, all six internal fixation models showed excellent performance in terms of yield load and fatigue life. CONCLUSION: CCS + MBP had the best initial mechanical stability in treatment for Pauwels type III fracture. However, the MBP was found to be more susceptible to shear stress, potentially increasing the risk of plate breakage. Furthermore, the DHS + DS exhibited superior biomechanical stability compared to CCS, DHS, and PFNA, thereby offering a more conducive environment for fracture healing. Additionally, it appeared that FNS represented a promising treatment strategy, warranting further validation in future studies.

[Progress in surgical treatment of osteochondral lesion of talus].

Objective: To provide a comprehensive overview of the surgical treatments of osteochondral lesion of talus (OLT) and offer valuable insights for clinical practice. Methods: The advantages and limitations of surgical treatments for OLT were comprehensively summarized through an extensive review of domestic and abroad relevant literature in recent years. Results: Currently, there exist numerous surgical treatments for the OLT, all of which can yield favorable outcomes. However, each method possesses its own set of merits and demerits. The short-term effectiveness of bone marrow stimulation in treating primary OLT with a diameter less than 15 mm is evident, but its long-term effectiveness diminishes over time. Autologous osteochondral transplantation (AOT) and osteochondral allograft transplantation (OAT) are suitable for OLT with large defects and subchondral bone cysts. However, incomplete anatomical matching between the donor and recipient bones may results in the formation of new subchondral bone cysts, while AOT also presents potential complications at the donor site. In contrast to AOT and OAT, particulated juvenile cartilage allograft transplantation obviates the need for additional osteotomy. Furthermore, juvenile cartilage exhibits enhanced potential in delivering active chondrocytes to the site of cartilage defect, surpassing that of adult cartilage in tissue repair efficacy. Cell transplantation has demonstrated satisfactory effectiveness; however, it is associated with challenges such as the requirement for secondary surgery and high costs. Autologous matrix-induced chondrogenesis technology has shown promising effectiveness in the treatment of primary and non-primary OLT and OLT with large defect and subchondral bone cysts. However, there is a scarcity of relevant studies, most of which exhibit low quality. Adjuvant therapy utilizing biological agents represents a novel approach to treating OLT; nevertheless, due to insufficient support from high-quality studies, it has not exhibited significant advantages over traditional treatment methods. Furthermore, its long-term effectiveness remain unclear. Conclusion: The optimal choice of surgical treatment for OLT is contingent not only upon the characteristics such as nature, size, and shape but also takes into consideration factors like advancements in medical technology, patient acceptance, economic status, and other pertinent aspects to deliver personalized treatment.

Identification of copy number variants contributing to hallux valgus.

Hallux valgus is a common form of foot deformity, and genetic factors contribute substantially to the pathogenesis of hallux valgus deformity. We conducted a genetic study on the structural variants underlying familial hallux valgus using whole exome sequencing approach. Twenty individuals from five hallux valgus families and two sporadic cases were included in this study. A total of 372 copy number variations were found and passed quality control filtering. Among them, 43 were only present in cases but not in controls or healthy individuals in the database of genomic variants. The genes covered by these copy number variations were enriched in gene sets related to immune signaling pathway, and cytochrome P450 metabolism. The hereditary CNVs demonstrate a dominant inheritance pattern. Two candidate pathogenic CNVs were further validated by quantitative-PCR. This study suggests that hallux valgus is a degenerative joint disease involving the dysregulation of immune and metabolism signaling pathways.

Does the Level of Syndesmotic Screw Insertion Affect Clinical Outcome after Ankle Fractures with Syndesmotic Instability?

OBJECTIVE: Ankle fractures are often combined with syndesmotic instability, requiring reduction and stabilization. However, the optimal level for syndesmotic screw positioning remains unclear. This study aims to evaluate the effect of different syndesmotic screw insertion levels on postoperative clinical outcomes and determine whether an optimal level exists. METHODS: This retrospective study included data from 43 adult patients with acute closed ankle fractures combined with intraoperative evidence of unstable syndesmotic injuries who underwent open reduction internal fixation from January 1, 2017 to March 1, 2018 according to the inclusion and exclusion criteria. All 43 patients were divided into three groups based on the syndesmotic screw placement level: trans-syndesmotic group: screw level of 2-3 cm; inferior-syndesmotic group: screw level <2 cm; and supra-syndesmotic group: screw level >3 cm. Clinical outcomes were measured at the final follow-up, including the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, Olerud-Molander Ankle Score (OMAS), short-form 36-item questionnaire (SF-36), visual analogue scale (VAS) score and restrictions in ankle range of motion (ROM). The relationships between screw placement level and clinical outcomes were analyzed with the Kruskal-Wallis H-test and Spearman correlation analysis. RESULTS: The median follow-up duration was 15 months (range, 10-22 months). No patients developed fracture nonunion or malunion or experienced hardware failure. The outcome scoring systems showed an overall score for the entire group of 94.91 points for the AOFAS ankle-hindfoot score, 83.14 for the OMAS, 96.65 for the SF-36, 1.77 for the VAS, 9.14° for the restrictions in dorsiflexion, and 1.30° for the restrictions in plantarflexion. There were no significant differences among three groups in clinical outcomes (P > 0.05). Neither the AOFAS score nor OMAS had significant correlations with screw insertion level (P = 0.825 and P = 0.585, respectively). No postoperative arthritis or widening of the tibiofibular space was observed at the final follow-up. CONCLUSION: Different syndesmotic screw placement levels appear not to affect the clinical outcomes of ankle fractures with syndesmotic instability. No optimal level was observed in this study. Our findings suggest other clinically acceptable options apart from syndesmotic screw placement 2-3 cm above the ankle.

Plate versus screws fixation for the posterior malleolar fragment in trimalleolar ankle fractures.

BACKGROUND: The fixation methods of posterior malleolar fracture (PMF) in trimalleolar ankle fractures is still controversial. We aim to compare clinical and radiological outcomes between plate fixation and screws fixation for PMF in trimalleolar ankle fractures. METHODS: Literature search was performed through PubMed, EMBASE, Cochrane Library and CNKI database from databases inception to May 2022 to identify randomized controlled trial (RCT) and comparative clinical study in English or Chinese. A meta-analysis was performed using RevMan 5.1 software, and systematic review was performed when the data extracted from included studies could not be synthesized. RESULTS: Two RCTs and six cohort studies were included. The meta-analysis results showed that articular step-off or gap in plate fixation was superior to antero-posterior screws fixation (RR = 0.28; 95%CI: 0.11, 0.76; P = 0.01). there were no significant differences in American Orthopaedic Foot & Ankle Society scores (MD = -0.19; 95%CI: -2.43, 2.05; P = 0.87), arthritis (RR = 1.67; 95%CI: 0.61, 4.55; P = 0.32), infection and total complication (RR = 1.42; 95%CI: 0.89, 2.25; P = 0.14). CONCLUSION: Plate fixation might have better articular step-off or gap, compared with "A to P" screws fixation for the posterior malleolus in trimalleolar ankle fractures. Screw fixation could achieve shorter surgical time than plate fixation. However, no significant differences were found in AOFAS scores, arthritis, infection, sural nerve injury and total complication during the comparisons.

SPECT/CT imaging features of cystic degeneration of the talus and their relation to pathological findings.

BACKGROUND: Osteochondral lesions of the talus (OLTs) are a common orthopedic condition. The image presentation is very similar to that of ischemic necrosis of the talus complicated by a talar neck fracture, but the two are very different lesions. When abnormalities in bone density (or signal) of the talar body (apex of the fornix) with concomitant bone defects and cystic changes are found on X-ray, computed tomography (CT), or magnetic resonance imaging, it is important to accurately determine the nature of the lesion and make a correct diagnosis for the treatment and prognosis of the patient. The purpose of this study was to explore the imaging features of three-phase single-photon emission computed tomography (SPECT)/CT images of cystic lesions of the talus. METHODS: A total of 189 patients with chronic pain in the ankle joint suspected to be caused by cystic degeneration of the talus were enrolled. All patients underwent 99mTc-methyl diphosphonate (99mTc-MDP) three-phase SPECT/CT bone imaging and delayed scans in our hospital. The location, range of involvement, classification, CT value, and radioactivity uptake of the sclerotic areas of cystic lesions on the talus, and the continuity of the articular surface, were recorded. All recorded parameters were analyzed in comparison with pathological results. RESULTS: Eighty-three percent (157/189) of the talar cysts were located on the medial fornix, largely involving the anterior middle part (43.27%), with larger cysts involving the posterior part (9.6%). Sixty-three percent (119/189) of the patients had type I lesions and 37% (70/189) had type II lesions. The articular surface of the medial dome of the talus was intact in all patients, but the subchondral bony articular surface was rough in 88% (166/189) of patients. The coincidence rate for the location, type, and range of involvement of cystic lesions with the pathological results was 87.83% (166/189). The mean CT value of the cystic lesions was 45 ± 15 HU (30-60 HU). The percentages of pathological chondrogenesis in high CT value ≥ 50 HU (19/70) and low CT value < 50 HU (51/70) groups were 89.47% (17/19) and 29.14% (15/51) (χ2 = 20.12, p < 0.001), respectively. The target/background ratio (T/B ratio) of the radioactivity-uptake area of the talus vault was 2.0 ± 0.5 (1.5-2.5). The percentages of pathological new trabecular bone in those with a T/B ratio ≥ 2.0 (157/189) and T/B ratio < 2.0 (32/189) were 82.80% (130/157) and 25.00% (8/32; χ2 = 45.08, p < 0.001), respectively. CONCLUSIONS: Three-phase bone imaging could identify damage of the talus caused by cystic degeneration, while delayed SPECT/CT images showed advantages for displaying bone microstructure, blood supplement, and bone metabolism when examining the location, range of involvement, classification, and repair of cystic lesions of the talus.

New insights into hallux valgus by whole exome sequencing study.

The traditional view is that the occurrence and development of hallux valgus (HV) are mainly due to environmental factors. Recent studies have suggested the large contribution of genetic heritability to HV, but it remains elusive about the genetic variants underlying the development of HV. To gain knowledge about the molecular mechanisms of HV pathogenesis by genetic approach, whole exome sequencing studies were performed in 10 individuals (7 affected by HV and 3 unaffected) from three independent families. Specific mutations were found to be related to the pathogenesis of HV and conform to the laws of inheritance. A total of 36 genes with functional candidate single nucleotide variants were identified. Genetic predisposition plays an important role in the development of HV. Interestingly, some of these genes are related to chronic arthritis, such as the complement encoding gene C7, or are related to long toe or long fingers, such as TTN, COL6A3, LARS, FIG4, and CBS. This study identified rare potentially pathogenic mutations represented by genes related to digital anomalies and chronic arthritis underlying the familial types of HV, which acquired new insights into the genetic and physiological foundations of HV, thereby might improve accurate prevention and drug development for HV.

[Advance of diagnosis and treatment of Haglund syndrome].

OBJECTIVE: To review the current research on the diagnosis and treatment of Haglund syndrome. METHODS: The domestic and foreign literature about Haglund syndrome in recent years was extensively reviewed to summarize and analyze the etiology, anatomy, clinical manifestations, diagnosis, and treatment of Haglund syndrome. RESULTS: The etiology of Haglund syndrome is not very clear, and it may be related to local friction and high gastrocnemius muscle tension, and there may be a certain genetic tendency. The local anatomy is more complex and there are many adjacent tissue structures. Haglund malformation may cause the impingement of the posterior heel bursa and Achilles tendon insertion, lead to wear of the posterior heel bursa and the Achilles tendon insertion, and finally result in pain. The FPA (Fowler-Philipp angle), CPA (calcaneal pith angle), PPL (parallel pitch lines), CLA (Chauveaux-Liet angle), and X/Y ratios (ratio of total calcaneal length to calcaneal tuberosity length) measured on X-ray film can be used for the diagnostic measurement of Haglund malformation. Treatment includes conservative and surgical treatment (open Haglund ostectomy, dorsal closed wedge osteotomy of the calcaneus, and arthroscopic Haglund osteotomy). CONCLUSION: Both open and arthroscopic Haglund ostectomy and dorsal closed wedge osteotomy of the calcaneus can achieve satisfactory results, but minimally invasive treatment is the current development trend. Surgeons should pay attention to the management of the calcification of Achilles tendon insertion and reconstruction of Achilles tendon insertion.

[Research progress of early postoperative rehabilitation for acute Achilles tendon rupture after surgical repair].

Objective: To summarize the latest research progress of early postoperative rehabilitation for acute Achilles tendon rupture after surgical repair. Methods: The high-quality randomized controlled trials and systematic reviews/meta-analyses regarding early postoperative rehabilitation for acute Achilles tendon rupture in recent years were reviewed. Results: There are three functional rehabilitations after acute Achilles tendon rupture surgery, including early postoperative mobilization, early weight-bearing with immobilization, and early weight-bearing combined with mobilization. The results of randomized controlled trials show that the effectiveness of early postoperative rehabilitation is similar or better than the early postoperative immobilization. The results of systematic reviews/meta-analyses show that the early postoperative rehabilitation is beneficial to the early function recovery of the Achilles tendon, can reduce the time for functional recovery, and do not adversely affect the outcomes. Conclusion: Early postoperative rehabilitation is beneficial to the functional recovery, and do not increase postoperative complications. There is still no uniform protocol of early postoperative rehabilitation and the timing of weight-bearing, and further studies are needed in the future.

A functional polymorphism at miR­491­5p binding site in the 3'UTR of MMP9 gene confers increased risk for pressure ulcers after hip fracture.

The roles of matrix metalloproteinase (MMP)9 in the control of pressure ulcers (PU) after hip fracture as well as how the rs1056629 in MMP9 3'UTR compromises the interaction between MMP9 and miR­491 were explored. Online miRNA database (http://www.bioguo.org) was utilized to explore gene polymorphism in MMP9 3'UTR that might break the interaction between MMP9 and miRNA. Luciferase assay was utilized to confirm the miRNA targeted MMP9. Real­time PCR, western blot analysis and immunohistochemistry were carried out to understand the roles of MMP9 in PU as well as how rs1056629 in MMP9 3'UTR compromises the interaction between MMP9 and miR­491. rs1056629 in MMP9 3'UTR that compromised the interaction between MMP9 and four miRNAs including miR­194­3p, miR­491, miR­1915­3p and miR­941, and only miR­491 among miR­194­3p, miR­491, miR­1915­3p and miR­941 decreased luciferase activity of wild­type MMP9 3'UTR, and luciferase activities of mutant­3 and mutant­4 MMP9 3'UTR in miR­491 overexpressing cells was comparable with scramble control. miR­194­3p, miR­491, miR­1915­3p and miR­941 levels in PU group was comparable with healthy control, and miR­194­3p, miR­491, miR­1915­3p and miR­941 in subjects carrying AA genotype was similar with those in AC and CC groups. MMP9 mRNA and protein, and histology score in subjects with PU were much higher, and were also much higher in AA group. Only miR­491 mimic among miR­194­3p, miR­491, miR­1915­3p and miR­941 mimics downregulated the MMP9 level, and only miR­491 inhibitor among miR­194­3p, miR­491, miR­1915­3p and miR­941 inhibitors upregulated the MMP9 level. Our study indicated that rs1056629 polymorphism could be a novel biomarker for predicting the occurrence of PU after a hip fracture.

Association Between Calcium or Vitamin D Supplementation and Fracture Incidence in Community-Dwelling Older Adults: A Systematic Review and Meta-analysis.

Importance: The increased social and economic burdens for osteoporosis-related fractures worldwide make the prevention of such injuries a major public health goal. Previous studies have reached mixed conclusions regarding the association between calcium, vitamin D, or combined calcium and vitamin D supplements and fracture incidence in older adults. Objective: To investigate whether calcium, vitamin D, or combined calcium and vitamin D supplements are associated with a lower fracture incidence in community-dwelling older adults. Data Sources: The PubMed, Cochrane library, and EMBASE databases were systematically searched from the inception dates to December 24, 2016, using the keywords calcium, vitamin D, and fracture to identify systematic reviews or meta-analyses. The primary randomized clinical trials included in systematic reviews or meta-analyses were identified, and an additional search for recently published randomized trials was performed from July 16, 2012, to July 16, 2017. Study Selection: Randomized clinical trials comparing calcium, vitamin D, or combined calcium and vitamin D supplements with a placebo or no treatment for fracture incidence in community-dwelling adults older than 50 years. Data Extraction and Synthesis: Two independent reviewers performed the data extraction and assessed study quality. A meta-analysis was performed to calculate risk ratios (RRs), absolute risk differences (ARDs), and 95% CIs using random-effects models. Main Outcomes and Measures: Hip fracture was defined as the primary outcome. Secondary outcomes were nonvertebral fracture, vertebral fracture, and total fracture. Results: A total of 33 randomized trials involving 51 145 participants fulfilled the inclusion criteria. There was no significant association of calcium or vitamin D with risk of hip fracture compared with placebo or no treatment (calcium: RR, 1.53 [95% CI, 0.97 to 2.42]; ARD, 0.01 [95% CI, 0.00 to 0.01]; vitamin D: RR, 1.21 [95% CI, 0.99 to 1.47]; ARD, 0.00 [95% CI, -0.00 to 0.01]. There was no significant association of combined calcium and vitamin D with hip fracture compared with placebo or no treatment (RR, 1.09 [95% CI, 0.85 to 1.39]; ARD, 0.00 [95% CI, -0.00 to 0.00]). No significant associations were found between calcium, vitamin D, or combined calcium and vitamin D supplements and the incidence of nonvertebral, vertebral, or total fractures. Subgroup analyses showed that these results were generally consistent regardless of the calcium or vitamin D dose, sex, fracture history, dietary calcium intake, and baseline serum 25-hydroxyvitamin D concentration. Conclusions and Relevance: In this meta-analysis of randomized clinical trials, the use of supplements that included calcium, vitamin D, or both compared with placebo or no treatment was not associated with a lower risk of fractures among community-dwelling older adults. These findings do not support the routine use of these supplements in community-dwelling older people.

Comparison of Posteromedial Versus Posterolateral Approach for Posterior Malleolus Fixation in Trimalleolar Ankle Fractures.

OBJECTIVE: To compare clinical and radiographic outcomes of posterior malleolar fractures (PMF) treated with lag screws from anterior to posterior versus posterior to anterior approach. METHODS: We retrospectively analyzed 48 patients with trimalleolar fractures who underwent open reduction and internal fixation (ORIF) with either posteromedial (PM) or posterolateral (PL) approaches between January 2012 and December 2014. Fixation of the posterior malleolus was made with anteroposterior screws in 20 patients using the PM approach and posteroanterior screws in 28 patients using the PL approach. The American Orthopedic Foot and Ankle Society (AOFAS) scores and range of motion (ROM) of the ankle were used as the main outcome measurements, and results were evaluated at the 6-month, 12-month and final follow-up. Postoperative radiographs and computed tomography scans were used to evaluate the residual gap/step-off. The degree of arthritis was evaluated on final follow-up using Bargon criteria. Other complications were also recorded to compare the clinical outcomes of the two approaches. RESULT: The mean duration of follow-up regardless of the approaches was 21.1 months (range, 15-54 months). None of the patients developed delayed union or nonunion. Functional bone healing was obtained in all patients at 10.7 weeks (range, 8-16 weeks). The mean AOFAS scores of the PM group at the postoperative 6-mouth, 12-month, and final follow-up were 91.4 (range, 82-100), 92.5 (range, 84-100), and 92.9 (range, 86-100), respectively. In the PL group, the mean AOFAS scores were 89.9 (range, 72-100), 91.4 (range, 77-100), and 91.9 (range, 77-100), respectively. At the final follow-up, the median loss of range of motion (ROM) for dorsiflexion and plantaflexion were 0°(0°, 5°) and 0°(0°, 0°), respectively, in both groups. There were no significant differences between the two approaches in AOFAS scores and ROM of the ankle in each period postoperatively (P > 0.05). Two patients in the PL group and 1 in the PM group developed Bargon grade 2 or 3 arthritis. We detected a 2-mm and 3-mm step-off in 1 patient in the PM and PL groups, respectively. CONCLUSION: Satisfactory results were obtained by using the two approaches for fixation of posterior malleolus, and the approaches have similar clinical and radiographic outcomes. Surgeons should choose the appropriate approach based on their experience.

Estrogen stimulates osteoprotegerin expression via the suppression of miR-145 expression in MG-63 cells.

Osteoprotegerin (OPG) is implicated in the pathogenesis of postmenopausal osteoporosis, and other metabolic bone diseases caused by estrogen deficiency. Previous studies have demonstrated that estrogen may stimulate OPG expression in osteoblast cells at the transcriptional level; however, whether estrogen can regulate OPG expression at a post-transcriptional level remains elusive. The present study aimed to investigate the role of microRNA (miRNA) in estrogen­mediated OPG production in human osteoblast­like MG­63 cells. The results from ELISA, western blotting and reverse transcription-quantitative polymerase chain reaction (RT­qPCR) confirmed that estrogen may upregulate OPG expression. Mechanistic studies indicated that estrogen increased the activity of a luciferase reporter harboring the OPG 3'­untranslated region (3'­UTR). Bioinformatics analysis demonstrated that there is a potential targeting site in the OPG 3'­UTR for miRNA (miR)­145, which is associated with osteoblast differentiation. The results of an RT­qPCR suggested that estrogen suppressed miR­145 expression. In addition, dual­luciferase assay, RT­qPCR and western blot analysis indicated that miR­145 directly targets and negatively regulates OPG expression. Furthermore, transfection of cells with miR­145 mimics was able to partially inhibit the induction of OPG expression by estrogen, thus confirming the role of miR­145 in estrogen­mediated OPG induction. Taken together, the results of the present study demonstrated that estrogen may post-transcriptionally regulate OPG expression through suppression of miR-145 expression.

Surgical interventions to treat humerus shaft fractures: A network meta-analysis of randomized controlled trials.

BACKGROUND: There are three main surgical techniques to treat humeral shaft fractures: open reduction and plate fixation (ORPF), intramedullary nail (IMN) fixation, and minimally invasive percutaneous osteosynthesis (MIPO). We performed a network meta-analysis to compare three surgical procedures, including ORPF, IMN fixation, and MIPO, to provide the optimum treatment for humerus shaft fractures. METHODS: MEDLINE, EMBASE, Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, and Cochrane library were researched for reports published up to May 2016. We only included randomized controlled trials (RCTs) comparing two or more of the three surgical procedures, including the ORPF, IMN, and MIPO techniques, for humeral shaft fractures in adults. The methodological quality was evaluated based on the Cochrane risk of bias tool. We used WinBUGS1.4 to conduct this Bayesian network meta-analysis. We used the odd ratios (ORs) with 95% confidence intervals (CIs) to calculate the dichotomous outcomes and analyzed the percentages of the surface under the cumulative ranking curve. RESULTS: Seventeen eligible publications reporting 16 RCTs were included in this study. Eight hundred and thirty-two participants were randomized to receive one of three surgical procedures. The results showed that shoulder impingement occurred more commonly in the IMN group than with either ORPF (OR, 0.13; 95% CI, 0.03-0.37) or MIPO fixation (OR, 0.08; 95% CI, 0.00-0.69). Iatrogenic radial nerve injury occurred more commonly in the ORPF group than in the MIPO group (OR, 11.09; 95% CI, 1.80-124.20). There were no significant differences among the three procedures in nonunion, delayed union, and infection. CONCLUSION: Compared with IMN and ORPF, MIPO technique is the preferred treatment method for humeral shaft fractures.

Early functional rehabilitation versus traditional immobilization for surgical Achilles tendon repair after acute rupture: a systematic review of overlapping meta-analyses.

Several meta-analyses comparing early functional rehabilitation and traditional immobilization following surgical Achilles tendon repair after acute rupture have been published. However, they have led to conflicting conclusions. The aims of this systematic review were to select high-quality meta-analyses from multiple discordant meta-analyses and to provide a postoperative rehabilitation strategy following surgical repair using currently available evidence. We performed a comprehensive search using the PubMed and Embase databases and the Cochrane Library. Assessment of Multiple Systematic Reviews (AMSTAR) instrument was used to assess the methodological quality. Three investigators independently applied the Jadad decision algorithm. Their results were then compared to ensure selection of a meta-analysis that provided the highest quality of evidence. Six meta-analyses met the eligibility criteria. AMSTAR scores ranged from 6 to 10. According to the Jadad decision algorithm, a high-quality meta-analysis with a greater number of RCTs was selected. This meta-analysis showed that early functional rehabilitation was superior to cast immobilization in terms of patient satisfaction and the time to return to pre-morbid sporting levels. There were no differences regarding major complications or the time before return to prior employment and sporting activity. Thus, we recommend early functional rehabilitation as the postoperative strategy for acute Achilles tendon ruptures.