A novel approach for anterior cruciate ligament tibial avulsion fracture: arthroscopic modified suture bridge fixation technique.

INTRODUCTION: Anterior cruciate ligament (ACL) tibial avulsion fracture is a rare injury, which usually happens in adults with traffic accidents or sports injuries. Surgery interventions are common treatment methods, they can restore knee function and help to return to normal life. In this study, we described an arthroscopic modified suture bridge fixation technique for ACL tibial avulsion fractures and explored the feasibility and therapeutic effects. MATERIALS AND METHODS: This retrospective study reviewed data from January 2020 to May 2022. Data were collected on 18 patients (10 males and 8 females) with ACL tibial avulsion fractures and underwent arthroscopic modified suture bridge fixation technique. The study analyzed surgical data about intraoperative blood loss, operation time, hospital stay, fracture healing time, and visual analog scale (VAS). Functional evaluation of the knee joint was performed using the anterior drawer test, Lysholm knee scoring scale, International Knee Documentation Committee (IKDC), and knee range of motion (ROM). RESULTS: All 18 patients were followed up between 12 and 20 months, with an average of 15.22 ± 1.96 months. The intraoperative blood loss was approximately 15-40 mL, averaging 25.78 ± 6.19 mL. The operation time was 65-85 min, with a mean of 74.89 ± 4.86 min. The hospital stay of patients was 3-5 days, with a mean of 3.89 ± 0.76 days. The mean fracture healing time was 8-12 weeks after surgery, with a mean of 9.22 ± 1.7 weeks. All incisions healed grade I without infection. There were no internal fixation failures, neurovascular injuries, and lower extremity deep venous thrombosis. The anterior drawer test was negative in all patients. At the final follow-up, the mean VAS score was 0-3, averaging 1.56 ± 0.71. The Lysholm score of the injured knee was 89-96, with an average of 92.50 ± 2.50; the IKDC score was 88-93, with an average of 90.44 ± 1.89; the knee ROM was 110-126°, with an average of 120.67° ± 4.31°. CONCLUSION: Results demonstrated that the modified suture bridge fixation technique under arthroscope could provide reliable fixation and favorable clinical effects for ACL tibial avulsion fractures. This is a simple, minimally invasive, effective, and clinically applicable surgical method for ACL tibial avulsion fracture.

Harnessing Nucleic Acids Nanotechnology for Bone/Cartilage Regeneration.

The effective regeneration of weight-bearing bone defects and critical-sized cartilage defects remains a significant clinical challenge. Traditional treatments such as autologous and allograft bone grafting have not been successful in achieving the desired outcomes, necessitating the need for innovative therapeutic approaches. Nucleic acids have attracted significant attention due to their ability to be designed to form discrete structures and programmed to perform specific functions at the nanoscale. The advantages of nucleic acid nanotechnology offer numerous opportunities for in-cell and in vivo applications, and hold great promise for advancing the field of biomaterials. In this review, the current abilities of nucleic acid nanotechnology to be applied in bone and cartilage regeneration are summarized and insights into the challenges and future directions for the development of this technology are provided.

RANKL from bone marrow adipose lineage cells promotes osteoclast formation and bone loss.

Receptor activator of NF-κB ligand (RANKL) is essential for osteoclast formation and bone remodeling. Nevertheless, the cellular source of RANKL for osteoclastogenesis has not been fully uncovered. Different from peripheral adipose tissue, bone marrow (BM) adipose lineage cells originate from bone marrow mesenchymal stromal cells (BMSCs). Here, we demonstrate that adiponectin promoter-driven Cre expression (AdipoqCre ) can target bone marrow adipose lineage cells. We cross the AdipoqCre mice with ranklfl/fl mice to conditionally delete RANKL from BM adipose lineage cells. Conditional deletion of RANKL increases cancellous bone mass of long bones in mice by reducing the formation of trabecular osteoclasts and inhibiting bone resorption but does not affect cortical bone thickness or resorption of calcified cartilage. AdipoqCre ; ranklfl/fl mice exhibit resistance to estrogen deficiency and rosiglitazone (ROS)-induced trabecular bone loss but show bone loss induced by unloading. BM adipose lineage cells therefore represent an essential source of RANKL for the formation of trabecula osteoclasts and resorption of cancellous bone during remodeling under physiological and pathological conditions. Targeting bone marrow adiposity is a promising way of preventing pathological bone loss.

A new method of anterior talofibular ligament reconstruction: Arthroscopically artificial ligament reconstruction with tensional remnant-repair.

PURPOSE: To investigate the clinical effects of arthroscopically artificial ligament reconstruction with tensional remnant-repair in patients who are obese, and/or with demand for highly intensive sports, and/or with poor-quality ligament remnants. METHODS: A retrospective case series study was performed on patients treated by arthroscopically anterior talofibular ligament (ATFL) reconstruction with tensional remnant repair technique from January 2019 to August 2021. General data, including demographics, surgical time, and postoperative adverse events, were recorded. The American Orthopaedic Foot and Ankle Society score (AOFAS), foot and ankle ability measure (FAAM), visual analog scale (VAS), and anterior talar translation were measured preoperatively and at 6 weeks, 3 months, and 2 years postoperatively. Ultrasonography examination was performed preoperatively and 2 years postoperatively to evaluate the ATFL. Data were analyzed using SPSS 19.0. F test was used to analyze the pre- and postoperative VAS, FAAM, and AOFAS scores. The significance was set at p < 0.05. RESULTS: There were 20 males and 10 females among the patients with a mean age of (30.71 ± 5.81) years. The average surgical time was (40.21 ± 8.59) min. No adverse events were observed after surgery. At 2 years postoperatively, the anterior talar translation test showed grade 0 laxity in all patients. VAS score significantly decreased from preoperatively to 6 weeks, 3 months, and 2 years postoperatively (p < 0.001). Improvement of FAAM score and the AOFAS score from preoperatively to 6 weeks, 3 months, and 2 years postoperatively was statistically significant (p < 0.001). At 3 months postoperatively, most patients (23/30) could return to their pre-injured activities of daily living status. At 2 years postoperatively, all patients were able to return to their pre-injured activities of daily living status, and almost every patient (18/19) who expected highly intensive sports returned to sports with only 1 obese patient failing to achieve the goal. The ultrasonography examination at 2 years postoperatively showed that there was a linear band structure of soft tissue on the tension-rich fiber tape image from the fibular to the talar attachment sits of ATFL. CONCLUSION: The novel arthroscopically artificial ligament reconstruction with tensional remnant-repair technique for ATFL achieved satisfactory clinical outcomes in the short and medium term after operation, and allowed early return to pre-injured activities, which could be a reliable option for patients with chronic lateral ankle instability.

Comparison between osteosynthesis with interlocking nail and minimally invasive plating for proximal- and middle-thirds of humeral shaft fractures.

PURPOSE: Options for the treatment of proximal- and middle-thirds of humeral shaft fractures include intramedullary interlocking nail (IMN) and minimally invasive plate osteosynthesis (MIPO). However, whether IMN provides better clinical outcomes than MIPO surgical technique still remains unclear. This study was designed to compare clinical outcomes of the IMN with MIPO technique for the treatment of proximal- and middle-thirds of humeral shaft fractures. METHOD: A retrospective cohort analysis of 55 proximal- and middle-thirds of humeral shaft fractures surgically treated using IMN (n = 25) or MIPO (n = 30) from January 2012 to January 2016. Peri-operative and follow-up data (a minimum of 1 year) of the patients (aged from 18 to 56 years) were collected. Operative time, union time, VAS scores, surgery-related complications, and implant removal rate were compared between the two groups in this study. Besides, the functional outcomes were evaluated using the Rating Scale of American Shoulder and Elbow Surgeons' Form (ASES) and Mayo Elbow Performance Score System (MEPS). RESULT: We found significantly shorter operative time and much less blood loss in IMN group, and lower VAS scores in the IMN group after surgery at first and third months but not at the sixth month. Complication rate was found to be relatively higher in the MIPO group when compared to the IMN group. No significant difference was observed between these two groups regarding ASES and MEPS scores. Three patients in the MIPO group suffered iatrogenic radial nerve injury and recovered after four to five months later. No implant failures occurred in either group. CONCLUSION: Intramedullary interlocking nail seemed to be superior to minimally invasive plate osteosynthesis in the treatment of proximal- and middle-thirds of humeral shaft fractures due to shorter operative time and union time, less early post-operative pain, and fewer complications. The intramedullary interlocking nail could be considered a better surgical option for the management of proximal middle humeral fractures, though it may also depend on the surgeons' skills and learning curve. Further in-depth prospective studies are in great need to verify our conclusion.

Intramedullary nails in combination with reconstruction plate in the treatment of unstable intertrochanteric femoral fractures with lateral wall damage.

BACKGROUND: The unstable intertrochanteric femur fracture remains a challenge for surgeons. However, few studies have compared the clinical effectiveness of intramedullary nail in combination with a reconstruction plate and intramedullary nail alone in the treatment of patients with unstable intertrochanteric femoral fractures with lateral wall damage. METHODS: This study retrospectively analyzed 16 patients with 31 A3 intertrochanteric fractures treated with the intramedullary nail in combination with reconstruction plate (the study group) and 19 patients with 31 A3 intertrochanteric fractures treated with intramedullary nail alone (the control group) between January 2012 and January 2018. The operation time, intra-operative blood loss, time of fracture healing, and complication rates of post-operative fixation failure were assessed between the two groups. At the follow-up of post-operative six and 12 months, Harris hip score (HHS) and the Parker-Palmer mobility score (PPMS) were used to evaluate the functional states and mobility levels. RESULTS: The distribution of all basic characteristics was similar between the two groups (P ˃ 0.05). The study group had longer operation time and more intra-operative blood loss in comparison with the control group (P < 0.001), while the study group had shorter fracture healing time (P = 0.03) and lower fixation failure rate as compared with the control group. Regarding the functional outcome, the study group had higher HHSs and PPMS than the control group (P = 0.003). CONCLUSIONS: Although intramedullary nails in combination with reconstruction plates had longer operation time and more intra-operative blood loss, it might be superior to intramedullary nail alone in terms of fracture healing time, fixation failure complication rate, and post-operative functional recovery.

Triptolide prevents bone loss via suppressing osteoclastogenesis through inhibiting PI3K-AKT-NFATc1 pathway.

Bone loss (osteopenia) is a common complication in human solid tumour. In addition, after surgical treatment of gynaecological tumour, osteoporosis often occurs due to the withdrawal of oestrogen. The major characteristic of osteoporosis is the low bone mass with micro-architectural deteriorated bone tissue. And the main cause is the overactivation of osteoclastogenesis, which is one of the most important therapeutic targets. Inflammation could induce the interaction of RANKL/RANK, which is the promoter of osteoclastogenesis. Triptolide is derived from the traditional Chinese herb lei gong teng, presented multiple biological effects, including anti-cancer, anti-inflammation and immunosuppression. We hypothesized that triptolide could inhibits osteoclastogenesis by suppressing inflammation activation. In this study, we confirmed that triptolide could suppress RANKL-induced osteoclastogenesis in bone marrow mononuclear cells (BMMCs) and RAW264.7 cells and inhibited the osteoclast bone resorption functions. PI3K-AKT-NFATc1 pathway is one of the most important downstream pathways of RANKL-induced osteogenesis. The experiments in vitro indicated that triptolide suppresses the activation of PI3K-AKT-NFATc1 pathway and the target point located at the upstream of AKT because both NFATc1 overexpression and AKT phosphorylation could ameliorate the triptolide suppression effects. The expression of MDM2 was elevated, which demonstrated the MDM-p53-induced cell death might contribute to the osteoclastogenesis suppression. Ovariectomy-induced bone loss and inflammation activation were also found to be ameliorated in the experiments in vivo. In summary, the new effect of anti-cancer drug triptolide was demonstrated to be anti-osteoclastogenesis, and we demonstrated triptolide might be a promising therapy for bone loss caused by tumour.

Guaiacol suppresses osteoclastogenesis by blocking interactions of RANK with TRAF6 and C-Src and inhibiting NF-κB, MAPK and AKT pathways.

Angelica sinensis (AS; Dang Gui), a traditional Chinese herb, has for centuries been used for the treatment of bone diseases, including osteoporosis and osteonecrosis. However, the effective ingredient and underlying mechanisms remain elusive. Here, we identified guaiacol as the active component of AS by two-dimensional cell membrane chromatography/C18 column/time-of-flight mass spectrometry (2D CMC/C18 column/TOFMS). Guaiacol suppressed osteoclastogenesis and osteoclast function in bone marrow monocytes (BMMCs) and RAW264.7 cells in vitro in a dose-dependent manner. Co-immunoprecipitation indicated that guaiacol blocked RANK-TRAF6 association and RANK-C-Src association. Moreover, guaiacol prevented phosphorylation of p65, p50, IκB (NF-κB pathway), ERK, JNK, c-fos, p38 (MAPK pathway) and Akt (AKT pathway), and reduced the expression levels of Cathepsin K, CTR, MMP-9 and TRAP. Guaiacol also suppressed the expression of nuclear factor of activated T-cells cytoplasmic 1(NFATc1) and the RANKL-induced Ca2+ oscillation. In vivo, it ameliorated ovariectomy-induced bone loss by suppressing excessive osteoclastogenesis. Taken together, our findings suggest that guaiacol inhibits RANKL-induced osteoclastogenesis by blocking the interactions of RANK with TRAF6 and C-Src, and by suppressing the NF-κB, MAPK and AKT signalling pathways. Therefore, this compound shows therapeutic potential for osteoclastogenesis-related bone diseases, including postmenopausal osteoporosis.

l-tetrahydropalmatine suppresses osteoclastogenesis in vivo and in vitro via blocking RANK-TRAF6 interactions and inhibiting NF-κB and MAPK pathways.

Bone homeostasis is delicately orchestrated by osteoblasts and osteoclasts. Various pathological bone loss situations result from the overactivated osteoclastogenesis. Receptor activator of nuclear factor κB ligand (RANKL)-activated NF-κB and MAPK pathways is vital for osteoclastogenesis. Here, we for the first time explored the effects of l-tetrahydropalmatine (l-THP), an active alkaloid derived from corydalis, on the formation and function of osteoclasts in vitro and in vivo. In RAW264.7 cells and bone marrow monocytes cells (BMMCs), l-THP inhibited osteoclastic differentiation at the early stage, down-regulated transcription level of osteoclastogenesis-related genes and impaired osteoclasts functions. Mechanically, Western blot showed that l-THP inhibited the phosphorylation of P50, P65, IκB, ERK, JNK and P38, and the electrophoretic mobility shift assay (EMSA) revealed that DNA binding activity of NF-κB was suppressed, ultimately inhibiting the expression of nuclear factor of activated T cells (NFATc1). Besides, Co-immunoprecipitation indicated that l-THP blocked the interactions of RANK and TNF receptor associated factor 6 (TRAF6) at an upstream site. In vivo, l-THP significantly inhibited ovariectomy-induced bone loss and osteoclastogenesis in mice. Collectively, our study demonstrated that l-THP suppressed osteoclastogenesis by blocking RANK-TRAF6 interactions and inhibiting NF-κB and MAPK pathways. l-THP is a promising agent for treating osteoclastogenesis-related diseases such as post-menopausal osteoporosis.

Neobavaisoflavone inhibits osteoclastogenesis through blocking RANKL signalling-mediated TRAF6 and c-Src recruitment and NF-κB, MAPK and Akt pathways.

Psoralea corylifolia (P corylifolia) has been popularly applied in traditional Chinese medicine decoction for treating osteoporosis and promoting fracture healing since centuries ago. However, the bioactive natural components remain unknown. In this study, applying comprehensive two-dimensional cell membrane chromatographic/C18 column/time-of-flight mass spectrometry (2D CMC/C18 column/TOFMS) system, neobavaisoflavone (NBIF), for the first time, was identified for the bioaffinity with RAW 264.7 cells membranes from the extracts of P corylifolia. Here, we revealed that NBIF inhibited RANKL-mediated osteoclastogenesis in bone marrow monocytes (BMMCs) and RAW264.7 cells dose dependently at the early stage. Moreover, NBIF inhibited osteoclasts function demonstrated by actin ring formation assay and pit-formation assay. With regard to the underlying molecular mechanism, co-immunoprecipitation showed that both the interactions of RANK with TRAF6 and with c-Src were disrupted. In addition, NBIF inhibited the phosphorylation of P50, P65, IκB in NF-κB pathway, ERK, JNK, P38 in MAPKs pathway, AKT in Akt pathway, accompanied with a blockade of calcium oscillation and inactivation of nuclear translocation of nuclear factor of activated T cells cytoplasmic 1 (NFATc1). In vivo, NBIF inhibited osteoclastogenesis, promoted osteogenesis and ameliorated bone loss in ovariectomized mice. In summary, P corylifolia-derived NBIF inhibited RANKL-mediated osteoclastogenesis by suppressing the recruitment of TRAF6 and c-Src to RANK, inactivating NF-κB, MAPKs, and Akt signalling pathways and inhibiting calcium oscillation and NFATc1 translocation. NBIF might serve as a promising candidate for the treatment of osteoclast-associated osteopenic diseases.

Reversal of Osteoporotic Activity by Endothelial Cell-Secreted Bone Targeting and Biocompatible Exosomes.

Exosomes, also known as extracellular vesicles, are naturally occurring, biocompatible, and bioacive nanoparticles ranging from 40 to 150 nm in diameter. Bone-secreted exosomes play important roles in bone homeostasis, the interruption of which can lead to diseases such as osteoporosis, rheumatoid arthritis, and osteopetrosis. Though the relationship between vascular and bone homeostasis has been recognized recently, the role of vascular endothelial cell (EC)-secreted exosomes (EC-Exos) in bone homeostasis is not well understood. Herein, we found that EC-Exos show more efficient bone targeting than osteoblast-derived exosomes or bone marrow mesenchymal stem cell-derived exosomes. We also found that EC-Exos can be internalized by bone marrow-derived macrophages (BMMs) to alter their morphology. EC-Exos can inhibit osteoclast activity in vitro and inhibit osteoporosis in an ovariectomized mouse model. Sequencing of exosome miRNA revealed that miR-155 was highly expressed in EC-Exos-treated BMMs. The miR-155 level in EC-Exos was much higher than that in BMMs and ECs, indicating that miR-155 was endogenous cargo of EC-derived vesicles. Blockage of BMMs miR-155 levels reversed the suppression by EC-Exos of osteoclast induction, confirming that exosomal miR-155 may have therapeutic potential against osteoporosis. Taken together, our findings suggest that EC-Exos may be utilized as a bone targeting and nontoxic nanomedicine for the treatment of bone resorption disorders.

Shikimic Acid Inhibits Osteoclastogenesis in Vivo and in Vitro by Blocking RANK/TRAF6 Association and Suppressing NF-κB and MAPK Signaling Pathways.

BACKGROUND/AIMS: Bone homeostasis is associated with the balance between bone-resorbing osteoclasts and bone-forming osteoblasts. Unbalanced bone homeostasis as a result of reduced osteogenesis or excessive osteoclastogenesis can lead to disorders such as osteoporosis, Paget's disease, and rheumatoid arthritis. Shikimic acid is a cyclohexanecarboxylic acid, reported to exhibit pharmacological properties including anti-inflammatory and antioxidant activities. However, its effects on bone homeostasis remain unknown. METHODS: First, the in vitro MTT cell viability assay was performed. Tartrate-resistant acid phosphatase (TRAP) and actin ring formation assays, as well as immunofluorescence staining were then performed to evaluate osteoclastogenesis. Potential signaling pathways were characterized by western blotting and verified in overexpression experiments. Related factors were examined by western blotting, reverse transcription polymerase chain reaction, electrophoretic mobility shift assay, and co-immunoprecipitation. Ovariectomized mice were used for the in vivo study. RESULTS: TRAP staining showed that shikimic acid significantly inhibited osteoclastogenesis and pit resorption in bone marrow monocytes and RAW264.7 cells, and actin ring formation assays showed that shikimic acid suppressed the bone resorption function of osteoclasts. Furthermore, shikimic acid inhibited the receptor activator of nuclear factor-κB RANK/tumor necrosis factor receptor-associated factor 6 (TRAF6) association, suppressed nuclear factor-κB and mitogen-activated protein kinase signaling pathways, and downregulated nuclear factor of activated T-cell cytoplasmic 1. The expression of osteoclastogenesis biomarkers, including TRAF6, calcitonin receptor, TRAP, cathepsin K, and matrix metalloproteinase-9, was inhibited. In vivo, shikimic acid also significantly ameliorated bone loss and prevented osteoclastogenesis in ovariectomized mice. CONCLUSION: Shikimic acid inhibited osteoclastogenesis and osteoclast function by blocking RANK ligand-induced recruitment of TRAF6, as well as downstream signaling pathways in vitro. Shikimic acid also reduced ovariectomy-induced osteoclastogenesis and bone loss in vivo.

Inhalation of Hydrogen of Different Concentrations Ameliorates Spinal Cord Injury in Mice by Protecting Spinal Cord Neurons from Apoptosis, Oxidative Injury and Mitochondrial Structure Damages.

BACKGROUND/AIMS: Hydrogen selectively neutralizes reactive oxygen species (ROS) and ameliorates various ROS-induced injuries. Spinal cord injury (SCI) is a serious injury to the central nervous system, and secondary SCI is closely related to excessive ROS generation. We hypothesized that hydrogen inhalation ameliorates SCI, and the mechanism of action may be related to the protective effects of hydrogen against oxidative stress, apoptosis, and mitochondrial damage. METHODS: Mechanically injured spinal cord neurons were incubated with different concentrations of hydrogen in vitro. Immunofluorescence staining and transmission electron microscopy were used to confirm the protective effects of hydrogen. ROS and related proteins were detected with dihydroethidium fluorescence staining, enzyme-linked immunosorbent assays, and western blotting. Terminal deoxynucleotidyl transferase dUTP nick end labeling assays, flow cytometry, and western blotting were used to detect neuronal apoptosis. ATP concentrations, Janus Green B staining, and mitochondrial permeability transition pore (mPTP) status were assessed to investigate mitochondrial damage. RNA sequencing was performed to screen potential target genes of hydrogen application. Hydrogen was administered to mice after spinal cord contusion injury was established for 42 days. The Basso Mouse Scale (BMS) and footprint analyses were used to assess locomotor functions, and immunofluorescence staining of the injured spinal cord segments was performed to detect oxidative stress status. RESULTS: Spinal cord neurons were preserved by hydrogen administration after mechanical injury in a dose-dependent manner. ROS generation, oxidative stress injury-related markers, and the number of apoptotic neurons were significantly reduced after hydrogen treatment. The ATP production and mPTP function in injured neurons were preserved by hydrogen incubation. The expression levels of Cox8b, Cox6a2, Cox7a1, Hspb7, and Atp2a1 were inhibited by hydrogen treatment. BMS scores and the footprint assessment of mice with SCI were improved by hydrogen inhalation. CONCLUSIONS: Hydrogen inhalation (75%) ameliorated SCI in vivo and attenuated neuronal mechanical injuries in vitro, and its protective effect on spinal cord neurons was exerted in a dose-dependent manner. The underlying mechanisms included reducing ROS generation and oxidative stress, inhibiting neuronal apoptosis, and restoring mitochondrial construction and function. Cox8b, Cox6a2, Cox7a1, Hspb7, and Atp2a1 were identified as potential target genes of hydrogen treatment.

Matrine prevents bone loss in ovariectomized mice by inhibiting RANKL-induced osteoclastogenesis.

Osteoporosis is a metabolic bone disease characterized by decreased bone density and strength due to excessive loss of bone protein and mineral content. The imbalance between osteogenesis by osteoblasts and osteoclastogenesis by osteoclasts contributes to the pathogenesis of postmenopausal osteoporosis. Estrogen withdrawal leads to increased levels of proinflammatory cytokines. Overactivated osteoclasts by inflammation play a vital role in the imbalance. Matrine is an alkaloid found in plants from the Sophora genus with various pharmacological effects, including anti-inflammatory activity. Here we demonstrate that matrine significantly prevented ovariectomy-induced bone loss and inhibited osteoclastogenesis in vivo with decreased serum levels of TRAcp5b, TNF-α, and IL-6. In vitro matrine significantly inhibited osteoclast differentiation induced by receptor activator for NF-κB ligand (RANKL) and M-CSF in bone marrow monocytes and RAW264.7 cells as demonstrated by tartrate-resistant acid phosphatase (TRAP) staining and actin-ring formation as well as bone resorption through pit formation assays. For molecular mechanisms, matrine abrogated RANKL-induced activation of NF-κB, AKT, and MAPK pathways and suppressed osteoclastogenesis-related marker expression, including matrix metalloproteinase 9, NFATc1, TRAP, C-Src, and cathepsin K. Our study demonstrates that matrine inhibits osteoclastogenesis through modulation of multiple pathways and that matrine is a promising agent in the treatment of osteoclast-related diseases such as osteoporosis.-Chen, X., Zhi, X., Pan, P., Cui, J., Cao, L., Weng, W., Zhou, Q., Wang, L., Zhai, X. Zhao, Q., Hu, H., Huang, B., Su, J. Matrine prevents bone loss in ovariectomized mice by inhibiting RANKL-induced osteoclastogenesis.

The chinese version of achilles tendon total rupture score: cross-cultural adaptation, reliability and validity.

BACKGROUND: The Achilles tendon Total Rupture Score (ATRS), which is originally developed in 2007 in Swedish, is the only patient-reported outcome measure (PROM) for specific outcome assessment of an Achilles tendon rupture.Purpose of this study is to translate and cross-culturally adapt Achilles tendon Total Rupture Score (ATRS) into simplified Chinese, and primarily evaluate the responsiveness, reliability and validity. METHODS: International recognized guideline which was designed by Beaton was followed to make the translation of ATRS from English into simplified Chinese version (CH-ATRS). A prospective cohort study was carried out for the cross-cultural adaptation. There were 112 participants included into the study. Psychometric properties including floor and ceiling effects, Cronbach's alpha, intraclass correlation coefficient, effect size, standard response mean, and construct validity were tested. RESULTS: The mean scores of CH-ATRS are 57.42 ± 13.70. No sign of floor or ceiling effect was found of CH-ATRS. High level of internal consistency was supported by the value of Cronbach's alpha (0.893). ICC (0.979, 95%CI: 0.984-0.993) was high to indicate the high test-retest reliability. Great responsive ness was proved with the high absolute value of ES and SRM (0.84 and 8.98, respectively). The total CH-ATRS score had very good correlation with physical function and body pain subscales of SF-36 (r = -0.758 and r = -0.694, respectively, p < 0.001), while poor correlation with vitality and role physical subscales of SF-36 (r = -0.033 and r = -0.025, respectively, p ≥ 0.05), which supported construct validity of CH-ATRS. CONCLUSION: This Chinese version of Achilles tendon Total Rupture Score (CH-ATRS) can be used as a reliable and valid instrument for Achilles tendon rupture assessing in Chinese-speaking population. Level of evidence II.

Surgical treatment of calcaneal fractures of Sanders type II and III by a minimally invasive technique using a locking plate.

The aim of the present study was to investigate the outcomes of surgical treatment of calcaneal fractures of Sanders type II and III using a minimally invasive technique and a locking plate. We reviewed 33 feet in 33 consecutive patients with Sanders type II and III calcaneal fractures who had undergone a minimally invasive technique using percutaneous reduction and locking plates. All operations were performed by the same surgeons. The postoperative evaluation included radiographs, determination of restoration of Böhler's angle and Gissane's angle, and administration of the American Orthopaedic Foot and Ankle Society ankle-hind foot scale, Maryland Foot Score, and visual analog scale of pain. The mean visual analog scale score was 1.6 ± 1.4 when radiographic fracture healing was observed. The median functional score of the 33 patients (33 feet) reached 82 (interquartile range 80 to 99) at the last follow-up evaluation according to the American Orthopaedic Foot and Ankle Society ankle-hind foot scale and 89 (interquartile range 80 to 99) according to Maryland Foot Score. All cases achieved restoration of a normal Böhler's angle and Gissane's angle. Postoperative superficial infections occurred in 2 patients, subtalar arthritis developed in 2, and no soft tissue necrosis was observed. For Sanders type II and III fractures of the calcaneus bone, treatment with a minimally invasive technique combining percutaneous reduction and locking plate fixation provided satisfactory clinical results, with a lower incidence of complications. However, longer term studies with a larger sample size and more randomized controlled trials are required to define the superiority of our minimally invasive technique compared with conventional surgical treatment of calcaneal fractures.

Closed reduction and internal fixation versus total hip arthroplasty for displaced femoral neck fracture.

OBJECTIVE: To compare the clinical effects between closed reduction and internal fixation (CRIF) and total hip arthroplasty (THA) for displaced femoral neck fracture. METHODS: In this prospective randomized study, 285 patients aged above 65 years with hip fractures (Garden III or IV) were included from January 2001 to December 2005. The cases were randomly allocated to either the CRIF group or THA group. Patients with pathological fractures (bone tumors or metabolic bone disease), preoperative avascular necrosis of the femoral head, osteoarthritis, rheumatoid arthritis, hemiplegia, long-term bed rest and complications affecting hip functions were excluded. RESULTS: During the 5-year follow-up, CRIF group had significantly higher rates of complication in hip joint, general complication and reoperation than THA group (38.3% vs. 12.7%, P<0.01; 45.3% vs. 21.7%, P<0.01; 33.6% vs. 10.2%, P<0.05 respectively). There was no difference in mortality between the two groups. Postoperative function of the hip joint in THA group recovered favorably with higher Harris scores. CONCLUSION: For displaced fractures of the femoral neck in elderly patients, THA can achieve a lower rate of complication and reoperation, as well as better postoperative recovery of hip joint function compared with CRIF.

Gut microbiota alterations in postmenopausal women with osteoporosis and osteopenia from Shanghai, China.

Background: The importance of the gut microbiota in maintaining bone homeostasis has been increasingly emphasized by recent research. This study aimed to identify whether and how the gut microbiome of postmenopausal women with osteoporosis and osteopenia may differ from that of healthy individuals. Methods: Fecal samples were collected from 27 individuals with osteoporosis (OP), 44 individuals with osteopenia (ON), and 23 normal controls (NC). The composition of the gut microbial community was analyzed by 16S rRNA gene sequencing. Results: No significant difference was found in the microbial composition between the three groups according to alpha and beta diversity. At the phylum level, Proteobacteria and Fusobacteriota were significantly higher and Synergistota was significantly lower in the ON group than in the NC group. At the genus level, Roseburia, Clostridia_UCG.014, Agathobacter, Dialister and Lactobacillus differed between the OP and NC groups as well as between the ON and NC groups (p < 0.05). Linear discriminant effect size (LEfSe) analysis results showed that one phylum community and eighteen genus communities were enriched in the NC, ON and OP groups, respectively. Spearman correlation analysis showed that the abundance of the Dialister genus was positively correlated with BMD and T score at the lumbar spine (p < 0.05). Functional predictions revealed that pathways relevant to amino acid biosynthesis, vitamin biosynthesis, and nucleotide metabolism were enriched in the NC group. On the other hand, pathways relevant to metabolites degradation and carbohydrate metabolism were mainly enriched in the ON and OP groups respectively. Conclusions: Our findings provide new epidemiologic evidence regarding the relationship between the gut microbiota and postmenopausal bone loss, laying a foundation for further exploration of therapeutic targets for the prevention and treatment of postmenopausal osteoporosis (PMO).

Nanoengineered 3D-printing scaffolds prepared by metal-coordination self-assembly for hyperthermia-catalytic osteosarcoma therapy and bone regeneration.

The integration of functional nanomaterials with tissue engineering scaffolds has emerged as a promising solution for simultaneously treating malignant bone tumors and repairing resected bone defects. However, achieving a uniform bioactive interface on 3D-printing polymer scaffolds with minimized microstructural heterogeneity remains a challenge. In this study, we report a facile metal-coordination self-assembly strategy for the surface engineering of 3D-printed polycaprolactone (PCL) scaffolds with nanostructured two-dimensional conjugated metal-organic frameworks (cMOFs) consisting of Cu ions and 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP). A tunable thickness of Cu-HHTP cMOF on PCL scaffolds was achieved via the alternative deposition of metal ions and HHTP. The resulting composite PCL@Cu-HHTP scaffolds not only demonstrated potent photothermal conversion capability for efficient OS ablation but also promoted the bone repair process by virtue of their cell-friendly hydrophilic interfaces. Therefore, the cMOF-engineered dual-functional 3D-printing scaffolds show promising potential for treating bone tumors by offering sequential anti-tumor effects and bone regeneration capabilities. This work also presents a new avenue for the interface engineering of bioactive scaffolds to meet multifaceted demands in osteosarcoma-related bone defects.

Injectable hydrogels for bone regeneration with tunable degradability via peptide chirality modification.

The degradability of hydrogels plays a pivotal role in bone regeneration, yet its precise effects on the bone repair process remain poorly understood. Traditional studies have been limited by the use of hydrogels with insufficient variation in degradation properties for thorough comparative analysis. Addressing this gap, our study introduces the development of matrix metalloproteinase (MMP)-responsive hydrogels engineered with a tunable degradation rate, specifically designed for bone regeneration applications. These innovative hydrogels are synthesized by integrating MMP-sensitive peptides, which exhibit chirality-transferred amino acids, with norbornene (NB)-modified 8-arm polyethylene glycol (PEG) macromers to form the hydrogel network. The degradation behavior of these hydrogels is manipulated through the chirality of the incorporated peptides, resulting in the classification into L, LD, and D hydrogels. Remarkably, the L hydrogel variant shows a significantly enhanced degradation rate, both in vitro and in vivo, which in turn fosters bone regeneration by promoting cell migration and upregulating osteogenic gene expression. This research highlights the fundamental role of hydrogel degradability in bone repair and lays the groundwork for the advancement of degradable hydrogel technologies for bone regeneration, offering new insights and potential for future biomaterials development.