Accelerated fracture healing by osteogenic Ti45Nb implants through the PI3K–Akt signaling pathway

The key to managing fracture is to achieve stable internal fixation,and currently,biologically and mechanically appropriate internal fixation devices are urgently needed.With excellent biocompatibility and corrosion resistance,titanium–niobium alloys have the potential to become a new generation of internal fixation materials for fractures.However,the role and mechanism of titanium–niobium alloys on promoting fracture healing are still undefined.Therefore,in this study,we systematically evaluated the bone-enabling properties of Ti45Nb via in vivo and in vitro experiments.In vitro,we found that Ti45Nb has an excellent ability to promote MC3T3-E1 cell adhesion and proliferation without obvious cytotoxicity.Alkaline phosphatase(ALP)activity and alizarin red staining and semiquantitative analysis showed that Ti45Nb enhanced the osteogenic differentiation of MC3T3-E1 cells compared to the Ti6Al4V control.In the polymerase chain reaction experiment,the expression of osteogenic genes in the Ti45Nb group,such as ALP,osteopontin(OPN),osteocalcin(OCN),type 1 collagen(Col-1)and runt-related transcription factor-2(Runx2),was significantly higher than that in the control group.Meanwhile,in the western blot experiment,the expression of osteogenic-related proteins in the Ti45Nb group was significantly increased,and the expression of PI3K–Akt-related proteins was also higher,which indicated that Ti45Nb might promote fracture healing by activating the PI3K–Akt signaling pathway.In vivo,we found that Ti45Nb implants accelerated fracture healing compared to Ti6Al4V,and the biosafety of Ti45Nb was confirmed by histological evaluation.Furthermore,immunohistochemical staining confirmed that Ti45Nb may promote osteogenesis by upregulating the PI3K/Akt signaling pathway.Our study demonstrated that Ti45Nb exerts an excellent ability to promote fracture healing as well as enhance osteoblast differentiation by activating the PI3K/Akt signaling pathway,and its good biosafety has been confirmed,which indicates its clinical translation potential.

Bone Injury and Fracture Healing Biology

Bones are organs of the skeletal system, providing shape, mechanical support, and protection to the body and facilitating the movement. In addition, bones contribute to the mineral homeostasis of the body and have recently been found to participate in endocrine regulation of energy metabolism. The well-known limitations associated with clinical use of autografts and allografts continue to drive efforts to develop bone graft substitutes, using the principles of biomaterials and tissue engineering. Under some stressful and continuous compressive conditions, the ability of the bone tissue to tolerate strength decreases. Whenever these forces overcome the toleration of the bone tissue, bone fracture occurs. years

Effects of immune cells on mesenchymal stem cells during fracture healing

In vertebrates,bone is considered an osteoimmune system which encompasses functions of a locomotive organ,a mineral reservoir,a hormonal organ,a stem cell pool and a cradle for immune cells.This osteoimmune system is based on cooperatively acting bone and immune cells,cohabitating within the bone marrow.They are highly interdependent,a fact that is confounded by shared progenitors,mediators,and signaling pathways.Successful fracture healing requires the participation of all the precursors,immune and bone cells found in the osteoimmune system.Recent evidence demonstrated that changes of the immune cell composition and function may negatively influence bone healing.In this review,first the interplay between different immune cell types and osteoprogenitor cells will be elaborated more closely.The separate paragraphs focus on the specific cell types,starting with the cells of the innate immune response followed by cells of the adaptive immune response,and the complement system as mediator between them.Finally,a brief overview on the challenges of preclinical testing of immunebased therapeutic strategies to support fracture healing will be given.

Optimal concentration of mesenchymal stem cells for fracture healing in a rat model with long bone fracture

BACKGROUND There is still no consensus on which concentration of mesenchymal stem cells(MSCs)to use for promoting fracture healing in a rat model of long bone fracture.AIM To assess the optimal concentration of MSCs for promoting fracture healing in a rat model.METHODS Wistar rats were divided into four groups according to MSC concentrations:Normal saline(C),2.5×10^(6)(L),5.0×10^(6)(M),and 10.0×10^(6)(H)groups.The MSCs were injected directly into the fracture site.The rats were sacrificed at 2 and 6 wk post-fracture.New bone formation[bone volume(BV)and percentage BV(PBV)]was evaluated using micro-computed tomography(CT).Histological analysis was performed to evaluate fracture healing score.The protein expression of factors related to MSC migration[stromal cell-derived factor 1(SDF-1),transforming growth factor-beta 1(TGF-β1)]and angiogenesis[vascular endothelial growth factor(VEGF)]was evaluated using western blot analysis.The expression of cytokines associated with osteogenesis[bone morphogenetic protein-2(BMP-2),TGF-β1 and VEGF]was evaluated using real-time polymerase chain reaction.RESULTS Micro-CT showed that BV and PBV was significantly increased in groups M and H compared to that in group C at 6 wk post-fracture(P=0.040,P=0.009;P=0.004,P=0.001,respectively).Significantly more cartilaginous tissue and immature bone were formed in groups M and H than in group C at 2 and 6 wk post-fracture(P=0.018,P=0.010;P=0.032,P=0.050,respectively).At 2 wk post fracture,SDF-1,TGF-β1 and VEGF expression were significantly higher in groups M and H than in group L(P=0.031,P=0.014;P<0.001,P<0.001;P=0.025,P<0.001,respectively).BMP-2 and VEGF expression were significantly higher in groups M and H than in group C at 6 wk postfracture(P=0.037,P=0.038;P=0.021,P=0.010).Compared to group L,TGF-β1 expression was significantly higher in groups H(P=0.016).There were no significant differences in expression levels of chemokines related to MSC migration,angiogenesis and cytokines associated with osteogenesis between M and H groups at 2 and 6 wk post-fracture.CONCLUSION The administration of at least 5.0×10^(6)MSCs was optimal to promote fracture healing in a rat model of long bone fractures.

Mice with a heterozygous Lrp6 deletion have impaired fracture healing

Bone fracture non-unions, the failure of a fracture to heal, occur in 10%-20% of fractures and are a costly and debilitating clinical problem. The Wnt/fl-catenin pathway is critical in bone development and fracture healing. Polymorphisms of linking low-density lipoprotein receptor-related protein 6 （LRP6）, a Wnt-binding receptor, have been associated with decreased bone mineral density and fragility fractures, although this remains controversial. Mice with a homozygous deletion of Lrp6 have severe skeletal abnormalities and are not viable, whereas mice with a heterozygous deletion have a combinatory effect with Lrp5 to decrease bone mineral density. As fracture healing closely models embryonic skeletal development, we investigated the process of fracture healing in mice heterozygous for Lrp6 （Lrp6~/-） and hypothesized that the heterozygous deletion of Lrp6 would impair fracture healing. Mid-diaphyseal femur fractures were induced in Lrp6~^- mice and wild-type controls （Lrp6~/~）. Fractures were analyzed using micro-computed tomography （~CT） scans, biomechanical testing, and histological analysis. Lrp6~/- mice had significantly decreased stiffness and strength at 28 days post fracture （PF） and significantly decreased BV/TV, total density, immature bone density, and mature area within the callus on day-14 and -21 PF; they had significantly increased empty callus area at days 14 and 21 PF. Our results demonstrate that the heterozygous deletion of Lrp6 impairs fracture healing, which suggests that Lrp6 has a role in fracture healing.

Effect of Absorbable Hydroxyapatite/Poly-DL-Lactide Rods on Experimental Fracture Healing

Summary: In order to investigate the effect of a new institute-designed absorbable hydroxyapatite microparticles/poly-DL-lactide (HA/PDLLA) fracture fixation devices on experimental fracture healing, 25 rabbits with a transverse transcondylar osteotomy of the distal femur were fixed in- tramedullary by a HA/PDLLA rod (4. 5 mm in diameter, 30-40 mm in length). The follow-up time lasted 1, 2, 4, 6 and 12 week(s). Roentgenographic, histological and ultrastructural analyses were conducted. The results showed that all osteotomies united within 6 weeks without delay. No accumulation of inflammatory cells was seen. Ultrastructural studies showed that polymorphonuclear neutrophils and macrophages were observed mainly at the 1st week, but only few were noted at the 2nd week. The inflammatory and debridement stages were not prolonged. Large amount of active fibroblasts and some chondroblasts were observed at the 2nd week, suggesting a fibrous callus stage. The main cellularity at 4th week was osteoblasts and osteocytes. Part of osteocytes had already entered the static stage at the 6th week. Our experiment showed that the HA/PDLLA had good biocompatibility, sufficient mechanical strength and caused no delay to the fracture healing.

Factors Affecting Time to Healing in Humeral Shaft Fractures Treated with SIGN Intramedullary Nailing

There is a tendency to treat humeral fractures with the use of splintage in resource poor countries due to a perceived high rate of complications with operative fixation. The Surgical Implant Generation Network (SIGN) intra medullary nail has provided an alternative in the management of humeral shaft fractures. Due to the paucity of research work in this area, our study evaluated factors that influence the time to fracture union in humeral shaft fractures. Fifty-eight humeral Diaphysial fractures were treated over six years. It is a retrospective study. Case notes and the database were analysed. The statistical analysis was done using the SPSS 24 software. The time to fracture healing was the primary outcome variable and how it was influenced by patient and implant variables was studied. The mean time to fracture healing was 17.38 weeks. All 58 fractures united. The mean time to fracture healing in the 20 - 29 years was 16.00 weeks which was lower than in older age groups. Fractures in males healed at 16.33 weeks and in females at 18.76 weeks. Patients with Diabetes Mellitus had a mean healing time of 29.00 weeks, while third proximal fractures healed in a mean time of 15.25 weeks. Age and sex had no significant influence on the time to fracture healing while Diabetes Mellitus, longer duration of antibiotic use, open fractures, and presence of fracture gap post fixation and third middle fractures had increased time to fracture healing.

Research of the molecular mechanism of Hai Honghua medicinal liquor in the treatment of fracture based on network pharmacology combined with molecular docking

Background:Hai Honghua medicinal liquor(HHML),a famous hospital formula composed of 19 traditional Chinese medicines,has been successfully applied in treating soft tissue injury,fresh closed fracture,limb dysfunction after fracture healing,shoulder,neck and leg pain,knee joint pain and other clinical multiple diseases for 30 years in clinical.However,research on the material basis of HHML for the treatment of fracture healing-related disorders is still in a gap.Therefore,it is particularly important to explore the active ingredients,core targets and potential pharmacological mechanisms of HHML to promote fracture healing.Methods:We screened the core active components of each traditional Chinese medicine in formula and its action targets through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Encyclopedia of Traditional Chinese Medicine database.The fracture related targets were retrieved from several different public databases,including GeneCards,Online Mendelian Inheritance in Man,DisGeNET and Therapeutic Target Database.Bioinformatics analysis to obtain key bioactive components,underlying targets and signaling pathways,containing the Venn diagram of the intersection with components and diseases gene targets,protein–protein interaction,as well as the Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis,and finally molecular docking.Results:A total of 249 bioactive ingredients of HHML and 325 HHML-fracture-related targets were screened.The network analysis revealed that quercetin,luteolin,kaempferol,Licochalcone A,naringenin and 8-Isopentenyl-kaempferol may be potential candidate agents.Multiple targets are involved including TP53,MAPK3,STAT3,AKT1,MAPK1,HSP90AA1,ESR1 and PIK3CA may be closely linked targets.PI3K-AKT signaling pathway may play a significant role of HHML in treatment of fracture.What’s more,molecular docking suggested that 8-isopentenyl kaempferol,glycyrrhiza chalcone A,and naringenin bound to AKT1,PIK3CA,and ESR1,respectively,exhibiting lower energy and more stable characteristics.Conclusions:The findings indicate the potential active ingredients,target proteins and molecular mechanisms of HHML for the treatment of fractures to provide the exact idea for the next research on the mechanism of action of HHML formula for fracture treatment.

Effects of Shang Ke Jie Gu tablet on fracture healing in rabbits

Objective:To study the effects of Shang Ke Jie Gu tablet on fracture healing in rabbits.Methods:40 New Zealand rabbits,half male and half female,were randomly divided into two groups:normal saline group(N group)and Shang Ke Jie Gu tablet group(S group).Each group consisted of 20 rabbits.Left radial fracture models in upper and middle sections were made in rabbits and then intra-gastric administration was given.Five rabbits in each group were killed on the 10 th,20^(th),30^(th) and 40^(th) day after surgery,left radius was taken to get an X-ray.The degree of healing was assessed by the evaluation criteria of Shanghai Orthopaedics Institute.Results:The degree of fracture healing in S group was higher in the comparison with that in N group.Conclusions:Shang Ke Jie Gu tablet might affect endochondral ossification during fracture healing of rabbits,and promote porosis and fracture healing.

Experimental Study on Anatomic Reduction of Lateral Pterygoid Muscle(Simulated Manipulation Fracture Reduction)and Condylar Free Reduction for Condylar Fracture

[Objectives]To compare the fracture healing of keeping lateral pterygoid muscle anatomic reduction(simulated manipulation fracture reduction)with condylar free reduction in the treatment of condylar fractures.[Methods]Twenty-four New Zealand rabbits were randomly divided into two groups to mandibular condylar neck fracture model was established.one team keep the lateral pterygoid muscle,the other excise it.Cervical vascular perfusion was done with ink before animals executed after operation 2,4,6 and 8 weeks.Bilateral anteroposterior and mediolateral condylar diameters measured.Changes of operation side condylar proliferating layer,microvessel number and bone parameters were observed and analyzed after slices and HE staining.[Results]The mediolateral condylar diameters of operation side were significantly smaller than health side in condylar free reduction group at the 4,6,8 weeks(P<0.05),but there was no statistical difference in the anteroposterior condylar diameters at each time point(P>0.05).There were no significant differences in the anteroposterior and mediolateral condylar diameters of the anatomic reduction lateral pterygoid muscle group compared between the operation side and health side(P>0.05).The number of microvessel in condylar free reduction group were smaller than those in anatomic reduction lateral pterygoid muscle group(P<0.05).There were significant differences in BV/TV,Tb.Th,Tb.Sp between the condylar free reduction group and the anatomic reduction lateral pterygoid muscle group(all P<0.05),and the Tb.N were significantly differences between two groups at the 4,6,8 weeks(P<0.05).[Conclusions]When the condyle is fractured it should keep lateral pterygoid muscle(manipulation fracture reduction)as possible,which is important in the fracture healing and functional recovering of mandibular.

Experimental observation of rat's early-stage fracture healing with different kinds of nerve injuries

To investigate the impact of different kinds of nerve injuries of early-stage fracture healing.Methods Three groups of rats were included in the experiment among which group 1 was inflicted with femoral fracture and T10 spinal cord transsection (SCI),group 2 was inflicted with femoral and peripheral nerve resection (PNR),and group 3 with simple femoral fracture as control group.Two weeks after operation the femoral bones were collected for X-ray checking and 2 more weeks later X-ray checking was performed again followed by pathomorphologic exams.Results X-ray result showed no massive calluses in the bones in the 2nd week postoperatively,while in the 4th week,callus appeared with larger size in group 3 than that of group 1 and with smaller size than that of group 2.It was the same with the result of pathomorphologic examining.Cortical bone bridges between fracture point and osteiod were also found in group 2 and there were less normal blood vessels and worse bone remodeling than that of group 3.There were relatively immature calluses with more fibroblast-like cells and disordered bone structure in group 2.Group 3 showed normal healing process and callus structure.Conclusion Early-stage bone fracture healing can be influenced significantly by different kinds of nerve injuries.6 refs,6 figs.

A distinct“repair”role of regulatory T cells in fracture healing

Regulatory T cells(Tregs)suppress immune responses and inflammation.Here,we described the distinct nonimmunological role of Tregs in fracture healing.The recruitment from the circulation pool,peripheral induction,and local expansion rapidly enriched Tregs in the injured bone.The Tregs in the injured bone displayed superiority in direct osteogenesis over Tregs from lymphoid organs.Punctual depletion of Tregs compromised the fracture healing process,which leads to increased bone nonunion.In addition,bone callus Tregs showed unique T-cell receptor repertoires.Amphiregulin was the most overexpressed protein in bone callus Tregs,and it can directly facilitate the proliferation and differentiation of osteogenic precursor cells by activation of phosphatidylinositol 3-kinase/protein kinase B signaling pathways.The results of loss-and gain-function studies further evidenced that amphiregulin can reverse the compromised healing caused by Treg dysfunction.Tregs also enriched in patient bone callus and amphiregulin can promote the osteogenesis of human pre-osteoblastic cells.Our findings indicate the distinct and nonredundant role of Tregs in fracture healing,which will provide a new therapeutic target and strategy in the clinical treatment of fractures.

Hypoxia inducible factor-1α related mechanism and TCM intervention in process of early fracture healing

As a common clinical disease, fracture is often accompanied by pain, swelling, bleeding as well as other symptoms and has a high disability rate, even threatening life, seriously endangering patients’ physical and psychological health and quality of life. Medical practitioners take many strategies for the treatment of fracture healing, including Traditional Chinese Medicine(TCM). In the early stage of fracture healing,the local fracture is often in a state of hypoxia, accompanied by the expression of hypoxia inducible factor-1α(HIF-1α), which is beneficial to wound healing. Through literature mining, we thought that hypoxia, HIF-1α and downstream factors affected the mechanism of fracture healing, as well as dominated this process. Therefore, we reviewed the local characteristics and related signaling pathways involved in the fracture healing process and summarized the intervention of TCM on these mechanisms,in order to inspirit the new strategy for fracture healing, as well as elaborate on the possible principles of TCM in treating fractures based on the HIF molecular mechanism.

Burden of routine orthopedic implant removal a single center retrospective study

BACKGROUND Open reduction and internal fixation represent prevalent orthopedic procedures,sparking ongoing discourse over whether to retain or remove asymptomatic implants.Achieving consensus on this matter is paramount for orthopedic surgeons.This study aims to quantify the impact of routine implant removal on patients and healthcare facilities.A retrospective analysis of implant removal cases from 2016 to 2022 at King Fahad Hospital of the University(KFHU)was conducted and subjected to statistical scrutiny.Among these cases,44%necessitated hospitalization exceeding one day,while 56%required only a single day.Adults exhibited a 55%need for extended hospital stays,contrasting with 22.8%among the pediatric cohort.The complication rate was 6%,with all patients experiencing at least one complication.Notably,34.1%required sick leave and 4.8%exceeded 14 d.General anesthesia was predominant(88%).Routine implant removal introduces unwarranted complications,particularly in adults,potentially prolonging hospitalization.This procedure strains hospital resources,tying up the operating room that could otherwise accommodate critical surgeries.Clearly defined institutional guidelines are imperative to regulate this practice.AIM To measure the burden of routine implant removal on the patients and hospital.METHODS This is a retrospective analysis study of 167 routine implant removal cases treated at KFHU,a tertiary hospital in Saudi Arabia.Data were collected in the orthopedic department at KFHU from February 2016 to August 2022,which includes routine asymptomatic implant removal cases across all age categories.Nonroutine indications such as infection,pain,implant failure,malunion,nonunion,restricted range of motion,and prominent hardware were excluded.Patients who had external fixators removed or joints replaced were also excluded.RESULTS Between February 2016 and August 2022,360 implants were retrieved;however,only 167 of those who met the inclusion criteria were included in this study.The remaining implants were rejected due to exclusion criteria.Among the cases,44%required more than one day in the hospital,whereas 56%required only one day.55%of adults required more than one day of hospitalization,while 22.8%of pediatric patients required more than one day of inpatient care.The complication rate was 6%,with each patient experiencing at least one complication.Sick leave was required in 34.1%of cases,with 4.8%requiring more than 14 d.The most common type of anesthesia used in the surgeries was general anesthesia(88%),and the mean(SD)surgery duration was 77.1(54.7)min.CONCLUSION Routine implant removal causes unnecessary complications,prolongs hospital stays,depletes resources and monopolizing operating rooms that could serve more critical procedures.

Effects of leptin on femoral fracture in rats

In this study, our objective was to evaluate effects of leptin on fracture healing in rats. Seventy two male SpragueDawley（SD） rats were randomized into 3 groups. Standardized femoral fractures were created in all the rats. Group A was treated with 1 mL normal saline（NS）, group B with 0.3μg/kg leptin in 1 mL NS, and group C with 0.5μg/kg leptin in 1 mL NS for 2 weeks intraperitoneally. Each group was divided into three subgroups including 8 rats for evaluation at 2, 4 and 8 weeks. Radiological evaluation showed that callus formation of group B and C was all significantly higher than group A at 8 weeks（P=0.04 and P = 0.013, respectively）. There was no statistically significant difference in fracture healing between group B and group C at 8 weeks（P = 0.197）. Histological evaluation revealed fracture healing of group B and C was better than group A at 4 weeks（P=0.01 and P= 0.002,respectively） and 8 weeks（P = 0.008 and P= 0.003, respectively）. Micro-computed tomography（Micro-CT） analysis demonstrated that greater amounts of bony callus and evidence of bone fusion were observed in group B and C at 4 weeks（P = 0.02 and P = 0.04, respectively） and 8 weeks（P= 0.005 and P = 0.001, respectively） compared to group A. Group C also had better fracture healing than group B at 8 weeks（P = 0.01）. In conclusion, leptin has a positive effect on rat femoral fracture healing.

RESORBABLE HIGH-STRENGTH ROD FOR FRACTURE INTERNAL FIXATION

Objective To find an ideal biomaterial for internal fixation. Methods Forty rabbits with fracture of the femur diaphysis (superiorcondyle) were treated by intramedullary nailing of femur with composites rod of resorbable DL-polylactic acid (PDLLA)-calcium metaphosphate (CMP), while steinmann's pin as control. The fracture healing, the material degradation and its mechanical properties were studied by X-ray films, macroscopic, microscopic and electron microscopic observations. Results No significant inflammatory reaction was found, and all the osteotomies were healed, while material was resorbed. Conclusion The PDLLA-CMP has excellent biocompatibility and mechanical properties, and it can be a promising implant material in orthopaedics surgery.

Minimally invasive treatment of forearm double fracture in adult using Acumed forearm intramedullary nail: A case report

BACKGROUND Currently,open reduction internal fixation is the conventional surgical method for treatment of double ulna and radius fracture.However,open reduction is associated with a high risk of complications.This case of forearm double fracture involved a patient treated using an Acumed intramedullary nail.The patient experienced good follow-up outcomes.The Acumed forearm intramedullary nail enables early functional exercise and hastens healing of the fracture.Few studies have reported on the use of this approach for the treatment of fractures.CASE SUMMARY A 23-year-old male patient was admitted to hospital after 5 h of pain,swelling,and limited activity of left forearm caused by a careless fall.Physical examination showed stable basic vital signs,swelling of the left forearm,and severe pain when pressing on the injured part of the forearm.Further,friction was felt at the broken end of the bone;the skin was not punctured.Movement of the left hand was normal,and the left radial artery pulse was normal.Three-dimensional computed tomography examination showed an ulna fracture of the left forearm and comminuted fracture of the radius.The fracture was located in the upper third of the radius,with significant displacement on the fracture side.Clinical diagnosis further confirmed the left radius comminuted fracture and ulna fracture.After analyzing the fracture pattern,age,and other patient characteristics,we chose an Acumed nail for treatment and achieved good follow-up outcomes.CONCLUSION Acumed forearm intramedullary nail for fixation of ulna and radius fracture reduced complication risk and resulted in good follow-up outcomes.

Waders(Scolopacidae)surviving despite malaligned leg fractures in the wild:kinematics of bipedal locomotion

Background: Bone fracture frequencies and survival rates are essential parameters in skeleton evolution, but information on the functional consequences of naturally healed fractures is scarce. No leg bone fracture healing in the wild has been reported so far from long-legged Charadriiformes(waders), which depend on bipedal locomotion for feeding.Methods: We documented a healed but malaligned tarsometatarsus fracture in a wild Willet(Tringa [Catoptrophorus]semipalmata), and a malaligned tibiotarsus fracture in a Curlew(Numenius arquata) skeleton from a museum collection. Functional consequences of the malalignments were evaluated by kinematic analyses of videos(Willet) and in silico 3D modeling(Curlew).Results: The Willet's left tarsometatarsus exhibited an angular malalignment of 70°, resulting in a limping gait that was less pronounced at high than at low walking speed. The bird seemed unable to club the toes of the left foot together, apparently a secondary effect of the deformity. The Curlew's tibiotarsus showed an angular and an axial malalignment, causing the foot to rotate outwards when the intertarsal joint was flexed. Despite the severe effects of their injuries, the birds had survived at least long enough for the fractures to heal completely.Conclusions: Somewhat unexpectedly, leg fractures are not necessarily fatal in long-legged waders, even if deformities occur in the healing process. Bipedal locomotion on vegetated grounds must have been impeded due to the bone malalignments in both analyzed cases. The birds probably alleviated the impact of their handicaps by shifting a larger proportion of their activities to vegetation-free habitats.

Effects of sclerostin antibody on bone healing

Promoting bone healing after a fracture has been a frequent subject of research.Recently,sclerostin antibody(Scl-Ab)has been introduced as a new anabolic agent for the treatment of osteoporosis.Scl-Ab activates the canonical Wnt(cWnt)-β-catenin pathway,leading to an increase in bone formation and decrease in bone resorption.Because of its rich osteogenic effects,preclinically,Scl-Ab has shown positive effects on bone healing in rodent models;researchers have reported an increase in bone mass,mechanical strength,histological bone formation,total mineralized callus volume,bone mineral density,neovascularization,proliferating cell nuclear antigen score,and bone morphogenic protein expression at the fracture site after Scl-Ab administration.In addition,in a rat critical-size femoral-defect model,the Scl-Ab-treated group demonstrated a higher bone healing rate.On the other hand,two clinical reports have researched Scl-Ab in bone healing and failed to show positive effects in the femur and tibia.This review discusses why Scl-Ab appears to be effective in animal models of fracture healing and not in clinical cases.

Axial load-share ratio testing to assess the healing of open tibial fractures treated with the Taylor Spatial Frame

Background:The Taylor Spatial Frame(TSF)has gained popularity among orthopedic surgeons for treating open fractures.However,a key challenge is the timely and safe removal of the frame.This study assessed the efficacy and safety of axial load-share ratio(ALSR)testing to evaluate callus healing strength after TSF treatment of open tibial fractures.Methods:A retrospective case-control study was conducted,analyzing 180 adult patients with open tibial fractures treated at Tianjin Hospital’s Orthopedic Limb Correction Unit between August 2019 and August 2022.All patients underwent TSF external fixation surgery,and were divided into two groups based on ALSR testing.Group I(92 patients)underwent ALSR testing,with frame removal if the test value fell below 5%.Traditional methods were used for fixator removal guidance in Group II(88 patients).Clinical outcomes,including fixation duration,complications after fixator removal,and Johner-Wruhs functional scores,were compared between the two groups.Results:The groups showed no statistically significant differences(P>0.05)in sex,age,injury side,body mass index,surgery timing,or fracture type.Group I had a significantly shorter fixation duration(25.85±5.57 weeks)compared to Group II(31.82±6.98 weeks)(P<0.05).Following fixator removal,Group I demonstrated superior Johner-Wruhs scores compared to Group II,indicating better outcomes(P<0.05).Complication rates did not differ significantly between the groups at the last follow-up(P>0.05).Conclusion:Regular postoperative ALSR testing could safely and effectively guide TSF removal following open tibial fracture treatment.This method significantly reduced fixation duration compared to traditional guidance methods while maintaining efficacy and safety.