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A new perspective on intervertebral disc calcification—from bench to bedside

Bone Research 2024年第1期12卷 50-61页

作者： Emanuel J.Novais Rajkishen Narayanan Jose A.Canseco Koen van de Wetering Christopher K.Kepler Alan S.Hilibrand Alexander R.Vaccaro Makarand V.Risbud Department of orthopaedic Surgery Sidney Kimmel Medical CollegeThomas Jefferson UniversityPhiladelphiaPAUSA Unidade Local de Saúde do Litoral Alentejano Orthopedic DepartmentSantiago do CacémPortugal Rothman Orthopedic institute at Thomas Jefferson University PhiladelphiaPAUSA

Disc degeneration primarily contributes to chronic low back and neck pain.Consequently,there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis,ectopic calcification,herniation,or mixed phenotypes.Amongst these phenotypes,disc calcification is the least studied.Ectopic calcification,by definition,is the pathological mineralization of soft tissues,widely studied in the context of conditions that afflict vasculature,skin,and cartilage.Clinically,disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment.It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics:hypertrophic chondrocyte-like cell differentiation;TNAP,ENPP1,and ANK upregulation;cell death;altered Pi and PPi homeostasis;and local inflammation.Recent studies in mouse models have provided a better understanding of the mechanisms underlying this phenotype.It is essential to recognize that the presentation and nature of mineralization differ between AF,NP,and EP compartments.Moreover,the combination of anatomic location,genetics,and environmental stressors,such as aging or trauma,govern the predisposition to calcification.Lastly,the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis,along with disc cell death and differentiation status.While there is limited understanding of this phenotype,understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.

关键词： degeneration metabolism intervertebral

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Malnutrition and Its Association with the Mortality of Patients with Femoral Intertrochanteric Fractures: A Retrospective Analysis of Japanese Patients

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Open Journal of Orthopedics 2024年第1期14卷 22-31页

作者： Taizo Kaneko Kyoko Matsudaira Kentaro Hayakawa Fumiaki Tokimura Tsuyoshi Miyazaki Department of orthopaedic Surgery Tokyo Metropolitan Institute for Geriatrics and Gerontology Tokyo Japan

Background: The incidence of femoral intertrochanteric fractures in older adults is higher than that of femoral neck fractures;however, both conditions are often analyzed together as proximal femoral fractures. Considering the difference in treatment, postoperative complication, and mortality risk, these two fractures should be analyzed separately. This study aimed to analyze 1-year mortality and its risk factors in patients with surgically treated femoral intertrochanteric fractures. Methods: Consecutive patients with intertrochanteric fractures who underwent surgical interventions at our institution between January 2017 and December 2021 were retrospectively reviewed. A total of 238 patients were eligible for inclusion in this study. Patients’ demographic and clinical information were retrospectively collected. Patients were divided into the 1-year mortality (n = 16) and survival (n = 222) groups. The incidence of 1-year mortality and its independent risk factors were investigated using univariate and multivariate logistic regression analyses. Results: The mean age of patients was 85.6 ± 8.5 years. The 1-year mortality rate was 6.7% (16/238). Preoperative albumin level, the Geriatric Nutritional Risk Index (GNRI), and malnutrition status (GNRI p = 0.02, p = 0.02, and p = 0.0011, respectively). Multivariate analysis showed that malnutrition status (GNRI p = 0.035) was an independent risk factor for 1-year mortality. Conclusion: Malnutrition status assessed using GNRI (GNRI < 92) was an independent risk factor for 1-year mortality. Our findings suggest that GNRI may be an effective screening tool for predicting postoperative 1-year mortality of patients with surgically treated femoral intertrochanteric fractures.

关键词： Intertrochanteric Fracture Mortality Geriatric Nutritional Risk Index Malnutrition Risk Factor

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Unicompartmental knee arthroplasty vs high tibial osteotomy for knee osteoarthritis:A comparison of clinical and radiological outcomes

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World Journal of Orthopedics 2024年第5期15卷 444-456页

作者： Frederick William Wyatt Oday Al-Dadah Translational and Clinical Research institute Faculty of Medical SciencesNewcastle UniversityNewcastle Upon Tyne NE24HHUnited Kingdom Department of Trauma and orthopaedic Surgery South Tyneside District HospitalSouth Shields NE340PLUnited Kingdom

BACKGROUND Unicompartmental knee arthroplasty(UKA)and high tibial osteotomy(HTO)are well-established operative interventions in the treatment of knee osteoarthritis.However,which intervention is more beneficial to patients with knee osteoarthritis remains unknown and a topic of much debate.Simultaneously,there is a paucity of research assessing the relationship between radiographic parameters of knee joint alignment and patient-reported clinical outcomes,preoperatively and following HTO or UKA.AIM To compare UKAs and HTOs as interventions for medial-compartment knee osteoarthritis:Examining differences in clinical outcome and investigating the relationship of joint alignment with respect to this.METHODS This longitudinal observational study assessed a total of 42 patients that had undergone UKA(n=23)and HTO(n=19)to treat medial compartment knee osteoarthritis.Patient-reported outcome measures(PROMs)were collected to evaluate clinical outcome.These included two disease-specific(Knee Injury and Osteoarthritis Outcome Score,Oxford Knee Score)and two generic(EQ-5D-5L,Short Form-12)PROMs.The radiographic parameters of knee alignment assessed were the:Hip-knee-ankle angle,mechanical axis deviation and angle of Mikulicz line.RESULTS Statistical analyses demonstrated significant(P<0.001),preoperative to postoperative,improvements in the PROM scores of both groups.There were,however,no significant inter-group differences in the postoperative PROM scores of the UKA and HTO group.Several significant correlations associated a more distolaterally angled Mikulicz line with worse knee function and overall health preoperatively(P<0.05).Postoperatively,two clusters of significant correlations were observed between the disease-specific PROM scores and knee joint alignment parameters(hip-knee-ankle angle,mechanical axis deviation)within the HTO group;yet no such associations were observed within the UKA group.CONCLUSION UKAs and HTOs are both efficacious operations that provide a comparable degree of clinical benefit to patients wi

关键词： Arthroplasty Osteotomy Medial compartment Osteoarthritis Knee alignment Patient reported outcome measures

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Irisin-loaded electrospun core-shell nanofibers as calvarial periosteum accelerate vascularized bone regeneration by activating the mitochondrial SIRT3 pathway

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Regenerative Biomaterials 2024年第1期3卷 44-57页

作者： Xi Hua Mingzhuang Hou Lei Deng Nanning Lv Yong Xu Xuesong Zhu Huilin Yang Qin Shi Hao Liu Fan He Department of orthopaedics The First Affiliated Hospital of Soochow UniversitySoochow UniversitySuzhou 215006China orthopaedic institute Suzhou Medical CollegeSoochow UniversitySuzhou 215000China Department of Orthopedics Suzhou Wuzhong People’s HospitalSuzhouJiangsu Province 215128China Department of Orthopedic Surgery Lianyungang Clinical College of Xuzhou Medical UniversityLianyungang 222003China

The scarcity of native periosteum poses a significant clinical barrier in the repair of critical-sized bone defects.The challenge of enhancing regenerative potential in bone healing is further compounded by oxidative stress at the fracture site.However,the introduction of artificial periosteum has demonstrated its ability to promote bone regeneration through the provision of appropriate mechanical support and controlled release of proosteogenic factors.In this study,a poly(L-lactic acid)(PLLA)/hyaluronic acid(HA)-based nanofibrous membrane was fabricated using the coaxial electrospinning technique.The incorporation of irisin into the core-shell structure of PLLA/HA nanofibers(PLLA/HA@Irisin)achieved its sustained release.In vitro experiments demonstrated that the PLLA/HA@Irisin membranes exhibited favorable biocompatibility.The osteogenic differentiation of bone marrow mesenchymal stem cells(BMMSCs)was improved by PLLA/HA@Irisin,as evidenced by a significant increase in alkaline phosphatase activity and matrix mineralization.Mechanistically,PLLA/HA@Irisin significantly enhanced the mitochondrial function of BMMSCs via the activation of the sirtuin 3 antioxidant pathway.To assess the therapeutic effectiveness,PLLA/HA@Irisin membranes were implanted in situ into critical-sized calvarial defects in rats.The results at 4 and 8 weeks post-surgery indicated that the implantation of PLLA/HA@Irisin exhibited superior efficacy in promoting vascularized bone formation,as demonstrated by the enhancement of bone matrix synthesis and the development of new blood vessels.The results of our study indicate that the electrospun PLLA/HA@Irisin nanofibers possess characteristics of a biomimetic periosteum,showing potential for effectively treating critical-sized bone defects by improving the mitochondrial function and maintaining redox homeostasis of BMMSCs.

关键词： periosteum irisin mitochondrial function critical-sized bone defect redox homeostasis

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Comparative Study of 3D-Printed Porous Titanium Alloy with Rod Designs of Three Different Geometric Structures for orthopaedic Implantation

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Acta Metallurgica Sinica(English Letters) 2024年第1期37卷 54-66页

作者： Jiaxin Li Haozhang Zhong Bojun Cao Zhaoyang Ran Jia Tan Liang Deng Yongqiang Hao Jinglong Yan Department of Orthopedics The Second Affiliated Hospital of Harbin Medical UniversityHarbin150001China Shanghai Engineering Research Center of Innovative orthopaedic Instruments and Personalized Medicine Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai200011China institute of Materials Modification and Modeling Shanghai Jiao Tong UniversityShanghai200240China

Porous titanium alloy is currently widely used in clinical treatment of orthopaedic diseases for its lower elastic modulus and ability to integrate with bone tissue.At the micro-level,cells can respond to different geometries,and at the macro-level,the geometric design of implants will also affect the biological function of cells.In this study,three kinds of porous scaffolds with square,triangular and circle rod shapes were designed and 3D printed.This study observed the proliferation and differentiation of MC3T3-E1 cells during surface culture of the three types of scaffolds.It also evaluated the characteristics of the three scaffolds by means of compression tests and scanning electron microscopy to provide a reference for the design of porous titanium alloy implants for clinical applications.The trends of cell proliferation and gene expression between the three types of scaffolds were observed after treatment with two inhibitors.The results show that the square rod porous scaffolds have the best proliferative and osteogenic activities,and these findings may be due to differences in piezo-type mechanosensitive ion channel component 1(Piezo1)and Yes-associated protein(YAP)expression caused by the macro-geometric topography.

关键词： Porous titanium scaffolds Geometric morphology Cell proliferation Structural design

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High formability Mg-Zn-Gd wire facilitates ACL reconstruction via its swift degradation to accelerate intra-tunnel endochondral ossification

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Journal of Magnesium and Alloys 2024年第1期12卷 295-315页

作者： Xuan He Ye Li Hongwei Miao Jiankun Xu Michael Tim-yun Ong Chenmin Wang Lizhen Zheng Jiali Wang Le Huang Haiyue Zu Zhi Yao Jie Mi Bingyang Dai Xu Li Patrick Shu-hang Yung Guangyin Yuan Ling Qin Musculoskeletal Research Laboratory of Department of orthopaedics&Traumatology and Innovative orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing institute of Health Sciences The Chinese University of Hong KongHong KongChina National Engineering Research Center of Light Alloy Net Forming School of Materials Science&EngineeringShanghai Jiao Tong UniversityShanghaiChina Department of orthopaedics and Traumatology Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina orthopaedic Department Peking University Third HospitalBeijingChina Department of Rehabilitation Sciences The Hong Kong Polytechnic UniversityHong KongChina

After reconstructing the anterior cruciate ligament(ACL),unsatisfactory bone tendon interface healing may often induce tunnel enlargement at the early healing stage.With good biological features and high formability,Magnesium-Zinc-Gadolinium(ZG21)wires are developed to bunch the tendon graft for matching the bone tunnel during transplantation.Microstructure,tensile strength,degradation,and cytotoxicity of ZG21 wire are evaluated.The rabbit model is used for assessing the biological effects of ZG21 wire by Micro-CT,histology,and mechanical test.The SEM/EDS,immunochemistry,and in vitro assessments are performed to investigate the underlying mechanism.Material tests demonstrate the high formability of ZG21 wire as surgical suture.Micro-CT shows ZG21 wire degradation accelerates tunnel bone formation,and histologically with earlier and more fibrocartilage regeneration at the healing interface.The mechanical test shows higher ultimate load in the ZG21 group.The SEM/EDS presents ZG21 wire degradation triggered calcium phosphate(Ca-P)deposition.IHC results demonstrate upregulation of Wnt3a,BMP2,and VEGF at the early phase and TGFβ3 and Type II collagen at the late phase of healing.In vitro tests also confirmed the Ca-P in the metal extract could elevate the expression of Wnt3a,βcatenin,ocn and opn to stimulate osteogenesis.Ex vivo tests of clinical samples indicated suturing with ZG21 wire did not weaken the ultimate loading of human tendon tissue.In conclusion,the ZG21 wire is feasible for tendon graft bunching.Its degradation products accelerated intra-tunnel endochondral ossification at the early healing stage and therefore enhanced bone-tendon interface healing in ACL reconstruction.

关键词： Magnesium wire ACL reconstruction Magnesium alloy Biomaterials Endochondral ossification

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Aging impairs the osteocytic regulation of collagen integrity and bone quality

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Bone Research 2024年第1期12卷 78-94页

作者： Charles A.Schurman Serra Kaya Neha Dole Nadja M.Maldonado Luna Natalia Castillo Ryan Potter Jacob P.Rose Joanna Bons Christina D.King Jordan B.Burton Birgit Schilling Simon Melov Simon Tang Eric Schaible Tamara Alliston Department of orthopaedic Surgery University of CaliforniaSan FranciscoCA 94143USA UC Berkeley/UCSF Graduate Program in Bioengineering San FranciscoCA 94143USA Buck institute for Research on Aging NovatoCA 94945USA Washington University in St Louis Department of OrthopedicsSt.LouisMO 63130USA Advanced Light Source Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA

Poor bone quality is a major factor in skeletal fragility in elderly individuals.The molecular mechanisms that establish and maintain bone quality,independent of bone mass,are unknown but are thought to be primarily determined by osteocytes.We hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling(PLR),which maintains bone material properties.We examined bones from young and aged mice with osteocyte-intrinsic repression of TGFβsignaling(TβRII^(ocy−/−))that suppresses PLR.The control aged bone displayed decreased TGFβsignaling and PLR,but aging did not worsen the existing PLR suppression in male TβRII^(ocy−/−)bone.This relationship impacted the behavior of collagen material at the nanoscale and tissue scale in macromechanical tests.The effects of age on bone mass,density,and mineral material behavior were independent of osteocytic TGFβ.We determined that the decline in bone quality with age arises from the loss of osteocyte function and the loss of TGFβ-dependent maintenance of collagen integrity.

关键词： maintain primarily integrity

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Evaluation of genetic response of mesenchymal stem cells to nanosecond pulsed electric fields by whole transcriptome sequencing

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World Journal of Stem Cells 2024年第3期16卷 305-323页

作者： Jian-Jing Lin Tong Ning Shi-Cheng Jia Ke-Jia Li Yong-Can Huang Qiang Liu Jian-Hao Lin Xin-Tao Zhang Department of Sports Medicine and Rehabilitation Peking University Shenzhen HospitalShenzhen 518036Guangdong ProvinceChina institute of Medical Science The Second HospitalCheeloo College of MedicineShandong UniversityJinan 250033Shandong ProvinceChina Department of Biomedical Engineering Institute of Future TechnologyPeking UniversityBeijing 100871China Shenzhen Engineering Laboratory of orthopaedic Regenerative Technologies Peking University Shenzhen HospitalShenzhen 518036Guangdong ProvinceChina Arthritis Clinical and Research Center Peking University People’s HospitalBeijing 100044China

BACKGROUND Mesenchymal stem cells(MSCs)modulated by various exogenous signals have been applied extensively in regenerative medicine research.Notably,nanosecond pulsed electric fields(nsPEFs),characterized by short duration and high strength,significantly influence cell phenotypes and regulate MSCs differentiation via multiple pathways.Consequently,we used transcriptomics to study changes in messenger RNA(mRNA),long noncoding RNA(lncRNA),microRNA(miRNA),and circular RNA expression during nsPEFs application.AIM To explore gene expression profiles and potential transcriptional regulatory mechanisms in MSCs pretreated with nsPEFs.METHODS The impact of nsPEFs on the MSCs transcriptome was investigated through whole transcriptome sequencing.MSCs were pretreated with 5-pulse nsPEFs(100 ns at 10 kV/cm,1 Hz),followed by total RNA isolation.Each transcript was normalized by fragments per kilobase per million.Fold change and difference significance were applied to screen the differentially expressed genes(DEGs).Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to elucidate gene functions,complemented by quantitative polymerase chain reaction verification.RESULTS In total,263 DEGs were discovered,with 92 upregulated and 171 downregulated.DEGs were predominantly enriched in epithelial cell proliferation,osteoblast differentiation,mesenchymal cell differentiation,nuclear division,and wound healing.Regarding cellular components,DEGs are primarily involved in condensed chromosome,chromosomal region,actin cytoskeleton,and kinetochore.From aspect of molecular functions,DEGs are mainly involved in glycosaminoglycan binding,integrin binding,nuclear steroid receptor activity,cytoskeletal motor activity,and steroid binding.Quantitative real-time polymerase chain reaction confirmed targeted transcript regulation.CONCLUSION Our systematic investigation of the wide-ranging transcriptional pattern modulated by nsPEFs revealed the differential expression of 263 mRNAs,2 miRNAs,and 65 lncRNAs.Our study demons

关键词： Nanosecond pulsed electric fields Whole transcriptome sequencing Mesenchymal stem cells Genetic response Stem cell engineering

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Osteoarticular Lesions of the Shoulder Girdle by Hippopotamus Bite: Highly Septic Lesion

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Open Journal of Orthopedics 2024年第2期14卷 114-121页

作者： Jr Pierre Germain Ochou Achié Jean Régis Akobe Yao Aboh Ganyn Robert Arnaud Assere Kouamé Jean-Eric Kouassi Adelaïde Aya Natacha Kouassi Ibrahim Soumahoro Zolopégué Marcel Soro Sédi Loues De Randolphe Akpro Gbalé Yannick Blé Kouamé Innocent M’bra Loukou Blaise Yao Bada Juste Léopold NiaoréSery Koffi Léopold Krah Michel Kodo Department of orthopaedic and Traumatological Surgery Bouaké University Hospital Bouaké Ivory Coast Raoul Follereau institute Manikro Centre Bouaké Ivory Coast

Hippopotamus bites are rare in medical consultations, despite several studies exposing their aggressive character. A case of a hippopotamus bite on the shoulder of a fisherman has been reported. In addition to the osteoarticular aspect representing a therapeutic problem, the infectious aspect was marked by sepsis, with a death in less than 48 hours. Based on this observation, a protocol for the initial management of large animal bites was submitted.

关键词： Bite Hippopotamus Septic Shock

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Effect of weight-adjusted antimicrobial antibiotic prophylaxis on postoperative dosage and surgical site infection incidence in total joint arthroplasty

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World Journal of Orthopedics 2024年第4期15卷 318-320页

作者： Ashim Gupta Vijay Kumar Jain Department of orthopaedics and Regenerative Medicine Future BiologicsLawrencevilleGA 30043United States Department of orthopaedics South Texas Orthopaedic Research Institute(STORI Inc.)LaredoTX 78045United States Department of Regenerative Medicine BioIntegrateLawrencevilleGA 30043United States Department of orthopaedics and Regenerative Medicine Regenerative OrthopaedicsNoida 201301India Department of orthopaedics Atal Bihari Vajpayee Institute of Medical SciencesDr Ram Manohar Lohia HospitalNew Delhi 110001India

Surgical site infections(SSI)following total joint arthroplasty pose a significant concern for both providers and patients across the globe.Currently,administration of antimicrobial antibiotic prophylaxis is used throughout the world to reduce the incidence of SSI.However,the correct dosage and frequency of administration remains debatable.In this editorial,we emphasized the determination of the effect of administration of weight-adjusted antimicrobial antibiotic prophylaxis regime on the incidence of SSI and postoperative dosage reduction compared to the conventionally used regime during total joint arthroplasty.The results demonstrated similar efficacy between both regimes with respect to the incidence of SSI.In addition,weight-adjustment led to reduced postoperative dosage and has the potential to reduce chances of achieving lower therapeutic concentration,drug resistance,drug toxicity,and costs.

关键词： Antibiotics Antimicrobial prophylaxis Weight-adjusted Surgical site infections Total joint arthroplasty Knee arthroplasty Hip arthroplasty

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