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1.
J Pain ; : 104497, 2024 Feb 10.
Article in English | MEDLINE | ID: mdl-38342191

ABSTRACT

This study aimed to enhance performance, identify additional predictors, and improve the interpretability of biopsychosocial machine learning models for low back pain (LBP). Using survey data from a 6-year nationwide study involving 17,609 adults aged ≥50 years (Korea National Health and Nutrition Examination Survey), we explored 119 factors to detect LBP in individuals who reported experiencing LBP for at least 30 days within the previous 3 months. Our primary model, model 1, employed eXtreme Gradient Boosting (XGBoost) and selected primary factors (PFs) based on their feature importance scores. To extend this, we introduced additional factors, such as lumbar X-ray findings, physical activity, sitting time, and nutrient intake levels, which were available only during specific survey periods, into models 2 to 4. Model performance was evaluated using the area under the curve, with predicted probabilities explained by SHapley Additive exPlanations. Eleven PFs were identified, and model 1 exhibited an enhanced area under the curve .8 (.77-.84, 95% confidence interval). The factors had varying impacts across individuals, underscoring the need for personalized assessment. Hip and knee joint pain were the most significant PFs. High levels of physical activity were found to have a negative association with LBP, whereas a high intake of omega-6 was found to have a positive association. Notably, we identified factor clusters, including hip joint pain and female sex, potentially linked to osteoarthritis. In summary, this study successfully developed effective XGBoost models for LBP detection, thereby providing valuable insight into LBP-related factors. Comprehensive LBP management, particularly in women with osteoarthritis, is crucial given the presence of multiple factors. PERSPECTIVE: This article introduces XGBoost models designed to detect LBP and explores the multifactorial aspects of LBP through the application of SHapley Additive exPlanations and network analysis on the 4 developed models. The utilization of this analytical system has the potential to aid in devising personalized management strategies to address LBP.

2.
Small ; 20(23): e2310734, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38143290

ABSTRACT

Achieving satisfactory bone tissue regeneration in osteoporotic patients with ordinary biomaterials is challenging because of the decreased bone mineral density and aberrant bone microenvironment. In addressing this issue, a biomimetic scaffold (PMEH/SP), incorporating 4-hexylresorcinol (4HR), and substance P (SP) into the poly(lactic-go-glycolic acid) (PLGA) scaffold with magnesium hydroxide (M) and extracellular matrix (E) is introduced, enabling the consecutive release of bioactive agents. 4HR and SP induced the phosphorylation of p38 MAPK and ERK in human umbilical vein endothelial cells (HUVECs), thereby upregulating VEGF expression level. The migration and tube-forming ability of endothelial cells can be promoted by the scaffold, which accelerates the formation and maturation of the bone. Moreover, 4HR played a crucial role in the inhibition of osteoclastogenesis by interrupting the IκB/NF-κB signaling pathway and exhibiting SP, thereby enhancing the migration and angiogenesis of HUVECs. Based on such a synergistic effect, osteoporosis can be suppressed, and bone regeneration can be achieved by inhibiting the RANKL pathway in vitro and in vivo, which is a commonly known mechanism of bone physiology. Therefore, the study presents a promising approach for developing a multifunctional regenerative material for sophisticated osteoporotic bone regeneration.


Subject(s)
Bone Regeneration , Human Umbilical Vein Endothelial Cells , Osteoporosis , Polylactic Acid-Polyglycolic Acid Copolymer , Tissue Scaffolds , Bone Regeneration/drug effects , Humans , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Tissue Scaffolds/chemistry , Osteoporosis/drug therapy , Osteoporosis/metabolism , Animals , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Osteogenesis/drug effects
3.
Cureus ; 15(3): e36657, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37102019

ABSTRACT

Infectious spondylitis is a rare but severe disease of the spine caused by bacteria or other pathogens. Particularly in immunocompromised patients, a definitive source of infection often remains uncertain. Among many pathogens, Streptococcus gordonii, a normal oral flora, is a very rare pathogen in infectious spondylitis. Only a few articles have reported infectious spondylitis caused by Streptococcus gordonii. To the best of our knowledge, there have been no reports of surgically treated infectious spondylitis caused by Streptococcus gordonii. Hence, in the current report, we present the case of a 76-year-old woman with known type 2 diabetes who was transferred to our medical center due to infectious spondylitis caused by Streptococcus gordonii following an L1 compression fracture and underwent an operation for treatment.

4.
J Foot Ankle Surg ; 61(4): e21-e24, 2022.
Article in English | MEDLINE | ID: mdl-34974978

ABSTRACT

A synovial fistula is the communication between the synovial space and the skin. In most cases, the fistula tract is located within the soft tissue; therefore, excision and closure of the fistula have been described as surgical treatment. Rarely, fistulas may form within the bone following procedures around the joint, such as core biopsy and bone tunneling for ligament reconstruction. In such cases, the insertion of materials filling the bone tunnel with cement or bone graft was introduced. This report describes a case of synovial fistula in the distal tibiofibular joint through a screw hole following the removal of supramalleolar osteotomy hardware. We present a novel technique to close the communication by inserting a larger sized screw as a plug.


Subject(s)
Fistula , Plastic Surgery Procedures , Ankle Joint/surgery , Bone Screws/adverse effects , Fistula/surgery , Humans , Osteotomy/adverse effects , Osteotomy/methods , Plastic Surgery Procedures/methods
5.
Stem Cells Transl Med ; 10(4): 554-567, 2021 04.
Article in English | MEDLINE | ID: mdl-33326694

ABSTRACT

Osteoporotic vertebral compression fractures (OVCFs) are serious health problems. We conducted a randomized, open-label, phase I/IIa study to determine the feasibility, safety, and effectiveness of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) and teriparatide (parathyroid hormone 1-34) in OVCFs. Twenty subjects with recent OVCFs were randomized to teriparatide (20 µg/day, daily subcutaneous injection for 6 months) treatment alone or combined treatment of WJ-MSCs (intramedullary [4 × 107 cells] injection and intravenous [2 × 108 cells] injection after 1 week) and teriparatide (20 µg/day, daily subcutaneous injection for 6 months). Fourteen subjects (teriparatide alone, n = 7; combined treatment, n = 7) completed follow-up assessment (visual analog scale [VAS], Oswestry Disability Index [ODI], Short Form-36 [SF-36], bone mineral density [BMD], bone turnover measured by osteocalcin and C-terminal telopeptide of type 1 collagen, dual-energy x-ray absorptiometry [DXA], computed tomography [CT]). Our results show that (a) combined treatment with WJ-MSCs and teriparatide is feasible and tolerable for the patients with OVCFs; (b) the mean VAS, ODI, and SF-36 scores significantly improved in the combined treatment group; (c) the level of bone turnover markers were not significantly different between the two groups; (d) BMD T-scores of spine and hip by DXA increased in both control and experimental groups without a statistical difference; and (e) baseline spine CT images and follow-up CT images at 6 and 12 months showed better microarchitecture in the combined treatment group. Our results indicate that combined treatment of WJ-MSCs and teriparatide is feasible and tolerable and has a clinical benefit for fracture healing by promoting bone architecture. Clinical trial registration: https://nedrug.mfds.go.kr/, MFDS: 201600282-30937.


Subject(s)
Bone Density Conservation Agents , Fractures, Compression , Mesenchymal Stem Cell Transplantation , Osteoporotic Fractures/therapy , Spinal Fractures , Teriparatide , Wharton Jelly , Bone Density , Bone Density Conservation Agents/therapeutic use , Fractures, Compression/therapy , Humans , Spinal Fractures/therapy , Teriparatide/therapeutic use , Wharton Jelly/cytology
6.
Int J Mol Sci ; 21(12)2020 Jun 16.
Article in English | MEDLINE | ID: mdl-32560070

ABSTRACT

Tauroursodeoxycholic acid (TUDCA) is a US FDA-approved hydrophilic bile acid for the treatment of chronic cholestatic liver disease. In the present study, we investigate the effects of TUDCA on the proliferation and differentiation of osteoblasts and its therapeutic effect on a mice model of osteoporosis. Following treatment with different concentrations of TUDCA, cell viability, differentiation, and mineralization were measured. Three-month-old female C57BL/6 mice were randomly divided into three groups (n = 8 mice per group): (i) normal mice as the control group, (ii) ovariectomy (OVX) group (receiving phosphate-buffered saline (PBS) treatment every other day for 4 weeks), and (iii) OVX group with TUDCA (receiving TUDCA treatment every other day for 4 weeks starting 6 weeks after OVX). At 11 weeks post-surgery, serum levels of procollagen type I N-terminal propeptides (PINP) and type I collagen crosslinked C-telopeptides (CTX) were measured, and all mice were sacrificed to examine the distal femur by micro-computed tomography (CT) scans and histology. TUDCA (100 nM, 1 µM) significantly increased the proliferation and viability of osteoblasts and osteoblast differentiation and mineralization when used in vitro. Furthermore, TUDCA neutralized the detrimental effects of methylprednisolone (methylprednisolone-induced osteoblast apoptosis). In the TUDCA treatment group the PINP level was higher and the CTX level was lower, but these levels were not significantly different compared to the PBS treatment group. Micro-CT and histology showed that the TUDCA treatment group preserved more trabecular structures in the distal femur compared to the PBS treatment group. In addition, the TUDCA treatment group increased the percentage bone volume with respect to the total bone volume, bone mineral density, and mice distal femur trabeculae compared with the PBS treatment group. Taken together, our findings suggest that TUDCA may provide a favorable effect on bones and could be used for the prevention and treatment of osteoporosis.


Subject(s)
Osteoporosis/drug therapy , Ovariectomy/adverse effects , Peptide Fragments/metabolism , Procollagen/metabolism , Taurochenodeoxycholic Acid/administration & dosage , Animals , Cell Differentiation/drug effects , Cell Survival/drug effects , Disease Models, Animal , Female , Gene Expression Regulation/drug effects , Humans , Methylprednisolone/adverse effects , Mice , Osteoblasts/cytology , Osteoblasts/drug effects , Osteoblasts/metabolism , Osteoporosis/etiology , Osteoporosis/metabolism , Random Allocation , Taurochenodeoxycholic Acid/pharmacology , Treatment Outcome
7.
Genes (Basel) ; 11(6)2020 06 02.
Article in English | MEDLINE | ID: mdl-32498429

ABSTRACT

As life expectancy increases, the prevalence of osteoporosis is increasing. In addition to vitamin D which is well established to have an association with osteoporosis, B vitamins, such as thiamine, folate (vitamin B9), and cobalamin (vitamin B12), could affect bone metabolism, bone quality, and fracture risk in humans by influencing homocysteine/folate metabolism. Despite the crucial role of B vitamins in bone metabolism, there are few studies regarding associations between B vitamin-related genes and osteoporosis. In this study, we investigated the genetic association of four single nucleotide polymorphisms (SNPs) within the 3'-untranslated regions of vitamin B-related genes, including TCN2 (encodes transcobalamin II), CD320 (encodes transcobalamin II receptor), SLC19A1 (encodes reduced folate carrier protein 1), and SLC19A2 (encodes thiamine carrier 1), with osteoporosis and osteoporotic vertebral compression fracture (OVCF). We recruited 301 postmenopausal women and performed genotyping of CD320 rs9426C>T,TCN2 rs10418C>T, SLC19A1 rs1051296G>T, and SLC19A2 rs16862199C>T using a polymerization chain reaction-restriction fragment length polymorphism assay. There was a significantly higher incidence of both osteoporosis (AOR 5.019; 95% CI, 1.533-16.430, p < 0.05) and OVCF (AOR, 5.760; 95% CI, 1.480-22.417, p < 0.05) in individuals with genotype CD320 CT+TT and high homocysteine concentrations. Allele combination analysis revealed that two combinations, namely CD320 C-TCN2 T-SLC19A1 T-SLC19A2 C (OR, 3.244; 95% CI, 1.478-7.120, p < 0.05) and CD320 T-TCN2 C-SLC19A1 G-SLC19A2 C (OR, 2.287; 95% CI, 1.094-4.782, p < 0.05), were significantly more frequent among the osteoporosis group. Our findings suggest that SNPs within the CD320 gene in 3´-UTR may contribute to osteoporosis and OVCF occurrences in some individuals. Furthermore, specific allele combinations of CD320, TCN2, SLC19A1, and SLC19A2 may contribute to increased susceptibility to osteoporosis and OVCF.


Subject(s)
Antigens, CD/genetics , Membrane Transport Proteins/genetics , Osteoporosis/genetics , Receptors, Cell Surface/genetics , Reduced Folate Carrier Protein/genetics , Transcobalamins/genetics , Vitamin B Complex/genetics , 3' Untranslated Regions/genetics , Alleles , Female , Folic Acid/genetics , Folic Acid/metabolism , Fractures, Compression/physiopathology , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , Humans , Osteoporosis/physiopathology , Osteoporotic Fractures/physiopathology , Postmenopause/genetics , Postmenopause/metabolism , Vitamin B 12/genetics , Vitamin B 12/metabolism , Vitamin B Complex/metabolism
8.
Orthop Traumatol Surg Res ; 105(7): 1407-1412, 2019 11.
Article in English | MEDLINE | ID: mdl-31542310

ABSTRACT

BACKGROUND: Two-dimensional (2D) and three-dimensional (3D) computed tomography (CT) have been increasingly used in various intra-articular fractures including pilon fracture. However, no study has investigated intraobserver and interobserver reliabilities of pilon fracture classification using 3D CT images. HYPOTHESIS: (1) Intraobserver and interobserver agreements of fracture classifications and treatment recommendations will improve by using 2D CT images compared to using plain radiographs only; (2) agreements will improve by adding 3D CT images compared to adding 2D CT images; and (3) agreements of orthopedic residents rather than specialists will be influenced more by imaging modality. MATERIALS AND METHODS: Ten orthopedic specialists and 10 residents completed a survey to classify the fractures according to the Rüedi-Allgöwer and AO/OTA classifications and to select treatment options using 25 pilon fracture images. The survey was conducted using plain radiographs, with 2D and 3D CT images introduced 3 and 6weeks later, respectively. Kappa coefficients were calculated to determine reliabilities. RESULTS: Intraobserver reliabilities for fracture classifications in specialists significantly improved by using 2D images compared to using plain radiographs only. Addition of 3D CT did not significantly improve intraobserver reliabilities compared to those with 2D CT. Use of 2D CT images significantly improved overall interobserver agreement of both classifications, with the improvement being greater for residents. Use of 3D CT images did not improve the interobserver reliability of both classifications. Overall interobserver reliabilities for treatment recommendations did not significantly differ according to the imaging modality. However, interobserver agreement among residents significantly improved from slight agreement using radiographs only to fair agreement using 2D CT images. DISCUSSION: Intraobserver and interobserver reliabilities of pilon fracture classification and treatment recommendations did not improve between using 3D and 2D CT. Using 2D CT images improved the intraobserver and interobserver reliabilities of the fracture classifications in specialists and the interobserver reliabilities of the fracture classifications and the treatment recommendations in residents. LEVEL OF EVIDENCE: IV, case control study.


Subject(s)
Ankle Fractures/diagnosis , Fracture Fixation/methods , Imaging, Three-Dimensional/methods , Intra-Articular Fractures/diagnosis , Tibial Fractures/diagnosis , Tomography, X-Ray Computed/methods , Ankle Fractures/classification , Ankle Fractures/surgery , Case-Control Studies , Humans , Intra-Articular Fractures/classification , Intra-Articular Fractures/surgery , ROC Curve , Reproducibility of Results , Tibial Fractures/classification , Tibial Fractures/surgery
9.
Medicine (Baltimore) ; 98(28): e14847, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31305388

ABSTRACT

RATIONALE: Atlantoaxial transarticular screw fixation has been an effective and appealing method for inducing fusion of the C1-C2 complex. This technique is usually performed with Gallie fusion. In performing Gallie fusion using sublaminar wiring, a major concern is the risk of dural tear associated with passing sublaminar wires through the epidural space. We present the first report on symptomatic symptomatic subdural hygroma (SDH) due to transarticular screw fixation with posterior wiring. PATIENTS CONCERNS: A 50-year-old man had sustained dens fracture 20 years ago and presented with severe neck pain following a recent traffic accident. The images showed atlantoaxial instability due to nonunion of the dens fracture and the patient underwent transarticular screw fixation with posterior sublaminar wiring using Gallie technique. When the U-shaped wire was passed under the arch of C1 from inferior to superior, a dural tear and cerebrospinal fluid (CSF) leak occurred. The site of dural tear was repaired by direct application of sutures. The patient was discharged in good condition. Fifteen day after surgery, the patient was readmitted with a history of a progressive headache associated with vomiting and vertigo. DIAGNONSIS: Brain CT and MRI showed bilateral posterior fossa and a right-sided supratentorial SDH. INTERVENTIONS: The patient underwent right occipital burr hole and evacuation of posterior fossa SDH due to deteriorating neurological status. OUTCOMES: The patient's condition gradually improved after the operation and became asymptomatic at 3-year follow-up. LESSONS: Posterior fossa and supratentorial SDH could occur resulting from any intraoperative dural tear and CSF leakage during posterior cervical spinal surgery. Symptomatic SDH after posterior cervical spinal surgery should be cautiously assessed and treated. LEVEL OF EVIDENCE: 5.


Subject(s)
Atlanto-Axial Joint/surgery , Joint Instability/surgery , Postoperative Complications , Spinal Fusion , Subdural Effusion/etiology , Atlanto-Axial Joint/diagnostic imaging , Bone Screws , Bone Wires , Diagnosis, Differential , Humans , Joint Instability/diagnostic imaging , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Postoperative Complications/surgery , Subdural Effusion/diagnostic imaging , Subdural Effusion/surgery
10.
Adv Exp Med Biol ; 1077: 355-368, 2018.
Article in English | MEDLINE | ID: mdl-30357698

ABSTRACT

Bone tissue engineering using titanium (Ti) implant and titanium dioxide (TiO2) with their modification is gaining increasing attention. Ti has been adopted as an implant material in dental and orthopedic fields due to its superior properties. However, it still requires modification in order to achieve robust osteointegration between the Ti implant and surrounding bone. To modify the Ti implant, numerous methods have been introduced to fabricate porous implant surfaces with a variety of coating materials. Among these, plasma spraying of hydroxyapatite (HA) has been the most commonly used with commercial success. Meanwhile, TiO2 nanotubes have been actively studied as the coating material for implants, and promising results have been reported about improving osteogenic activity around implants recently. Also porous three-dimensional constructs based on TiO2 have been proposed as scaffolding material with high biocompatibility and osteoconductivity in large bone defects. However, the use of the TiO2 scaffolds in load-bearing environment is somewhat limited. In order to optimize the TiO2 scaffolds, studies have tried to combine various materials with TiO2 scaffolds including drug, mesenchymal stem cells, Al2O3-SiO2 solid and HA. This article will shortly introduce the properties of Ti and Ti-based implants with their modification, and review the progress of bone tissue engineering using the TiO2 nanotubes and scaffolds.


Subject(s)
Bone and Bones , Prostheses and Implants , Tissue Engineering , Titanium , Aluminum Oxide , Durapatite , Humans , Silicon Dioxide , Surface Properties
11.
Int J Mol Sci ; 19(3)2018 Mar 12.
Article in English | MEDLINE | ID: mdl-29534533

ABSTRACT

Postmenopausal osteoporosis is one of the most prominent diseases in postmenopausal women and it is increasing in prevalence with the aging population. Furthermore, osteoporosis and osteoporotic vertebral compression fractures (OVCFs) are related to mortality and decreased quality of life. Therefore, searching for biomarkers that are able to identify postmenopausal women who are at high risk of developing OVCFs is an effective strategy for improving the quality of life of patients and alleviating social and economic burdens. In this study, we investigated methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) gene polymorphisms in postmenopausal women with OVCF. We recruited 301 postmenopausal women and performed genotyping for the presence of MTHFR 2572C>A, 4869C>G and TS 1100C>T, 1170A>G. Genotyping was analyzed using the polymerization chain reaction restriction fragment length polymorphism assay. MTHFR 2572C>A and TS 1100C>T were associated with the prevalence of osteoporosis (MTHFR 2572CC versus CA+AA: odd ratio [OR] adjusted age, hypertention [HTN], and diabetes mellitus [DM] = 0.49, p = 0.012) and the occurrence of OVCFs (MTHFR 2572CC versus CA+AA: OR adjusted age, HTN, and DM = 0.38, p = 0.013; TS 1100CC versus CT+TT: OR adjusted age, HTN, and DM = 0.46, p = 0.02). Our novel finding is the identification of MTHFR and TS genetic variants that decrease susceptibility to OVCFs. Our findings suggest that polymorphisms in the MTHFR and TS genes are associated with susceptibility to osteoporosis and OVCFs in postmenopausal women.


Subject(s)
Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Osteoporosis, Postmenopausal/genetics , Osteoporotic Fractures/genetics , Polymorphism, Single Nucleotide , Spinal Fractures/genetics , Thymidylate Synthase/genetics , 3' Untranslated Regions , Aged , Case-Control Studies , Female , Fractures, Compression/genetics , Humans , Middle Aged
12.
BMC Pediatr ; 18(1): 97, 2018 03 05.
Article in English | MEDLINE | ID: mdl-29506496

ABSTRACT

BACKGROUND: Germ cell tumors (GCTs) in children are rare neoplasms with diverse pathological findings according to the site and age of presentation. The most common symptoms in children with mediastinal GCTs, which are nonspecific, are dyspnea, chest pain, cough, hemoptysis, vena cava occlusion syndrome, and fatigue/weakness. Because of these nonspecific symptoms, it is difficult to suspect a mediastinal mass. A posterior mediastinal tumor causing spinal cord compression is an important example of an oncologic emergency arising from a neurogenic tumor. CASE PRESENTATION: Children with posterior mediastinum GCTs can be easily mistaken as having a neurogenic tumor because of site of tumor origin. We treated our 7-year-old patient with emergency decompression surgery and high-dose steroid pulse therapy to prevent secondary injury to the spinal cord. Primary injury was a result of spinal cord compression due to the initial manifestation of GCT in the posterior mediastinum. Cisplatin-based chemotherapy was also administered. The patient was followed up regularly for 3 years and is undergoing rehabilitation without any signs of recurrence. CONCLUSIONS: We present an extremely rare case of a child with paraparesis caused by extradural spinal cord compression as the initial manifestation of GCT in the posterior mediastinum. The child was treated with emergency decompression surgery and high-dose pulse steroid therapy to prevent secondary injury to the spinal cord.


Subject(s)
Mediastinal Neoplasms/diagnosis , Neoplasms, Germ Cell and Embryonal/diagnosis , Spinal Cord Compression/etiology , Child , Humans , Male , Mediastinal Neoplasms/complications , Neoplasms, Germ Cell and Embryonal/complications , Thoracic Vertebrae
13.
J Orthop Res ; 36(1): 244-253, 2018 01.
Article in English | MEDLINE | ID: mdl-28741852

ABSTRACT

Genetic factors have been shown to be a small but significant predictor for osteoporosis and osteoporotic fracture risk. We performed a case-control association study to determine the association between miR-146a, miR-149, miR-196a2, and miR-499 polymorphisms and osteoporotic vertebral compression fracture (OVCF) susceptibility. In total, 286 unrelated postmenopausal Korean women (57 with OVCFs, 55 with non-OVCFs, and 174 healthy controls) were recruited. All subjects underwent dual energy X-ray absorptiometry to determine BMD at the lumbar spine and femoral neck. We focused on four single nucleotide polymorphisms (SNPs) of pre-miRNA sequences including miR-146aC>G (rs2910164), miR-149T>C (rs2292832), miR-196a2T>C (rs11614913), and miR-499A>G (rs3746444). Genotype frequencies of these four SNPs were determined using polymerase chain reaction-restriction fragment length polymorphism analysis. The TT genotype of miR-149aT>C was less frequent in subjects with OVCFs, suggesting a protective effect against OVCF risk (Odds ratio [OR], 0.435; 95% confidence interval [CI], 0.22-0.85, p = 0.014), whereas the miR-146aCG/ miR-196a2TC combined genotype was more frequent in OVCF patients (OR, 5.163; 95%CI, 1.057-25.21, p = 0.043), suggesting an increase in OVCF risk. Additionally, combinations of miR-146a, -149, -196a2, and -449 showed a significant association with increased prevalence of OVCFs in postmenopausal women. In particular, the miR-146aG/-149T/-196a2C/-449G allele combination was significantly associated with an increased risk of OVCF (OR, 35.01; 95% CI, 1.919-638.6, p = 0.001). Our findings suggest that the TT genotype of miR-149aT>C may contribute to decreased susceptibility to OVCF in Korean postmenopausal women. Conversely, the miR-146aCG/ miR-196a2TC combined genotype and the miR-146aG/-149T/-196a2C/-449G allele combination may contribute to increased susceptibility to OVCF. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:244-253, 2018.


Subject(s)
Fractures, Compression/genetics , Genetic Predisposition to Disease , MicroRNAs/genetics , Osteoporotic Fractures/genetics , Polymorphism, Single Nucleotide , Aged , Case-Control Studies , Female , Genotype , Humans , Middle Aged , Postmenopause
14.
Stem Cell Res Ther ; 8(1): 262, 2017 Nov 15.
Article in English | MEDLINE | ID: mdl-29141662

ABSTRACT

BACKGROUND: Adipose tissue-derived mesenchymal stem cells (AT-MSCs) offer potential as a therapeutic option for chronic discogenic low back pain (LBP) because of their immunomodulatory functions and capacity for cartilage differentiation. The goal of this study was to assess the safety and tolerability of a single intradiscal implantation of combined AT-MSCs and hyaluronic acid (HA) derivative in patients with chronic discogenic LBP. METHODS: We performed a single-arm phase I clinical trial with a 12-month follow-up and enrolled 10 eligible chronic LBP patients. Chronic LBP had lasted for more than 3 months with a minimum intensity of 4/10 on a visual analogue scale (VAS) and disability level ≥ 30% on the Oswestry Disability Index (ODI). The 10 patients underwent a single intradiscal injection of combined HA derivative and AT-MSCs at a dose of 2 × 107 cells/disc (n = 5) or 4 × 107 cells/disc (n = 5). Safety and treatment outcomes were evaluated by assessing VAS, ODI, Short Form-36 (SF-36), and imaging (lumbar spine X-ray imaging and MRI) at regular intervals over 1 year. RESULTS: No patients were lost at any point during the 1-year clinical study. We observed no procedure or stem cell-related adverse events or serious adverse events during the 1-year follow-up period. VAS, ODI, and SF-36 scores significantly improved in both groups receiving both low (cases 2, 4, and 5) and high (cases 7, 8, and 9) cell doses, and did not differ significantly between the two groups. Among six patients who achieved significant improvement in VAS, ODI, and SF-36, three patients (cases 4, 8, and 9) were determined to have increased water content based on an increased apparent diffusion coefficient on diffusion MRI. CONCLUSIONS: Combined implantation of AT-MSCs and HA derivative in chronic discogenic LBP is safe and tolerable. However, the efficacy of combined AT-MSCs and HA should be investigated in a randomized controlled trial in a larger population. TRIAL REGISTRATION: ClinicalTrials.gov NCT02338271 . Registered 7 January 2015.


Subject(s)
Hyaluronic Acid/therapeutic use , Intervertebral Disc Degeneration/therapy , Low Back Pain/therapy , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Adipose Tissue/cytology , Adipose Tissue/physiology , Adult , Cell Differentiation , Chronic Disease , Female , Follow-Up Studies , Humans , Injections, Intralesional , Intervertebral Disc/drug effects , Intervertebral Disc/pathology , Intervertebral Disc/physiopathology , Intervertebral Disc Degeneration/pathology , Intervertebral Disc Degeneration/physiopathology , Low Back Pain/pathology , Low Back Pain/physiopathology , Male , Mesenchymal Stem Cells/physiology , Middle Aged , Pain Measurement , Patient Safety , Transplantation, Autologous , Treatment Outcome , Water/metabolism
15.
Arthroscopy ; 33(4): 828-834, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28237080

ABSTRACT

PURPOSE: To investigate which method can predict tibiofibular diastasis more accurately among the tibiofibular interval at the ankle joint level or previous parameters taken 1 cm above the joint line. METHODS: An arthroscopic examination was performed in 78 consecutive patients with anterolateral ankle pain. Four different methods were performed to take measurements of the tibiofibular interval using an axial computed tomography (CT) scan under existing arthroscopic diagnosis. Three previously reported parameters were assessed at 1 cm above the joint level. In the first method, 2 measurements were obtained. The anterior measurement was the closest distance between the anterior border of the fibula and anterior tibial tubercle. The posterior measurement was the closest distance between the medial border of the fibula and posterior tibial tubercle. In the second method, an angle between the fibular axis and the line connecting the anterior and posterior tibial tubercle was measured. In the third method, the nearest distance between the line perpendicular to the line connecting the tubercles at the anterior tubercle of the distal tibia and the anterior-most margin of the fibula was measured. The fourth method, which was developed in this study, measured the narrowest tibiofibular distance at the joint level. Data were analyzed using Student's t-test and the receiver operating characteristic curve to make comparisons among 4 CT-based parameters. RESULTS: In the comparison between the patients with arthroscopic diastasis and without diastasis, the posterior parameter in the first method and the narrowest tibiofibular distance at the joint level in the fourth method showed a significant difference (P < .05) The areas under the receiver operating characteristic curve (AUCs) of the anterior and posterior parameter of the first method were 0.58 (95% confidence interval [CI], 0.43-0.73; P = .167) of anterior measurement and 0.6 (95% CI, 0.45-0.75; P = .029) of posterior measurement, respectively. The second and third methods presented AUCs of 0.59 (95% CI, 0.44-0.74; P = .458) and 0.48 (95% CI, 0.33-0.64; P = .987), respectively. The fourth method presented an AUC of 0.86 (95% CI, 0.75-0.94; P = .000). When the syndesmosis was measured at the joint level, 2 mm of syndesmosis interval as a cutoff value showed 76% of sensitivity and 81% of specificity. CONCLUSIONS: Syndesmosis assessment using an axial CT scan at the joint level best correlated with the arthroscopic examination. When there is more than 2 mm of widening in syndesmosis on the axial CT scan at the joint level, there is a high likelihood of diastasis of the distal tibiofibular syndesmosis in patients who are suspicious clinically to have acute or chronic syndesmosis lesion. LEVEL OF EVIDENCE: Level III, retrospective comparative study.


Subject(s)
Ankle Joint/diagnostic imaging , Diastasis, Bone/diagnostic imaging , Adolescent , Adult , Ankle Joint/pathology , Arthroscopy/methods , Diastasis, Bone/diagnosis , Diastasis, Bone/pathology , Female , Fibula/diagnostic imaging , Fibula/pathology , Humans , Knee Joint/diagnostic imaging , Knee Joint/pathology , Male , Middle Aged , ROC Curve , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Tibia/diagnostic imaging , Tibia/pathology , Tomography, X-Ray Computed/methods , Young Adult
16.
Int J Mol Sci ; 17(12)2016 Dec 09.
Article in English | MEDLINE | ID: mdl-27941685

ABSTRACT

Osteoporosis and osteoporotic fractures are strongly associated with mortality and morbidity, both in developing and developed countries. Menopause accelerates bone loss due to estrogen deficiency and age-related linear bone loss. We investigated plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms in postmenopausal women with osteoporotic vertebral compression fractures (OVCFs). In this case-control study, 355 postmenopausal women were genotyped for the presence of PAI-1 gene polymorphisms -844A > G, -675 4G > 5G, 43G > A, 9785A > G, and 11053T > G. Genetic polymorphisms of PAI-1 were analyzed by the polymerization chain reaction restriction fragment length polymorphism assay, and their association with disease status and folate and homocysteine levels was determined in 158 OVCF patients and 197 control subjects. The PAI-1 -675 5G5G (adjusted odds ratio (AOR), 3.302; p = 0.017) and 43GA + AA (AOR, 2.087; p = 0.042) genotype frequencies showed significant association with the increased prevalence of OVCFs in postmenopausal women. In addition, we performed gene-environment interaction studies and demonstrated an association between PAI-1 gene polymorphisms and OVCF prevalence. Our novel finding is the identification of several PAI-1 genetic variants that increase susceptibility to OVCF. Our findings suggest that polymorphisms in PAI-1 may contribute to OVCF, and that they can be developed as biomarkers for evaluating OVCF risk.


Subject(s)
Fractures, Compression/genetics , Plasminogen Activator Inhibitor 1/genetics , Polymorphism, Genetic/genetics , Aged , Aged, 80 and over , Case-Control Studies , Female , Fractures, Compression/pathology , Genetic Predisposition to Disease/genetics , Genotype , Haplotypes/genetics , Humans , Middle Aged , Osteoporosis/genetics , Osteoporosis/pathology , Postmenopause
17.
J Bone Joint Surg Am ; 97(5): 381-8, 2015 Mar 04.
Article in English | MEDLINE | ID: mdl-25740028

ABSTRACT

BACKGROUND: Although the supramalleolar osteotomy can shift the weight-bearing axis laterally, it cannot reconstruct a widened ankle mortise caused by progression of medial ankle osteoarthritis. The aim of this study was to evaluate radiographic and clinical outcomes of distal tibial osteotomy without fibular osteotomy in patients with medial ankle osteoarthritis and mortise widening. METHODS: Distal tibial osteotomy without fibular osteotomy was performed in eighteen patients to treat medial ankle osteoarthritis with mortise widening. Fifteen women and three men with a mean age of fifty-seven years (range, forty-nine to sixty-four years) were followed for a mean of thirty-four months (range, twenty-four to sixty-six months). Mortise widening was diagnosed using valgus stress radiographs and intraoperative examination. The clinical outcome was assessed with the American Orthopaedic Foot & Ankle Society (AOFAS) score, visual analog scale (VAS) score for pain, and the ankle osteoarthritis scale (AOS) score. The translation of the talus within the ankle mortise, talar tilt, medial distal tibial angle, and anterior distal tibial angle were evaluated on weight-bearing radiographs made preoperatively and postoperatively. RESULTS: The AOFAS score improved significantly from 78.4 points (95% confidence interval [CI], 74.6 to 80.5 points) to 89 points (95% CI, 86.5 to 90.5 points) (p < 0.001). The VAS score for pain also decreased significantly from 6.7 points (95% CI, 6 to 7.5 points) to 2.7 points (95% CI, 2.3 to 3.3 points) (p < 0.001). The mean AOS score was 29.8 points (95% CI, 22 to 38.2 points) at the latest follow-up. The center of the talus moved laterally within the ankle mortise after the distal tibial osteotomy. The mean medial distal tibial angle changed from 86.6° (95% CI, 85.7° to 87.6°) to 92.9° (95% CI, 91.6° to 94.3°) (p < 0.001), and the mean anterior distal tibial angle changed from 81.1° (95% CI, 78.6° to 83.6°) to 84.3° (95% CI, 81.9° to 86.4°) (p < 0.001). However, talar tilt was not corrected significantly (p = 0.916). CONCLUSIONS: Distal tibial osteotomy without fibular osteotomy reduces pain in the short term in patients with ankle arthritis, a widened mortise, and minimal talar tilt.


Subject(s)
Ankle/surgery , Osteoarthritis/surgery , Osteotomy/methods , Tibia/surgery , Ankle/diagnostic imaging , Ankle/physiopathology , Cohort Studies , Female , Humans , Male , Middle Aged , Osteoarthritis/diagnostic imaging , Radiography , Range of Motion, Articular , Retrospective Studies , Treatment Outcome
18.
Eur Spine J ; 24(12): 2872-9, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25787945

ABSTRACT

BACKGROUND: No previous reports have mentioned bone loss of the superior adjacent vertebra immediately posterior to the anterior flange of Bryan cervical disc (Medtronic Sofamor Danek, Memphis, TN, USA), which plays a central role to prevent posterior migration of the device. The purpose of this study is to describe a new potential complication, bone loss immediately posterior to the anterior total disc replacement (TDR) flange on the superior adjacent vertebra following the Bryan cervical TDR and to discuss the possible mechanism. METHODS: The authors retrospectively reviewed 37 patients undergoing cervical TDR with the Bryan cervical disc. The clinical and radiological outcome data were collected at 1, 3, 6, 12, 24, and 36 months postoperatively, and at last follow-up, which ranged from 42 to 113 moths (average, 60.1 months). Clinical evaluation included the visual analog scale and neck disability index, and the radiographic evaluation included measurements of the functional spinal unit range of motion on flexion and extension and identification of radiographic changes such as bone loss. RESULTS: The Bryan TDR showed good mid-term clinical and radiological outcomes. Interestingly, however, bone loss was noted immediately posterior to the TDR flange on superior adjacent vertebra in 3 total patients; at 3 months (n = 2) and 6 months (n = 1). Although the bone loss was increased up to 6 months, this did not progress and no degradation of clinical and radiological outcomes occurred at last follow-up. CONCLUSIONS: Bone loss immediately posterior to the anterior TDR flange on the superior adjacent vertebra can occur in the early postoperative period due to possibly stress shielding effect. However, it did not result in clinical changes or increased rates of graft failure at last follow-up. A long-term follow-up study is mandatory to evaluate the long-term effects of the bone loss.


Subject(s)
Bone Diseases, Metabolic/etiology , Cervical Vertebrae/surgery , Intervertebral Disc Degeneration/etiology , Intervertebral Disc Degeneration/surgery , Joint Prosthesis , Postoperative Complications/etiology , Total Disc Replacement/adverse effects , Adult , Cervical Vertebrae/diagnostic imaging , Disability Evaluation , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pain Measurement , Radiography , Retrospective Studies , Treatment Outcome
19.
JBJS Essent Surg Tech ; 5(2): e9, 2015 May 27.
Article in English | MEDLINE | ID: mdl-30473917

ABSTRACT

INTRODUCTION: A patient with medial ankle osteoarthritis and a widened ankle mortise can be treated successfully with an oblique distal tibial osteotomy, without fibular osteotomy, to narrow the mortise and shift the weight-bearing axis to a more normal position. STEP 1 PATIENT POSITIONING AND PREOPERATIVE ASSESSMENT: With the patient under spinal or general anesthesia, check for mortise widening with a valgus stress test. STEP 2 SURGICAL APPROACH: Expose the ankle joint through an anterior approach. STEP 3 CORRECTIVE OSTEOTOMY: Perform an oblique osteotomy of the distal part of the tibia and narrow the widened mortise by shifting the osteotomized fragment. STEP 4 FIXATION AND BONE-GRAFTING: Stabilize the osteotomy site with a locking plate and apply bone graft to the osteotomy site. STEP 5 CLOSURE: Close the soft tissue in layers. RESULTS: Eighteen patients (fifteen female and three male; mean age, fifty-seven years) with symptomatic medial ankle osteoarthritis and mortise widening underwent distal tibial oblique osteotomy without fibular osteotomy between 2008 and 2011.IndicationsContraindicationsPitfalls & Challenges.

20.
Clin Orthop Surg ; 1(3): 128-31, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19885047

ABSTRACT

BACKGROUND: There is no accepted landmark for the mechanical axis of the femoral axis in sagittal plane in conventional total knee arthroplasty. METHODS: As palpable anatomic landmarks of the femur, lateral epicondyle, and anterior margin of the greater trochanter were identified. The line connecting these two landmarks was defined as the "palpable sagittal axis". The mechanical axis of the femur was compared with the palpable sagittal axis and the distal femoral anterior cortex axis. These axes were also compared with sagittal bowing of the femur. RESULTS: The distal femoral anterior cortex axis and the palpable sagittal axis were flexed by 4.1 degrees and 2.4 degrees more than the sagittal mechanical axes, respectively (p < 0.05). However, the palpable sagittal axis was not correlated with sagittal bowing of the femur (Spearman's rs, 0.17; p = 0.14). CONCLUSIONS: The palpable sagittal axis showed a consistent relationship with the sagittal mechanical femoral axes regardless of the severity of the sagittal bowing of the femur.


Subject(s)
Arthroplasty, Replacement, Knee/methods , Femur/surgery , Aged , Aged, 80 and over , Biomechanical Phenomena , Female , Femur/anatomy & histology , Humans , Knee Joint/anatomy & histology , Knee Joint/surgery , Male , Middle Aged
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