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Since their discovery in 1981, quasicrystals have challenged traditional crystallography, showcasing the diversity of material structures. Quasicrystals are ordered structures in higher-dimensional Cartesian coordinate systems projected into lower dimensions. Exploring whether materials can grow into high-symmetry ordered structures in different mathematical coordinate systems is an intriguing topic. This paper reports a new crystallization growth mode in InSiO thin films, exhibiting high symmetry in spherical and cylindrical coordinate systems, named cylindrical symmetric rotating crystals (CSRC). These crystals show rotational symmetry in their lattice structure, consistent with cylindrical symmetry. They are also part of spherical crystals, which theoretically have one of the highest symmetries. Theoretical predictions suggest that a two-dimensional slice of a spherical crystal in conventional grating mode SEM images will display relatively complete Kikuchi patterns due to the wave properties of incident electrons, unlike crystals or quasicrystals, which show surface morphology from the particle properties of incident electrons. We formed InSiO CSRC by heating InSiO amorphous films and observed relatively complete Kikuchi patterns that quantitatively relate to the incident electron beam direction and energy. These findings align with theoretical predictions, indicating that the Kikuchi patterns in SEM images result from Bragg diffraction through coherent electron scattering within the crystals. Quantitative analysis of these patterns provides information on the lattice structure, constants, crystal orientation, stress information, defect concentration, and Brillouin zone of the InSiO material. This method of obtaining microstructural information directly from SEM images applies only to CSRC, not to conventional or quasicrystal samples.

To advance the development of materials through data-driven scientific methods, appropriate methods for building machine learning (ML)-ready feature tables from measured and computed data must be established. In materials development, X-ray diffraction (XRD) is an effective technique for analysing crystal structures and other microstructural features that have information that can explain material properties. Therefore, the fully automated extraction of peak features from XRD data without the bias of an analyst is a significant challenge. This study aimed to establish an efficient and robust approach for constructing peak feature tables that follow ML standards (ML-ready) from XRD data. We challenge peak feature extraction in the situation where only the peak function profile is known a priori, without knowledge of the measurement material or crystal structure factor. We utilized Bayesian estimation to extract peak features from XRD data and subsequently performed Bayesian regression analysis with feature selection to predict the material property. The proposed method focused only on the tops of peaks within localized regions of interest (ROIs) and extracted peak features quickly and accurately. This process facilitated the rapid extracting of major peak features from the XRD data and the construction of an ML-ready feature table. We then applied Bayesian linear regression to the maximum energy product [Formula: see text], using the extracted peak features as the explanatory variable. The outcomes yielded reasonable and robust regression results. Thus, the findings of this study indicated that 004 peak height and area were important features for predicting [Formula: see text].

ABSTRACTCrystalline phase structure is essential for understanding the performance and properties of a material. Therefore, this study identified and quantified the crystalline phase structure of a sample based on the diffraction pattern observed when the crystalline sample was irradiated with electromagnetic waves such as X-rays. Conventional analysis necessitates experienced and knowledgeable researchers to shorten the list from many candidate crystalline phase structures. However, the Conventional diffraction pattern analysis is highly analyst-dependent and not objective. Additionally, there is no established method for discussing the confidence intervals of the analysis results. Thus, this study aimed to establish a method for automatically inferring crystalline phase structures from diffraction patterns using Bayesian inference. Our method successfully identified true crystalline phase structures with a high probability from 50 candidate crystalline phase structures. Further, the mixing ratios of selected crystalline phase structures were estimated with a high degree of accuracy. This study provided reasonable results for well-crystallized samples that clearly identified the crystalline phase structures.

The Kikuchi bands arise from Bragg diffraction of incoherent electrons scattered within a crystalline specimen and can be observed in both the transmission and reflection modes of scanning electron microscopy (SEM). Converging, rocking, or grazing incidence beams must be used to generate divergent electron sources to obtain the Kikuchi pattern. This paper report the observation of Kikuchi pattern from SEM images of an exceptional rotating crystal with continuous rotation in the local crystal direction and satisfying cylindrical symmetry, named a cylindrically symmetric rotating crystal. By retracing the Kikuchi line pattern, it is possible to obtain the lattice structure information of the presented sample from the conventional SEM images. SEM images of cylindrically symmetric rotating crystals reflect the interactions between electrons and the sample in both the real- and momentum-space. It is a very interesting and representative new case for the study of the contrast mechanism in SEM.

Abstract Background Bone morphogenetic protein 2 (BMP2) can enhance posterolateral spinal fusion (PLSF). The minimum effective dose that may stimulate mesenchymal stem cells however remains unknown. Nano‐hydroxyapatite (nHAp) polyethylene glycol (PEG)/polylactic acid (PLA) was combined with recombinant human BMP2 (rhBMP2). We in vitro evaluated proliferation, differentiation, and osteogenic genes of human bone marrow mesenchymal stem cells with 0.5, 1.0, and 3.0 μg/mL rhBMP2 doses in this study. Methods In vitro experimental study was designed to proliferation by a real‐time quantitative cell analysis system and the osteogenic differentiation by alkaline phosphatase (ALP) activity and osteogenic marker (Runx2, OPN, and OCN) gene expressions of human derived bone marrow mesenchymal stem cells (hBMMSCs). nHAp was produced by wet chemical process and characterized by Fourier transform infrared spectrophotometer, scanning electron microscopy, and energy‐dispersive x‐ray spectroscopy. PEG/PLA polymer was produced at a 51:49 molar ratio. 0.5, 1.0, and 3.0 μg/mL rhBMP2 and nHAp was combined with the polymers. hBMMSCs were characterized by multipotency assays and surface markers were assessed by flow cytometer. The hBMMSC‐rhBMP2 containing nHAp‐PEG/PLA composite interaction was evaluated by transmission electron microscopy. Proliferative effect was evaluated by real‐time proliferation analysis, and osteogenic capacity was evaluated by ALP activity assay and qPCR. Results hBMMSC proliferation in the 0.5 μg/mL rhBMP2 + nHAp‐PEG/PLA and the 1.0 μg/mL rhBMP2 + nHAp‐PEG/PLA groups were higher compared to control. 1.0 μg/mL rhBMP2 + nHAp‐PEG/PLA and 3.0 μg/mL rhBMP2 + nHAp‐PEG/PLA containing composites induced ALP activity on days 3 and 10. 0.5 μg/mL rhBMP2 + nHAp‐PEG/PLA application stimulated Runx2 and OPN gene expressions. Conclusion rhBMP2 + nHAp‐PEG/PLA composites stimulate hBMMSC proliferation and differentiation. The nHAp‐PEG/PLA composite with low dose of rhBMP2 may enhance bone formation in future clinical PLSF applications.

Fractography is a practical method of determining the cause of a mechanical-structure failure. Accurate decisions regarding fracture-mode classification require experience and knowledge, which may be difficult to share. Therefore, a database of fracture-surface images should be created, and the decision algorithm typically used by experts must be digitized. In recent years, although image classification using deep learning has been successful, it requires a large amount of data and is difficult to interpret. We propose a step-by-step fracture-mode classification method using fracture-surface images, from low to high magnification, based on the fractography knowledge of experts. Fracture-mode classification is performed using texture features for each patch image that is cut out from the fracture-surface image. The fracture mode for the fracture-surface image is voted based on the results of the patch-image classification. In the classification experiments of three fracture modes, the proposed method classifies the fracture mode in patch images with an accuracy of approximately 90%. Moreover, the classification results of the patch images are voted to correctly classify all fracture-surface images as their respective mode, even from a small dataset.

There is an urgent need to develop automatic analysis methods for the large number of X-ray photoelectron spectroscopy (×PS) spectra being obtained by methods such as 3D chemical analysis and operand analysis. In a previous study, we developed an automatic analysis method for mixed materials that can decompose the XPS spectra and estimate the compositional ratios by comparison with XPS reference spectra of many candidate single-phase compounds. This method needs access to the XPS reference spectrum of every possible compound in the sample. However, in many practical cases, the necessary XPS reference spectra are not always available. In this study, we developed an automatic analysis method to estimate the compositional ratios, even when all necessary XPS reference spectra are not available, i.e. the measured XPS spectra contain unknown peak structures. In particular, the new method can automatically estimate the number of unknown peaks by the combination of a genetic algorithm and the Bayesian information criterion. We applied the method to analyze the depth-resolved XPS spectra of a $${\rm{Pb(Zr,Ti)}}{{\rm{O}}_{\rm{3}}}$$ (PZT) piezoelectric film and successfully identified the change in the chemical states of the components in the film without ambiguity.

X-ray photo-electron spectroscopy (XPS) peak structure (i.e. peak parameters and the number of peaks) offers critical insights in chemical analysis of materials. Reference XPS spectral data are available for single-phases of compounds, as cited in various research papers and databases. Herein, we consider how individual peak structure varies among different reference spectra for the same single-phase of a compound. We developed a technique that automatically estimates common peak structures from multiple spectral data sets. Specifically, we developed a peak separation method that considers both common peak parameters and measurement-derived fluctuations. The proposed method can uniquely estimate the common peak structure of multiple XPS spectral data sets. For example, we applied the proposed approach to Ti 2p XPS results for $${\rm{Ti}}{{\rm{O}}_{\rm{2}}}$$ from 15 previous reports. In this way, we confirmed that estimated structure has high interpret-ability.

X-ray photoelectron spectroscopy (XPS) is a widely used measurement technique in material surface analysis, but its analysis is subject to operator arbitrariness in the results. In a previous paper, a method based on genetic algorithms was proposed to estimate the composition ratios of compounds from XPS data using reference spectra and it was shown that it is possible to analyze them automatically from the reference spectra data. In this paper, we newly proposed a Bayesian spectral decomposition method based on the exchange Monte Carlo method and tested it on artificial data. This method provides a posterior distribution of the model parameters. This not only allows the estimation of compositional ratios for samples, but also allows statistical reliability assessment. In addition, we simulated an artificial data analysis to clarify the effect on the identification of compounds and the estimation of their compositional ratios by varying the signal-to-noise ratio of the data.

This study proposes a framework to estimate the metal temperature from an optical micrograph of metals by using a machine learning approach. Specifically, 38 image statistical parameters such as area, contour, and circularity are calculated for the precipitate region determined through optical microscopy. Sparse modeling is then conducted to build a statistical model to estimate the Larson-Miller parameter (LMP), which is generally used in the evaluation of creep strength. This allows for the prediction of the metal temperature from the optical micrographs. The prediction performance of the proposed method is analyzed by applying it to KA-SUS304J1HTB (18Cr-9Ni-3Cu-Nb-N steel), reported in the NIMS Creep Data Sheets No. 56A and No. M-11. Consequently, temperature prediction is successfully achieved for unknown data with an error within ± 10°C.

Abstract Transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) play important roles in bone metabolism. Smad ubiquitination regulatory factors (Smurfs) regulate TGF-β/BMP signaling via ubiquitination, resulting in degradation of signaling molecules to prevent excessive activation of TGF-β/BMP signaling. Though Smurf2 has been shown to negatively regulate TGF-β/Smad signaling, its involvement in BMP/Smad signaling in bone metabolism has not been thoroughly investigated. In the present study, we sought to evaluate the role of Smurf2 in BMP/Smad signaling in bone metabolism. Absorbable collagen sponges containing 3 μg of recombinant human BMP2 (rhBMP2) were implanted in the dorsal muscle pouches of wild type (WT) and Smurf2 −/− mice. The rhBMP2-induced ectopic bone in Smurf2 − /− mice showed greater bone mass, higher mineral apposition and bone formation rates, and greater osteoblast numbers than the ectopic bone in WT mice. In WT mice, the ectopic bone consisted of a thin discontinuous outer cortical shell and scant inner trabecular bone. In contrast, in Smurf2 −/− mice, the induced bone consisted of a thick, continuous outer cortical shell and abundant inner trabecular bone. Additionally, rhBMP2-stimulated bone marrow stromal cells (BMSCs) from Smurf2 −/− mice showed increased osteogenic differentiation. Smurf2 induced the ubiquitination of Smad1/5. BMP/Smad signaling was enhanced in Smurf2 −/− BMSCs stimulated with rhBMP2, and the inhibition of BMP/Smad signaling suppressed osteogenic differentiation of these BMSCs. These findings demonstrate that Smurf2 negatively regulates BMP/Smad signaling, thereby identifying a new regulatory mechanism in bone metabolism.

Osteosarcoma is the most common malignant bone tumor in adolescence and childhood. Metastatic osteosarcoma has a poor prognosis with an overall 5‐year survival rate of approximately 20%. TAS‐115 is a novel multiple receptor tyrosine kinase inhibitor that is currently undergoing clinical trials. Using the mouse highly lung‐metastatic osteosarcoma cell line, LM8, we showed that TAS‐115 suppressed the growth of subcutaneous grafted tumor and lung metastasis of osteosarcoma at least partially through the inhibition of platelet‐derived growth factor receptor alpha, AXL, and Fms‐like tyrosine kinase 3 phosphorylation. We also show that these signaling pathways are activated in various human osteosarcoma cell lines and are involved in proliferation. Our results suggest that TAS‐115 may have potential for development into a novel treatment for metastatic osteosarcoma.

Abstract Purpose Partial meniscectomy can cause osteoarthritic changes in knees, as inner portion as well as peripheral portion of meniscus is important. The hypothesis of this study was that the amount of the inner resection of medial meniscus affected the in situ forces through the meniscus and the tibial varus and external rotation under axial load. Methods Fourteen intact porcine knees were investigated with a six-degree of freedom robotic system and force/moment, and the three-dimensional path of intact knees were recorded by universal force sensor when an axial load of 300-N was applied at four different flexion angles (30°, 60°, 90°, and 120°). The same examination was performed on three phased inner resections (30%, 60%, and 90% width) of the medial meniscus. Finally, all paths were reproduced after total medial meniscectomy, and in situ forces of the medial meniscus were calculated based on the superposition principle. Changes in tibiofemoral varus/valgus and internal/external rotation alignment during an axial load were also calculated. Results In situ forces of the medial meniscus decreased according to the amount of meniscal resection at all flexion angles. The reduction was significant in knees with inner resections of > 60% width at all flexion angles and even of 30% width at a flexion angle of 120° (p

Abstract Background Chondroblastoma (CB) is a rare locally aggressive bone tumor that commonly occurs in the epiphysis or apophysis of long bones. Although surgical treatment of CB carries potential risk for physeal or articular cartilage damage, risk factors for joint degeneration have not been well described. In addition, we have mainly used synthetic bone substitute (SBS) to fill the bone defect after intralesional curettage as treatment for CB. This study thus aimed to evaluate the incidence of and risk factors for adjacent-joint radiographic degeneration after SBS treatment for CB. Methods We retrospectively reviewed 48 patients treated for CB at our institutions between 1996 and 2017. Clinical data, radiographic images, treatments, and local recurrence were analyzed. Results We identified 40 patients [29 males and 11 females with a mean age of 19 years (range, 8–35 years)] who received SBS to fill the defect after curettage with a minimum follow-up of 1 year. The mean follow-up period was 71 months (range, 13–239 months). A total of 8 patients (20%) developed local recurrence. Radiographic analysis showed that 5 patients (16.7%) developed radiographic joint degeneration. Joint degeneration was significantly associated with the affected joint (p = 0.004). Conclusions Curettage and SBS filling had been found to be a reasonable treatment method for CB, which commonly occurs in the epiphysis or apophysis. Radiographic joint degeneration was not uncommon after CB treatment, especially in the talus and proximal humerus.

We develop an automatic peak fitting algorithm using the Bayesian information criterion (BIC) fitting method with confidence-interval estimation in spectral decomposition. First, spectral decomposition is carried out by adopting the Bayesian exchange Monte Carlo method for various artificial spectral data, and the confidence interval of fitting parameters is evaluated. From the results, an approximated model formula that expresses the confidence interval of parameters and the relationship between the peak-to-peak distance and the signal-to-noise ratio is derived. Next, for real spectral data, we compare the confidence interval of each peak parameter obtained using the Bayesian exchange Monte Carlo method with the confidence interval obtained from the BIC-fitting with the model selection function and the proposed approximated formula. We thus confirm that the parameter confidence intervals obtained using the two methods agree well. It is therefore possible to not only simply estimate the appropriate number of peaks by BIC-fitting but also obtain the confidence interval of fitting parameters.

The TPP-2M formula is the most popular empirical formula for the estimation of the electron inelastic mean free paths (IMFPs) in solids from several simple material parameters. The TPP-2M formula, however, poorly describes several materials because it relies heavily on the traditional least-squares analysis. Herein, we propose a new framework based on machine learning to overcome the weakness. This framework allows a selection from an enormous number of combined terms (descriptors) to build a new formula that describes the electron IMFPs. The resulting framework not only provides higher average accuracy and stability but also reveals the physics meanings of several newly found descriptors. Using the identified principle descriptors, a complete physics picture of electron IMFPs is obtained, including both single and collective electron behaviors of inelastic scattering. Our findings suggest that machine learning is robust and efficient to predict the IMFP and has great potential in building a regression framework for data-driven problems. Furthermore, this method could be applicable to find empirical formula for given experimental data using a series of parameters given a priori, holds potential to find a deeper connection between experimental data and a priori parameters.

Mechanical loading contributes to bone development, growth, and metabolism. However, the mechanisms underlying long bone mineralization via changes in loading during the growth period are unclear. The aim of the present study was to investigate the regulatory mechanisms underlying endochondral ossification and endosteal mineralization by developing an ex vivo organ culture model with cyclic axial mechanical loads. The metacarpal bones of 3-week-old C57BL/6 mice were exposed to mechanical loading (0, 7.8, and 78 mN) for 1 h/day for 4 days. Histomorphometry revealed that axial mechanical loading regulated the thickness of the calcified zone in the growth plate and endosteal mineralization in the diaphysis in a load-dependent manner. Mechanical loading also resulted in load-dependent upregulation of endochondral ossification and bone mineralization-related genes, including bone morphogenetic protein 2 (Bmp2). Recombinant human BMP-2 administration caused similar changes in tissue structures. Conversely, inhibition of the BMP-Smad pathway diminished the stimulatory effects of mechanical loading and BMP-2 administration, suggesting that the effects of mechanical loading may be exerted through activation of the BMP-Smad pathway with the results of gene ontology and pathway analyses. Mechanical loading increased alkaline phosphatase activity and decreased carbonic anhydrase IX (Car9) mRNA expression, resulting in a significant pH increase in the culture supernatant. We hypothesize that, through activation of the BMP-Smad pathway, mechanical loading downregulates Car9, which may alkalize the local milieu, thereby inducing bone formation and long bone mineralization. Our results showed that cyclic axial mechanical loading increased endochondral ossification and endosteal mineralization in developing mouse long bones, which may have resulted from changes in the pH, ALP activity, and Pi/PPi of the extracellular environment. These findings advance our understanding of the regulation of mineralization mechanisms by mechanical loading mediated through activation of the BMP-Smad pathway.

Effects of high magnetic fields [MFs, ≥ 1 T (T)] on osteoblastic differentiation and the orientation of cells or matrix proteins have been reported. However, the effect of low MFs (< 1 T) on the orientation of bone formation is not well known. This study was performed to verify the effects of low MFs on osteoblastic differentiation, bone formation, and orientation of both cells and newly formed bone. An apparatus was prepared with two magnets (190 mT) aligned in parallel to generate a parallel MF. In vitro, bone marrow-derived stromal cells of rats were used to assess the effects of low MFs on cell orientation, osteoblastic differentiation, and mineralization. A bone morphogenetic protein (BMP)-2-induced ectopic bone model was used to elucidate the effect of low MFs on microstructural indices, trabecula orientation, and the apatite c-axis orientation of newly formed bone. Low MFs resulted in an increased ratio of cells oriented perpendicular to the direction of the MF and promoted osteoblastic differentiation in vitro. Moreover, in vivo analysis demonstrated that low MFs promoted bone formation and changed the orientation of trabeculae and apatite crystal in a direction perpendicular to the MF. These changes led to an increase in the mechanical strength of rhBMP-2-induced bone. These results suggest that the application of low MFs has potential to facilitate the regeneration of bone with sufficient mechanical strength by controlling the orientation of newly formed bone.

Study Design An open-label, non-randomized prospective study. Purpose Teriparatide (TPTD) is known to be an antiosteoporotic agent that may accelerate the healing of fractures. This study was designed to investigate the effect of once-weekly TPTD administration on vertebral stability and bony union after acute osteoporotic vertebral fracture (OVF). Overview of Literature Once-weekly TPTD administration can lead to early vertebral stability and promote bony union of fractured vertebrae in patients with severe osteoporosis. Methods Forty-eight subjects with acute OVF were assigned to receive activated vitamin D3 and calcium supplementation or onceweekly subcutaneous injection of TPTD (56.5 μg) in combination with activated vitamin D3 and calcium supplementation for 12 weeks. Vertebral stability was assessed using lateral plain radiography. Vertebral height at the anterior location (VHa) and the difference in VHa {ΔVHa=VHa (supine position)−VHa (weight-bearing position)} were measured at baseline and 12 weeks after starting treatment. Bony union was defined as the absence of a vertebral cleft or abnormal motion (ΔVHa >2 mm). Results Although not significant, ΔVHa, indicating vertebral stability, tended to be lower in the TPTD group at 12 weeks (p =0.17). As for subjects with severe osteoporosis, ΔVHa at 12 weeks was significantly lower in the TPTD group than in the control group (mean ΔVHa: control group, 3.1 mm (n=15); TPTD group, 1.4 mm (n=16); p =0.02). The rate of bony union was significantly higher in the TPTD group than in the control group (control group, 40%; TPTD group, 81%; p =0.03). Conclusions Once-weekly TPTD administration may facilitate early bony union after acute OVF accompanied by severe osteoporosis.

Background/objectives: It is important to restore the tibiofemoral relationship as well as the anterior knee laxity for more successful anterior cruciate ligament (ACL) reconstruction, since a residual abnormality in the tibiofemoral relationship would lead an abnormal stress on the articular cartilages/menisci and consequently increase the risk of osteoarthritis in the future. This study aimed to sequentially clarify the three-dimensional tibiofemoral relationship before and after anatomic anterior cruciate ligament (ACL) reconstruction under an anterior tibial load with a gravity-assisted radiographic technique in the prone position. Methods: Fifteen patients with unilateral ACL injury participated in the study. Anatomic triple-bundle ACL reconstruction was performed using semitendinosus tendon autografts. During the computed tomography scans that were performed preoperatively, and those performed at 3 weeks and at 6 months postoperatively, the patients lay in the prone position with the knee flexed at 15°, wherein the calf weight could exert an anterior drawer force on the tibia due to gravity. Three-dimensional the tibial position relative to the femur were evaluated for each time point, followed by calculation of side-to-side differences in the parameters between the ACL-deficient/ACL-reconstructed knees and the contralateral intact knees. Seven healthy volunteers were enrolled in the control group and the side-to-side differences (right minus left) in these parameters were calculated. Results: The tibia in the ACL-deficient knee was located anteriorly by 3.5 ± 1.1 mm and rotated internally by 2.4° ± 2.3°; these values were significantly larger than the corresponding values of −0.2 ± 1.5 mm and 0.1° ± 2.2° in the control group. However, at 3 weeks postoperatively, the tibia in the ACL-reconstructed knee was over-constrained as compared to that in the control group; it was located posteriorly by 2.5 ± 1.4 mm and rotated externally by 3.4° ± 3.4°. At 6 months postoperatively, no significant difference was observed in the tibial displacements/rotations between the patient and control groups. The side-to-side difference in the anterior knee laxity at the manual maximum anterior load was 0.1 ± 1.2 mm at 6 months postoperatively, with a significant improvement over the preoperative value of 7.4 ± 2.5 mm. Conclusions: Anatomic ACL reconstruction could restore not only the normal anterior knee laxity, but also the normal tibiofemoral relationship even under an anterior tibial load. Keywords: Anatomic triple-bundle, Anterior cruciate ligament reconstruction, Computed tomography, Prone position, Tibiofemoral relationship, Three-dimensional

Abstract Background Soft-tissue sarcomas (STS) are rare malignant tumors those are resistant to chemotherapy. We have previously reported the 3-year follow-up result on the efficacy of perioperative chemotherapy with doxorubicin (DXR) and ifosfamide (IFM) for high-risk STS of the extremities (JCOG0304). In the present study, we analyzed the 10-year follow-up results of JCOG0304. Methods Patients with operable, high-risk STS (T2bN0M0, AJCC 6th edition) of the extremities were treated with 3 courses of preoperative and 2 courses of postoperative chemotherapy, which consisted of 60 mg/m2 of DXR plus 10 g/m2 of IFM over a 3-week interval. The primary study endpoint was progression-free survival (PFS) estimated by Kaplan-Meier methods. Prognostic factors were evaluated by univariable and multivariable Cox proportional hazards model. Results A total of 72 patients were enrolled between March 2004 and September 2008, with 70 of these patients being eligible. The median follow-up period was 10.0 years for all eligible patients. Local recurrence and distant metastasis were observed in 5 and 19 patients, respectively. The 10-year PFS was 65.7% (95% CI: 53.4–75.5%) with no PFS events being detected during the last 5 years of follow-up. The 10-year overall survival was 78.1% (95% CI: 66.3–86.2%). Secondary malignancy was detected in 6 patients. The subgroup analysis demonstrated that there was significant difference in survival with regard to primary tumor size. Conclusions Only a few long-term results of clinical trials for perioperative chemotherapy treatment of STS have been reported. Our results demonstrate that the 10-year outcome of JCOG0304 for patients with operable, high-risk STS of the extremities was stable and remained favorable during the last 5 years of follow-up. Trial registration This trial was registered at the UMIN Clinical Trials Registry as C000000096 on August 30, 2005.

Abstract Background Ultrasonic (US) devices are used in laparoscopic, dental, and spinal surgeries, while it is difficult to use for the joint under irrigation and perfusion solutions due to lack of power. A new US device is developed with greater voltage improvement and has been implemented in the arthroscopic field. The aim is to compare the characteristics of the US devices with the conventional ones in water. Methods Twenty bone blocks from the porcine femur were settled in a holder in water. A 4.0 mm diameter abrader burr moved 15 mm along the long axis of the bone block in ten blocks for three times. A 4.3 mm wide curette blade powered by ultrasonic vibration was moved in the same manner in the other ten blocks. The gutter shape, including the gutter depth and the bottom angle of the gutter, and the curetted area ratio of the gutter were assessed. Forty bones blocks from the porcine femurs were clamped with a holder in water, while the cortical bone surface must be located on the side. A 5 mm diameter drill excavated the bone along the previously-inserted guide wire to the 15 mm depth for twenty blocks. Next, the US excavation probe of 5x4mm rectangular shape was moved to the same depth in the other twenty blocks. Each ten block was cut in half along the bone tunnel and was assessed the surface roughness at three area, while the cross-sectional area (CSA) of the tunnel were measured and the ratio of the measured CSA was calculated based on an expected CSA in the remaining ten blocks for each device. Results The depth of curettage and bottom angle were significantly smaller with the US device than with the abrader burr at all planes, while the curetted area ratio created by each device was mostly equal to the other. Surface roughness was similar in two evacuating devices except one area. CSA ratio with the US excavation device was significantly smaller than that with the drill. Conclusion US curettage has an advantage to flatly curette bone surfaces, while a bone tunnel can be accurately created with the US device.

Following publication of the original article [1], the authors noticed that two corrections were not implemented during the production process.

Abstract Background The aim of this study is to evaluate the retention rates and reasons for discontinuation for seven biological disease-modifying antirheumatic drugs (bDMARDs) in a real-world setting of patients with rheumatoid arthritis (RA). Methods This multi-center, retrospective study assessed 4466 treatment courses of 2494 patients with bDMARDs from 2009 to 2017 (females, 82.4%; baseline age, 57.4 years; disease duration 8.5 years; rheumatoid factor positivity 78.6%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate, 4.3; concomitant prednisolone (PSL) 2.7 mg/day (43.1%) and methotrexate (MTX) 5.0 mg/week (61.8%); and 63.6% patients were bio-naïve). Treatment courses included tocilizumab (TCZ; n = 895), etanercept (ETN; n = 891), infliximab (IFX; n = 748), abatacept (ABT; n = 681), adalimumab (ADA; n = 558), golimumab (GLM; n = 464), and certolizumab pegol (CZP; n = 229). Drug retention rates and discontinuation reasons were estimated at 36 months using the Kaplan-Meier method and adjusted for potential confounders (age, sex, disease duration, concomitant PSL and MTX, and switched number of bDMARDs) using Cox proportional hazards modeling. Results A total of 56.9% of treatment courses were stopped, with 25.8% stopping due to lack of effectiveness, 12.7% due to non-toxic reasons, 11.9% due to toxic adverse events, and 6.4% due to disease remission. Drug retention rates for each discontinuation reason were as follows: lack of effectiveness [from 65.5% (IFX) to 81.7% (TCZ); with significant differences between groups (Cox P

Septic arthritis of small joints with associated osteomyelitis is difficult to treat and repeated surgical debridement and prolonged antibiotic administration are often needed. We report on the surgical technique and outcome of 3 patients with chronic arthritis and superimposed osteomyelitis at a distal interphalangeal joint of the right index finger. All patients were treated in a single surgical stage consisting of irrigating and debriding the tendon and tendon sheath, and filling the distal phalanx and middle phalangeal bone marrow with granules of calcium phosphate cement impregnated with vancomycin. No patients showed signs of recurrence of infection at 1 year or longer after operation although all progressed to autofusion of the distal interphalangeal joint. Key words: antibiotic-impregnated calcium phosphate paste, finger infectious arthritis, interphalangeal joint, osteomyelitis, outpatient

Discontinuation of denosumab is associated with the increase of bone turnover markers to above-baseline levels (so-called rebound in bone turnover) and rapid bone loss. Several studies have reported vertebral fractures (VFs), particularly multiple spontaneous clinical VFs (MSCVFs), occurring after discontinuation of denosumab. There is currently no recommendation for the management of VFs including MSCVFs. Presently, romosozumab is the strongest anti-osteoporotic agent that inhibits sclerostin and rapidly increases bone mass, but it is uncertain that romosozumab is an effective treatment choice to treat VFs occurring after discontinuation of denosumab. Herein we reported a novel case of a 60-year-old woman who was treated with romosozumab after discontinuation of denosumab and subsequently suffered MSCVFs under romosozumab treatment. She had a history of two osteoporotic VFs (T6 and T8) and received five doses of 60 mg denosumab every 6 months following the osteoporosis diagnosis. As per the patient's convenience, the sixth denosumab injection was postponed. To improve the persistent low bone mass in the lumbar spine (T-score −3.8), 210 mg romosozumab was administered monthly after 9 months following the last denosumab injection. At the first romosozumab injection, she had no clinical symptoms such as low back pain, but her bone formation and resorption marker levels elevated compared with those treated with denosumab. After three doses of romosozumab, spontaneous severe low back pain occurred, and time-course radiographs revealed five new VFs (T12, L2, L3, L4, and L5). Romosozumab administration had no suppressive effect on bone resorption during the rebound in bone turnover after discontinuation of denosumab. This case suggests that romosozumab is not effective in preventing VFs or MSCVFs after denosumab discontinuation.

Background:. Osteoporotic fragility fractures frequently occur at the distal part of the radius. This suggests that initial osteoporosis evaluation at this site may inform screening and treatment to prevent additional fractures. The purpose of this study was to investigate the utility of distal forearm dual x-ray absorptiometry (DXA) as a screening tool to assess the risk of fragility fractures at the distal part of the radius. Methods:. This retrospective, case-control study included postmenopausal women who had sustained a distal radial fracture (fracture group, n = 110) and postmenopausal women with no history of fracture (control group, n = 95). DXA measurements at the spine, hip, and distal part of the forearm (ultra-distal, mid-distal, and one-third distal sections) were compared between the groups on the basis of bone mineral density (BMD), T-score, and the proportion of patients with a T-score of ≤–2.5 standard deviations (SD). We also investigated the regional differences on the basis of T-score among the skeletal sites. Furthermore, the reliability of distal forearm DXA measurements was validated by assessing the statistical correlation (r) with volumetric BMD by computed tomography (CT). Results:. Compared with the control group, the fracture group showed significantly lower BMD and T-scores and higher proportions of patients with a T-score of ≤–2.5 SD at the ultra-distal, mid-distal, and one-third distal forearm; however, the spine and hip measurements did not differ significantly between the 2 groups. With respect to regional differences, in the fracture group, T-scores were significantly lower and the proportions of patients with a T-score of ≤–2.5 SD were significantly higher for the 3 distal forearm sites compared with the spine and hip. DXA measurements at all 3 of the distal forearm regions exhibited high correlation with volumetric BMD by CT (r = 0.83 to 0.92). Conclusions:. Some postmenopausal women were found to exhibit bone loss preferentially at the distal part of the radius, which may render them vulnerable to fragility fractures. Forearm DXA for the assessment of local bone loss may demonstrate benefit in screening for those at risk for distal radial fractures and facilitate the early identification of patients who require intervention for osteoporosis. Level of Evidence:. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Background and Objectives. Osteoarticular extracorporeal irradiated autograft is an alternative operation technique to prosthetic devices or allografts for reconstruction after resection of bone malignancies. The aim of this study is to assess the complications, radiographic changes, and functional outcomes of osteoarticular ECIA. Methods. We retrospectively reviewed 33 patients who underwent osteoarticular ECIA after bone tumor resection from 1988 to 2014. We investigated complications, radiographic changes by the International Society of Limb Salvage graft evaluation criteria, and functional outcomes according to the Musculoskeletal Tumor Society scoring system. Results. Fifteen patients were reoperated upon due to infection (n = 9), protruding fixation implant (n = 4), or fracture of the grafted bone (n = 2). The average radiographic evaluation score was 66.4%, and the median functional score was 23 (77%). The radiographic score for the proximal humerus or proximal tibia was lower than that for the other locations. The functional score was not different among the autograft sites but was related to the radiographic score. Conclusion. Although osteoarticular ECIA is one of the reasonable surgical options for patients with tumors for which reliable prostheses are not available, we do not recommend osteoarticular ECIA as a routine procedure because of high complication rate.

Abstract Background Soft tissue sarcomas (STS) are rare malignant tumors. The efficacy of preoperative chemotherapy for STS is evaluated using various tumor size-based radiological response criteria. However, it is still unclear which set of criteria would show the best association with pathological response and survival of the patients with STS. Methods We compared radiological responses to preoperative chemotherapy for operable STS by the Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST, World Health Organization criteria, Japanese Orthopaedic Association criteria, and modified Choi criteria and analyzed the association with pathological response and survival using the data from the Japan Clinical Oncology Group (JCOG) study JCOG0304, a phase II clinical trial evaluating the efficacy of perioperative chemotherapy for STS in the extremities. Results Seventy eligible patients in JCOG0304 were analyzed. The results demonstrated that none of the size-based radiological response criteria showed significant association with pathological response to preoperative chemotherapy for STS. The difference between overall survival of the patients assessed as partial response and stable disease/progressive disease by RECIST was not significant (hazard ratio 1.37, p = 0.63), and calculated C-index was 0.50. All other response criteria also could not exhibit significant association between radiological responses and survival. Conclusion In the present study, none of the radiological response criteria analyzed demonstrated association of response to preoperative chemotherapy with pathological response or survival of the patients with operable STS. Further prospective investigation is required to develop criteria to evaluate not only tumor shrinkage but biological effects of preoperative chemotherapy for the patients with localized STS. Trial registration UMIN Clinical Trials Registry C000000096. Registered 30 August, 2005 (retrospectively registered).

Abstract Background Giant cell tumor of bone (GCTB) is an intermediate tumor known to be locally aggressive, but rarely metastasizing. To plan a prospective study of GCTB, we performed a questionnaire survey for institutions participating in the Bone and Soft Tissue Tumor Study Group (BSTTSG) in the Japan Clinical Oncology Group (JCOG) in 2015. Methods We reviewed 158 consecutive patients with primary GCTB treated with curettage without perioperative denosumab from 2008 to 2010 in Japan. We investigated local and distant recurrence rates after definitive curettage. We also investigated the recurrence rate after treatment with preoperative and/or postoperative denosumab with curettage in recent years. There were 40 patients treated with perioperative denosumab, and the factors affecting recurrence in them were investigated. Results Answers were available from 24 of 30 institutions (80.0%) participating in JCOG BSTTSG. Thirty (19.0%) and 4 (2.5%) of 158 patients developed local and distant recurrence after curettage without perioperative denosumab from 2008 to 2010, respectively. Campanacci grade and embolization before surgery were significantly associated with increasing incidence of local recurrence after curettage (p = 0.034 and p = 0.022, respectively). In patients treated with perioperative desnosumab, 120 mg denosumab was administered subcutaneously for a median 6 (2–41) and 6 (1–14) times in preoperative and postoperative settings, respectively. The recurrence rates were 6 of 21 (28.6%), 2 of 9 (22.2%), and 0 of 10 (0.0%) in the preoperative, postoperative, and both pre- and postoperative denosumab treatment groups, respectively. With all of the preoperative treatments, administration exceeding five times was significantly associated with a decreased incidence of local recurrence after curettage (p

Communication between osteoblasts and osteoclasts is essential for bone homeostasis, but the mode of interaction is unclear. The authors use intravital two-photon microscopy in mice to show that these cells directly interact, regulating activity of osteoclasts, and that the interaction is modulated by parathyroid hormone administration.

Abstract Articular cartilage does not heal spontaneously due to its limited healing capacity, and thus effective treatments for cartilage injuries has remained challenging. Since the first report by Brittberg et al. in 1994, autologous chondrocyte implantation (ACI) has been introduced into the clinic. Recently, as an alternative for chondrocyte-based therapy, mesenchymal stem cell (MSC)-based therapy has received considerable research attention because of the relative ease in handling for tissue harvest, and subsequent cell expansion and differentiation. In this review, we discuss the latest developments regarding stem cell-based therapies for cartilage repair, with special focus on recent scaffold-free approaches.

Abstract Background In the meniscal repair procedures, a high ultimate load capacity and low cyclic creep at the repair site are favorable and lead to good biological incorporation of the tear site after surgery. Previous biomechanical tensile tests of the meniscal sutures have identified the suture knot as the weakest point. We hypothesized that the strength of a suture knot depends on the suture shape, and therefore, we compared three differently shaped suture materials composed of the same material and quantity per length. The purpose of this study was to determine whether a novel flat and wide repair material (FWRM), which consists of braided multi-threads that are cross-sectionally flat and wide, improves the ultimate load of knot breakage in a biomechanical experiment using a porcine trans-capsular meniscal repair model. Methods Eighteen fresh-frozen porcine knees (n = 6 in each group) were used. A longitudinal tear in the middle segment of the medial meniscus was created and repaired with a trans-capsular inside-out method using the following suture materials: No. 2–0 braided polyester conventional suture, hollow suture, and FWRM. After the separation of the inner segment of the meniscus with leaving, the suture stability of the repaired menisci was biomechanically analyzed with a video camera system for widening after a cyclic load between 5 and 20 N was applied 300 times. Ultimate failure load and stiffness at 5 mm/ min were also analyzed. Results We found no significant difference in suture widening after cyclic load tests [conventional suture, mean 0.51 mm (S.D. 0.39 mm); hollow suture, mean 0.23 mm (S.D. 0.11 mm); and FWRM, mean 0.54 mm (S.D. 0.08 mm)]. The failure mode in all specimens was knot breakage. Compared with those of the other groups, the ultimate failure load of FWRM was statistically significantly higher in the load-to-failure tests (conventional suture, mean 58.8 N [S.D. 8.25 N]; hollow suture, mean 79.4 N [S.D. 10.2 N]; and FWRM, mean 97.4 N [S.D. 3.65 N]; p

Abstract Background Recent morphological analyses of vertebrae in patients with scoliosis have revealed three-dimensional (3D) deformities in the vertebral bodies. However, it remains controversial whether these deformities are secondary changes caused by asymmetrical vertebral loading or primary changes caused by aberrant asymmetrical vertebral growth. Furthermore, the difference in vertebral morphology between scoliosis with different pathogeneses remains unclear. This study was aimed to investigate the difference in the coronal asymmetry of vertebral bodies between neuromuscular scoliosis (NS) in Duchenne muscular dystrophy (DMD) and idiopathic scoliosis (IS) using in vivo 3D analysis. Methods Twelve male skeletally immature patients with NS in DMD and 13 female skeletally immature patients with IS who underwent corrective fusion at our institution were included retrospectively. 3D bone models of the apical and adjacent upper and lower vertebrae in the major curve in the NS patients and in the main and compensatory curves in the IS patients were constructed using an image processing workstation. The heights of the concave and convex sides of the vertebral bodies were measured at the anterior, middle, and posterior and the concave-to-convex vertebral height ratios (VHR) were calculated. Results The mean VHRs (anterior/middle/posterior) for the main curve for IS (0.897 ± 0.072/0.832 ± 0.086/0.883 ± 0.059) were significantly smaller than those for NS (0.970 ± 0.048/0.934 ± 0.081/0.958 ± 0.043) in all three parts (p

Abstract Background Three-dimensional (3D) reconstructed computed tomography (CT) is crucial for the reliable and accurate evaluation of tunnel enlargement after anterior cruciate ligament (ACL) reconstruction. The purposes of this study were to evaluate the tibial tunnel enlargement at the tunnel aperture and inside the tunnel and to clarify the morphological change at the tunnel footprint 1 year after the anatomic triple-bundle (ATB) ACL reconstruction using 3D CT models. Methods Eighteen patients with unilateral ACL rupture were evaluated. The ATB ACL reconstruction with a semitendinosus tendon autograft was performed. 3D computer models of the tibia and the three tibial tunnels were reconstructed from CT data obtained 3 weeks and 1 year after surgery. The cross-sectional areas (CSAs) of the two anterior and the one posterior tunnels were measured at the tunnel aperture and 5 and 10 mm distal from the aperture and compared between the two periods. The locations of the center and the anterior, posterior, medial, and lateral edges of each tunnel footprint were also measured and compared between the two periods. Results The CSA of the posterior tunnel was significantly enlarged at the aperture by 40.4%, whereas that of the anterior tunnels did not change significantly, although the enlargement rate was 6.1%. On the other hand, the CSA was significantly reduced at 10 mm distal from the aperture in the anterior tunnels. The enlargement rate in the posterior tunnel was significantly greater than that in the anterior tunnels at the aperture. The center of the posterior tunnel footprint significantly shifted postero-laterally. The anterior and posterior edges of the posterior tunnel footprint demonstrated a significant posterior shift, while the lateral edge significantly shifted laterally. There was no significant shift of the center or all the edges of the anterior tunnels footprint. Conclusions The posterior tibial tunnel was significantly enlarged at the aperture by 40% with the morphological change in the postero-lateral direction reflected by the ACL fiber orientation 1 year after the ATB ACL reconstruction. The proper tibial tunnel location in the ACL reconstruction should be determined considering the tunnel enlargement in postero-lateral direction after surgery.

Abstract Background Anterior cruciate ligament (ACL) injury is often accompanied with medial collateral ligament (MCL) injury. Assessment of varus-valgus (V-V) instability in the ACL-deficient knee is crucial for the management of the concomitant ACL-collateral ligaments injury. We evaluated the V-V laxity and investigated the effect of additional posterior tibial load on the laxity in the ACL-deficient knee. Our hypothesis was that the V-V laxity in the ACL-deficient knee was greater than that in the intact knee and attenuated by additional posterior tibial load. Methods Eight fresh-frozen porcine knees were used, and a 6°-of-freedom (DOF) robotic system was utilized. A 5 Nm of V-V torque was applied to the intact knee, the ACL-deficient knee, and the ACL-deficient knee with 30 N of constant posterior tibial load, at 30° and 60° of flexion. Then, the 3D path in the intact knee was reproduced on the ACL-deficient knee. The total V-V angle under 5 Nm of V-V torque was assessed and compared among the three statuses. The in situ forces of the ACL under 5 Nm of varus and valgus torques, respectively, were also calculated. Results The total V-V angle in the ACL-deficient knee under 5 Nm of V-V torque was significantly greater than that in the intact knee, whereas the angle in the ACL-deficient knee with 30 N of posterior tibial load was significantly smaller than that in the ACL-deficient knee and approached that in the intact knee, at both 30° and 60° of flexion. The in situ force of the ACL was approximately 30 N at 30° and 16 N at 60° of flexion under 5 Nm of both varus and valgus torques. Conclusions The V-V laxity in the isolated ACL-deficient knee was greater than that in the intact knee. The increased laxity was attenuated and approached that in the intact knee by adding posterior tibial load. Application of posterior tibial load is necessary for accurate assessment of V-V instability in the ACL-deficient knee. Clinically, the V-V laxity in the combined ACL-MCL or ACL-LCL injured knee may be overestimated without posterior tibial load.

Quantitative characterization of supported nanomaterials is challenging, because the nanomaterial signals cannot easily be deconvoluted from those of the substrate. Here, the authors introduce an inventive approach to overcome this problem for electron-based surface analysis techniques.

Abstract Background The prognosis of synovial sarcoma (SS), an aggressive soft tissue sarcoma, remains poor. We previously reported that c-MET or platelet-derived growth factor receptor α (PDGFRα) signalling pathway is related to SS progression based upon the findings of phospho-receptor tyrosine kinase (RTK) arrays. TAS-115 is a novel c-MET/ vascular endothelial growth factor receptor-targeting tyrosine kinase inhibitor that has been shown to inhibit multiple RTKs. Here we aimed to investigate the therapeutic potential of TAS-115 against SS. Methods We first evaluated which signalling pathway was relevant to the viability of three human SS cell lines: Yamato-SS, SYO-1 and HS-SY-II. Next, we assessed the anticancer activity and mechanism of action of TAS-115 in these SS cell lines. Finally, we compared the ability of TAS-115 to inhibit c-MET and PDGFRα phosphorylation with that of pazopanib. Results We classified the SS cell lines as c-MET-dependent or PDGFRα-dependent based upon the differences in the signalling pathway relevant for growth and/or survival. We also found that c-MET and PDGFRα were the primary activators of both phosphatidylinositol 3-kinase/AKT and mitogen-activated protein kinase pathways in c-MET-dependent and PDGFRα-dependent SS cells, respectively. TAS-115 treatment blocked the phosphorylation of PDGFRα as well as that of c-MET and their downstream effectors, leading to marked growth inhibition in both types of SS cell lines in in vitro and in vivo studies. Furthermore, PDGFRα phosphorylation, on at least four representative autophosphorylation sites, was impeded by TAS-115 equivalently to pazopanib. Conclusions These experimental results have demonstrated the significance of c-MET and PDGFRα signalling for growth and/or survival of SS tumours. TAS-115 monotherapy may benefit SS patients whose tumours are dependent upon either c-MET or PDGFRα signalling by functioning as a multiple tyrosine kinase inhibitor to suppress c-MET as well as PDGFRα pathways.

Background: Bone morphogenetic protein (BMP)-based tissue engineering has focused on inducing new bone efficiently. However, modeling and remodeling of BMP-induced bone have rarely been discussed. Teriparatide (parathyroid hormone [PTH] 1-34) administration initially increases markers of bone formation, followed by an increase in bone resorption markers. This unique activity would be expected to accelerate the modeling and remodeling of new BMP-induced bone. Methods: Male Sprague-Dawley rats underwent posterolateral spinal fusion surgery and implantation of collagen sponge containing either 50 μg recombinant human (rh)BMP-2 or saline. PTH 1-34 (60 μg/kg, 3 times/week) or saline injections were continued from preoperative week 2 week to postoperative week 12. The volume and quality of newly formed bone were monitored by in vivo micro-computed tomography and analyses of bone histomorphometry and serum bone metabolism markers were conducted at postoperative week 12. Results: Microstructural indices of the newly formed bone were significantly improved by PTH 1-34 administration, which significantly decreased the tissue volumes of the fusion mass at postoperative week 12 compared to that at postoperative week 2. Bone histomorphometry and serum analyses showed that PTH administration significantly increased both bone formation and resorption markers. Analysis of the histomorphometry of cortical bone identified predominant periosteal bone resorption and endosteal bone formation. Conclusions: Long-term intermittent administration of PTH 1-34 significantly accelerated the modeling and remodeling of new BMP-induced bone. Clinical relevance: Our results suggest that the combined administration of rhBMP-2 and PTH 1-34 facilitates qualitative and quantitative improvements in bone regeneration, by accelerating bone modeling and remodeling. Keywords: Bone morphogenetic protein, Bone remodeling, Bone modeling, PTH 1-34, Bone regeneration

BackgroundThe aim of this study is to evaluate the retention rates and reasons for discontinuation for seven biological disease-modifying antirheumatic drugs (bDMARDs) in a real-world setting of elderly patients (65 years of age or older) with rheumatoid arthritis (RA).MethodsThis multi-center, retrospective study assessed 1,098 treatment courses of 661 patients with bDMARDs from 2009 to 2018 (females, 80.7%; baseline age, 71.7 years; disease duration 10.5 years; rheumatoid factor positivity 81.3%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate, 4.6; concomitant prednisolone dose 2.8 mg/day (45.6%) and methotrexate dose 4.4 mg/week (56.4%); and 60.2% patients were bio-naïve). Treatment courses included abatacept (ABT; n = 272), tocilizumab (TCZ; n = 234), etanercept (ETN; n = 184), golimumab (GLM; n = 159), infliximab (IFX; n = 101), adalimumab (ADA; n = 97), and certolizumab pegol (CZP; n = 51). Drug retention rates and discontinuation reasons were estimated at 36 months using the Kaplan-Meier method and adjusted for potential clinical confounders (age, sex, disease duration, concomitant PSL and MTX, starting date and switched number of bDMARDs) by Cox proportional hazards modeling.ResultsA total of 51.2% of treatment courses were stopped, with 25.1% stopping due to lack of effectiveness, 11.8% due to toxic adverse events, 9.7% due to non-toxic reasons, and 4.6% due to remission. Drug retention rates for each discontinuation reason were as follows; lack of effectiveness [from 55.4% (ETN) to 81.6% (ABT); with significant differences between groups (Cox PConclusionsABT showed lowest discontinuation rate by lack of effectiveness and by toxic adverse events, which lead to highest overall retention rates (excluding non-toxic reasons and remission) among seven bDMARDs in adjusted model of elderly RA patients.

Synovial mesenchymal stem cell (SMSC) is the promising cell source of cartilage regeneration but has several issues to overcome such as limited cell proliferation and heterogeneity of cartilage regeneration ability. Previous reports demonstrated that basic fibroblast growth factor (bFGF) can promote proliferation and cartilage differentiation potential of MSCs in vitro, although no reports show its beneficial effect in vivo. The purpose of this study is to investigate the promoting effect of bFGF on cartilage regeneration using human SMSC in vivo. SMSCs were cultured with or without bFGF in a growth medium, and 2 × 105 cells were aggregated to form a synovial pellet. Synovial pellets were implanted into osteochondral defects induced in the femoral trochlea of severe combined immunodeficient mice, and histological evaluation was performed after eight weeks. The presence of implanted SMSCs was confirmed by the observation of human vimentin immunostaining-positive cells. Interestingly, broad lacunae structures and cartilage substrate stained by Safranin-O were observed only in the bFGF (+) group. The bFGF (+) group had significantly higher O’Driscoll scores in the cartilage repair than the bFGF (−) group. The addition of bFGF to SMSC growth culture may be a useful treatment option to promote cartilage regeneration in vivo.

Cancellous bone grafts from the calcaneus have been used for the foot and ankle as well as iliac bone graft; however, there is a sparse report for calcaneal bone transplantation in the field of rheumatoid foot surgery. In this study, safety and usefulness of calcaneal bone grafts, and combination with interconnected porous hydroxyapatite ceramic, was evaluated in rheumatoid arthritis foot surgeries. Of six rheumatoid arthritis cases, three (talo-navicular joint fusion) used a calcaneal bone graft alone, and the remaining three cases (subtalar joint and talo-navicular joint fusion) used a combination of calcaneal bone graft and interconnected porous hydroxyapatite ceramic augmented with dense calcium hydroxyapatite for subtalar bony defect (1.5–2.0 cm) after the correction. Pre- and postoperative Japanese Society for Surgery of the Foot rheumatoid arthritis foot ankle scale scores were obtained for the clinical assessment. As radiographic assessment, tibio-calcaneal angle, calcaneal pitch, talo-1st metatarsal angle, and pronated foot index were also evaluated. After starting weight-bearing or walking, there was no pain and skin trouble at the fusion and harvesting sites. All cases achieved bony fusion within 6–10 weeks. Japanese Society for Surgery of the Foot rheumatoid arthritis foot ankle score was improved in all six cases. Furthermore, tibio-calcaneal angle, talo-1st metatarsal angle, and pronated foot index were also improved at latest follow-up in all cases. In conclusion, autologous bone grafting from the calcaneus was safe and convenient even in rheumatoid foot surgeries. For larger bony defects (1.5–2.0 cm), combination use with interconnected porous hydroxyapatite ceramic augmented with dense calcium hydroxyapatite was also useful.

In the physiochemical sciences, plasma is used to describe an ionized gas. Previous studies have implicated plasma surface treatment in the enhancement of hydrophilicity of implanted musculoskeletal reconstructive materials. Hydroxyapatite (HA) ceramics, widely used in bone tissue regeneration, have made great advancements to skeletal surgery. In the present study, we investigate the impact of low-pressure plasma on the interconnected porous calcium hydroxyapatite (IP-CHA) both in vitro and in vivo. Our results indicate that dielectric barrier discharge (DBD) plasma, when used with oxygen, can augment the hydrophilicity of non-porous HA surfaces and the osteoconductivity of the IP-CHA disc via increased water penetration of inner porous structures, as demonstrated through microfocus computed tomography (μCT) assay. In vivo implantation of plasma-treated IP-CHA displayed superior bone ingrowth than untreated IP-CHA. Though plasma-treated IP-CHA did not alter osteoblast cell proliferation, it accelerated osteogenic differentiation of seeded marrow mesenchymal stem cells. In vitro X-ray photoelectron spectroscopy (XPS) revealed that this plasma treatment increases levels of oxygen, rather than nitrogen, on the plasma-treated IP-CHA surface. These findings suggest that plasma treatment, an easy and simple processing, can significantly improve the osteoconductive potential of commonly used artificial bones such as IP-CHA. Further optimization of plasma treatment and longer-term follow-up of in vivo application are required toward its clinical application.

The purpose of this study was to evaluate the retention and discontinuation reasons of seven biological disease-modifying antirheumatic drugs (bDMARDs) in a real-world setting of patients with rheumatoid arthritis (RA). 1,037 treatment courses with bDMARDs from 2009 to 2016 [female, 81.8%; baseline age, 59.6 y; disease duration 7.8 y; rheumatoid factor positivity 81.5%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR), 4.4; concomitant prednisolone 43.5% and methotrexate 68.6%; Bio-naïve, 57.1%; abatacept (ABT), 21.3%; tocilizumab (TCZ), 20.7%; golimumab (GLM), 16.9%; etanercept (ETN), 13.6%; adalimumab (ADA), 11.1%; infliximab (IFX), 8.5%; certolizumab pegol (CZP), 7.9%] were included in this multi-center, retrospective study. Drug retention and discontinuation reasons at 36 months were estimated using the Kaplan-Meier method and adjusted by potent confounders using Cox proportional hazards modeling. As a result, 455 treatment courses (43.9%) were stopped, with 217 (20.9%) stopping due to inefficacy, 113 (10.9%) due to non-toxic reasons, 86 (8.3%) due to toxic adverse events, and 39 (3.8%) due to remission. Drug retention rates in the adjusted model were as follows: total retention (ABT, 60.7%; ADA, 32.7%; CZP, 43.3%; ETN, 51.9%; GLM, 45.4%; IFX, 31.1%; and TCZ, 59.2%; P < 0.001); inefficacy (ABT, 81.4%; ADA, 65.7%; CZP, 60.7%; ETN, 71.3%; GLM, 68.5%; IFX, 65.0%; and TCZ, 81.4%; P = 0.015), toxic adverse events (ABT, 89.8%; ADA, 80.5%; CZP, 83.9%; ETN, 89.2%; GLM, 85.5%; IFX, 75.6%; and TCZ, 77.2%; P = 0.50), and remission (ABT, 95.5%; ADA, 88.1%; CZP, 91.1%; ETN, 97.5%; GLM, 94.7%; IFX, 86.4%; and TCZ, 98.4%; P < 0.001). In the treatment of RA, ABT and TCZ showed higher overall retention, and TCZ showed lower inefficacy compared to IFX, while IFX showed higher discontinuation due to remission compared to ABT, ETN, GLM, and TCZ in adjusted modeling.

Study DesignProspective cohort study.PurposeTo identify differences in time-dependent perioperative changes between the Japanese Orthopaedic Association (JOA) score and the JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) score in patients with cervical spondylotic myelopathy (CSM) and posterior longitudinal ligament (OPLL) who underwent cervical laminoplasty.Overview of LiteratureThe JOA score does not take into consideration patient satisfaction or quality of life. Accordingly, the JOACMEQ was designed in 2007 as a patient-centered assessment tool.MethodsWe studied 21 patients who underwent cervical laminoplasty. We objectively evaluated the time-dependent changes in JOACMEQ scores and JOA scores for all patients before surgery and at 2 weeks, 3 months, 6 months, and 1 year after surgery.ResultsThe average total JOA score and the recovery rate improved significantly after surgery in both groups, with a slightly better recovery rate in the OPLL group. Cervical spine function improved significantly in the CSM group but not in the OPLL group. Upper- and lower-extremity functions were more stable in the CSM group than in the OPLL group. The effectiveness rate of the JOACMEQ for measuring quality of life was quite low in both groups. In both groups, the Spearman contingency coefficients were dispersed widely except for upper- and lower-extremity function.ConclusionsScores for upper- and lower-extremity function on the JOACMEQ correlated well with JOA scores. Because the JOACMEQ can also assess cervical spine function and quality of life, factors that cannot be assessed by the JOA score alone, the JOACMEQ is a more comprehensive evaluation tool.

The purpose of this retrospective study is to clarify the difference in plantar pressure distribution during walking and related patient-based outcomes between forefoot joint-preserving arthroplasty and resection-replacement arthroplasty in patients with rheumatoid arthritis (RA).Four groups of patients were recruited. Group1 included 22 feet of 11 healthy controls (age 48.6 years), Group2 included 36 feet of 28 RA patients with deformed non-operated feet (age 64.8 years, Disease activity score assessing 28 joints with CRP [DAS28-CRP] 2.3), Group3 included 27 feet of 20 RA patients with metatarsal head resection-replacement arthroplasty (age 60.7 years, post-operative duration 5.6 years, DAS28-CRP 2.4), and Group4 included 34 feet of 29 RA patients with metatarsophalangeal (MTP) joint-preserving arthroplasty (age 64.6 years, post-operative duration 3.2 years, DAS28-CRP 2.3). Patients were cross-sectionally examined by F-SCAN II to evaluate walking plantar pressure, and the self-administered foot evaluation questionnaire (SAFE-Q). Twenty joint-preserving arthroplasty feet were longitudinally examined at both pre- and post-operation.In the 1st MTP joint, Group4 showed higher pressure distribution (13.7%) than Group2 (8.0%) and Group3 (6.7%) (P

Mesenchymal stem cell- (MSC-) based therapy is a promising treatment for cartilage. However, repair tissue in general fails to regenerate an original hyaline-like tissue. In this study, we focused on increasing the expression levels for insulin-like growth factor-1 (IGF-1) to improve repair tissue quality. The IGF-1 gene was introduced into human synovial MSCs with a lentiviral vector and examined the levels of gene expression and morphological status of MSCs under chondrogenic differentiation condition using pellet cultures. The size of the pellets derived from IGF-1-MSCs were significantly larger than those of the control group. The abundance of glycosaminoglycan (GAG) was also significantly higher in the IGF-1-MSC group. The histology of the IGF-1-induced pellets demonstrated similarities to hyaline cartilage without exhibiting features of a hypertrophic chondrocyte phenotype. Expression levels for the Col2A1 gene and protein were significantly higher in the IGF-1 pellets than in the control pellets, but expression levels for Col10, MMP-13, ALP, and Osterix were not higher. Thus, IGF-1 gene transfer to human synovial MSCs led to an improved chondrogenic differentiation capacity without the detectable induction of a hypertrophic or osteogenic phenotype.

All living tissues and cells on Earth are subject to gravitational acceleration, but no reports have verified whether acceleration mode influences bone formation and healing. Therefore, this study was to compare the effects of two acceleration modes, vibration and constant (centrifugal) accelerations, on bone formation and healing in the trunk using BMP 2-induced ectopic bone formation (EBF) mouse model and a rib fracture healing (RFH) rat model. Additionally, we tried to verify the difference in mechanism of effect on bone formation by accelerations between these two models. Three groups (low- and high-magnitude vibration and control-VA groups) were evaluated in the vibration acceleration study, and two groups (centrifuge acceleration and control-CA groups) were used in the constant acceleration study. In each model, the intervention was applied for ten minutes per day from three days after surgery for eleven days (EBF model) or nine days (RFH model). All animals were sacrificed the day after the intervention ended. In the EBF model, ectopic bone was evaluated by macroscopic and histological observations, wet weight, radiography and microfocus computed tomography (micro-CT). In the RFH model, whole fracture-repaired ribs were excised with removal of soft tissue, and evaluated radiologically and histologically. Ectopic bones in the low-magnitude group (EBF model) had significantly greater wet weight and were significantly larger (macroscopically and radiographically) than those in the other two groups, whereas the size and wet weight of ectopic bones in the centrifuge acceleration group showed no significant difference compared those in control-CA group. All ectopic bones showed calcified trabeculae and maturated bone marrow. Micro-CT showed that bone volume (BV) in the low-magnitude group of EBF model was significantly higher than those in the other two groups (3.1±1.2mm3 v.s. 1.8±1.2mm3 in high-magnitude group and 1.3±0.9mm3 in control-VA group), but BV in the centrifuge acceleration group had no significant difference compared those in control-CA group. Union rate and BV in the low-magnitude group of RFH model were also significantly higher than those in the other groups (Union rate: 60% v.s. 0% in the high-magnitude group and 10% in the control-VA group, BV: 0.69±0.30mm3 v.s. 0.15±0.09mm3 in high-magnitude group and 0.22±0.17mm3 in control-VA group). BV/TV in the low-magnitude group of RFH model was significantly higher than that in control-VA group (59.4±14.9% v.s. 35.8±13.5%). On the other hand, radiographic union rate (10% in centrifuge acceleration group v.s. 20% in control-CA group) and micro-CT parameters in RFH model were not significantly different between two groups in the constant acceleration studies. Radiographic images of non-union rib fractures showed cartilage at the fracture site and poor new bone formation, whereas union samples showed only new bone. In conclusion, low-magnitude vibration acceleration promoted bone formation at the trunk in both BMP-induced ectopic bone formation and rib fracture healing models. However, the micro-CT parameters were not similar between two models, which suggested that there might be difference in the mechanism of effect by vibration between two models.

Purpose: The purpose of this study was to clarify the risk factors for graft rupture or contralateral anterior cruciate ligament (ACL) tear after anatomic ACL reconstruction. Methods: One hundred and eighty one patients with unilateral ACL injury underwent the anatomic double-bundle ACL reconstruction using autogenous semitendinosus tendon grafts. Of these, 149 patients were directly followed-up for more than 5 years (60–108 months) after the primary operation. For those with graft rupture or contralateral ACL tear, timing at re-injury and cause of re-injury were recorded. Demographic factors such as height, body weight, sex, age at operation and sports activity level, as well as the surgical factors such as graft diameter and associated meniscal injury were noted. Results: Eighteen patients (12.1%) sustained the graft rupture or the contralateral ACL injury in obvious accidents. Of them, ACL graft rupture occurred in seven patients (4.7%), whereas contralateral ACL injury occurred in 11 patients (7.4%). There was a high correlation between graft rupture and age (r = −0.962, p

Arthritis is inflammation of the joints accompanied by osteochondral destruction. It can take many forms, including osteoarthritis, rheumatoid arthritis, and psoriatic arthritis. These diseases share one commonality—osteochondral destruction based on inflammation. The background includes a close interaction between osseous tissues and immune cells through various inflammatory cytokines. However, the tissues and cytokines that play major roles are different in each disease, and as a result, the mechanism of osteochondral destruction also differs. In recent years, there have been many findings regarding not only extracellular signaling pathways but also intracellular signaling pathways. In particular, we anticipate that the intracellular signals of osteoclasts, which play a central role in bone destruction, will become novel therapeutic targets. In this review, we have summarized the pathology of arthritis and the latest findings on the mechanism of osteochondral destruction, as well as present and future therapeutic strategies for these targets.