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Background Lipomatous tumors represent the most common type of soft tissue neoplasms. Mouse double minute 2 homolog (MDM2)/cyclin-dependent kinase 4 (CDK4) immunostaining is considered effective in differentiating between benign lipomas and intermediate malignant atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDLPSs). However, these tumors have traditionally been diagnosed histopathologically using hematoxylin and eosin-stained specimens, which is referred to here as morphological diagnosis. In this study, the accuracy of morphological diagnoses that had been made before MDM2/CDK4 immunostaining became available for distinguishing between lipoma and ALT/WDLPS was examined. Methods The study participants were 109 patients with a morphological diagnosis of lipoma (68 patients) or ALT/WDLPS (41 patients) who had undergone surgical resection of the tumor in our hospital between 2009 and 2012. Tissue samples from all patients were used for MDM2/CDK4 immunostaining and the confirmation of MDM2/CDK4 amplification by fluorescence in situ hybridization (FISH). Results Of the 41 patients with a morphological diagnosis of ALT/WDLPS, only 17 were positive for MDM2 FISH. In addition, one of the 68 patients with a morphological diagnosis of lipoma showed MDM2 amplification by FISH. When the definitive diagnosis of ALT/WDLPS was made by the positive results of MDM2 FISH, the sensitivity and specificity of morphological diagnosis were 41.5% and 98.5%, respectively. The sensitivity of MDM2 and CDK4 immunostaining was 55.6% and 40.0%, respectively, and their specificity was 87.0% and 84.6%, respectively. This indicates that the diagnostic accuracy of these immunostaining assays was not particularly high. The clinical features suggesting ALT/WDLPS were: patient age (older), maximum tumor diameter (large, cut-off value of 125 mm), tumor location (lower limb), and tumor depth (deep-seated). Conclusions Morphological diagnosis alone can accurately diagnose lipomas. However, it has a propensity to overdiagnose ALT/WDLPS. Thus, MDM2 FISH should be used more proactively, not only for lesions with obvious morphological abnormalities, but also for lipomatous tumors that are clinically suggestive of ALT/WDLPS.

PurposeTibial condylar valgus osteotomy (TCVO) is a type of opening-wedge high tibial osteotomy for advanced medial knee osteoarthritis (OA) with subluxated lateral joint. We report the concept, the current surgical technique with a locking plate, and the short-term clinical and radiological results of this procedure.Methods11 knees with medial OA and a widened lateral joint were treated by TCVO (KL stage III: 6, IV: 5). In this procedure, by the L-shaped osteotomy from the medial side of the proximal tibia to the intercondylar eminence and the valgus correction, lateralization of the mechanical axis and reduction of the subluxated lateral joint are obtained with early postoperative weight-bearing. Before, 6 months, 1, and 5 years after the operation, a visual analog scale (VAS), the Western Ontario and McMaster Universities Arthritis Index (WOMAC), alignment of the lower extremity, and congruency and stability of the femorotibial joint were investigated.ResultsThe VAS improved from an average of 73 mm to 13 mm, and the total WOMAC score from 52 to 14 before to 5 years after the operation, respectively. The mechanical axis changed from 1 to 60%, and the FTA changed from 186° to 171°. The joint line convergence angle (JLCA) changed from 6° to 1°, and the angle difference of JLCA between varus and valgus stress improved from 8° to 4° after the procedure.ConclusionImprovements in pain and activities of daily living were observed by TCVO along with valgus correction of the lower extremity and stabilization of the femorotibial joint.

IntroductionThis pre-specified exploratory analysis investigated the effect of denosumab on bone mineral density (BMD) and bone microarchitecture in patients with rheumatoid arthritis (RA) treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs).Materials and methodsIn this open-label, parallel-group study, patients were randomly assigned (1:1) to continuous treatment with csDMARDs plus denosumab or continuous treatment with csDMARD therapy alone for 12 months. BMD and bone microarchitecture were measured by dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT).ResultsOf 46 patients enrolled in the primary study, 43 were included in the full analysis set. The mean age was 65.3 years, 88.4% were female, and 60.5% had osteoporosis. Areal BMD of the lumbar spine increased from baseline to 6 and 12 months in both groups, but the increase was higher in the csDMARDs plus denosumab group. Areal BMD of the total hip and femoral neck increased from baseline to 6 and 12 months only in the csDMARDs plus denosumab group. Cortical volumetric BMD and cortical thickness of the distal tibia increased in the csDMARDs plus denosumab group at 6 and 12 months but decreased in the csDMARD therapy alone group. Trabecular bone parameters of the distal tibia improved only in the csDMARDs plus denosumab group at 12 months.ConclusionDenosumab may be recommended for patients with RA treated with csDMARDs to increase BMD and improve bone microarchitecture.

IntroductionSecond-generation high-resolution peripheral quantitative computed tomography (HR-pQCT) has provide higher quality of bone images with a voxel size of 61 µm, enabling direct measurements of trabecular thickness. In addition to the standard parameters, the non-metric trabecular parameters such as trabecular morphology (plate to rod-like structures), connectivity, and anisotropy can also be analyzed. The purpose of this study is to investigate deterioration of bone microstructure in healthy Japanese women by measuring standard and non-metric parameters using HR-pQCT.Materials and methodsStudy participants were 61 healthy Japanese women (31–70 years). The distal radius and tibia were scanned using second-generation HR-pQCT, and microstructures of trabecular and cortical bone were measured. Non-metric trabecular parameters included structure model index (SMI), trabecular bone pattern factor (TBPf), connectivity density (Conn.D), number of nodes (N.Nd/TV), degree of anisotropy (DA), and star volume of marrow space (V*ms). Estimated bone strength was evaluated by micro finite element analysis. Associations between bone microstructure, estimated bone strength, age, and menopause were analyzed.ResultsTrabecular number declined with age, and trabecular separation increased. SMI and TBPf increased, Conn.D and N.Nd/TV declined, and V*ms increased. Cortical BMD and thickness declined with age, and porosity increased. Stiffness and failure load decreased with age. Cortical thickness and estimated bone strength were affected by menopause. Cortical thickness was most associated with estimated bone strength.ConclusionsTrabecular and cortical bone microstructure were deteriorated markedly with age. Cortical thickness decreased after menopause and was most related to bone strength. Non-metric parameters give additional information about osteoporotic changes of trabecular bone.

IntroductionRelationship of quantitative ultrasound (QUS) with high-resolution peripheral quantitative computed tomography (HR-pQCT), dual-energy X-ray absorptiometry (DXA), and bone-related biochemical markers was analyzed.Materials and methodsThe subjects were 480 individuals. Speed of sound (SOS) was measured by calcaneal QUS. Volumetric bone mineral density (vBMD) and microarchitecture of trabecular and cortical bone in the distal radius and tibia were assessed by HR-pQCT. Areal bone mineral density (aBMD) in the lumbar spine and proximal femur were measured by DXA. TRACP-5b, P1NP, 25 (OH) vitamin D, and pentosidine were evaluated by biochemical tests. The correlation of each parameter was analyzed for all subjects and by sex and age group.ResultsQUS was moderately correlated with Tb.vBMD and Tb.BV/TV in the radius and tibia. No correlation was seen with Ct.vBMD or cortical porosity (Ct.Po). Although a correlation was seen with cortical thickness (Ct.Th) in the tibia in all subjects, no correlation was seen in women aged ≥ 60 years.QUS showed moderate correlations with aBMD in the proximal femur. Although moderate correlation was seen with aBMD in the lumbar spine in all subjects, no correlation was seen in subjects aged ≥ 60 years. No significant correlations were seen between QUS and biochemical markers.ConclusionsModerate correlations were seen between QUS and Tb.vBMD and microarchitecture in the radius and tibia and aBMD of the proximal femur. On the other hand, practically no correlations were seen with Ct.vBMD or Ct.Po and the bone-related biochemical markers. Only in middle age, moderate correlations were seen with Ct.Th in the tibia and with aBMD of the lumbar spine.

Primary culture of skeletal muscle stem cells (MuSCs) is indispensable to study the dynamics of muscle regeneration and homeostasis. Here we describe the modified pre-plating method for isolating MuSCs in culture with greatly improved purity, yield, and procedure time. The protocol is based on the distinct adhesion characteristics of MuSCs. We reduced the procedure time to 2.5 days to obtain highly purified MuSCs through a newly employed re-plating step, which repeats incubation and cell-suspension. The re-plating step efficiently traps remaining fibroblastic cells, but not MuSCs, on a collagen-coated dish. Additionally, we confirmed that MuSCs can be isolated from small amounts of human/mouse muscle tissues, enabling us to perform experiments with amount-limited specimens. Thus, our method can be performed with basic laboratory equipment suitable for most facilities and without sophisticated MuSC handling techniques.

IntroductionAlthough aromatase inhibitors (AIs) are typical drugs for cancer treatment-induced bone loss, their effects on the bone microstructure remain unclear. In this study, we evaluated changes in the bone mineral density (BMD) and bone microstructure associated with AI treatment using high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with early breast cancer.Materials and methodsThis prospective, single-arm, observational study included non-osteoporotic, postmenopausal women with hormone receptor-positive breast cancer. Patients underwent dual-energy X-ray absorptiometry (DXA), HR-pQCT, and tartrate-resistant acid phosphatase-5b (TRACP-5b) or procollagen type-I N-terminal propeptide measurements at baseline and 6 and 12 months after AI therapy. The primary endpoint was changes in the total volumetric BMD (Tt.vBMD), trabecular vBMD (Tb.vBMD), and cortical vBMD (Ct.vBMD) longitudinally at the distal radius and tibia.ResultsTwenty women were included (median age 57.5 years; range 55–72 years). At 12 months, HR-pQCT indicated a significant decrease in the Tt.vBMD (median distal radius − 5.3%, p < 0.01; distal tibia − 3.2%, p < 0.01), Tb.vBMD (− 3.2%, p < 0.01; − 1.0%, p < 0.05, respectively), and Ct.vBMD (− 3.2%, p < 0.01; − 2.7%, p < 0.01, respectively). Estimated bone strength was also significantly decreased. The DXA BMD value in the total hip (p < 0.01) and femoral neck (p = 0.03), but not in the lumbar spine, was significantly decreased. The TRACP-5b levels was significantly negatively associated with changes in the Tt.vBMD in both the distal radius and tibia (r =  − 0.53, r =  − 0.47, respectively)ConclusionPostmenopausal women who received AIs for early breast cancer experienced significant trabecular and cortical bone deterioration and a decrease in estimated bone strength within only 1 year.

This exploratory study aimed to examine the impact of abatacept treatment on bone structure in patients with rheumatoid arthritis (RA) using high-resolution peripheral quantitative computed tomography (HR-pQCT). RA patients initiating either abatacept or newly introduced csDMARDs were enrolled in this prospective, non-randomized, two-group study. Bone structure in the 2nd and 3rd metacarpal heads was assessed using HR-pQCT at 0, 6, and 12 months after enrollment. Synovitis was evaluated using musculoskeletal ultrasound and MRI. The adjusted mean between-group differences (abatacept–csDMARDs group) were estimated using a mixed-effect model. Thirty-five patients (abatacept group: n = 15; csDMARDs group: n = 20) were analyzed. Changes in erosion volume, depth and width were numerically smaller in the abatacept group compared to the csDMARDs group (adjusted mean between-group differences: − 1.86 mm 3 , − 0.02 mm, and − 0.09 mm, respectively). Over a 12-month period, 5 erosions emerged in the csDMARDs group, while only 1 erosion appeared in the abatacept group. Compared to csDMARDs, abatacept better preserved bone microarchitecture; several components of bone microarchitecture were significantly worsened at 6 months in the csDMARDs group, but were not deteriorated at 6 months in the abatacept group. Changes in synovitis scores were similar between the two treatment groups. Our results indicate that abatacept prevented the progression of bone erosion including new occurrence, and also prevented worsening of bone strength independently with synovitis compared to csDMARDs including MTX. Thus, abatacept treatment may provide benefits not only in inhibiting the progress of bone erosion but also in preventing bone microarchitectural deterioration.

The purpose of this study was to establish an algorithm for measuring bone erosions at metacarpophalangeal (MCP) joints using high-resolution peripheral quantitative computed tomography (HR-pQCT), to investigate the precision of measurements, and to assess longitudinal changes in bone erosions among patients with rheumatoid arthritis (RA). The 2nd and 3rd MCP joints were scanned at a voxel size of 60.7 μm using second-generation HR-pQCT. Bone erosions on MCP joints were identified using a semi-automated algorithm we developed, and each erosion parameter was measured. Measurement reproducibility was evaluated in 19 healthy subjects using intraclass correlation coefficients (ICCs) and root mean square percent coefficient of variance (RMS%CV). Finally, longitudinal changes in bone erosions over a period of 12 months were assessed in 26 patients with RA based on the calculated least significant change (LSC). Reproducibilities for measurement parameters regarding bone erosions with our algorithm were good (all ICCs ≥ 0.98; all RMS%CVs < 5%). No erosion parameters showed significant changes after 12 months of treatment in terms of median values in all erosions, while both progression and repair of erosions were observed individually (e.g., erosion volume: progression, 26% (+0.62 mm3); repair, 34% (-0.85 mm3); no change, 40%). The measurement algorithm developed for bone erosions at MCP joints showed good reproducibility. Both progression and repair of bone erosions were observed in patients with RA even after 12 months of appropriate treatment. Our algorithm may be useful to investigate the etiology of RA and assess drug efficacy.

IntroductionHigh-resolution peripheral quantitative computed tomography (HR-pQCT) has enabled us to observe the changes in bone microarchitecture over time in vivo. In this study, the process of fracture healing was analyzed using HR-pQCT in patients with distal radius fracture who underwent osteosynthesis.Materials and methodsA total of 10 fracture sites identified from four patients with a distal radius fracture who underwent internal fixation with a volar locking plate (mean age 68.8 years, all women) were investigated. HR-pQCT was performed within a week (baseline) 4, 12, and 24 weeks after fracture. Rectangular region of interest (ROI) was established in the fracture site, inner callus, and external callus area, and the changes in bone mineral density (BMD) in each region were analyzed.ResultsFrom baseline to 24 weeks post-fracture, the BMD changed from 105.5 (95% CI 98.6–113) to 428.0 (331–554) mgHA/ccm at the fracture site, from 111.0 (104–119) to 375.3 (290–486) mgHA/ccm at the inner callus area, and from 98.5 (91.6–106) to 171.6 (132–222) mgHA/ccm at the external callus area. The BMD increased at the fracture site and inner callus area, but increased only slightly at the external callus area. At 24 weeks post-fracture, the BMD at the fracture site and inner callus area was significantly higher than the external callus area.ConclusionIn the healing process of postoperative distal radius fractures, increased BMD at the inner surface of the fracture site was confirmed in all fractures. Bone formation on the endosteal side may be a necessary condition for bone union of distal radius fractures.