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Background Musculoskeletal disorders are a key cause of morbidity in elderly people. How musculoskeletal disorders relate to healthy life expectancy remain elusive. Hence, we aimed to estimate gains in healthy life expectancy from the elimination of musculoskeletal diseases and injuries by using recent national health statistics data in Japan. Methods Mortality data were taken from Japanese national life tables and death certificates in 2016. Information on medical diagnoses, injuries, and activity were obtained from the 2016 Comprehensive Survey of Living Conditions. We examined five disorders: rheumatoid arthritis, arthrosis, low back pain, osteoporosis, and fracture. The prevalence of limitations in activities of daily living (ADL) in the population after eliminating the disorder was estimated as the proportion of outpatients without the disorder and ADL limitations, inpatients without the disorder in hospitals and clinics, and people without the disorder who reside in long-term elderly care facilities. Results There were small gains in life expectancy from elimination of all selected musculoskeletal disorders (0.0–0.1 years). Elimination of rheumatoid arthritis, osteoporosis, and fracture slightly increased the expected years without activity limitation (0.1–0.4) and slightly decreased years with activity limitation (0.1–0.4 years). Meanwhile, elimination of arthrosis, low back pain, and arthrosis and low back pain moderately increased expected years without activity limitation (0.3–1.5 years) and decreased years with activity limitation (0.3–1.5 years). In addition, elimination of rheumatoid arthritis, arthrosis, low back pain, osteoporosis, and fracture decreased expected years with ADL limitations (0.0–0.8 years) and non-ADL limitations (0.0–0.3 years). A combination of arthrosis and low back pain showed a moderate decrease in expected years with both ADL limitations (0.7–1.1 years) and non-ADL limitations (0.3–0.4). Conclusions These findings provide clinical evidence that among the musculoskeletal disorders low back pain and arthrosis are the key factors for the elongation of healthy life expectancy.

Heterotopic ossification (HO) is a pathological condition in which ectopic bone forms within soft tissues such as skeletal muscle. Human platelet-derived growth factor receptor α positive (PDGFRα+) cells, which were proved to be the original cells of HO were incubated in osteogenic differentiation medium with Food and Drug Administration-approved compounds. Alkaline phosphatase activity was measured as a screening to inhibit osteogenic differentiation. For the compounds which inhibited osteogenic differentiation of PDGFRα+ cells, we examined dose dependency of its effect using alizarin red S staining and its cell toxicity using WST-8. In addition, regulation of bone morphogenetic proteins (BMP)-Smad signaling which is the major signal of osteogenic differentiation was investigated by Western blotting to elucidate the mechanism of osteogenesis inhibitory effect by the compound. In vivo experiment, complete transverse incision of Achilles tendons in mice was made and mice were fed the compound by mixing with drinking water after operation. Ten weeks after operation, we assessed and quantified HO by micro-computed tomography scan. Intriguingly, we discovered desloratadine inhibited osteogenic differentiation of PDGFRα+ cells using the drug repositioning method. Desloratadine inhibited osteogenic differentiation of the cells dose dependently without cell toxicity. Desloratadine suppressed phosphorylation of Smad1/5/8 induced by BMP2 in PDGFRα+ cells. In Achilles tenotomy mice model, desloratadine treatment significantly inhibited ectopic bone formation compared with control. In conclusion, we discovered desloratadine inhibited osteogenic differentiation using human PDGFRα+ cells and proved its efficacy using Achilles tenotomy ectopic bone formation model in vivo. Our study paved the way to inhibit HO in early clinical use because of its guaranteed safety.

Osteosarcoma is a malignant tumor that produces neoplastic bone or osteoid osteoma. In human multicentric osteosarcoma (HMOS), a unique variant of human osteosarcoma (HOS), multiple bone lesions occur simultaneously or asynchronously before lung metastasis. HMOS is associated with an extremely poor prognosis, and effective treatment options are lacking. Using the proteins in our previously generated HMOS cell lines as antigens, we generated antibodies using a human antibody phage library. We obtained antibody clones recognizing 95 independent antigens and developed a fluorescence probe-based enzyme-linked immunosorbent assay (ELISA) technique capable of evaluating the reactivity of these antibodies by fluorescence intensity, allowing simple, rapid, and high-throughput selection of antibody clones. These results were highly correlated with those using flow cytometry. Subsequently, the HMOS cell lysate was incubated with the antibody, the antigen–antibody complex was recovered with magnetic beads, and the protein bands from electrophoresis were analyzed using liquid chromatography-mass spectrometry (LC/MS). CAVIN1/polymerase I transcript release factor was specifically detected in the HMOS cells. In conclusion, we found via a novel high-throughput screening method that CAVIN1/PTRF is an HMOS-specific cell membrane biomarker and an antigen capable of producing human antibodies. In the future, antibody–drug conjugate targeting of these specific proteins may be promising for clinical applications.

Hallux rigidus and metatarsus primus elevatus (MPE) are associated, but their causal relationship remains unknown. Several surgical approaches for treating hallux rigidus are available. We evaluated morphological characteristics of hallux rigidus with different grades to determine the optimal surgical approach. The amount of degenerative change in the metatarsophalangeal joint on the preoperative roentgenograms was graded on a scale of 1-3. We analyzed the morphology of hallux rigidus using X-ray image mapping developed by our team.This study involved weight-bearing, dorsoplantar, and lateral foot X-rays of 36 feet from 26 patients underwent surgery for hallux rigidus (Group R) at our institution, and 26 normal feet (Group N). A two-dimensional coordinate system was used to analyze the sharps of these feet by converting each dot on the radiographs into X and Y coordinates. Diagrams of the feet from each group were drawn for comparison. Feet with grades 2 (Group R2) and 3 (Group R3) hallux rigidus and normal feet were compared by Kruskal-Wallis test.Mapping revealed that the tip of distal phalanges of the second, and third toes in Group R medially shifted (P 0.05) in dorsoplantar image of the feet, and that the medial point, a part of the talus, navicular, cuneiform, and first metatarsal bone in Group R, shifted lower (P 0.05) in lateral feet images of the feet. Multiple comparisons revealed a significant navicular bone depression in grade 3 hallux rigidus compared with normal feet. A significant difference was observed between Group N and R3 but not between Group R2 and N or R3.X-ray morphological analysis of the foot revealed MPE in Group R. Elevation gradually increased as hallux rigidus grade worsened. Therefore, osteotomy combined with cheilectomy, whereby the first metatarsal bone can be tilted toward the plantar side, are useful for treating a higher-grade hallux rigidus.Level III, comparative study.

Background Muscle regenerative capacity reduces during aging. Decline in the muscle stem cell (MuSC) pool is thought to be a cause of age-related muscle regeneration insufficiency. However, why the number of MuSCs decreases with age remains unclear. We previously found that the calcitonin receptor (Calcr) is expressed by MuSCs and plays a pivotal role in maintaining the MuSC pool. In this study, we examined whether Calcr is involved in the age-related decrease in MuSC number. Methods Calcr expression in MuSCs was assessed by immunofluorescence staining using muscle sections during postnatal growth and during aging. The role of Calcr during development, postnatal growth and adult stage was examined using mice conditionally deleted Calcr in myogenic lineage cells. To explore the significance of Calcr signaling on age-related changes in MuSC number, expression levels of endogenous Calcr ligands were examined. Results Immunohistological examination revealed that Calcr expression grew stronger as MuSCs became quiescent. Conditional Calcr deletion in early myogenic lineage cells did not affect the initial capacity of the MuSC pool, but promoted age-dependent MuSC loss. Expression of endogenous Calcr ligands remained unchanged with aging. Calcr expression in MuSCs, however, decreased significantly in aged muscle compared with young muscle in both mice and humans, and this reduction was accompanied by a loss of MuSCs. Conclusions Our study revealed significant reduction of Calcr in MuSCs with age, possibly leading to age-related loss of the MuSC pool. Thus, Calcr signaling could represent a promising target for preventing aging-associated muscle regeneration insufficiency.

Postoperative complications of thoracic wall resection include respiratory complications, skin necrosis and infection. The aim of the present study was to examine postoperative complications in patients who required combined thoracic wall resection during the surgical removal of a tumor. The present study included 68 patients; there were 50 patients with lung tumors and 18 patients with musculoskeletal tumors. The clinical factors associated with complications were compared between the two groups. Preoperative and postoperative pulmonary function tests were performed to examine the residual pulmonary function in 16 patients. Thoracic cage reconstruction was performed in 46 patients. Postoperative complications occurred in 30 (44.1%) patients, and one patient died from postoperative pneumonitis. Compared with the pulmonary function preoperative test results, the postoperative results revealed a decrease in the mean vital capacity percentage and an increase in the mean forced expiratory volume within 1 sec as a percent of the forced vital capacity. In patients with lung tumors, pneumonectomy can result in an increased rate of complications following thoracic wall resection. Residual pulmonary function is affected by impaired thoracic cage expansion and removal of the lung. However, the results of the present study demonstrated that these complications can be somewhat stabilized by thoracic wall reconstruction.

Age-related sarcopenia constitutes an important health problem associated with adverse outcomes. Sarcopenia is closely associated with fat infiltration in muscle, which is attributable to interstitial mesenchymal progenitors. Mesenchymal progenitors are non-myogenic in nature but are required for homeostatic muscle maintenance. However, the underlying mechanism of mesenchymal progenitor-dependent muscle maintenance is not clear, nor is the precise role of mesenchymal progenitors in sarcopenia. Here, we show that mice genetically engineered to specifically deplete mesenchymal progenitors exhibited phenotypes markedly similar to sarcopenia, including muscle weakness, myofiber atrophy, alterations of fiber types, and denervation at neuromuscular junctions. Through searching for genes responsible for mesenchymal progenitor-dependent muscle maintenance, we found that Bmp3b is specifically expressed in mesenchymal progenitors, whereas its expression level is significantly decreased during aging or adipogenic differentiation. The functional importance of Bmp3b in maintaining myofiber mass as well as muscle-nerve interaction was demonstrated using knockout mice and cultured cells treated with Bmp3b. Furthermore, the administration of recombinant BMP3B in aged mice reversed their sarcopenic phenotypes. These results reveal previously unrecognized mechanisms by which the mesenchymal progenitors ensure muscle integrity and suggest that age-related changes in mesenchymal progenitors have a considerable impact on the development of sarcopenia.

Background and Purpose Wrist swelling is a frequent clinical manifestation of Kienböck's disease, but no study has reported the site and pathology of wrist swelling in this disease. The aim of this study is to elucidate the site and pathology of wrist swelling in Kienböck's disease. Materials and Methods Dorsal and palmar soft tissue thicknesses of the wrist were measured on standard lateral radiographs of the wrist in 26 patients with Kienböck's disease and 30 subjects without intra-articular lesion. Axial magnetic resonance imaging (MRI) views were examined to detect the site of swelling. The dorsal capsular ligament in three patients with Kienböck's disease underwent histological examination. Results Radiographic study confirmed dorsal wrist swelling in 24 of 26 (92%) patients examined compared with the contralateral unaffected wrists. MRI demonstrated thickening of the dorsal capsular ligament and extensor layer with synovial proliferation. Histological examination revealed nonspecific chronic inflammation. Conclusion Dorsal wrist swelling in Kienböck's disease is a common manifestation and constitutes a part of pathology of Kienböck's disease, although further study is required to clarify the relation between wrist swelling and etiology of Kienböck's disease. Level of Evidence This is a Level III study.

We explored the effects of chondroitin sulfate on knee osteoarthritis in a one-year, randomized, double-blind, dose-comparison study. Patients with painful, Kellgren-Lawrence grade 2-3, osteoarthritis of the knee were treated with oral chondroitin sulfate at a dose of either 260 mg/d (low-dose group, control group) or 1560 mg/d (high-dose group). Symptoms were evaluated by the Lequesne's index and visual analog scale for pain. We made subgroup analyses according to background symptom severity (Lequesne's index ≥8 or

We analyzed 428 femoral metastases initially treated with radiotherapy between 2002 and 2011 to clarify the clinical details of post-irradiation fractures of femoral metastasis. Patients included 161 men and 167 women, with a mean age of 62 years. Fracture incidence, fracture site, fracture risk based on X-ray images before radiotherapy, and interval from completion of radiotherapy to fracture occurrence were assessed. In addition, 24 pathological specimens obtained during 27 surgeries for these fractures were examined. Fractures occurred in 7.7% of 428 femoral metastases (total 33: 28 actual fractures and five virtual fractures with progressive pain and bone destruction). The fracture rate was 7.8% in the proximal femur and 1.5% in the shaft (P = 0.001). Fractures occurred a median of 4.4 months after radiotherapy, with 39.4% occurring within 3 months and 63.6% within 6 months. Among femurs with high fracture risk according to Harrington’s criteria or Mirels’ score, the fracture rate was 13.9% and 11.8%, respectively. Viable tumor cells were detected in all five patients with painful virtual fracture, in 85.7% of femurs with actual fractures that occurred within 3 months, and in only 25.0% of actual fractures occurring after 3 months. Post-irradiation fractures of femoral metastasis most frequently occurred within 3 months after radiotherapy, and were more common in the peritrochanteric area than in the shaft. Radiological evidence of impending fracture did not correlate with a high fracture rate. Actual fractures occurring after more than 3 months were likely caused by post-irradiation fragility of the femur, without viable tumor cells.

Objective The usefulness of computed tomography (CT) for measuring bone defect volume in the alveolar cleft has attracted considerable attention in recent years. Moreover, 320-row area detector CT (320-ADCT) is currently widely utilized. This technology helps to acquire smooth three-dimensional images, with a reduced exposure dose and improved image resolution, similar to those of dental cone-beam CT (CBCT). We compared the exposure dose of 320-ADCT with that of dental CBCT, and analyzed the reliability of a volumetric method for measuring bone defects in the alveolar cleft using 320-ADCT, both experimentally and clinically. Methods We performed thermoluminescent dosimeter measurements using an anthropomorphic RANDO phantom. Additionally, we evaluated the reproducibility of the volumetric measurement method for the bone defective volume using CT images of simulated bone defects in pigs. In addition, we evaluated the inter-rater reliability of the volumetrically measured values of bone defects in 20 patients with a unilateral cleft. Results The exposure doses of 320-row area detector CT and CBCT were similar. The errors of volumetric values between calculated and actual bone defects created in pigs were up to 7.6%. Inter-rater reliability of the calculated volumes of bone defect was evaluated as high, according to Bland–Altman analysis. Conclusions CT examination with a low exposure dose and precise analysis is feasible without the use of highly specialized dental CBCT.

A lot of good outcomes have been reported after opening-wedge high tibial osteotomy (OWHTO) and closing-wedge high tibial osteotomy (CWHTO).The purpose of this study was to examine the rotational alignment after OWHTO and CWHTO performed by the same surgeon in one hospital. The sample included 30 knees from 24 patients. In all cases, the same orthopaedic surgeon performed the osteotomy surgeries using the same method. The tibial external rotation angle (TERA) was measured using the CT images of proximal tibial plateau and distal tibial malleolus from the consecutive axial CT slices of tibia. In this study, two considerations were examined. The first was the change in rotation angle, which was defined by TERA noted before and after the operation. The second was the relationship between the correction angle of the osteotomy and the rotation angle change of the distal tibia. The first was evaluated using the paired-Student’s t-test, while the second was analyzed with Pearson’s correlation coefficient. In the OWHTO group, the mean TERA was 21.4± 7.0° preoperatively and 20.2 ± 8.0° postoperatively, but no significant difference was seen between pre- and post-operation measurements (p = 0.21). Significant TERA increasing (that is, external rotation of the distal tibia) was seen postoperatively in only three knees. In the CWHTO group, the mean TERA was 19.9 ± 10.5° preoperatively and 16.5 ± 9.5° postoperatively, and significant difference was seen between pre- and post-operative TERA (p < 0.05). No significant correlation was seen between the correction angle and the change of the rotation angle in either group (r = 0.40, r = 0.12) . In the OWHTO group, both internal and external rotation of the distal tibia can occur after surgery. In the CWHTO group, the distal tibia rotated internally postoperatively. No significant correlation was seen between the correction angle and the change in the rotation angle in either group

We examined the clinical features and functional outcomes of surgically repaired subcutaneous flexor tendon ruptures in patients with rheumatoid arthritis (RA).This retrospective study included 41 fingers of 24 RA patients who underwent surgical treatment for flexor tendon ruptures. Evaluations performed at the time of presentation following rupture were C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and disease activity score in 28 joints (DAS28)-ESR, as well as Larsen grading for carpal bone destruction. The ruptured tendon and postoperative active range of motion (ROM) of digits were also examined.The mean CRP was 2.4 mg/dl, ESR was 52 mm/h, and the DAS28-ESR was 4.5. Carpal bone destruction according to Larsen grade IV-V was observed in 18/24 patients. Affected digits were most commonly the thumb (12) and the ring and little fingers (9 each). Tendon ruptures were most common in the carpal tunnel in zone IV. The mean postoperative finger ROM (flexion/extension) was 38°/2° for the interphalangeal (IP) joint of the thumb and 23°/-2° for the distal interphalangeal joint of the other four fingers.Patients with flexor tendon ruptures present with high disease activity and advanced bone destruction. It is important to reduce the risk of progressive bone destruction and subsequent tendon rupture via tight control of disease activity.

Introduction: The aim of this study was to validate the potential association between cigarette smoking and cubital tunnel syndrome (CubTS). Methods: One hundred patients with CubTS were compared with 100 controls with ulnar abutment syndrome matched for age, gender, and BMI. The smoking status was compared between patients and controls using the sign test and the Wilcoxon signed rank test. Conditional logistic regression was used to calculate the association between CubTS and pack-years smoked. Results: A significant association was found between increased pack-years smoked and CubTS. A significant difference in the number of never smokers and ever smokers was observed between the patients with CubTS and controls. The difference in mean pack-years in the patients and controls was highly significant. A dose-dependent association with pack-years was found between patients and controls. Discussion: High cumulative cigarette smoking is associated with CubTS. This article is protected by copyright. All rights reserved.

Background: It is well known that acute compartment syndrome is associated with fracture of the forearm, while involvement of soft tissue injury including musculotendinous injury remains unclear. The purpose of this study was to evaluate the soft tissue involvement, including musculotendinous ruptures, in acute compartment syndrome of the upper limb.Methods: We retrospectively enrolled 16 patients who underwent surgical treatment for acute compartment syndrome of the upper extremity. The average age of the patients was 47 years (range, 14 to 79) and the mean follow-up period after the surgery was 15 months (range, 12 to 29). Complications included at least one presentation at the final follow up of sensory disturbances or motor disturbances. We examined the presence of musculotendinous injury mechanism of injury, presence of fracture, the performance of skin grafting, and complications.Results: Mechanism of injury of “caught in a machine” was found in six cases. Three of these patients had musculotendinous ruptures and all muscle tears were revealed by intraoperative findings. No patients had muscle ruptures with other injury mechanisms. Seven out of 16 patients (44%) developed complications at final follow-up. Skin grafting was performed in six patients, and five of these patients developed complications. Only one of the nine patients without complications underwent skin grafting.Conclusions: In cases of high-energy injuries, the surgeon should suspect the presence of a musculotendinous injury prior to surgery.

Objectives: High-dose fondaparinux therapy at 7.5 mg/day (FPX 7.5 mg) for deep vein thrombosis (DVT) may increase the risk of hemorrhage. We investigated the efficacy and safety of FPX 7.5 mg to treat DVT after total knee arthroplasty. Methods: This study included 101 patients (91 with osteoarthritis, 10 with rheumatoid arthritis; mean age at total knee arthroplasty: 72.9 years) with asymptomatic postoperative DVT. Medical prophylaxis for DVT was started on postoperative day 1. Vascular ultrasound was conducted within 2 days postoperatively; patients were switched to FPX 7.5 mg after DVT diagnosis. Ultrasound was repeated to monitor DVT resolution. Adverse reactions were assessed. Results: DVT resolved in 72 patients (71.3%) receiving FPX 7.5 mg. There were no significant differences between patients with versus without DVT resolution in the timing of FPX 7.5 mg therapy, treatment period, age, body mass index, or D-dimer or hemoglobin levels. There was no significant difference in DVT outcome between patients starting FPX 7.5 mg within 4 days postoperatively versus on day 5 or later, or between patients treated for ≤7 versus ≥8 days. Hemoglobin decreased to ≤7 g/dL in three patients (2.9%). Conclusions: FPX 7.5 mg can be expected to resolve DVT in 71.3% of patients; however, the risk of associated hemorrhagic complications may be higher than the risk of pulmonary embolism. To treat DVT with FPX 7.5 mg without compromising safety, patients should be selected carefully and the timing of treatment should be adjusted appropriately.

International audience; Myogenic stem cells are a promising avenue for the treatment of muscular disorders. Freshly isolated muscle stem cells have a remarkable engraftment ability in vivo, but their cell number is limited. Current conventional culture conditions do not allow muscle stem cells to expand in vitro with their bona fide engraftment efficiency, requiring the improvement of culture procedures for achieving successful cell-therapy for muscle disorders. Here we expanded mouse muscle stem cells and human myoblasts with Notch ligands, DLL1, DLL4, and JAG1 to activate Notch signaling in vitro and to investigate whether these cells could retain their engraftment efficiency. Notch signaling promotes the expansion of Pax7+MyoDmouse muscle stem-like cells and inhibits differentiation even after passage in vitro. Treatment with Notch ligands induced the Notch target genes and generated PAX7+MYODstem- like cells from human myoblasts previously cultured on conventional culture plates. However, cells treated with Notch ligands exhibit a stem cell-like state in culture, yet their regenerative ability was less than that of freshly isolated cells in vivo and was comparable to that of the control. These unexpected findings suggest that artificial maintenance of Notch signaling alone is insufficient for improving regenerative capacity of mouse and human donor-muscle cells and suggest that combinatorial events are critical to achieve muscle stem cell and myoblast engraftment potential.

Background: Acetabular dysplasia (AD) is the main cause of hip osteoarthritis in Japan. A simple method to evaluate acetabular dysplasia would be helpful for early treatment or prevention of hip osteoarthritis. Acetabular dysplasia is reported to be associated with pathological transverse growth of the pelvis, indicating that the distance between the 2 anterior superior iliac spines might be useful for screening and detection of acetabular dysplasia. The purpose of this study was to determine if the acetabular dysplasia radiographic parameters are related to the distance between the 2 anterior superior iliac spines in patients with hip osteoarthritis. Material/Methods: In this study, data obtained in a previous multi-institutional examination of patients with hip osteoarthritis in Japan were evaluated. The anterior superior iliac spine distances of 176 female patients (mean age, 54 years; range, 18-85 years) were measured by physical examination. The relationship between the anterior superior iliac spine distance and acetabular dysplasia was analyzed, and the anterior superior iliac spine distances of the patients with acetabular dysplasia who were at relatively high risk for hip osteoarthritis were compared with that of the patients at lower risk. Results: A statistically significant relationship between the anterior superior iliac spine distance and all of the acetabular dysplasia parameters was observed. The anterior superior iliac spine distances of the acetabular dysplasia patients with a relatively high risk for radiographic acetabular dysplasia parameters were significantly smaller than those of patients at lower risk. Even after adjustment for age, height, and weight, significantly increased relative risk for having high risk AD was found in patients with an ASIS distance of less than 24.5 cm. Conclusions: There was a significant relationship between the anterior superior iliac spine distance and the degree of acetabular dysplasia., Medical Science Monitor, 20, pp.116-122; 2014

Background The objectives of the present study were to assess the mid-term results of cementless total knee arthroplasty (TKA) with the porous tantalum monoblock tibial component and to examine the time course of bone changes on plain radiographs. Methods The subjects were 32 patients, 29 patients were available for follow-up. We investigated the mid-term results of TKA after a mean follow-up period of 7 years and 8 months. We also examined changes of the bone over time on plain radiographs. Results The Knee Society Clinical Rating scores showed significant improvement. Bone changes around the tibial component were as follows: new bone formation and longitudinal trabecular thickening in 41.4% (Type A), only longitudinal trabecular thickening in 41.4% (Type B), and no changes in 17.2% (Type C). Type A and B changes were more frequent in patients with osteoarthritis, whereas Type C was only seen in patients with rheumatoid arthritis. Three knees had an initial gap, but this disappeared in all cases, and no new radiolucent lines were detected. Stress shielding was observed in seven knees (21.9%), but there was no implant loosening related to it. When we examined the relationship between the mechanical axis and the locations of the tips of the tibial pegs in patients with or without stress shielding, no significant differences were found. Conclusions The results of mid-term follow-up have demonstrated favorable bone ingrowth, suggesting that porous tantalum is a promising material for cementless TKA.

Objective: We performed comprehensive proteomic analyses of articular cartilage by using the isobaric tags for relative and absolute quantitation (iTRAQ) method, and searched for candidate biomarkers for osteoarthritis (OA).Methods: Articular cartilage was collected from patients with OA or femoral neck fracture for the control group. Molecular variations were detected by the iTRAQ method, and quantitative analyses were performed by western blot.Results: Using the iTRAQ method, we identified 76 proteins with different expression levels in OA patients and the control group. Among these proteins, we selected LECT2 (leukocyte cell-derived chemotaxin-2), BAALC (brain and acute leukemia, cytoplasmic), and PRDX6 (peroxiredoxin-6), which had not been reported as biomarkers for OA.Conclusions: Use of these proteins in combination with conventional OA biomarkers may better reflect the grade and prognosis of OA.

Assessments of serum 25-hydroxyvitamin D levels in 1,683 Japanese from a population-based cohort revealed prevalences of vitamin D insufficiency and deficiency were 81.3 and 1.2%, respectively. Vitamin D deficiency was significantly associated with female sex, examined month, current smoking, lack of regular walking, higher intact parathyroid hormone (iPTH), and poor daily vitamin D intake.To clarify the characteristics of subjects with vitamin D insufficiency and deficiency among men and women in the general Japanese population.We initiated research on osteoarthritis/osteoporosis against disability (ROAD), a large-scale population-based cohort study, in 2005-2007. Blood examination was performed to measure serum 25-hydroxyvitamin D (25D) and iPTH levels and biochemical markers of bone turnover in 1,683 participants (595 men, 1,088 women). Participants completed an interviewer-administered questionnaire, measurements of bone mineral density, and x-ray examination. Vitamin D deficiency and insufficiency were defined by serum 25D levels10 and ≥10 but30 ng/mL, respectively.The prevalence of vitamin D insufficiency and deficiency was 81.3 and 1.2%, respectively. Multinominal logistic regression analyses using potentially confounding variables revealed vitamin D insufficiency was significantly associated with age (+1 year, relative risk ratio, 0.98; 95% confidence interval, 0.96-0.99), gender (women vs. men, 2.28; 1.59-3.30), residing areas (coastal area vs. mountainous area, 0.58; 0.41-0.81), examined month (October, November, December vs. January, 0.51; 0.34-0.76), and serum levels of iPTH (+1 pg/mL, 1.02; 1.01-1.03). Vitamin D deficiency was significantly characterised by female sex (20.5; 3.1-136.7), examined month (0.28; 0.09-0.95), current smoking habit (6.39; 1.78-23.0), lack of regular outside walking (3.96; 1.34-11.7), higher iPTH (1.02; 1.01-1.03) and poor daily vitamin D intake (+10 μg/day, 0.48; 0.24-0.93).A high prevalence of vitamin D insufficiency and a low prevalence of vitamin D deficiency were found in Japanese men and women, and the characteristics of vitamin D status were clarified.

Enophthalmos is caused by an increase of orbital volume after blowout fracture and is one of the most critical complications of such fractures, but is often masked by swelling soon after injury. If surgery is performed after swelling resolves, it becomes more difficult to treat enophthalmos because of atrophy and fibrosis. Accordingly, it is important to estimate the severity of enophthalmos soon after injury. We developed a new criterion for determining whether orbital fractures are indicated for surgery in Asian patients using analysis of orbital volume. We retrospectively calculated the orbital volume of patients treated surgically or conservatively and analyzed the correlation between changes of orbital volume and the severity of enophthalmos. Regression analysis of the correlation between enophthalmos and increased orbital volume (y = 0.8x + 0.2; correlation coefficient: 0.92) showed that enophthalmos of 2.0 mm corresponded to an increase in orbital volume of 2.25 cm3. This result is similar to data reported previously for Caucasian patients — enophthalmos of 2.0 mm is a common surgical indication worldwide. Our results suggest that an increase of orbital volume of >2.25 cm3 could be a new criterion for surgical treatment of blowout fractures in Asians.

Synovial tissue in rheumatoid arthritis (RA) shows dense infiltration of plasmacytes. The purpose of the present study is to identify and localize autoantibodies produced in these immunocytes in RA synovitis. We developed a novel screening system for detecting specific autoantigens. Protein antigens recognized by antibodies in the serum and synovial tissue extract from five RA patients were screened with the AlphaScreen method. For screening, a biotinylated human autoantigen library was constructed by the wheat germ cell-free protein synthesis system. The AlphaScreen analysis of 2183 proteins detected a limited number of antigens reactive with the serum and synovial tissue extract. Eighteen biotinylated proteins, containing top five showing high signals in each synovitis tissue extract, were utilized as probes for the enzyme-labeled antigen method, in order to visualize the site of specific antibody production in synovial lesions. Specific antibodies against two proteins, tripartite motif-containing 21 (TRIM21, also known as SSA/Ro52) and F-box only protein 2 (FBXO2), were visualized in the cytoplasm of plasmacytes in two RA synovitis lesions, respectively. Absorption experiments using unlabeled proteins confirmed the specificity of staining. No positive signals against these two proteins were identified in the additionally evaluated RA and osteoarthritis synovial lesions. The present study indicated 1) the usefulness of screening the human autoantigen library with the AlphaScreen assay for detecting autoantibodies in RA synovitis, and 2) the applicability of biotinylated proteins to the enzyme-labeled antigen method for visualizing the site of autoantibody production within the lesion.

Aim As society ages, there is a vast number of elderly people with locomotive syndrome. In this study, the factors associated with functional limitations in daily living activities evaluated by female hip osteoarthritis (OA) patients were investigated. Methods This study was a cross‐sectional study. The subjects were 353 female patients who were newly diagnosed with hip OA at an orthopedic clinic with no history of hip joint surgery. Outcome indices were functional limitations in two daily living activities obtained from a questionnaire completed by the patients: (i) standing up (standing from a crouched position) and (ii) stair‐climbing (climbing and/or descending stairs). The odds ratios (ORs) and 95% confidence intervals (CIs) were computed for explanatory variables using the proportional odds model in logistic regression to evaluate their associations with functional limitations. Results Functional limitations in standing up were associated with heavy weight (third tertile vs. first tertile: 1.91, 1.11–3.27), participation in sports at school (0.62, 0.40–0.98), parity (vs. nullipara: 1.96, 1.08–3.56), old age and OA stage. Associations with functional limitations in stair‐climbing were seen with short height (< 151.0 cm vs. ≥ 156.0 cm: 2.05, 1.02–4.12), bilateral involvement (vs. unilateral: 1.71, 1.01–2.88), old age and OA stage. Conclusion Old age, OA stage, heavy weight, parity, shorter height and bilateral OA were associated with functional limitations in standing up and/or stair‐climbing, whereas participation in sports such as club activities in school maintained standing up.

Background This retrospective study was designed to investigate prognostic factors for postoperative outcomes for cubital tunnel syndrome (CubTS) using multiple logistic regression analysis with a large number of patients. Methods Eighty-three patients with CubTS who underwent surgeries were enrolled. The following potential prognostic factors for disease severity were selected according to previous reports: sex, age, type of surgery, disease duration, body mass index, cervical lesion, presence of diabetes mellitus, Workers' Compensation status, preoperative severity, and preoperative electrodiagnostic testing. Postoperative severity of disease was assessed 2 years after surgery by Messina's criteria which is an outcome measure specifically for CubTS. Bivariate analysis was performed to select candidate prognostic factors for multiple linear regression analyses. Multiple logistic regression analysis was conducted to identify the association between postoperative severity and selected prognostic factors. Results Both bivariate and multiple linear regression analysis revealed only preoperative severity as an independent risk factor for poor prognosis, while other factors did not show any significant association. Conclusions Although conflicting results exist regarding prognosis of CubTS, this study supports evidence from previous studies and concludes early surgical intervention portends the most favorable prognosis.

The aim of this study was to validate the potential association between cigarette smoking and cubital tunnel syndrome (CubTS).One hundred patients with CubTS were compared with 100 controls with ulnar abutment syndrome matched for age, gender, and body mass index. The smoking status was compared between patients and controls using the sign test and the Wilcoxon signed rank test. Conditional logistic regression was used to calculate the association between CubTS and pack-years smoked.A significant association was found between increased pack-years smoked and CubTS. A significant difference in the number of never smokers and ever smokers was observed between the patients with CubTS and controls. The difference in mean pack-years in the patients and controls was highly significant. A dose-dependent association with pack-years was found between patients and controls.High cumulative cigarette smoking is associated with CubTS. Muscle Nerve 54: 1136-1138, 2016.

Background In Japan, the majority of hip osteoarthritis (OA) was caused by acetabular dysplasia, and about 90 % of patients were female. The present study focused on Japanese female patients with hip OA due to acetabular dysplasia, and examined the associated factors with OA staging at diagnosis, in special reference to body weight. Methods Study subjects were 336 Japanese women who were newly diagnosed with hip OA caused by acetabular dysplasia at 15 hospitals in 2008. The self-administered questionnaire elicited patients’ body weight at age 20 and at OA diagnosis. Four ranked OA staging according to radiographic findings of the hip joint (pre-OA, initial stage, advanced stage or terminal stage) was regarded as the outcome index. Proportional odds models in logistic regression were used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs) for severer stage of OA. Results At diagnosis, 45 % of patients suffered from terminal stage of OA, whereas 13 % and 14 % were categorized into pre-OA and initial stage, respectively. After adjustment for potential confounders, weight gain since age 20 revealed the increased ORs for severer OA stage at diagnosis (OR 2.02; 95 % CI, 1.07–3.80). Other significant characteristics were age (67+ vs. 20–49 years, OR 12.4), lower education (junior high school vs. junior college or higher, OR 4.00), parity (OR 2.19), lower acetabular head index (

Summary Skeletal muscle contains two distinct stem/progenitor populations. One is the satellite cell, which acts as a muscle stem cell, and the other is the mesenchymal progenitor, which contributes to muscle pathogeneses such as fat infiltration and fibrosis. Detailed and accurate characterization of these progenitors in humans remains elusive. Here, we performed comprehensive cell-surface protein profiling of the two progenitor populations residing in human skeletal muscle and identified three previously unrecognized markers: CD82 and CD318 for satellite cells and CD201 for mesenchymal progenitors. These markers distinguish myogenic and mesenchymal progenitors, and enable efficient isolation of the two types of progenitors. Functional study revealed that CD82 ensures expansion and preservation of myogenic progenitors by suppressing excessive differentiation, and CD201 signaling favors adipogenesis of mesenchymal progenitors. Thus, cell-surface proteins identified here are not only useful markers but also functionally important molecules, and provide valuable insight into human muscle biology and diseases., Graphical Abstract, Highlights • CD82 and CD318 are expressed on human muscle satellite cells • CD201 is expressed on interstitial mesenchymal progenitors in human muscle • CD82 suppresses premature differentiation of satellite cells • CD201 signaling favors adipogenesis of mesenchymal progenitors, In this article, Uezumi and colleagues identify previously unrecognized markers of human skeletal muscle-derived progenitors: CD82 and CD318 for satellite cells and CD201 for mesenchymal progenitors. They demonstrate that these markers are not only useful for cell identification and isolation but also functionally important in the regulation of myogenesis and adipogenesis.

We conducted a nationwide epidemiologic study regarding hip osteoarthritis (OA) in Japan, and a previous report found these patients to be unique in comparison to Caucasians. This report focused on the data regarding each hip joint, and the involvement of acetabular dysplasia with hip OA was analyzed.Seven hundred twenty OA hips were examined. Sixty-five joints with osteonecrosis of the femoral head and 215 non-OA contralateral joints of the unilateral patients were examined as controls. The revised system of stage classification for hip OA of the Japanese Orthopedic Association (JOA) was used according to the reproducibility in order to ensure reliable data from the multiple institutions. The acetabular dysplasia indexes were also chosen according to the reproducibility and measured in the radiograph of bilateral hip joints. The clinical score was assessed using the JOA scoring system. The relative risk of the grade of acetabular dysplasia indexes for hip OA was calculated as the odds ratio and the 95% confidence interval.The stage of the OA joints deteriorated with increasing age. The clinical scores also decreased. The grade of the acetabular dysplasia indexes of the OA joints was significantly higher than that of the control joints. Each index of acetabular dysplasia demonstrated significantly increased odds ratios for hip OA. Among the OA joints, the deterioration of the OA stage was found to be significantly associated with an increasing grade of acetabular dysplasia. The odds ratio for OA deterioration in the acetabular dysplasia index was also obtained. The joints of females tended to have a higher grade and prevalence of acetabular dysplasia than those of males.These findings confirmed a high prevalence of acetabular dysplasia in hip OA joints in Japan. Acetabular dysplasia was one of the most important factors associated with hip OA.

The following articles have been retracted by the Editorial Board of Experimental Animals, because some parts of their contents were published elsewhere.

Transformed sarcomas rarely arise from bone infarct lesions, although the majority of bone sarcomas are primary in origin. However, the pathogenesis of the condition is unknown. In this report, we describe a malignant fibrous histiocytoma with a p53 gene mutation. A 59-year-old woman complained of having pain in her left knee for three months. Plain radiographs of the distal metaphysis of her left femur revealed an ill-defined lytic lesion, which was consistent with a malignant tumor in the infarct lesion. An open biopsy specimen did not show any evidence of malignancy. Immunohistochemical examination of the biopsy specimen failed to show p53 protein-positive cells. However, a mutation in the p53 gene was detected when polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) analysis was performed. A functionally relevant p53 missense mutation in codon 273 of exon 8 [CGT (Arg) -CAT (His)] was confirmed by direct sequencing. We concluded that this lesion was a malignant bone tumor arising from the bone infarct lesion, and we thus performed a wide resection. The histopathological diagnosis of the resected specimen was that it was a malignant fibrous histiocytoma associated with bone infarction. Immunohistochemistry revealed that the tumor cells were positive for the p53 protein. To our knowledge, our patient is the first patient having a bone infarct-associated sarcoma with a p53 gene mutation. Identification of the p53 mutation helps in diagnosing the malignant transformation of the bone infarct lesion. One pathogenesis of this condition may be a mutation in the p53 gene.

Human multicentric osteosarcoma (HMOS) is a rare, aggressive variant of osteosarcoma, and its etiology is not clear. We used newly established HMOS cells, which were derived from primary (HMOS-A) and secondary (HMOS-P) lesions, respectively, to perform a basic study analyzing the cellular biology and gene expression of HMOS. We performed a cell growth assay, an invasion assay, DNA microarray analysis, quantitative real-time RT–PCR (Qrt-PCR), and a telomerase assay and compared the results between HMOS-A, HMOS-P, and human osteosarcoma (HOS) cell lines (MNNG-HOS and Saos-2). The cell biological analysis revealed that HMOS-A and HMOS-P had similar characteristics to Saos-2, and the invasion assay showed that they had similar characteristics to MNNG-HOS. The DNA microarray study showed that the gene expression profiles of HMOS-A and HMOS-P were similar to that of MNNG-HOS, but the overexpression of MMP-2, MMP-9, and MT1-MMP was observed in HMOS-A and HMOS-P, which was correlated with the invasiveness of the extracellular matrix, and collagen type-4 (COL-4) and VEGF were also detected. HMOS-A and HMOS-P showed low telomerase activity similar to Saos-2, which are known to be telomerase negative, but a similar telomere length and telomerase protein to MNNG-HOS. HMOS-A and HMOS-P demonstrated strong invasive ability, and their gene expression profiles correlated with the invasiveness of the extracellular matrix. Their telomerase activity was low, but they did not shown the typical features of alternative lengthening of telomeres (ALT). HMOS-A and HMOS-P are useful models for further study of various biological aspects and therapeutic manipulation of HMOS.

This retrospective cohort study was designed to validate the reliability of measurement of the lateral capitellohumeral angle (LCHA), an index of sagittal angulation of the elbow, in healthy children. The results were compared to the Baumann angle (BA), which is a similar concept to LCHA. Sixty-two radiographs of the elbow in healthy children (range, 2–11 years) were reviewed by 6 examiners at 2 sessions. The mean value and reliability of the measurement of LCHA and BA were assessed. Intraobserver reliability and interobserver reliability were calculated using intraclass correlation coefficients (ICCs). The mean LCHA value was 45° (range, 22° to 70°) and the mean BA was 71° (range, 56° to 86°). The ICCs for intraobserver reliability of the LCHA measurements were almost perfect for 2 examiners, substantial for 3 examiners, and moderate for 1 examiner with a mean value of 0.77 (range, 0.57–0.95). For BA measurements, the ICCs were almost perfect for 1 examiner and substantial for 5 examiners with a mean value of 0.74 (range, 0.66–0.83). The ICCs for interobserver reliability between the first and second measurements were both moderate for LCHA (0.56 and 0.51) and for BA (0.52 and 0.50). LCHA showed almost the same reliability in measurement as BA, which is the gold standard assessment for coronal alignment of the elbow. LCHA showed moderate-to-good reliability in the evaluation of sagittal plane elbow alignment.

We are planning a multicenter survey on coxarthrosis and acetabular dysplasia in Japan. To collect reliable data, we performed a preliminary study to elucidate the observer agreement on assessment items.We collected radiographs of hip joints in eight patients with various findings of coxarthrosis. Twelve registered orthopedic specialists evaluated them regarding the roentgenographic stage of coxarthrosis and five indexes of acetabular dysplasia (acetabular angle, center-edge angle, acetabular roof obliquity, acetabular head quotient, approximate acetabular quotient). To assess observer agreement, we calculated the value of the kappa statistic for stages and the coefficient of variation for the indexes. The same 12 specialists then assessed the coxarthritis stage on the same radiographs 1 month after the first evaluation based on our own descriptions of the roentgenographic stages.For the first evaluation of the roentgenographic stage, the value of the kappa statistic was 0.448; and for the second evaluation it was 0.600. The results of the coefficient of variation for the indexes of acetabular dysplasia, ranked in ascending order, were as follows: acetabular angle, acetabular head quotient, acetabular roof obliquity, center-edge angle, approximate acetabular quotient.For the upcoming multicenter survey, clear descriptions of the stages of coxarthrosis and selection of appropriate indexes can be helpful for collecting dependable results.

The beneficial effects of alfacalcidol (ALF) on bone mass, bone formation, and bone resorption have been established in ovariectomized rats. Our previous studies showed that high-dose glucocorticoid (GC) administration (methylprednisolone sodium succinate, 5.0 mg/kg, s.c., 3 times a week) for 4 wk induced cancellous osteopenia without significantly affecting cortical bone mass in Sprague-Dawley rats, and that high-dose GC administration for 8 wk also resulted in cortical osteopenia. The purpose of the present study was to examine the effects of ALF on cancellous and cortical bone mass in GC-treated rats. Forty female Sprague-Dawley rats, 3 mo of age, were randomized by the stratified weight method into four groups of 10 rats each, as follows: age-matched control group (CON); 8-wk GC administration with administration of vehicle during the latter 4 wk of treatment (GC group); 8-wk GC administration with administration of a low dose of ALF (0.08 Ag/kg) during the latter 4 wk of treatment (low-dose ALF group); 8-wk administration of GC with administration of a high dose ofALF (0.16 microg/kg) during the latter 4 wk of treatment (high-dose ALF group). The GC (methylprednisolone sodium succinate, 5.0 mg/kg) was administered subcutaneously 3 times a week, and ALF was administered orally 5 times a week. At the end of the experiment, static and dynamic bone histomorphometric analyses were performed on cancellous bone of the proximal tibial metaphysis and cortical bone of the tibial diaphysis. Eight-week GC administration resulted in loss of the cancellous bone volume/total tissue volume (BV/TV) and percent cortical area (Ct Ar) as a result of decreased trabecular bone formation, increased trabecular and endocortical bone resorption, and decreased periosteal bone formation. Low-dose ALF restored the cancellous BV/TV by mildly suppressing bone resorption and restoring bone formation, whereas high-dose ALF increased it beyond the value observed in the age-matched controls by strongly suppressing bone resorption and markedly increasing bone formation. Both low- and high-dose ALF prevented the GC-induced reduction of the percent Ct Ar by increasing periosteal bone formation and suppressing endocortical bone resorption. The effects of ALF on cancellous bone mass, bone formation, and bone resorption were all dose-dependent. The present study showed the beneficial effects of ALF on cancellous and cortical bone mass in GC-treated rats.

Background Preserving the hip joint to delay arthroplasty for patients with acetabular dysplasia-associated early-stage osteoarthritis has become more common, and several surgical procedures have demonstrated pain relief and improved hip joint function. Periacetabular osteotomy, one of the joint-preserving surgical procedures of the hip, provides favorable outcomes, although there are no reports of total hip arthroplasty being used to treat pseudoarthrosis of the periacetabular osteotomy segment. Therefore, we report a case of pseudoarthrosis in the osteotomy segment after periacetabular osteotomy. The patient was treated using modified total hip arthroplasty and achieved a favorable short-term outcome. Case presentation A 62-year-old Japanese woman was diagnosed with bilateral acetabular dysplasia at the age of 50 years, and underwent right and left periacetabular osteotomy at the ages of 52 and 55 years, respectively. When she was 61-years old, she experienced repeated episodes of left coxalgia during walking, with increasing pain at rest, and subsequently visited our department. Plain radiography and computed tomography of her left hip joint confirmed pseudoarthrosis of the periacetabular osteotomy segment. In addition, narrowing of her left hip joint space was observed, which indicated advanced osteoarthritis of the hip. Therefore, she underwent left total hip arthroplasty when she was 62-years old. During the surgery, fibrous fusion of the periacetabular osteotomy segment was confirmed via fluoroscopy, although no abnormal mobility was observed. Thus, the osteotomy segment was fixed with one absorbable screw and two bone pegs (which were prepared using allogeneic bone), and the acetabular cup was fixed using cement. Her postoperative course was generally favorable and bone fusion of the periacetabular osteotomy segment was confirmed at 3 years and 6 months after surgery. Her modified Harris hip score was 43 before the surgery and had improved to 90 at the final follow-up. Conclusions Modified total hip arthroplasty was successfully used to treat osteoarthritis of the hip and pseudoarthrosis of the periacetabular osteotomy segment. This procedure achieved pseudoarthrosis region bone fusion and a favorable postoperative outcome.

We present a rare concurrence of enchondroma and periosteal chondroma in the right distal fibula that mimicked chondrosarcoma in a 13-year-old boy. Radiographs and CT scans showed a periosteal lesion producing saucerization without periosteal reaction and calcification in the distal metaphysis of the right fibula. MRI showed an intramedullary lesion adjacent to the periosteal lesion, although it was invisible at CT. There was no cortical breach on imaging and gross examination. Because both lesions represented benign cartilaginous tumors on histology, concurrent periosteal chondroma and enchondroma of the fibula was diagnosed. This combination in the same bone in a patient without enchondromatosis is exceedingly rare. Such imaging features may be confused with those of chondrosarcoma.