Analysis of proteins released from osteoarthritic cartilage by compressive loading.

In osteoarthritis (OA), synovial pathology may be induced by proteins released from degenerated cartilage. This study was conducted to identify the proteins released from OA cartilage. OA cartilage was obtained from OA knees at macroscopically preserved areas (PRES) and degenerated areas (DEG), while control cartilage (CONT) was collected from non-arthritic knees. Released proteins were obtained from these cartilage samples by repeatedly applying compressive loading, which simulated loading on cartilage in vivo. The released proteins were analyzed comprehensively by antibody array analyses and a quantitative proteomic analysis. For several proteins, the exact amounts released were determined by Luminex assays. The amount of active TGF-ß that was released was determined by an assay using genetically-engineered HEK cells. The results of the antibody array and proteomic analyses revealed that various biologically active proteins are released from OA cartilage, particularly from DEG, by loading. The Luminex assay confirmed that several alarmins, complement proteins C3a and C5a, and several angiogenic proteins including FGF-1, FGF-2 and VEGF-A were released in greater amounts from DEG than from CONT. The HEK cell assay indicated that active TGF-ß was released from DEG at biologically significant levels. These findings may be helpful in understanding the pathology of OA.

Erratum for Lumbar Fusion including Sacroiliac Joint Fixation Increases the Stress and Angular Motion at the Hip Joint: A Finite Element Study.

[This corrects the article DOI: 10.22603/ssrr.2021-0231.].

Lumbar Fusion including Sacroiliac Joint Fixation Increases the Stress and Angular Motion at the Hip Joint: A Finite Element Study.

Introduction: Adult spinal fusion surgery improves lumbar alignment and patient satisfaction. Adult spinal deformity surgery improves saggital balance not only lumbar lesion, but also at hip joint coverage. It was expected that hip joint coverage rate was improved and joint stress decreased. However, it was reported that adjacent joint disease at hip joint was induced by adult spinal fusion surgery including sacroiliac joint fixation on an X-ray study. The mechanism is still unclear. We aimed to investigate the association between lumbosacral fusion including sacroiliac joint fixation and contact stress of the hip joint. Methods: A 40-year-old woman with intact lumbar vertebrae underwent computed tomography. A three-dimensional nonlinear finite element model was constructed from the L4 vertebra to the femoral bone with triangular shell elements (thickness, 2 mm; size, 3 mm) for the cortical bone's outer surface and 2-mm (lumbar spine) or 3-mm (femoral bone) tetrahedral solid elements for the remaining bone. We constructed the following four models: a non-fusion model (NF), a L4-5 fusion model (L5F), a L4-S1 fusion model (S1F), and a L4-S2 alar iliac screw fixation model (S2F). A compressive load of 400 N was applied vertically to the L4 vertebra and a 10-Nm bending moment was additionally applied to the L4 vertebra to stimulate flexion, extension, left lateral bending, and axial rotation. Each model's hip joint's von Mises stress and angular motion were analyzed. Results: The hip joint's angular motion in NF, L5F, S1F, and S2F gradually increased; the S2F model presented the greatest angular motion. Conclusions: The average and maximum contact stress of the hip joint was the highest in the S2F model. Thus, lumbosacral fusion surgery with sacroiliac joint fixation placed added stress on the hip joint. We propose that this was a consequence of adjacent joint spinopelvic fixation. Lumbar-to-pelvic fixation increases the angular motion and stress at the hip joint.

Evaluation of bone strength using finite-element analysis in patients with ossification of the posterior longitudinal ligament.

BACKGROUND CONTEXT: Patients with ossification of the posterior longitudinal ligament (OPLL) are often reported to have increased bone mineral density (BMD). The bone strength of the proximal femur measured by quantitative computed tomography-based finite element analysis (QCT/FEA) is reportedly comparable between healthy subjects with and without OPLL. However, the bone strength in symptomatic OPLL patients remains unknown. PURPOSE: To investigate bone strength measured by QCT/FEA in symptomatic patients with OPLL. STUDY DESIGN/SETTING: A single-center prospective observational study. PATIENT SAMPLE: A total of 157 patients with cervical or thoracic compressive myelopathy were included in the study. OUTCOME MEASURES: We analyzed patients' characteristics, Japanese Orthopedic Association (JOA) score, serum laboratory tests including calcium (Ca), inorganic phosphate (Pi), and bone turnover markers, BMD of the proximal femur and lumbar spine measured using dual-energy X-ray absorptiometry, and predicted bone strength (PBS) of the proximal femur and lumbar spine measured using QCT/FEA. METHODS: Eligible patients were divided into the non-OPLL and OPLL groups. We compared the patients' characteristics, JOA scores, laboratory data, BMD, and PBS of the proximal femur and lumbar spine between the non-OPLL and OPLL groups among total, male, and female patients by performing Fisher's exact test for categorical variables and the unpaired t test for continuous variables. Then, we used the inverse probability weighted logistic regression model after calculating propensity scores to compare the bone metabolism-associated markers, BMD, and PBS measurements between the groups. RESULTS: Among the eligible 157 patients, 68 were in the non-OPLL group and 89 were in the OPLL group. Compared with the non-OPLL group, the OPLL group had a significantly younger age and higher BMI in the total, male, and female patients. The JOA scores in the total and female patients were significantly higher in the OPLL group than in the non-OPLL group. The OPLL group showed significantly lower Ca levels in the female patients and significantly lower Pi levels in the total or male patients compared with the non-OPLL group in the inverse probability weighting method. The BMD of the proximal femur and lumbar spine and the PBS of the proximal femur were significantly higher in the OPLL group than in the non-OPLL group. There were no significant differences in the PBS and BMD between the male subgroups. However, the BMD and PBS of the proximal femur and lumbar spine were significantly higher in the OPLL females than in the non-OPLL females. CONCLUSIONS: Hyperostosis of the posterior longitudinal ligament in OPLL was associated with higher bone strength by QCT/FEA, especially in female OPLL patients.

Fracture of ossified Achilles tendons: A review of cases.

Fracture of an ossification of the Achilles tendon (OAT) is a rare entity, and its etiology, pathology, and treatment remain unclear. We reviewed and scrutinized 18 cases (16 articles) of the fracture of an OAT. The most common etiologies of the ossifications include previous surgery and trauma. The fractures often occur without any trigger or with minimal trigger. The long, > 5 cm, ossification in the body of the Achilles tendon may have a higher risk of fracture. The OAT itself is often asymptomatic; however, its fracture causes severe local pain, swelling, and weakness of plantar flexion, which forces patients to undergo aggressive treatments. Regarding the treatments of the fractures, nonoperative treatment by immobilizing ankle joint could be an option for elderly patients. However, because it often cannot produce satisfactory results in younger patients, surgical treatment is typically recommended. Excision of the fractured mass and repairing the tendon is applicable if the remnant is enough. If there is a defect after the excision, reconstruction with autologous grafts or adjacent tendon transfer is performed. Gastrocnemius fascia turndown flap, hamstring tendon and tensor fascia lata are used as autologous grafts, whereas peroneus brevis and flexor hallucis longus tendons are used for the tendon transfer. If the fracture of an OAT is treated properly, the functional result will be satisfactory.

The attenuation of insulin-like growth factor signaling may be responsible for relative reduction in matrix synthesis in degenerated areas of osteoarthritic cartilage.

BACKGROUND: In osteoarthritis (OA), cartilage matrix is lost gradually despite enhanced matrix synthesis by chondrocytes. This paradox may be explained, at least partly, by reduced chondrocyte anabolism in degenerated area of OA cartilage. However, to date, it is not known why chondrocyte anabolism is suppressed in those areas. METHODS: Cartilage was obtained from control knees and end-stage OA knees in macroscopically preserved areas and degenerated areas, and gene expression was analyzed in respective regions of cartilage using laser capture microdissection and qPCR. For the cartilage protein analysis, cartilage was obtained from preserved areas and degenerated areas of OA knees in pairs, and proteins were extracted using urea buffer. Protein concentrations were determined by Luminex and compared between the areas. Cartilage explants prepared from preserved areas and degenerated areas of OA knees were cultured in the presence or absence of an AKT inhibitor, and the gene expression was evaluated by qPCR. Finally, the expression of SP1 was evaluated in OA and control cartilage, and the significance of Sp1 on the expression of IGF1R and IRS1 was investigated in experiments using primary cultured chondrocytes. RESULTS: Within OA cartilage, the expression of IGF-1, IGF-2, IGF1R and IRS1 was reduced in degenerated areas compared to preserved areas, while the expression of all six IGF-binding protein genes examined was enhanced in the former areas. Consistent results were obtained by a protein analysis. In explant culture, the inhibition of AKT signaling abrogated the abundant matrix gene expression in the preserved areas over the degenerated areas, indicating that suppressed matrix synthesis in degenerated areas may be ascribed, at least partly, to attenuated IGF signaling. Within OA cartilage, the expression of Sp1 was considerably reduced in severely degenerated areas compared to preserved areas, which correlated well with the expression of IGF1R and IRS1. In experiments using primary cultured chondrocytes, the expression of IGF1R and IRS1 was enhanced by the induction of Sp1 expression and reduced by the suppression of Sp1 expression. CONCLUSIONS: The results of this study suggest that attenuated IGF signaling may be responsible, at least partly, for the reduced matrix synthesis in degenerated areas of OA cartilage.

Evaluations of daily teriparatide using finite-element analysis over 12 months in rheumatoid arthritis patients.

INTRODUCTION: The objective of this study was to quantitatively evaluate the effects of daily teriparatide on rheumatoid arthritis patients using predicted bone strength (PBS) assessed by quantitative computed tomography-based finite-element analysis (QCT/FEA) and using bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DXA), and to prospectively investigate clinical determinants associated with PBS and BMD increases. MATERIALS AND METHODS: Participants comprised 39 patients (mean age, 69 years; disease activity score assessing 28 joints with CRP, 3.0; previous vertebral fractures, 82%) enrolled in this study. BMD by DXA and PBS by QCT/FEA of lumbar spine (LS) and proximal femur were measured at baseline, and after 6 and 12 months. In the groups showing increases in these values, variables that may have affected these increases were evaluated using univariate logistic regression analysis. RESULTS: Daily teriparatide treatment significantly increased not only LS BMD, but also LS PBS in RA patients with osteoporosis after both 6 and 12 months of treatment. Increases in N-terminal type I procollagen propeptide (PINP) at 1 and 3 months were significantly associated with increased LS PBS at 12 months according to univariate logistic regression analysis. The threshold value for increased PINP at 1 month for increased PBS at 12 months was 75 µg/L. CONCLUSIONS: Increased LS PBS at 12 months was predicted by increased PINP at 1 month from baseline.

Prediction of the pathological fracture risk during stance and fall-loading configurations for metastases in the proximal femur, using a computed tomography-based finite element method.

BACKGROUND: It is important to assess the fracture risk associated with metastasis in the proximal femur. The study aimed to clarify the effect of tumor location on the risk of pathological fracture of the proximal femur and investigate the fracture risk not only in the stance-loading configuration (SC), but also in the fall-loading configuration (FC) using a computed tomography (CT)-based finite element (FE) method based on a simulated metastatic model. METHODS: The axial CT scans of the proximal femora of non-osteoporotic healthy men (n = 4; age range, 42-48 years) and osteoporotic post-menopausal women (n = 4; age range, 69-78 years) were obtained with a calibration phantom, from which the three-dimensional FE models were constructed. A single 15-mm-diameter spherical void simulating a tumor was created at various locations from the neck to subtrochanteric level. Nonlinear FE analyses were performed. RESULTS: The mean predicted fracture loads without spherical voids in the SC were 7700 N in men and 4370 N in women. With the void at the medial femoral neck and in the region anteromedial to lesser trochanter, the mean predicted fracture load significantly reduced to 51.3% and 59.4% in men and 34.1% and 64.5% in women, respectively. The mean predicted fracture loads without a spherical void in the FC were 2500 N in men and 1862 N in women. With the void at the medial and posterior femoral neck, the predicted fracture load was significantly reduced to 65.7% and 79.7% in men and 48.3% and 65.4% in women, respectively. CONCLUSIONS: These results showed that the risk of pathologic fracture was quite high in both the SC and FC when the lytic lesion existed along the principal compressive trabecular trajectory or posterior neck. Prophylactic intervention should be considered for metastases at these locations.

Assessing joint destruction in the knees of patients with rheumatoid arthritis by using a semi-automated software for magnetic resonance imaging: therapeutic effect of methotrexate plus etanercept compared with methotrexate monotherapy.

OBJECTIVES: To evaluate the prevention of knee joint destruction and clinical efficacy of methotrexate (MTX) plus etanercept (ETN) compared with MTX monotherapy in patients with rheumatoid arthritis (RA) by using semi-automated software for magnetic resonance imaging (MRI) scan analysis. MATERIALS AND METHODS: This study enrolled patients with active moderate-to-severe RA who displayed an inadequate response to oral MTX at screening. Patients were assigned to receive either MTX plus ETN or MTX monotherapy (≥10 mg/week). The primary endpoint was the quantitative knee cartilage volume using our software developed for MRI scan analysis. RESULTS: A total of 18 female patients were enrolled in this study and allocated to the MTX + ETN group (n = 9) or the MTX monotherapy group (n = 9). At 52 weeks, the quantitative knee cartilage volume was significantly reduced compared with baseline in both groups (MTX plus ETN group: 2.3 ± 2.3 cm3; MTX monotherapy group: 2.4 ± 1.6 cm3); however, the difference was not significant. CONCLUSION: The semi-automated software for MRI scan analysis can reveal useful and potentially clinically important information about the characteristics of knee joint destruction in patients with RA.

[New methods for the evaluation of bone quality. Bone quality evaluation by QCT.]

In osteoporosis, the risk of fracture is influenced by decrease of bone mineral density and deterioration of bone quality. The latter includes deterioration of the material and structural properties of bone. These changes arise from the influence of changes in hormonal balance, aging, changes in mechanical stress, lifestyle-related diseases, etc. on bone absorption and bone formation as the coupled functions of osteoclasts and osteoblasts. Deterioration of bone quality occurs at various levels ranging from the molecular to the tissue level, or even at the individual level, and leads to an increased fracture risk. In this chapter, bone quality evaluation using quantitative computed tomography is discussed among evaluation methods of various fracture risk.

The effect of cartilage degeneration on ultrasound speed in human articular cartilage.

OBJECTIVES: We investigated the effect of cartilage degeneration on ultrasound speed in human articular cartilage in vitro. METHODS: Ultrasound speed was calculated by the time-of-flight method for 22 femoral condyle osteochondral blocks obtained from osteoarthritis patients. In parallel, histological evaluation of specimens was performed using the modified Mankin and OARSI scores. RESULTS: The mean ultrasound speed was 1757 ± 109 m/s. Ultrasound speed showed significant negative correlation with OARSI score, and a decreasing tendency with high Mankin scores. Good correlation was found between the optically measured and the calculated cartilage thickness. CONCLUSION: Our results show that articular cartilage degeneration has relatively little influence on ultrasound speed. In addition, morphological evaluation of articular cartilage using a preset value of ultrasound speed seems to offer relatively accurate results.

The impact of joint disease on the Modified Health Assessment Questionnaire scores in rheumatoid arthritis patients: A cross-sectional study using the National Database of Rheumatic Diseases by iR-net in Japan.

OBJECTIVES: To investigate the effect of bilateral and unilateral joint disease on the Modified Health Assessment Questionnaire (MHAQ) scores and the differences in joint weighting in rheumatoid arthritis patients. METHODS: A total of 9212 subjects from the Japanese nationwide cohort database NinJa, 2011, were analyzed. The presence or absence of disease in each joint, including swelling and/or tenderness, was investigated. The correlations between bilateral and unilateral disease in each joint and MHAQ scores were investigated using multivariable logistic regression analysis. RESULTS: The patients' mean age and disease duration was 63.2 and 12.2 years, respectively. The Disease Activity Score-28 was 3.3. The odds ratios of physical impairment according to the MHAQ using multivariable logistic regression models for bilateral and unilateral joints, respectively, were: shoulder, 4.0 and 1.8; elbow, 2.6 and 1.8; wrist, 1.9 and 1.5; hip, 1.7 and 3.0; knee, 2.6 and 1.9; ankle, 2.3 and 2.0, finger, 1.4 and 1.2; and toe, 1.0 and 1.1. The shoulder, elbow, wrist, knee, and ankle had a significant effect on physical impairment. CONCLUSIONS: The MHAQ score was significantly affected by shoulder, elbow, wrist, knee, and ankle joint disease. Furthermore, bilateral disease tended to have a greater effect on physical impairment than unilateral disease.

Prediction of proximal femur strength by a quantitative computed tomography-based finite element method--Creation of predicted strength data of the proximal femur according to age range in a normal population.

OBJECTIVE: The objective of this study was to investigate the factors that affect the predicted bone strength of proximal femur in Japanese population. METHODS: Participants (552 men and 273 women) in a health checkup program with computed tomography (CT) at the University of Tokyo Hospital were enrolled in this study. Three-dimensional finite element models of the proximal femur were constructed from CT data of the participants with simultaneous scans of a calibration phantom containing hydroxyapatite rods. Multiple regression analysis was performed to analyze the relationship between the predicted bone strength and clinical factors. RESULTS: Average predicted strength of proximal femur was lower in women than in men in all age ranges. Predicted bone strength in women under both stance and fall configurations significantly decreased with age, and that in men had the tendency to decrease with age. Body weight positively affected the predicted bone strength in both men and women. CONCLUSIONS: This is the first cross-sectional analysis of the predicted bone strength of the proximal femur in Japanese population of wide age range. Age and body weight critically affected bone strength of proximal femur determined by quantitative CT-based finite element method, in particular in women, under both stance and fall configurations.

Prevalence of total knee arthroplasty and its predictive factors in Japanese patients with rheumatoid arthritis: Analysis using the NinJa cohort.

OBJECTIVES: The aim of this study was to clarify the prevalence and the predictive factors for undergoing total knee arthroplasty (TKA) among patients with rheumatoid arthritis (RA). METHODS: The data of 1,134 patients with RA who were enrolled in the Japanese nationwide cohort database NinJa in 2003 and consecutively followed up until 2009 were analyzed. RESULTS: Seventy-six patients underwent TKA during the observation period. The yearly progression of the modified Health Assessment Questionnaire or mHAQ score from 2003 to 2004, but not the yearly progression of the Disease Activity Score in 28 Joints or DAS28 or patient visual analog scale (VAS) score, was significantly higher in the patients who underwent TKA than those who did not. Multivariate analysis showed that knee involvement in the disease, high Steinbrocker stage (III or IV), and high patient VAS score at the time of enrollment were powerful predictive factors, with hazard ratios of 4.01, 3.71, and 1.20, respectively. According to survival analysis with TKA as an endpoint, patients with knee involvement in the disease at the time of enrollment had a significantly worse 5-year survival rate than did those without knee involvement (83.5% vs. 97.0%, respectively). CONCLUSION: Several factors were elucidated as predictive factors for undergoing TKA among patients with RA.

Successful treatment of a fracture of a huge Achilles tendon ossification with autologous hamstring tendon graft and gastrocnemius fascia flap: a case report.

BACKGROUND: Fracture of an ossified Achilles tendon is a rare entity, and no standard treatment has been established. This is the first report to describe the use of a hamstring tendon graft and gastrocnemius fascia flap for Achilles tendon reconstruction. CASE PRESENTATION: We present the case of a 50-year-old woman with fracture of an ossified Achilles tendon. She presented to our clinic with acute right hindfoot pain, which started suddenly while going up the stairs. Plain radiography and magnetic resonance imaging revealed a massive ossification on the right Achilles tendon extending over 14 cm in length; the ossification was fractured at 5 cm proximal to the calcaneus insertion. Surgical treatment included removal of the ossified tendon and reconstruction with an autologous hamstring tendon graft and gastrocnemius fascia flap. One year after surgery, she was able to walk with little pain or discomfort and to stand on her right tiptoe. CONCLUSION: Our novel surgical procedure may be useful in the treatment of fractured ossified Achilles tendons and large Achilles tendon defects.

[Anti-osteoporosis drugs based on the guidelines for the Prevention and Treatment of Osteoporosis (2011 edition) ].

The aim of osteoporosis treatment is to reduce fracture risk. Many kinds of anti-osteoporosis drugs are available in these days, and most of them increase bone mineral density and reduce the risk of fractures. Japanese 2011 guidelines for prevention and treatment of osteoporosis documents the recommendation level of each osteoporosis drugs. It is important to select drugs appropriate for each osteoporosis patient considering the mechanisms of drug action and their clinical efficiency.

Development of femoral bone fracture model simulating muscular contraction force by pneumatic rubber actuator.

In femoral fracture reduction, orthopedic surgeons must pull distal bone fragments with great traction force and return them to their correct positions, by referring to 2D-fluoroscopic images. Since this method is physically burdensome, the introduction of robotic assistance is desirable. While such robots have been developed, adequate control methods have not yet been established because of the lack of experimental data. It is difficult to obtain accurate data using cadavers or animals because they are different from the living human body's muscle characteristics and anatomy. Therefore, an experimental model for simulating human femoral characteristics is required. In this research, human muscles are reproduced using a McKibben-type pneumatic rubber actuator (artificial muscle) to develop a model that simulates typical femur muscles using artificial muscles.

[Secondary osteoporosis or secondary contributors to bone loss in fracture. Therapeutic intervention of rheumatoid arthritis bone loss].

In rheumatoid arthritis (RA) , the osteoclast pathway is activated by abnormal immune conditions accompanied by chronic inflammation resulting in periarticular osteoporosis and local bone destruction around joints. In addition, multiple factors lead to systemic osteoporosis, including reduced physical activity and pharmacotherapies such as steroids. These conditions cause decreased bone mineral density and bone quality, and expose patients to an increased risk of fracture. When treating patients with RA osteoporosis, it is important to improve systemic osteoporosis using anti-osteoporotic agents, and to suppress fracture risk by controlling inflammation (which is associated with periarticular osteoporosis and bone destruction) with a combination of disease-modifying anti-rheumatic drugs or biological agents.

[Bone structure in rheumatoid arthritis].

In rheumatoid arthritis (RA) , the osteoclast pathway is activated by abnormal immune conditions accompanied by chronic inflammation, resulting in periarticular osteoporosis and local bone destruction around joints. In addition, multiple factors, including reduced physical activity and pharmacotherapies such as steroids, lead to systemic osteoporosis. These conditions cause decreasing bone mineral density and deterioration of bone quality, and expose patients to increased risk of fracture. Understanding the bone structures of RA and evaluating fracture risk are central to the treatment of RA.

[Rheumatoid arthritis and bone -periarticular and systemic bone loss-].

In rheumatoid arthritis (RA) , the osteoclast pathway is activated by an abnormal immune condition accompanied by chronic inflammation, resulting in periarticular osteoporosis and local bone destruction around joints. In addition, multiple factors including pharmacotherapies such as steroids, and reduced physical activity, lead to systemic osteoporosis. These conditions expose patients to increased fracture risk. In RA treatment, it is important to achieve suppression of fracture risk by controlling inflammation, which is associated with periarticular osteoporosis and bone destruction, using disease-modifying anti-rheumatic drugs or biologic agents and by improving systemic osteoporosis using anti-osteoporotic agents.