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Fractures associated with osteoporosis are a major public health concern. Current treatments for fractures are limited to surgery or fixation, leading to long‐term bedrest, which is linked to increased mortality. Alternatively, utilization of physical agents has been suggested as a promising therapeutic approach for fractures. Here, we examined the effects of ultrasound, radial extracorporeal shock waves, and electrical stimulation on normal or osteoporotic fracture healing. Femoral bone defects were created in normal or ovariectomized rats. Rats were divided into four groups: untreated, and treated with ultrasound, shock waves, or electrical stimulation after surgery. Samples were collected at 2 or 4 weeks after surgery, and the healing process was evaluated with micro‐CT, histological, and immunohistochemical analyses. Ultrasound at intensities of 0.5 and 1.0 W/cm2, but not 0.05 W/cm2, accelerated new bone formation. Shock wave exposure also increased newly formed bone, but formed abnormal periosteal callus around the defect site. Conversely, electrical stimulation did not affect the healing process. Ultrasound exposure increased osteoblast activity and cell proliferation and decreased sclerostin‐positive osteocytes. We demonstrated that higher‐intensity ultrasound and radial extracorporeal shock waves accelerate fracture healing, but shock wave treatment may increase the risk of periosteal callus formation. [ABSTRACT FROM AUTHOR]

This study aimed to examine the effects of an episode of in vivo cyclic loading on rat knee articular cartilage (AC) under medium‐term observation, while also investigating relevant factors associated with the progression of post‐traumatic osteoarthritis (PTOA). Twelve‐week‐old Wistar rats underwent one episode comprising 60 cycles of 20 N or 50 N dynamic compression on the right knee joint. Spatiotemporal changes in the AC after loading were evaluated using histology and immunohistochemistry at 3 days and 1, 2, 4, and 8 weeks after loading (n = 6 for each condition). Chondrocyte vitality was assessed at 1, 3, 6, and 12 hours after loading (n = 2 for each condition). A localized AC lesion on the lateral femoral condyle was confirmed in all subjects. The surface and intermediate cartilage in the affected area degenerated after loading, but the calcified cartilage remained intact. Expression of type II collagen in the lesion cartilage was upregulated after loading, whereas the superficial lubricin layer was eroded in response to cyclic compression. However, the distribution of superficial lubricin gradually recovered to the normal level 4 weeks after loading‐induced injury. We confirmed that 60 repetitions of cyclic loading exceeding 20 N could result in cartilage damage in the rat knee. Endogenous repairs in well‐structured joints work well to rebuild protective layers on the lesion cartilage surface, which may be the latent factor delaying the progression of PTOA. [ABSTRACT FROM AUTHOR]

ABSTRACT This cross-sectional study examined the relationship of flat feet with knee pain, disability, and physical performance in patients with knee osteoarthritis (OA). Orthopedic clinic participants ( n = 95; age 61-91 years; 68.4% women) with Kellgren-Lawrence (K/L) grade ≥1 in the medial compartment underwent evaluation of navicular height and foot length for flat feet. Knee pain intensity, disability, and physical performance were evaluated using the Japanese Knee Osteoarthritis Measure, 10-m walk, timed up and go, and five-repetition chair stand tests. Of the 95 enrolled patients, 24 (25.3%) had bilateral flat feet, and significantly higher knee pain compared to patients with no flat feet (11.3 ± 8.23 points vs. 6.58 ± 6.37 points; p = 0.043). A ordinal logistic regression analysis showed that bilateral flat feet were significantly associated with increased knee pain (proportional odds ratio: 5.48, 95% confidence interval: 1.96, 15.3; p = 0.001) compared with no flat feet, adjusted for age, sex, body mass index, and tibiofemoral joint K/L grade, which is consistent across various different cutoffs of the definition of flat feet. Physical performance was similar between patients with and without bilateral flat feet. The presence of unilateral flat feet was not significantly associated with any outcome measures. These findings indicate that bilateral, but not unilateral, flat feet are associated with worse knee pain. A prospective study investigating a causal relationship between bilateral flat feet posture and knee pain as well as disability would be of particular interest to verify the potential adverse effect of altered foot posture. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2490-2498, 2017. [ABSTRACT FROM AUTHOR]

An understanding of the articular cartilage degenerative process is necessary for the prevention and treatment of joint disease. The present study aimed to examine how long-term immobilization-induced cartilage degeneration is aggravated by remobilization. Sixty 8-week-old male Wistar rats were used in this study. The unilateral knee joint was immobilized using an external fixator for 8 weeks. The rats were killed at 0 and 3 days, and at 1, 2, 4 and 8 weeks after removing the fixator. After the rats were killed, the maximum knee extension angles were measured. Histological sections at the medial mid-condylar region (non-contact, transitional and contact regions of the femur and tibia) were prepared and scored. The cartilage thickness and number of chondrocytes were measured, and CD44 and Col2-3/4c expression levels were assessed immunohistochemically. The histological assessment revealed progressive aggravation of cartilage degeneration in the transitional region, with a decreased number of chondrocytes and CD44-positive chondrocytes as well as poor scoring over time, particularly in the tibia. Cyst formation was confirmed in the transitional region of the tibia at 8 weeks post-remobilization. The cartilage thickness in the transitional region was thicker than that in the contact region, particularly in the tibia. Col2-3/4c expression was observed in the non-contact and transitional regions, and the knee extension angle was recovered. In conclusion, immobilization-induced cartilage degeneration was aggravated by remobilization over time in the transitional region, followed by observations of a decreased number of chondrocytes and morphological disparity between different cartilage regions. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical impact in knee osteoarthritis (OA) of coexisting patellofemoral (PF) joint OA (PFOA) in Japanese patients with medial tibiofemoral (TF) joint OA (TFOA).Methods: Patients with medial knee OA (n = 143) were enrolled. The radiographic severity of the TF and PF joints, anatomic axis angle of the TF joint, patellar alignment, trochlear morphology, patellar height, and passive range of motion (ROM) of the painful knee were evaluated. Additionally, the Japanese Knee Osteoarthritis Measure (JKOM) was used to investigate the association between the presence of PFOA and clinical symptoms.Results: PFOA was present in 98 of 143 patients (68.5%) with medial knee OA. Quantile regression analysis revealed that coexisting PFOA was associated with the pain-related subcategory of the JKOM. Furthermore, multiple logistic regression analysis showed that coexisting PFOA was associated with higher odds of reporting knee pain on using stairs while ascending (odds ratio [OR] 4.81 [95% confidence interval (95% CI) 1.73, 14.3]) and descending (OR 3.86 [95% CI 1.44, 10.8]). A more varus knee alignment and lower knee flexion ROM, which are features of patients with coexisting PFOA, were associated with knee pain while ascending/descending stairs. However, patellar alignment, trochlear morphology, and patellar height were not significantly associated with knee pain.Conclusion: PFOA coexisting with medial knee OA was associated with worse clinical symptoms, particularly while ascending/descending stairs, although patellar alignment did not contribute to reporting knee pain. Further studies that include evaluation of the PF joint are warranted to develop a basis for an optimal intervention based on compartmental involvement. [ABSTRACT FROM AUTHOR]

Objective. To investigate the association between knee pain during gait and 4 clinical phenotypes based on static varus alignment and varus thrust in patients with medial knee osteoarthritis (OA). Methods. Patients in an orthopedic clinic (n5266) diagnosed as having knee OA (Kellgren/Lawrence [K/L] grade ≥1) were divided into 4 phenotype groups according to the presence or absence of static varus alignment and varus thrust (dynamic varus): no varus (n5173), dynamic varus (n517), static varus (n550), and static varus1dynamic varus (n526).The knee range of motion, spatiotemporal gait parameters, visual analog scale scores for knee pain, and scores on the Japanese Knee Osteoarthritis Measure were used to assess clinical outcomes. Multiple logistic regression analyses identified the relationship between knee pain during gait and the 4 phenotypes, adjusted for possible risk factors, including age, sex, body mass index, K/L grade, and gait velocity. Results. Multiple logistic regression analysis showed that varus thrust without varus alignment was associated with knee pain during gait (odds ratio [OR] 3.30, 95% confidence interval [95% CI] 1.08-12.4), and that varus thrust combined with varus alignment was strongly associated with knee pain during gait (OR 17.1, 95% CI 3.19- 320.0). Sensitivity analyses applying alternative cutoff values for defining static varus alignment showed comparable results. Conclusion. Varus thrust with or without static varus alignment was associated with the occurrence of knee pain during gait. Tailored interventions based on individual malalignment phenotypes may improve clinical outcomes in patients with knee OA. [ABSTRACT FROM AUTHOR]

ABSTRACT To date, there have been few studies on how temperature affects the phenotype and metabolism of human chondrocytes. Thus, the purpose of this study was to elucidate the effects of culture temperature on chondrocyte redifferentiation and extracellular matrix (ECM) formation using dedifferentiated mature human chondrocytes in vitro. Dedifferentiated chondrocytes were cultured in a pellet culture system for up to 21 days. The pellets were randomly divided into three groups with different culture temperature (32, 37, and 41°C). Chondrocyte redifferentiation and ECM formation were evaluated by wet weight, messenger ribonucleic acid (mRNA), histological, and biochemical analyses. The results showed that the wet weight and the mRNA expressions of collagen type II A1 and cartilage oligomeric matrix protein at 37°C were higher than the corresponding values at 32°C. The histological and biochemical analyses revealed that the syntheses of type II collagen and proteoglycan were promoted at 37°C compared to those at 32°C, whereas they were considerably inhibited at 41°C. In conclusion, the results obtained herein indicated that temperature affects chondrocyte redifferentiation and ECM formation, and modulation of temperature might thus represent an advantageous means to regulate the phenotype and biosynthetic activity of chondrocytes. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:633-639, 2015. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine the ultrastructural changes of surface cartilage collagen fibers, which differ by region and the length of the experimental period in an immobilization model of rat. Male Wistar rats were randomly divided into histological or macroscopic and ultrastructural assessment groups. The left knees of all the animals were surgically immobilized by external fixation for 1, 2, 4, 8 or 16 weeks ( n = 5/time point). Sagittal histological sections of the medial mid-condylar region of the knee were obtained and assessed in four specific regions (contact and peripheral regions of the femur and tibia) and two zones (superficial and deep). To semi-quantify the staining intensity of the collagen fibers in the cartilage, picrosirius red staining was used. The cartilage surface changes of all the assessed regions were investigated by scanning electron microscopy ( SEM). From histological and SEM observations, the fibrillation and irregular changes of the cartilage surface were more severe in the peripheral region than in the contact region. Interestingly, at 16 weeks post-immobilization, we observed non-fibrous structures at both the contact and peripheral regions. The collagen fiber staining intensity decreased in the contact region compared with the peripheral region. In conclusion, the alteration of surface collagen fiber ultrastructure and collagen staining intensity differed by the specific cartilage regions after immobilization. These results demonstrate that the progressive degeneration of cartilage is region specific, and depends on the length of the immobilization period. [ABSTRACT FROM AUTHOR]

ABSTRACT The purpose of this study was to analyze histologic, biochemical, and biomechanical differences between zonal, regional, and anatomic locations of porcine menisci. We evaluated six menisci removed from pigs. Medial and lateral menisci were divided into three regions: anterior, middle, and posterior. In each portion, the central zone (CZ) and peripheral zone (PZ) were examined histologically (hematoxylin & eosin, safranin O/Fast green, and picrosiriusred staining), using scanning electron microscopy, biochemically (hydroxyproline assay for collagen content and dimethylmethylene blue assay for glycosaminoglycan [GAG] content), and biomechanically (compression testing). Collagen content in the CZ was lower than that in the PZ. GAG content in the CZ was higher than that in the PZ. GAG content in the PZ of the posterior portion was significantly higher than that in the anterior and middle portions. Compression strength in the CZ was higher than that in the PZ. The differences in cellular phenotype, vascular penetration, and ECM not only between CZ and PZ but also among the anterior, middle, and posterior portions were clarified in the immature porcine meniscus. This result helps further our understanding of the biological characteristic of the meniscus. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1602-1611, 2014. [ABSTRACT FROM AUTHOR]

ABSTRACT The aim of this study was to elucidate whether the levels of serum biomarkers reflect the progression of osteoarthritis (OA) induced by different levels of exercise. Thirty-five Wistar rats subjected to anterior cruciate ligament transaction (ACLT) were divided into three groups: Control, moderate running, and intense running. Twelve rats (moderate running without ACLT) were allocated as a naive group. Running was performed on a motorized treadmill, at a speed of 18 m/min for 30 min/day (moderate and naive) or 60 min/day (intense) for 3 days per week. After 2 or 4 weeks, OA histopathology in the knees was evaluated using the Osteoarthritis Research Society International (OARSI) score, and the serum levels of cleaved collagen type II (C2C) and procollagen II C-propeptide (CPII) were analyzed. The OARSI score deteriorated in the intense running group after 2 weeks and the serum C2C/CPII ratio suggested the development of OA. At 4 weeks, the C2C/CPII ratio suggested there would be deterioration in the OARSI score but the score did not differ significantly between the moderate and intense running groups. C2C/CPII ratio had 13-25% correlation with the OARSI histological score. Thus, in rat experimental OA, the OARSI score could be partially predicted by the C2C/CPII ratio as a serum biomarker of OA. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1026-1031, 2013 [ABSTRACT FROM AUTHOR]

The aim was to use repeat delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) to estimate glycosaminoglycan (GAG) content in reparative cartilage after osteochondral autogenous transfer (OAT). The study group comprised 7 knees of 7 patients that were examined three times by dGEMRIC, at 3, 6, and 12 months using a 1.5 Tesla MRI system in both OAT operated and nonoperated condyles at 90 min after the injection. The gadolinium diethylene triamine pentaacetic acid (Gd-DTPA)2− containing contrast medium (0.2 mmols/kg) was injected intravenously. The mean T1 values of the plug cartilage at 3, 6, and 12 months after OAT was 230 ± 40, 213 ± 31, and 230 ± 23 ms (mean ± SD), respectively. There were differences between the plug and control cartilage at 3 ( p < 0.01) and 12 ( p < 0.05) months after OAT, but not at 6 months ( p = 0.089). No T1 changes were detected between the plug cartilage at the different time points after OAT. The fact that the GAG content of the OAT plugs were maintained for 12-month study period suggest that no major deterioration of load-bearing properties occurs in the cartilage after the OAT. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:221-225, 2012 [ABSTRACT FROM AUTHOR]

The aim of this study was to determine how alendronate (ALN) alters cartilage degeneration and periarticular bone quality in a rabbit anterior cruciate ligament transection (ACLT) model of osteoarthritis (OA). Thirty rabbits underwent an ACLT on the left knee and a sham operation on the right knee. Fifteen rabbits received weekly subcutaneous injections of ALN (0.14 mg/kg) and 15 rabbits (the control [cont] group) received saline. Animal knees were divided into four groups: cont/sham, cont/ACLT, ALN/sham, and ALN/ACLT. Histological, radiological, and immunohistochemical indices were evaluated for each group. Bone volume ratios by micro-computed tomography showed that ALN prevented periarticular bone loss. Histologically, the cont/ACLT group had significantly worse cartilage damage than the cont/sham group 12 weeks after the surgery. However, the ALN/ACLT group had mild cartilage degeneration compared with that of the ALN/sham group. Immunohistochemical analysis showed that ALN suppressed the expression of matrix metalloproteinase-13, interleukin-1β, type-X collagen, vascular endothelial growth factor, and receptor activator of nuclear factor κB ligand in OA cartilage. ALN had a chondroprotective effect in an experimental rabbit model of OA. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1572-1577, 2011 [ABSTRACT FROM AUTHOR]

We previously developed a novel ultrasound assessment system featuring wavelet transform to evaluate the material properties of articular cartilage. We aimed in this study to demonstrate the feasibility of quantitative evaluation of meniscus using ultrasound and to elucidate the relationships between its acoustic, mechanical, and biochemical properties. Meniscal disc specimens from mature pigs were assessed by ultrasound and compression testing, and their correlation was analyzed. A positive correlation was found between the ultrasound signal intensity and apparent Young's modulus ( r = 0.61). Subsequently, the porcine meniscal discs were treated with various enzymes and then characterized by ultrasound, by compression tests, by biochemical analyses, and by histology and immunohistochemistry. The signal intensity was decreased not by hyaluronidase but by collagenase treatment. Hyaluronidase-treated menisci showed a discrepancy between acoustic and mechanical properties, suggesting that the ultrasound reflection could not detect a reduction in proteoglycan content. Also, ultrasound signal intensity could only reflect superficial layers of the material. Several limitations exist at present, and further studies and improvements of the device are required. However, given the noninvasive nature and the requirement of only small equipment, this ultrasound assessment system will be an instrumental diagnostic tool for meniscal function in both research and clinical fields. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:884-893, 2007 [ABSTRACT FROM AUTHOR]