Navigation-Assisted One-Stage Total Knee Arthroplasty With Extra-Articular Corrective Osteotomy for Knee Osteoarthritis With Femoral and Tibial Extra-Articular Deformity: A Case Report.

Background: Knee osteoarthritis (OA) with extra-articular deformity (EAD) is a rare condition for which achieving accurate alignment with total knee arthroplasty (TKA) is difficult. Extra-articular corrective osteotomy may be necessary for severe deformities. Case Presentation: A 76-year-old man underwent TKA for knee OA with EAD due to malunion after fractures of the femur and tibia. The femoral varus and the tibial valgus/recurvatum deformities were mild and corrected by intra-articular osteotomy using navigation (i.e., navigation-assisted standard TKA). However, the femoral antecurvatum deformity was severe, and we performed extra-articular corrective osteotomy simultaneously with TKA. Navigation was used not only for TKA but also for extra-articular corrective osteotomies. The osteotomy site was fixed with a cemented stem and metaphyseal sleeve. The postoperative hip-knee-ankle angle was 1° varus, the femoral implant was implanted at 0.5° varus/0.5° flexion, and the tibial implant was implanted at 0.5° varus/0° posterior slope. Two years after surgery, improvements were obtained in the range of motion from 15°-95° to 0°-110°, the Knee Society Score from 39 to 92 points, and the functional score from 35 to 100 points. Conclusions: One-stage TKA with extra-articular corrective osteotomy achieved good clinical results due to accurate alignment using navigation and firm fixation of the osteotomy site using cemented-stem and metaphyseal sleeve without any fixation devices.

Osteoporosis should be evaluated by bone mineral density at the combination of the lumbar spine and ipsilateral femoral neck in female patients with knee osteoarthritis scheduled for knee arthroplasty: A retrospective observational study.

BACKGROUND: Knee arthroplasty is a well-established surgery with good clinical outcomes. However, periprosthetic fractures and aseptic loosening negatively impact clinical outcomes, and osteoporosis is one of the causes of such complication. Osteoporosis is usually evaluated by bone mineral density of the lumbar spine and hip using dual-energy X-ray absorptiometry (DXA). However, the prevalence of this disease in patients with knee osteoarthritis scheduled for knee arthroplasty may be underestimated due to differences in the measurement sites. This study aimed to determine the appropriate measurement site for DXA that would not miss osteoporosis in female patients with knee osteoarthritis undergoing knee arthroplasty. METHODS: We measured bone mineral density preoperatively in the consecutive 50 female patients with knee osteoarthritis scheduled for knee arthroplasty by dual-energy X-ray absorptiometry at five sites: the lumbar spine, bilateral-total hip, and femoral neck. We then compared the prevalence of osteoporosis among the four combinations of the lumbar spine and single hip site (ipsilateral or contralateral total hip or femoral neck). RESULTS: Osteoporosis prevalence in the combination of the lumbar spine and ipsilateral or contralateral total hip was 32%, and that in the combination of the lumbar spine and contralateral femoral neck was 44%. Notably, the disease's prevalence in the combination of the lumbar spine and ipsilateral femoral neck was 50%, which was significantly higher than that in the other combinations. CONCLUSION: Osteoporosis should be evaluated by bone mineral density in the combination of the lumbar spine and ipsilateral femoral neck in female patients with knee osteoarthritis scheduled for knee arthroplasty.

Knee joint synovial hemangioma treated with arthroscopic resection without hemarthrosis: A case report.

INTRODUCTION: Intra-articular synovial hemangioma of the knee is a relatively rare benign tumor that if left undiagnosed and treated may be followed by degenerative cartilaginous changes and osteoarthritis. However, the non-specific symptoms of synovial hemangiomas limit its early diagnosis. We report our encounter with synovial hemangioma of the knee in which the diagnosis was based on a > 20-year history of chronic pain without joint swelling or hematoma. PRESENTATION OF CASE: A 34-year-old man with a localized vascular malformation on the upper edge of the left patella presented with pain and a restricted range of motion. CT and MRI revealed a tumorous lesion at this location. Upon excision of the lesion, the patient's symptoms disappeared, with no recurrence at the 1-year follow-up. DISCUSSION: Accurate diagnosis and appropriate early treatment are necessary for synovial hemangiomas to forestall articular cartilage degeneration due to recurrent intra-articular hemorrhages. CONCLUSION: Synovial hemangioma should be considered when a patient presents with recurrent knee pain, even in the absence of swelling or episodes of joint effusion.

Onset of Chronic Expanding Hematoma 25 Years After Total Hip Arthroplasty.

Chronic expanding hematoma (CEH) is a rare anatomical condition that gradually expands due to trauma or surgery. We report the case of a 56-year-old woman who developed CEH 25 years after metal-on-polyethylene total hip arthroplasty. She presented with swelling and radiating pain in the right inguinal region. Tocilizumab was administered for treating rheumatoid arthritis and renal amyloid A amyloidosis. Diagnostic imaging and partial resection revealed a soft tissue mass and a CEH, respectively. The symptoms recurred 6 months later; dialysis was initiated, and the CEH was resected under general anesthesia, leading to improvement. This case report emphasizes the importance of prompt diagnosis and intervention in CEH management for preventing further complications and improving the patient's quality of life.

Phenotypic classification of knee osteoarthritis according to pain mechanisms; a clinical observational study.

BACKGROUND: Pain in knee osteoarthritis is considered to be nociceptive. Recently, involvement of neuropathic pain and psychosocial factors in knee osteoarthritis has been reported. However, the following details are unclear: 1) How often are neuropathic pain and psychosocial factors involved? And 2) Which patients are associated with neuropathic pain and psychosocial factors? METHODS: In 104 patients with knee osteoarthritis, we evaluated neuropathic pain factor with a painDETECT questionnaire and catastrophic thinking using the pain catastrophizing scale. Pain intensity was assessed using the visual analog scale; patients with scores below the median were defined as low-pain group and others as high-pain group. Radiographic severity was categorized according to the Kellgren-Lawrence classification, with grades I-II and III-IV defined as low- and high-grades, respectively. We compared the painDETECT and pain catastrophizing scale scores between the low- and high-pain groups and low- and high-grade groups. Furthermore, the painDETECT and pain catastrophizing scale scores were compared among the following four groups: low-grade/low-pain, low-grade/high-pain, high-grade/low-pain, and high-grade/high-pain. RESULTS: Neuropathic pain factor and catastrophic thinking were found in 16% and 34% of patients, respectively. There were no significant differences in both painDETECT and pain catastrophizing scale scores between the two pain intensity groups. Between the two groups of radiographic severity, there was no significant difference in the painDETECT scores; however, the pain catastrophizing scale score was significantly high in the low-grade group. In addition, there was no significant difference in the painDETECT scores among the four groups; however, the pain catastrophizing scale scores were significantly higher in low-grade/high-pain than in high-grade/low-pain patients. CONCLUSIONS: Therefore, 64% had only nociceptive pain factor. Catastrophic thinking was strong in patients with low radiographic severity, especially in those with high pain intensity. Patients with neuropathic pain factor could not be identified from radiographic severity and pain intensity.

Knee osteoarthritis with patellar dislocation treated by total knee arthroplasty using a lateral parapatellar approach-ingenuity of exposure and closure.

Knee osteoarthritis with patellar dislocation is a rare and difficult-to-treat condition. Several reports of total knee arthroplasty (TKA) combined with various realignment procedures have been published. A 77-year-old man with knee pain was referred to our hospital. Plain radiography revealed a laterally dislocated patella, with osteoarthritic changes in the femorotibial joint. He simply underwent TKA via a lateral parapatellar approach without realignment. We devised methods of exposure and closure to maximize the effect of lateral release by the lateral parapatellar approach. TKA using the lateral parapatellar approach might be effective in treating knee osteoarthritis with patellar dislocation.

Good Postoperative Flexion Angle Improves Knee Function and Improvement of Flexion Angle Increases Patient Satisfaction After Total Knee Arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) is a well-established procedure for treating knee joint diseases. However, the postoperative range of motion (ROM) varies and is an important indicator of TKA success. Recently, patient-reported outcome measures (PROMs) and patient satisfaction have drawn attention. However, the relationship between ROM and knee function obtained by PROM and satisfaction is not well understood. METHODS: We retrospectively reviewed the data of 375 patients who underwent 500 primary TKA procedures. We measured the ROM before and after surgery. Knee joint function was evaluated using the Knee Injury Osteoarthritis Outcome Score, a PROM, and patients were classified into good function and poor function groups. Patient satisfaction was evaluated on a 5-graded scale as overall satisfaction, and patients were divided into a satisfied or a dissatisfied group according to the obtained scores. ROM was compared between the 2 groups, then significantly different factors were analyzed using multiple logistic regression analysis. Moreover, cut-off points of ROM for obtaining good function and patient satisfaction were determined using ROC curve analysis. RESULTS: The postoperative flexion angle had a significant effect on knee function (P < .001). The cut-off value of the postoperative flexion angle for good knee function was 120°. The improvement in flexion angle had a significant effect on patient satisfaction (P = .004). The cut-off value for the improvement in the flexion angle was 5°. CONCLUSION: The postoperative flexion angle had a significant effect on knee function and improvement in the flexion angle had a significant effect on patient satisfaction.

Consideration of differences in drug usage between young-onset and elderly-onset rheumatoid arthritis with target of low disease activity.

OBJECTIVES: Elderly-onset rheumatoid arthritis (EORA) is reported to differ from young-onset rheumatoid arthritis (YORA) with regard to patient background and drug treatment. We examined the amount of drug administered to patients who achieved low disease activity (LDA) for rheumatoid arthritis at our hospital. METHODS: Demographics, clinical history, and treatments were compared between patients with EORA (n = 70) and YORA (n = 190). RESULTS: There was a significant difference in the average age (73.8 vs. 57.8 years), disease duration (6.66 vs. 14.7 years), and sex (62.9% males vs. 83.7% females), but no difference in rheumatoid factor positivity (85.3% vs. 80.7%), anti-citrullinated peptide antibody positivity (86.5% vs. 87.7%), simplified disease activity index (4.28 vs. 4.59), or disease activity score 28-CRP (1.99 vs. 2.04) in the EORA and YORA groups, respectively. There were also no significant differences in prednisolone use (37.1% vs. 36.3%), amount of methotrexate administered (MTX) (1.45 vs. 1.41 mg), and MTX use (55.7% vs. 65.3%). However, the MTX dose (2.89 vs. 4.09 mg/week, p = .011) and overall biologics use (32.9% vs. 56.3%, p = .0012) were significantly lower in patients with EORA than in those with YORA. CONCLUSION: Patients with EORA may be able to achieve LDA with lower drug dosage than those with YORA.

Effects of malalignment and disease activity on osteophyte formation in knees of rheumatoid arthritis patients.

PURPOSE: Rheumatoid arthritis (RA) patients with secondary osteoarthritis (OA) in a knee joint following a total knee arthroplasty (TKA) procedure have been increasing. Here, we investigated osteophyte formation in knee joints of RA patients and associated factors. METHODS: We retrospectively examined findings of 35 knees in 30 RA patients (26 females, 4 males; mean age: 63.0 years; median disease duration: 15 years) who underwent TKA, including preoperative anteroposterior view radiographs of the knee joint. Using the ImageJ software package, osteophyte size in the medial femur (MF), medial tibia (MT), lateral femur (LF), and lateral tibia (LT) regions was also determined. RESULTS: The mean femorotibial angle was 179°, while Larsen grade was 2 in 1, 3 in 12, 4 in 18, and 5 in 2 patients. Osteophyte sizes in the MF, MT, LF, and LT regions were 37.2, 17.0, 27.2, and 4.57 mm2, respectively, and significantly greater in the medial compartment (MC; MF+MT) than the lateral compartment (LC; LF+LT) (p < 0.001). In varus cases, osteophyte size in the MC was significantly larger than normal and valgus cases (p = 0.0016). Furthermore, osteophyte size in the MC was negatively correlated with the inflammatory markers C-reactive protein (r = -0.492, p = 0.0027) and erythrocyte sedimentation rate (r = -0.529, p = 0.0016), whereas that in the LC was negatively correlated with disease activity (r = -0.589, p = 0.0023). CONCLUSION: Our results suggest that alignment and disease activity influence osteophyte formation in RA patients, with secondary OA a more prominent symptom in RA patients with controlled inflammation.

Comparison of recovery of mobility and self-efficacy after total knee arthroplasty based on two different protocols: A prospective cohort study.

Objectives: The purpose of this study was to compare the recovery of mobility and self-efficacy following total knee arthroplasty (TKA) between the 5-day and the 28-day protocol. This prospective cohort study was carried out at two hospitals.Methods: In total, 104 patients who underwent TKA were enrolled. The primary outcomes measured were Life Space Assessment (LSA) for mobility and modified-Gait Efficacy Scale (mGES) for self-efficacy. Knee Society Score (KSS) was used to estimate the functional outcomes. These assessments were performed in all patients preoperatively, and at 1, 3, and 6 months postoperatively. After calculating the propensity score using covariates, such as patient characteristics, LSA, mGES, and KSS at baseline, propensity score-adjusted multivariate analysis of covariance (MANCOVA) was performed.Results: MANCOVA revealed significant differences in LSA and mGES, but not in KSS, between the two protocols. The adjusted means of LSA and mGES in the 28-day protocol were significantly greater than those in the 5-day protocol in all the postoperative assessments.Conclusion: Mobility and self-efficacy were greater following the 28-day protocol than the 5-day protocol after TKA. Our findings suggest that the modified treatment procedure for improving mobility and self-efficacy is necessary to introduce the early discharge protocol in Japan.

Total knee arthroplasty for treatment of osteoarthritis with prolonged patellar dislocation.

Prolonged dislocation of the patella is a rare condition and is often related to severe osteoarthritis (OA) of the femorotibial (FT) joint. For this condition's treatment, numerous surgical techniques using total knee arthroplasty (TKA) have been published. To the best of our knowledge, this case report is the first description of the use of lateral release alone to treat recurrent patellar subluxation with TKA. An interesting point in this case is that the patient had a good recovery after TKA in spite of quite a long-term (a duration of almost 55 years) dislocation of her patella and development of secondary OA. We describe a case that we treated by TKA for FT-OA with a prolonged patellar dislocation. We were able to obtain good patellar reduction without additional surgery by performing adequate lateral release of the patellar retinaculum. This clinical case indicates the usefulness of lateral patellar retinaculum release for obtaining stable patellar tracking in TKA for FT-OA with remaining lateral patellar dislocation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Double-Layered Lateral Meniscus in an 8-Year-Old Child: Report of a Rare Case.

Reports of congenital abnormalities of the lateral meniscus include discoid meniscus, accessory meniscus, double-layered meniscus, and ring-shaped meniscus. Particularly, only a few cases of double-layered meniscus have been reported. We report a case of double-layered lateral meniscus, in which an additional semicircular meniscus was observed under the normal lateral meniscus. The accessory hemimeniscus was resected by means of arthroscopic surgery. This case demonstrates an interesting and extremely rare anatomical abnormality of the lateral meniscus.

Improved quality of cartilage repair by bone marrow mesenchymal stem cells for treatment of an osteochondral defect in a cynomolgus macaque model.

BACKGROUND AND PURPOSE: Integration of repaired cartilage with surrounding native cartilage is a major challenge for successful tissue-engineering strategies of cartilage repair. We investigated whether incorporation of mesenchymal stem cells (MSCs) into the collagen scaffold improves integration and repair of cartilage defects in a cynomolgus macaque model. METHODS: Cynomolgus macaque bone marrow-derived MSCs were isolated and incorporated into type-I collagen gel. Full-thickness osteochondral defects (3 mm in diameter, 5 mm in depth) were created in the patellar groove of 36 knees of 18 macaques and were either left untreated (null group, n = 12), had collagen gel alone inserted (gel group, n = 12), or had collagen gel incorporating MSCs inserted (MSC group, n = 12). After 6, 12, and 24 weeks, the cartilage integration and tissue response were evaluated macroscopically and histologically (4 null, 4 gel, and 4 MSC knees at each time point). RESULTS: The gel group showed most cartilage-rich reparative tissue covering the defect, owing to formation of excessive cartilage extruding though the insufficient subchondral bone. Despite the fact that a lower amount of new cartilage was produced, the MSC group had better-quality cartilage with regular surface, seamless integration with neighboring naïve cartilage, and reconstruction of trabecular subchondral bone. INTERPRETATION: Even with intensive investigation, MSC-based cell therapy has not yet been established in experimental cartilage repair. Our model using cynomolgus macaques had optimized conditions, and the method using MSCs is superior to other experimental settings, allowing the possibility that the procedure might be introduced to future clinical practice.

The COX-2 selective blocker etodolac inhibits TNFα-induced apoptosis in isolated rabbit articular chondrocytes.

Chondrocyte apoptosis contributes to the disruption of cartilage integrity in osteoarthritis (OA). Recently, we reported that activation of volume-sensitive Cl- current (ICl,vol) mediates cell shrinkage, triggering apoptosis in rabbit articular chondrocytes. A cyclooxygenase (COX) blocker is frequently used for the treatment of OA. In the present study, we examined in vitro effects of selective blockers of COX on the TNFα-induced activation of ICl,vol in rabbit chondrocytes using the patch-clamp technique. Exposure of isolated chondrocytes to TNFα resulted in an obvious increase in membrane Cl- conductance. The TNFα-evoked Cl- current exhibited electrophysiological and pharmacological properties similar to those of ICl,vol. Pretreatment of cells with selective COX-2 blocker etodolac markedly inhibited ICl,vol activation by TNFα as well as subsequent apoptotic events such as apoptotic cell volume decrease (AVD) and elevation of caspase-3/7 activity. In contrast, a COX-1 blocker had no effect on the decrease in cell volume or the increase in caspase-3/7 activity induced by TNFα. Thus, the COX-2-selective blocker had an inhibitory effect on TNFα-induced apoptotic events, which suggests that this drug would have efficacy for the treatment of OA.

Spatiotemporal control of proliferation and differentiation of bone marrow-derived mesenchymal stem cells recruited using collagen hydrogel for repair of articular cartilage defects.

Articular cartilage has a poor healing capacity, and cartilage regeneration is not always warranted to achieve healing. On the other hand, collagen scaffolds have been shown to support regeneration of articular cartilage defects in animal models, whereas bone morphogenetic protein-2 (BMP-2) is known to cause chondrogenic differentiation of marrow-derived mesenchymal stem cells (MSCs). The purpose of this study was to evaluate the effectiveness of intra-articular administration of BMP-2 into bone marrow-derived MSCs recruited to defects using original collagen hydrogel in rabbits at various time points. Full-thickness defects were created in both knees, then collagen hydrogels were transplanted, and BMP-2 was supplied for 1-week periods, as follows. BMP-2 was administered immediately after the operation for 1 week (BMP0-1 group), and BMP-2 was administered between weeks 1 and 2 after the operation (BMP1-2 group). BMP2 was administered between weeks 2 and 3 (BMP2-3 group). Specimens were then obtained, and bromodeoxyuridine (BrdU)-positive cells were enumerated and histologic grading was also performed. In addition, the gene expression analysis was performed using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) assays. Enumeration of BrdU-positive cells showed a significant increase in the BMP0-1 group compared with the other groups. Similarly, histologic scores in the BMP0-1 group were superior for up to 8 weeks. Finally, RT-PCR findings revealed that immediate BMP-2 administration enhanced chondrogenic differentiation.

In-advance trans-medullary stimulation of bone marrow enhances spontaneous repair of full-thickness articular cartilage defects in rabbits.

Mesenchymal stromal cells (MSCs), especially those lying close to cartilage defects, are an important cell source for cartilage regeneration. We hypothesize that a larger number of MSCs might become available, if the bone marrow in the immediate vicinity of the subchondral bone is stimulated for MSCs in advance of the creation of cartilage defects. A trans-medullary passage-way reaching the immediate vicinity of the subchondral bone was created 4 days prior to the creation of cartilage defects. In another setting, basic fibroblast growth factor (bFGF) was administered through the trans-medullary passage-way in order to augment the stimulation of MSCs. The rabbits were killed at various times after the creation of cartilage defects. Triple staining of bromodeoxyuridine (BrdU), CD44 and CD45 and histological evaluation were subsequently performed. A considerable proportion of the proliferating cells were identified as bone-marrow-derived MSCs. Enumeration of BrdU-positive cells demonstrated that trans-medullary stimulation, especially with bFGF, increased the number of proliferating cells. The histological grading score of trans-medullary stimulation with bFGF group was superior to that of the other groups. Thus, in-advance stimulation of the bone marrow effectively increases the number of proliferating cells. The putative progenitor cells for chondrocytes stimulated thereby are likely to be recruited to the osteochondral defects at the appropriate time, contributing to the repair of full-thickness articular cartilage defects at the early follow-up time point.

[Investigation of simplified international diagnostic criteria for autoimmune hepatitis].

The simplified international diagnostic criteria for autoimmune hepatitis (AIH), re-revised by the International AIH Group in 2008, were investigated in 114 patients with AIH from 15 centers in Japan. While applying of the criteria, we had to pay attention to anti-nuclear antibody measurement methods, and liver histology scoring. Definite and probable AIH were diagnosed in 83 and 22 patients, respectively. The criteria were found to be useful for the diagnosis of AIH in Japan. However, 9 patients who did not meet the diagnostic criteria showed normal immunoglobulin G levels or were negative for autoantibodies. As the criteria were unreliable for diagnosing such atypical cases in the present series, we speculated that we should not rely solely on these, criteria and take a more holistic approach to diagnosis in such cases.

Roles of double-balloon endoscopy in the diagnosis and treatment of Crohn's disease: a multicenter experience.

BACKGROUND: Double-balloon endoscopy (DBE) examinations are not yet widely accepted as routine procedures for examining the small bowel of patients with Crohn's disease (CD). AIM: To evaluate the feasibility and usefulness of DBE for CD in tertiary-care hospitals. METHODS: Between July 2004 and September 2008, 1444 DBE procedures were performed for 704 patients in 6 tertiary-care hospitals. Patient profile, indication, diagnosis and treatment of DBE were evaluated using a multicenter database. RESULTS: DBE examinations were most frequently performed in 75 patients with CD, corresponding to 10.5% of all the patients examined by DBE. Fifty patients were diagnosed with CD before DBE, while DBE was performed for the diagnosis of 25 new CD patients. Small bowel lesions were often detected even when the terminal ileum was not involved. In the 75 patients, 21 patients were asymptomatic at the time of DBE examinations. Active inflammatory lesions were detected in 51.2% of the CD patients, and were even detected in 33.3% of the asymptomatic CD patients. The treatment was altered in 53.3% of the CD patients after the DBE evaluation. No severe complications were experienced. CONCLUSIONS: DBE procedures can be safely performed in patients with CD and should be considered for the precise evaluation of and to determine the treatment strategy for CD.

Effect of dynamic compressive loading and its combination with a growth factor on the chondrocytic phenotype of 3-dimensional scaffold-embedded chondrocytes.

BACKGROUND AND PURPOSE: Three-dimensionally (3D-) embedded chondrocytes have been suggested to maintain the chondrocytic phenotype. Furthermore, mechanical stress and growth factors have been found to be capable of enhancing cell proliferation and ECM synthesis. We investigated the effect of mechanical loading and growth factors on reactivation of the 3D-embedded chondrocytes. METHODS: Freshly isolated chondrocytes from rat articular cartilage were grown in monolayer cultures and then in collagen gel. Real-time RT-PCR and histological analysis for aggrecan and type II and type I collagen was performed to evaluate their chondrocytic activity. Then, the 3D-embedded chondrocytes were cultured under either mechanical loading alone or in combination with growth factor. The dynamic compression (5% compression, 0.33 Hz) was loaded for 4 durations: 0, 10, 60, and 120 min/day. The growth factor administered was either basic fibroblast growth factor (bFGF) or bone morphogenetic protein-2 (BMP-2). RESULTS: Mechanical loading statistically significantly reactivated the aggrecan and type II collagen expression with loading of 60 min/day as compared to the other durations. The presence of BMP-2 and bFGF clearly enhanced the aggrecan and type II collagen expression of 3D-embedded chondrocytes. Unlike previous reports using monolayer chondrocytes, however, BMP-2 or bFGF did not augment the chondrocytic phenotype when applied together with mechanical loading. INTERPRETATION: Dynamic compression effectively reactivated the dedifferentiated chondrocytes in 3D culture. However, the growth factors did not play any synergistic role when applied with dynamic compressive loading, suggesting that growth factors should be administered at different time points during regeneration of the transplantation-ready cartilage.

Chondroitin sulfate for the treatment of hip and knee osteoarthritis: current status and future trends.

AIMS: Osteoarthritis (OA) is a common joint disorder and a major socio-economic burden. Chondroitin sulfate (CS), which has chondroprotective properties, is a promising candidate for the therapeutic treatment of OA. Here, we summarize current knowledge as well as future trends of CS for the treatment of hip and knee OA. MAIN METHODS: We retrospectively reviewed pharmacokinetics, pharmacodynamics, clinical efficacy, safety and tolerability of CS for the treatment of OA. KEY FINDINGS: The safety and tolerability of CS are confirmed. CS is effective, at least in part, for the treatment of OA, and its therapeutic benefits occur through three main mechanisms: 1) stimulation of extracellular matrix production by chondrocytes; 2) suppression of inflammatory mediators; and 3) inhibition of cartilage degeneration. SIGNIFICANCE: CS is a safe and tolerable therapeutic agent for the management of OA. Its effects include benefits that are not achieved by current medicines and include chondroprotection and the prevention of joint space narrowing. Such positive effects of CS represent a breakthrough in the treatment of hip and knee OA.