Mitsuaki Kubota

The fracture sites of atypical femoral fractures are associated with the weight-bearing lower limb alignment

PURPOSE Atypical femoral fractures (AFFs) are stress-related fractures that are speculated to associate with long-term treatment with bisphosphonates for osteoporosis. A history of AFF is a high risk factor for the development of a subsequent AFF in the same location of the contralateral femur, suggesting that a patients individual anatomical factor(s) are related to the fracture site of AFFs. In this study, we investigated the radiographs of fourteen AFFs (four bilateral fractures among ten patients) treated at six hospitals associated with our university between 2005 and 2010. The fracture site and standing femorotibial angle (FTA), which reflects the mechanical axis of the lower limb, were measured on weight-bearing lower limb radiographs. The fracture site and FTA of patients with typical femoral fractures (TFF) were compared to those of patients with AFFs. The correlations were examined using Spearmans rank correlation coefficients. The fracture locations in the femora were almost the same in the patients with bilateral AFFs. There was a positive correlation between the fracture site and the standing FTA in the patients with AFFs (r=0.82, 95% confidence interval; 0.49 to 0.94), indicating that the larger the standing FTA (varus alignment), the more distal the site of the fracture in the femur. The FTA of the patients with atypical diaphyseal femoral fracture were significantly larger compared to that of those with not only atypical subtrochanteric fractures but also TFFs. In conclusion, the fracture sites of AFFs are associated with the standing lower limb alignment, while those of TFFs are not.

Intra-articular hyaluronic acid injection versus oral non-steroidal anti-inflammatory drug for the treatment of knee osteoarthritis: a multi-center, randomized, open-label, non-inferiority trial

IntroductionWhile many of the commonly used conservative treatments for knee osteoarthritis (OA) have been recognized to be effective, there is still insufficient evidence available. Among the pharmacological treatments for knee OA, oral non-steroidal anti-inflammatory drugs (NSAIDs) act rapidly and are recommended for the management of OA. However, frequent and serious adverse effects of NSAIDs have been recognized. Intra-articular injections of hyaluronic acid (IA-HA) for the treatment of knee OA have been shown to reduce pain and improve joint function. However, there has been no qualified direct comparison study of the efficacy and safety between IA-HA and NSAIDs for patients with knee OA. The aim of this study was to clarify the efficacy and safety of early-phase IA-HA in comparison to those of NSAIDs for patients with knee OA.MethodsThis multicenter, randomized, open-label, parallel-group, non-inferiority comparison study with an oral NSAID involved a total of 200 patients with knee OA. An independent, computer-generated randomization sequence was used to randomly assign patients in a 1:1 ratio to NSAIDs three times per day for five weeks (n = 100) or IA-HA once a week for five weeks (n = 100). The primary endpoint was the percentage change in the patient-oriented outcome measure for knee OA, the Japanese Knee Osteoarthritis Measure (JKOM) score. All patients were questioned regarding any adverse events during treatment. The full analysis set (FAS) was used for analysis. The margin of non-inferiority was 10%.ResultsThe analyses of primary endpoint included 98 patients in the IA-HA group and 86 patients in the NSAID group. The difference in the percentage changes of the JKOM score between the two intervention arms (IA-HA; -34.7% (P<0.001), NSAID; -32.2% (P<0.001)) was -2.5% (95% confidence interval (CI): -14.0 to 9.1), indicating IA-HA was not inferior to NSAID. The frequency of both withdrawal and adverse events in the IA-HA group were significantly lower than those in the NSAID group (P = 0.026 and 0.004, respectively).ConclusionsThe early efficacy of IA-HA is suggested to be not inferior to that of NSAIDs, and that the safety of the early phase of IA-HA is superior to that of NSAIDs for patients with knee OA.Trial registrationUMIN Clinical Trials Registry (UMIN- CTR), UMIN000001026.

Correlations between both the expression levels of inflammatory mediators and growth factor in medial perimeniscal synovial tissue and the severity of medial knee osteoarthritis

An enhanced expression of the inflammatory mediators in the perimeniscal synovium in knee osteoarthritis (OA) has been suggested to contribute to progressive cartilage degeneration. However, whether the expression levels of these molecules correlated with the severity of OA still remained unclear. Medial perimeniscal synovial samples were obtained from 23 patients with Kellgren-Lawrence (K/L) grades 2 to 4 of medial knee OA. Immunohistochemical analysis of the synovium revealed that the MMP-1, COX-2 and IL-1β expression of the patients with K/L 4 to be significantly reduced in comparison to those with either K/L 2 or 3, while the TGF-β expression showed the opposite. The synovial expression of MMP-1 and IL-1β showed a significant negative correlation with the severity of OA, while that of TGF-β again showed the opposite. In conclusion, although synovial inflammation remained active, the MMP-1, COX-2 and IL-1β expression in synovium decreased depending upon the severity of OA, while the TGF-β expression increased.

Correlation between synovitis detected on enhanced-magnetic resonance imaging and a histological analysis with a patient-oriented outcome measure for Japanese patients with end-stage knee osteoarthritis receiving joint replacement surgery

Osteoarthritis (OA) is a disease that primarily results in the degeneration and destruction of the articular cartilage. However, synovitis that occurs secondarily by this primary phenomenon is crucial for both the structural and symptomatic progression of the disease. The Japanese Knee Osteoarthritis Measure (JKOM) was created as an outcome measure for Japanese patients with knee OA. This study was conducted to determine whether synovitis in knee OA correlates with the current disability of patients with knee OA who required total knee arthroplasty (TKA). Thirty-four Japanese patients with end-stage knee OA who required TKA were included in this study. The visual analog scale (VAS, 0–100) for pain and the JKOM score, as well as the Western Ontario and McMaster Universities Arthritis Index (WOMAC), were examined before the operation. Synovial samples were taken at the time of the operation. A histological analysis and gadolinium-enhanced magnetic resonance imaging (Gd-MRI) were conducted to evaluate synovitis. Correlations between the synovitis score evaluated by histological analysis and Gd-MRI with either the pain VAS score or the JKOM score were examined using Spearman’s rank correlation coefficient. Neither the synovitis scores evaluated by the histological analysis nor those by a Gd-MRI correlated with the pain VAS score (n = 34, r = 0.25, p = 0.18 and r = 0.08, p = 0.75, respectively) and WOMAC (n = 14, r = 0.35, p = 0.22 and r = 0.45, p = 0.16, respectively) of the patients. However, they significantly correlated with the JKOM score of the patients (n = 34, r = 0.55, p = 0.001 and r = 0.71, p = 0.001, respectively). The severity of synovitis in OA was closely correlated with the current functional impairment and disability of the patients receiving TKA with end-stage knee OA.

Therapeutic home exercise versus intraarticular hyaluronate injection for osteoarthritis of the knee: 6-month prospective randomized open-labeled trial

BackgroundTreatment for osteoarthritis (OA) of the knee is controversial. Only a few studies have compared the effects of intraarticular injection of hyaluronate with those of home exercise for knee OA. We prospectively evaluated the therapeutic effects of each treatment.MethodsA total of 102 female subjects (mean age 70.4 years) were randomly divided into two groups and followed up to the 24th week. The primary outcome measure was judged by three pain/function scales as follows: a visual analogue scale, the Japanese Knee Osteoarthritis Measure, and the Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International criteria. For secondary outcome measures, all data were categorized for logistic regression analysis and the chi-squared test to address factors affecting these outcomes.ResultsThe two treatment groups demonstrated equal improvement regarding all three scales, and there was statistically no difference in between-group analyses, although there seemed to be better improvement in range of motion at 24 weeks in the home exercise group. In categorical analysis, OA stage was classified as early and advanced OA at 3 mm of joint space width obtained from standing anteroposterior radiographs. Logistic regression analysis revealed that the OA stage at the baseline of the knee affected these improvements. For early OA the improvement rate regarding hydrops was significantly higher in the home exercise group, whereas for advanced OA there was a tendency for the rate of improvement in ROM to be inferior in the hyaluronidate group.ConclusionsTaking into account the cost, convenience, and invasiveness to patients, exercise is thought to have some advantage over intraarticular injection of hyaluronate for the therapy of OA of the knee.

Additive effects of glucosamine or risedronate for the treatment of osteoarthritis of the knee combined with home exercise: a prospective randomized 18-month trial

We have previously demonstrated the efficacy of therapeutic exercise for osteoarthritis (OA) of the knee. This study was performed to examine the additive effects of glucosamine or risedronate on the exercise therapy. In this study, 142 female patients with moderate OA of the knee, who had been recommended to undergo home exercise at the first visit to the hospital, were randomly given glucosamine hydrochloride, risedronate, or no additive. Although improvement after 18 months was observed in all groups using individual scales for evaluation of pain and function of the knee, no significant differences were observed between the groups regarding any of the scales, indicating no significant additive effect of glucosamine or risedronate. One reason for the lack of effect of glucosamine or risedronate on OA of the knee may be that the effect of these agents was occluded by the effect of therapeutic exercise to improve pain and function of the knee. This finding means that even if glucosamine and risedronate were to have an effect on OA of the knee, the effect would not be greater than the effect of knee exercise to improve the symptoms.

ACL Reconstruction Preserving the ACL Remnant Achieves Good Clinical Outcomes and Can Reduce Subsequent Graft Rupture

Background: Although anterior cruciate ligament (ACL) reconstruction techniques that preserve remnant tissues have been described, complete preservation may be difficult, with little known about its clinical advantages. Purpose: To compare clinical outcomes in patients undergoing ACL reconstruction with and without ACL remnant preservation. Study Design: Case-control study. Methods: Of 372 patients who underwent surgical treatment of an ACL injury between September 2006 and July 2010, 154 had no remaining identifiable ligament tissue and were excluded from this study. Attempts were made to preserve the ACL remnant as much as possible in the remaining 218 patients. These patients were divided into 2 groups: those in whom the remnant was preserved (group 1, n = 85) and those in whom the remnant was not preserved (group 2, n = 98). Patients were followed for at least 24 months. Outcomes, including graft rupture, were compared in the 2 groups. Results: Time from injury to surgery was significantly shorter (7.3 ± 16.3 vs 16.0 ± 30.3 months; P < .05) and the preinjury Tegner activity was significantly higher (7.6 ± 1.4 vs 7.1 ± 1.2; P < .05; 95% confidence interval, 1.2-13.7) in group 1 than in group 2. The postoperative negative ratio of the pivot-shift test was similar in the 2 groups (87% vs 81%). Anterior stability of the knee, as measured by a KT-2000 arthrometer, was significantly better in group 1 than in group 2 (1.0 ± 0.8 vs 1.3 ± 1.0 mm; P < .05). ACL graft rupture occurred in 1 patient (1.1%) in group 1 and in 7 patients (7.1%) in group 2 (P < .05). Regression analysis showed that preservation of the remnant decreased the likelihood of graft rupture (odds ratio, 11.2; 95% confidence interval, 1.2-101.7). Conclusion: These findings confirmed that preserving the remnant tissue of the ACL may facilitate recovery of function and decrease graft rupture after primary reconstruction.

A longitudinal study of the relationship between the status of bone marrow abnormalities and progression of knee osteoarthritis

BackgroundBone marrow abnormalities (BMAs) detected on magnetic resonance imaging (MRI) are suggested to be involved in the pathogenesis of osteoarthritis (OA), and the size of the BMAs is associated with the progression of OA. However, it still remains unclear as to whether the associations of BMA size and OA severity are observed equally or whether they differ from early to advanced stages of OA. In the present study we examined whether BMA enlargement and OA progression differed according to the severity of OA.MethodsOne hundred and eighty patients with knee OA were enrolled in the present study, and 122 of these patients completed this study. Radiography and knee MRI were done two times in all patients, at the baseline and 6 months or later at the time of patient follow-up. The severity of OA was evaluated by radiography using the Kellgren-Lawrence (K-L) grade. The patients who showed a deterioration in the K-L grade during the follow-up examination (59/122) were defined as the deterioration group. T2-weighted fat-suppressed MR images were used to score the size of the BMAs according to the whole-organ magnetic resonance imaging score (WORMS). A new scoring system, the spacial BMA score (s-score) was defined to assess the size of the BMAs three-dimensionally.ResultsIn patients with K-L grade 2, the s-score changes during the follow-up period in the deterioration group were significantly increased in comparison to those in the no-change group (P = 0.04), and no significant s-score changes were observed in patients with either K-L grade 1 or 3 (P = 0.07 and 0.57) between the deterioration group and the no-change group during the follow-up examination. In patients with K-L grade 3, the s-score at the baseline in the deterioration group was higher than that in the no-change group (P = 0.05).ConclusionsThe relationship between the size and enlargement of BMAs and the progression of OA changed depending upon the severity of OA.

Reference intervals of serum hyaluronic acid corresponding to the radiographic severity of knee osteoarthritis in women

BackgroudWhile serum levels of hyarulonic acid (sHA) is known to be useful for a burden of disease biomarker in knee OA, it is far from practical. The reference intervals must be established for biomarkers to be useful for clinical interpretation. The aim of this study was to establish the reference intervals of sHA corresponding to the radiographic severity of knee OA for elucidating whether sHA can be useful as a burden of disease marker for individual patient with knee OA.Methods372 women with Kellgren & Lawrence grade (K/L) 1 through 4 painful knee OA were enrolled in this study. The patients included 54 with K/L 1, 96 with K/L 2, 97 with K/L 3, and 118 with K/L 4. Serum samples were obtained from all subjects on the day that radiographs taken. A HA binding protein based latex agglutination assay that employed an ELISA format was used to measure sHA. Age and BMI adjusted one way ANOVA was used to set the reference intervals of sHA.ResultsThe reference intervals for sHA corresponding to the patients with K/L 4 (49.6 – 66.5 ng/ml) was established without any overlap against to those with K/L 1, 2 and 3, while those with K/L 1, 2 and 3 showed considerable overlap.ConclusionsThese results indicate that sHA can be available as a burden of disease marker for the individuals with severe knee OA (K/L 4), while it is not for those with primary to moderate knee OA (K/L 1–3).

Reconstruction of a ruptured patellar tendon using ipsilateral semitendinosus and gracilis tendons with preserved distal insertions: two case reports

BackgroundAcute patellar tendon ruptures with poor tissue quality. Ruptures that have been neglected are difficult to repair. Several surgical techniques for the repair of the patellar tendon have been reported, however, these techniques remain difficult because of contractures, adhesions, and atrophy of the quadriceps muscle after surgery.Case presentationWe report the cases of 2 Japanese patients (Case 1: a 16-year-old male and Case 2: a 43-year-old male) with patellar tendon ruptures who were treated by reconstruction using semitendinosus-gracilis (STG) tendons with preserved distal insertions. Retaining the original insertion of the STG appears to preserve its viability and provide the revascularization necessary to accelerate healing. Both tendons were placed in front of the patella, in a figure-of-eight fashion, providing stability to the patella.ConclusionBoth patients recovered near normal strength and stability of the patellar tendon as well as restoration of function after the operation.