Objective: The objective of this study was to examine the efficacy of switching therapy of biologic agents in the treatment of rheumatoid arthritis (RA).
Methods: We examined 22 patients with RA (including 17 women, mean age 61.3 years, mean disease duration 11.9 years) followed up for more than 52 weeks after switching from their first biologic agent. The Disease Activity Score 28 (DAS 28)/erythrocyte sedimentation rate (ESR) and the continuation rate (CR, by Kaplan-Meier method) of the second biologic agent were investigated. In addition, we evaluated DAS 28-ESR and CR separately for anti-tumor necrosis factor alpha (TNF-α) antibody agents (infliximab and adalimumab), etanercept, and tocilizumab.
Results: DAS 28-ESR was significantly improved starting 4 weeks after switching to the second biologic agent and was maintained up to 52 weeks. The CR of the second biologic agent was 81.8% at 12 weeks, 68.2% at 24 weeks, and 62.5% at 104 weeks. When DAS 28-ESR was evaluated separately for each agent, switching to etanercept or tocilizumab showed significant improvement, but switching to an anti-TNF-α antibody did not. While the CR of etanercept was 84.6% at 52 weeks, the CR after switching from etanercept to other agents was 40.0% at 24 weeks.
Conclusion: Switching therapy of biologic agents is an available option, especially switching to etanercept; however, switching from etanercept to other biologic agents tended to make subsequent treatment difficult.

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Objective: The objective of this study was to investigate whether repeat treatment with the tumor necrosis factor-α (TNF-α) antagonist etanercept can be effective after the initial clinical response to this drug was lost.
Methods: This retrospective, observational study analyzed data from all patients with rheumatoid arthritis (RA) who were treated with etanercept at our institution between 2005 and 2009. All patients fulfilled the 1987 American College of Rheumatology (ACR) criteria for RA.
Results: Etanercept was initially administered to 135 patients with RA between 2005 and 2009. Twenty of these patients switched to another biological agent because of adverse events or an absence or secondary loss of efficacy. Three of these 20 patients switched to different biological agents and returned to etanercept because their initial response to etanercept was better than that to any of the others. Disease activity was high in all three patients before initial etanercept therapy and each had clinically responded by 24 weeks. However, the initial clinical effect was lost between 1.5 and 3.5 years thereafter and tocilizumab was administered, but the effect was again lost between 3 and 18 months later. Two patients did not respond to subsequent treatment with adalimumab and infliximab. Etanercept administered once again reduced disease activity in all three patients, none of whom developed any acute side effects.
Conclusions: Repeat administration of etanercept significantly improved clinical disease activity and inflammatory parameters in three patients with RA who were refractory to biological anti-TNF agents.

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Objective: The therapeutic effects of both salazosulfapyridine (SASP) and methotrexate (MTX) are known to be dose dependent, but in Japan there are dosage restrictions on both agents. With consideration of their different mechanisms of action, we retrospectively assessed the efficacy and safety of SASP and MTX as add-on combination therapy for effect insufficiency with each drug separately in patients with rheumatoid arthritis (RA).
Methods: Of the RA patients treated at our hospital over the past 9 years, 243 were administered SASP+MTX combination therapy. The subjects of this study were 200 patients (SASP+MTX group) who took SASP+MTX for at least 12 months, and 100 patients given MTX monotherapy (MTX group).
Results: Of the 200 subjects in the SASP+MTX group, 70% had late-stage RA. Nevertheless, the Disease Activity Score 28 (DAS 28) improved in this group from a mean pretreatment score of 5.87 to 3.73 after 12 months treatment. Greater improvement was seen in the SASP+MTX group than in the MTX group, with clinical remission achieved in 10% of subjects and a good response according to the European League Against Rheumatism (EULAR) response criteria in 90% of subjects.
Conclusion: Our results suggest that the additional combination therapy of SASP and MTX deserves consideration before using biological agents in the treatment of RA.

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Objective: The aims of this study were first to investigate changes in lower limb alignment after total hip arthroplasty (THA) and second to examine the influence of lower limb alignment on leg length discrepancy (LLD) after THA.
Methods: Forty-three patients (34 women and 9 men) with unilateral hip osteoarthritis who underwent primary THA were included in this study. The mean age at surgery was 64.9 years (range: 4480). For all patients, we obtained antero-posterior radiographs of the pelvis and whole lower limbs in the standing position before and 12 months after THA. On these radiographs, we measured LLD, as well as the femorotibial angle (FTA) and deviation of the mechanical axis at the knee joint (%MA) as parameters of lower limb alignment. We compared the LLD as measured on radiographs of the pelvis to that on radiographs of the whole lower limbs and investigated the influence of lower limb alignment on the difference in LLD between the two types of radiographs.
Results: The affected leg was initially more valgus than the unaffected leg (p＜0.01), but it tended to be varus after THA (p＜0.01). The discrepancy in FTA between affected and unaffected legs was smaller at 12 months postoperatively; however, the affected leg was still more valgus than the unaffected leg (p＜0.01). When the %MA at the knee joint was the same on the affected and unaffected sides, the LLD as measured on radiographs of the pelvis was the same as that on radiographs of the whole lower limbs. As the deviation of the mechanical axis from the center of the knee joint became greater on the affected side, the LLD as measured on radiographs of the whole lower limbs became shorter than that on the radiographs of the pelvis.
Conclusion: Lower limb alignment tended to be varus after THA. When there was a discrepancy in lower limb alignment between the affected and unaffected legs, a difference in LLD was found between radiographs of the pelvis and of the whole lower limbs. Lower limb alignment should therefore be considered when correcting leg length discrepancy in THA.

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Objective: The objective of this study was to assess the usefulness of a taper-lock stem prosthesis with a changeable neck for the adjustment of leg-length discrepancy (LLD) and offset of the femoral neck.
Methods: Twenty patients underwent 23 primary total hip arthroplasties with a taper-lock stem prosthesis with a changeable neck (Kinectiv, Zimmer). The original diseases were osteoarthritis in 16 cases, avascular necrosis of the femoral head in 4, rheumatoid arthritis in 4, and rapidly destructive coxopathy in 1. The modified Watson-Jones approach was used in all cases. The mean age at the time of operation was 72 years, and the mean follow-up period was 6 months. The control group underwent 21 arthroplasties performed with a non-modular neck taper-lock stem prosthesis (Accolade TMZF, Stryker). The LLD and the offset of the femoral neck were measured.
Results: The JOA hip score improved from 47.2 points preoperatively to 84.9 points at the final follow-up. Perioperative complications included one fissure fracture of the proximal femur and one case of peroneal nerve palsy, but there was no postoperative dislocation. Only seven neck variations without version-controlled type were used in this series, although there were 60 options available. The mean inclination angle of the acetabular sockets was 38.7° and the mean anteversion angle was 15.4°. All cases were within Lewinneks safe zone. The mean preoperative LLD was 8.6±6.3 mm, but the postoperative LLD was adjusted to 4.0±2.7 mm. The preoperative offset ratio of the femoral neck to the unaffected side was 0.95±0.12, but the postoperative offset ratio was adjusted to 1.025±0.05. No significant difference was found in the adjustment of LLD or femoral neck ratio between the two groups.
Conclusion: The short-term clinical results of total hip arthroplasty using a taper-lock stem prosthesis with a changeable neck were excellent. Adjustment of the LLD and the offset of the femoral neck were accurately obtained, but there was no significant difference between the two groups.

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Objective: Total hip arthroplasty (THA) in patients with rheumatoid arthritis (RA) is considered a way to relieve pain and reconstruct the articular function of the hip joint. Previously, cemented THA was considered the gold-standard procedure for such a patient population; however, several authors have recently demonstrated excellent mid-term results with uncemented THA in RA patients. Currently, it is still controversial which procedure is more appropriate for this patient population. In this study, we evaluate the efficacy and safety of uncemented THA in patients with RA.
Methods: In our institute, 60 uncemented THAs in 47 patients with RA were carried out from January 1990 to December 2000. Of these 60 THAs, 31 THAs (23 patients) were lost to follow up, and the remaining 29 THAs (24 patients) were included in this study. The mean age at surgery was 51.3 years; the mean follow-up period after surgery was 12.3 years (minimum 10 years). We evaluated the clinical results (in terms of JOA score) and radiographic findings.
Results: One THA had been revised for aseptic loosening of the acetabular component 8 years after primary surgery. The mean JOA score of the remaining 28 THAs was significantly improved at 70.1 points from 38.7 points preoperatively. In radiographs, the fixations of the acetabular component were stable in 18 THAs and possibly stable in 10 according to Tompkins criteria; the biological fixations of the femoral components were considered bone ingrowth fixation in 27 THAs and fibrous stable fixation in 1, according to Engh’s criteria. Nonprogressive subsidence of the femoral component was observed in 7 THAs.
Conclusion: In this study, we demonstrated satisfactory long-term (minimum 10 years) results of uncemented THA for patients with RA. We consider that uncemented THA is a promising candidate for such a patient population.

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 Cup arthroplasty used to be performed for osteoarthritis of the hip in younger patients in order to preserve bone stock in our hospital. We report four cases of total hip arthroplasty (THA) after cup arthroplasties.
Case 1. The patient was a 51-year-old woman. She was diagnosed with osteoarthritis of the hip secondary to developmental dislocation of the hip (DDH) and underwent a left cup arthroplasty at the age of 23 years. Twenty-eight years later she underwent left THA. During the operation, it was very difficult to pull down the femur, and the procedure resulted in a distal femur fracture.
Case 2. The patient was a 62-year-old woman. She was diagnosed with osteoarthritis of the hip secondary to DDH and underwent a right cup arthroplasty at the age of 38 years. Twenty-four years later she underwent right THA. The formation of osteophyte in the acetabulum prevented dislocation of the femoral head. In situ osteotomy of the femoral neck was necessary.
Case 3. The patient was a 78-year-old woman. She was diagnosed with rheumatoid arthritis and underwent a left cup arthroplasty at the age of 49 years. Twenty-nine years later, she underwent left THA due to pain progression and leg length discrepancy. The weakness of the bone resulted in a fracture in the superior margin of the obturator foramen, resulting in the migration of acetabular reinforcement. She underwent a repeat operation.
Case 4. The patient was a 43-year-old man. He was diagnosed with post-traumatic osteoarthritis of the hip and underwent a right cup arthroplasty at the age of 31 years. Twelve years later, he underwent right THA.
 In these four cases, THAs were performed on average 23 years after cup arthroplasties, and the Hip score, as defined by the Japanese Orthopaedic Society, improved from 41.8 points preoperatively to 71.3 points at the final follow-up. The features of patients who have undergone cup arthroplasty include a poor range of motion and leg length discrepancy due to migration of the cup. The problem is that surgeons have difficulty in pulling down the femur to deal with acetabular cavitary bone defects during the operation. It was very useful to use modular-neck stems and transplant the bone with acetabular reinforcements. In conclusion, we recommend that cup arthroplasties be converted to THAs before the cups migrate severely into the acetabulum.

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Objective: The tibial crest and fibula are used as a landmark for extramedullary tibial alignment in total knee arthroplasty. We studied the accuracy of using this landmark for extramedullary alignment in total knee arthroplasty.
Methods: We evaluated 60 knees in 47 patients. Computed tomography-based simulation software was used to perform evaluations using preoperative TKA planning (ZedKnee, LEXI, Tokyo, Japan). We defined the mechanical axis of the tibia as a straight line from the center of the tibial tray to the center of the tibial distal plafond. The proximal tibial crest line was taken as the line connecting the two points at 10 cm and 15 cm distal to the knee joint line. The fibular axis was defined as a straight line from the center of the fibular head to the center of the lateral maleolli. The angles between the proximal tibial crest line and the mechanical axis in the coronal and sagittal planes and the angle between the fibular axis and the sagittal mechanical axis were measured.
Results: The mean angles between the mechanical axis and the proximal tibial crest line were 0.3°±2.5° (range -4.9° to 6.8°) of varus in the coronal plane and 3.1°±1.1° (range 1° to 5.6°) of anterior slope in the sagittal plane. Forty-seven tibias (78.3%) were within 3 in the coronal plane and 41 tibias (68.3%) were from 2° to 4° of anterior slope in the sagittal plane. In patients with more than 3° of varus or more than 4° of anterior slope, tibial lengths were significantly shorter (p＜0.01 in the coronal plane and p＜0.05 in the sagittal plane). The angle between the mechanical axis and the proximal tibial crest line was significantly correlated with tibial length (r=0.63, p＜0.01 in the coronal plane). The mean angle between the fibular axis and the sagittal mechanical axis was 1.5°±0.8° (range -0.7° to 3.1°) of posterior slope and was highly consistent.
Conclusion: Although surgeons have to be careful, and in patients with short or long tibia, reference to other landmarks is mandatory, the proximal tibial crest is a useful landmark in total knee arthroplasty; we rediscovered that the fibula is a reliable landmark in the sagittal plane.

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Objective: We performed total knee arthroplasty (TKA) with a low-contact-stress rotating-platform (LCS RP) mobile-bearing prosthesis (Depuy, Warsaw, IN) in patients with osteoarthritis (OA) of the knee. The purpose of the present study was to measure the potential effects of the posterior condylar offset, the tibial slope, and several other factors on the range of knee flexion.
Methods: A total of 120 patients (148 affected knees) who had undergone LCS RP TKA 6 months or more prior to the start of the study were enrolled [37 men (41 affected knees) and 83 women (107 affected knees) with a mean age of 77.4±5.7 years (range: 65-90 years) ]. We developed a simple index, the posterior condylar offset ratio (PCOR), which is the ratio of the posterior offset to the diameter of the patella on a true lateral view, and we investigated the relationship between PCOR and the postoperative range of knee flexion and the postoperative tibial slope. We also investigated the relationship between the preoperative PCOR and the postoperative range of knee flexion and the condylar twist angle, joint line, patella height, lateral shift ratio, tilting angle, and preoperative flexion. Using The Knee Society total knee arthroplasty roentgenographic evaluation and scoring system, we measured the alignment of these components. The relationships were assessed using Spearman’s correlation coefficient (r).
Results: We found no correlation between postoperative PCOR and the postoperative range of knee flexion or postoperative tibial slope (r = 0.02, r =-0.10), and no correlation between the postoperative range of knee flexion and postoperative tibial slope (r =0.01). In addition, we found no correlation between the postoperative range of knee flexion and the other factors we measured, but we did find a moderate correlation between the postoperative range of knee flexion and the preoperative range of knee flexion (r =0.48).
Conclusion: In this study, when using LCS RP TKA, we found that the only factor correlated to the postoperative range of knee flexion was the preoperative range of knee flexion. This suggested that we need to improve the preoperative range of knee flexion contracture before performing TKA.

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Objective: The aim of this study was to investigate the early clinical outcome after total knee arthroplasty (TKA) using the FINE TKA system.
Methods: Forty people who underwent 42 TKAs using the FINE TKA system participated in this study. Functional evaluations were performed at admission, discharge, and 23 months and 6 months after surgery. Evaluations consisted of the range of motion of the knee and radiographic measurements of the angle of implantation (Knee Society score).
Results: Japanese Orthopedic Association (JOA) scores after more than 6 months were significantly improved as compared to the scores at initial evaluation (p＜0.001). The range of knee flexion was 130.7° at admission, 130.0° at discharge, 120.7° at 2-3 months after surgery, and 122.3° at the last evaluation. The angle of implantation (α, β, γ, δ angle) was favorable.
Conclusion: Our study shows that the FINE TKA system has satisfactory clinical performance that is comparable to that achieved using other prostheses designed for Japanese patients to achieve good early clinical outcomes.

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Objective: The drain-clamping (DC) method using intraarticular tranexamic acid (TA) administration is reportedly effective for controlling bleeding after total knee arthroplasty (TKA). However, there is concern that this method causes venous thromboembolism (VTE) and that a resulting thrombus may stabilize and persist without degradation. This study aimed to examine the efficacy of the DC method with TA administration and its influence on VTE.
Methods: We studied 52 knees in 48 patients who underwent TKA and in whom contrast-enhanced computed tomography (CT) was carried out on postoperative days 1 and 14 at our artificial joint center between January 2009 and January 2010. The TA group consisted of 42 knees treated by the DC method with intraarticular administration of 1000 mg TA and 20 ml physiological saline via the drain after surgical wound closure. The non-TA group consisted of 10 knees treated by the DC method without TA administration. In both groups, the drain was clamped for 3 h and then unclamped. VTE was diagnosed using contrast-enhanced CT. Total blood loss, VTE incidence, and thrombus persistence from postoperative days 1 to 14 were evaluated.
Results: Total blood loss was 516±228 ml in the TA group and 973±284 ml in the non-TA group; the blood loss was significantly lower in the former group. VTE incidence was 50% in the TA group and 40% in the non-TA group on postoperative day 1 and 38% and 50%, respectively, on postoperative day 14. Thrombus persistence was 57.1% in the TA and 100% in the non-TA group. Thrombus persistence was actually lower in the TA group, i.e., TA had no apparent adverse effect on thrombus persistence.
Conclusion: The DC method with TA may be useful for its sufficient hemostatic effect and it has a minimal effect on the incidence or persistence of VTE.

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Objective: Lower limb joint arthroplasty poses a high risk of deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE). Careful clinical follow-up for DVT is required, but the period over which DVTs disappear remains to be elucidated. The purpose of this study was to investigate the disappearance period of DVTs by ultrasonography of the lower extremities and measurement of D-dimer levels.
Methods: We prospectively evaluated 134 joints in 109 patients who underwent lower limb joint arthroplasty between June 2008 and September 2010; procedures included total knee arthroplasty (TKA), unicompartmental knee arthroplasty (UKA), and total hip arthroplasty (THA). Measurement of D-dimer levels and ultrasonographic evaluation of the lower extremities were performed preoperatively and on the first and seventh postoperative days. Ultrasonography was also carried out periodically thereafter, and the disappearance period of DVTs was evaluated by ultrasonography. For physical thromboprophylaxis, we used graduated compression stockings (GCS) and intermittent pneumatic compression (IPC). Furthermore, subcutaneous injection of fondaparinux (2.5 mg/day) was done for pharmacological prevention.
Results: Preoperative DVT was found in 5 of 20 joints; all were distal DVTs. Mean D-dimer levels preoperatively and on the first and the seventh days were 1.1 (0.34.2), 8.6 (217.9), and 10.1 (2.353.9) mg/ml, respectively. Twenty (14.9%) of 134 joints were found to have DVT. DVT disappeared in 13 of 20 joints; the mean disappearance period of DVT was 7.5 months postoperatively. There were no patients with PTE. Only one patient had clinical symptoms of DVT, i.e., swelling of the lower leg. The other patients had no symptoms.
Conclusion: In this study, DVT relating to lower limb arthroplasty had disappeared 7.5 months after surgery. Postoperative ultrasonography of lower extremities was effective for evaluation of DVT.

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Objective: There is growing evidence that injection in the knee joint under the guidance of ultrasound (US) leads to accurate needle placement and results in a clinically significant improvement compared with traditional palpation-guided methods. This study was conducted to assess the usefulness of the corticosteroid injection method in medial collateral ligament (MCL) with protrusion of the medial meniscus using US for patients with osteoarthritis (OA) of the knee.
Methods: A total of 55 outpatients with knee OA were prospectively randomized into two groups, a medial collateral ligament (MCL) injection group and an intra-articular injection group, according to the approach employed for the corticosteroid injection. At the final assessment, the subjects were asked how many days they needed to take nonsteroidal anti-inflammatory drugs (NSAIDs) due to pain related to knee OA during the 4-week study. The number of days the subjects needed NSAIDs was compared between the MCL and intra-articular injection groups.
Results: Four patients withdrew from the study, and so the 51 subjects who completed the 4-week study were evaluated. There were significant differences demonstrated between the intra-articular injection group (n=26, 15.3±7.7 days) and the MCL injection group (n=25, 9.1±7.4 days) in terms of the number of days the subjects needed NSAIDs (p=0.004).
Conclusion: The protrusion of the medial meniscus with displacement of the MCL is strongly and independently associated with weight-bearing pain in knee OA. The results from the present study indicated that corticosteroid injection in the MCL is useful to relieve acute pain due to knee OA.

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