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Objectives: To clarify the effects of follow-on therapy after denosumab (DMAb) discontinuation. Methods: In this retrospective, multicenter study, postmenopausal patients with osteoporosis who were previously treated by oral bisphosphonates (BP) (n = 26) or teriparatide (TPTD) (n = 27) were switched to DMAb (administered 2.6 times), and then discontinued. Patients (73.1 years, T-scores of the lumbar spine [LS] - 2.7 and femoral neck [FN] - 2.2) were switched to either (1) raloxifene (RAL) (n = 13) or BP [(2) weekly or monthly BP (wmBP) (n = 29) or (3) zoledronate (ZOL) (n = 11)], based on each physician's decision (mean interval after final DMAb administration was 7.2 months). Bone mineral density (BMD) at final DMAb administration were set as baseline. Results: Changes in LS BMD at 1.5 years after final DMAb administration were -2.7% in the RAL, 0.7% in the wmBP, and 1.9% in the ZOL (p = .31 between groups), and in FN BMD were -3.8%, -0.8%, and 1.8%, respectively (p = .02 between the RAL and ZOL; p = .048 between the RAL and BP). Clinical vertebral fracture incidence during 1.5 years after final DMAb administration was 23.1% in the RAL, 3.4% in the wmBP, and 0.0% in the ZOL (p = .048 between the RAL and ZOL; p = .015 between the RAL and BP). No significant differences were observed in these parameters between the wmBP and ZOL. Conclusion: These results may contribute to the selection of adequate follow-on therapy after DMAb discontinuation, although further investigations are required. [ABSTRACT FROM AUTHOR]

Objectives: To establish anti-C1q monoclonal antibodies which can measure serum C1q levels discriminating disease severity subsets of rheumatoid arthritis (RA) within 5 years of onset. Methods: In this multi-centre, longitudinal, observational study, 122 RA patients [102 females, baseline age 58.5 years, rheumatoid factor (RF) positivity 78.7%, serum C-reactive protein (CRP) 1.2 mg/dl, and concomitant methotrexate (MTX) 4.9mg/week (29.5%)] within 5 years of onset (disease duration 21.0 months) were enrolled from 1985 to 2000. Patients were not treated by more than 8mg/week of MTX or biologics which may strongly affect the course of joint destruction. Disease severity at 10-15 years of onset was classified according to the number of destructed joints of overall 68 joints on plain radio- graphs (36 patients were mild RA group involving only peripheral joints and 86 were severe RA group involving large axial joints). Baseline serum C1q levels were evaluated by ELISA with newly developed 4 monoclonal anti-C1q antibodies, and compared between two groups as well as conventional RA disease activity markers. Results: There were no significant differences between two groups in baseline conventional RA disease activity markers such as RF, erythrocyte sedimentation rate, CRP, and matrix metalloproteinase-3. However, compared to mild RA group, severe RA group showed higher baseline serum C1q levels (µg/ml) evaluated by anti-C1q monoclonal antibodies of no.33 (104.8 ±22.3 vs. 118.3 ±19.3; p = .0024), no. 40 (102.6±21.9 vs 121.2±22.3; p = .000069), no. 54 (102.1 ±22.5 vs. 119.3±26.9; p = .00052), and no. 76 (105.6±21.8 vs. 122.6±26.4; p = .00043). Receiver operating characteristic curve analysis revealed that in patients with serum C1q levels of ≥110.5 µg/ml (measured by antibody no. 40), 78.9% (75/95) belonged to severe RA group. Conclusion: Measuring serum C1q levels of RA within 5 years of onset by newly developed anti-C1q antibodies may be useful in predicting the prognosis of disease severity evaluated by the extent of joint destruction. [ABSTRACT FROM AUTHOR]

Objectives: Joint-preserving rheumatoid forefoot surgery improves clinical outcomes, but postoperative range of motion (ROM) of the metatarsophalangeal (MTP) joint remains an issue. The objective of this study was to evaluate the effect of ROM exercise from the early period after lesser toe MTP joint-preserving surgery. Methods: A retrospective, observational study of 22 rheumatoid arthritis patients who underwent modified metatarsal shortening offset osteotomy was completed. Lesser toe scales were administered using the Japanese Society for Surgery of the Foot (JSSF) standard rating system, and the maximum distance of continuous walking was checked to evaluate clinical outcomes. Maximum passive ROM of the lesser toe MTP joints and the extension angle of the 2nd MTP joint at the terminal stance phase during gait were measured and evaluated. Results: Pain scores and ROM-related indices of the JSSF lesser toe scale improved significantly in the exercise group. The extension angle of the 2nd MTP joint at the terminal stance phase during gait was increased, and the maximum distance of continuous walking seemed longer. Conclusion: Passive/active ROM exercise from 2-weeks after surgery can improve a patient's activity and forefoot function through increasing ROM of the MTP joint at the terminal stance phase. [ABSTRACT FROM AUTHOR]

Objectives: To clarify the effect of combining medial capsule interposition with modified scarf osteot- omy for hallux valgus. Methods: A multicenter, retrospective study included 64 cases [59 osteoarthritis patients (excluding rheumatoid arthritis); age 68.8 years, range 40-93 years] of modified scarf osteotomy which were performed from 2013 to 2017 and followed for 26.6 (range, 13-50) months. Patients were treated by either (1) without medial capsule interposition (33 cases) or (2) combined with interposition (31 cases) at each senior surgeon-s discretion. The Japanese Society for Surgery of the Foot (JSSF) hallux metatar-sophalangeal (MTP)-interphalangeal scale was evaluated along with radiographic parameters (hallux valgus angle [HVA], first and second metatarsals intermetatarsal angles, and Hardy grade). Results: All JSSF scale and radiographic parameters were similar at baseline and significantly improved at final follow-up in both groups (pre-operation vs. final follow-up: p<.001). However, compared to without interposition group, interposition group showed significantly higher improvement in the JSSF scale (pre-operation to final follow-up: p value between the two groups at final follow-up) for pain (without interposition: 19.4-34.2, interposition: 18.4-37.1; p=.02), function (without interposition: 20.8-33.6, interposition: 18.3-36.6; p=.005), total score (without interposition: 41.5-81.8, interposition: 38.5-88.5; p<.001), and the MTP joint space (without interposition: 1.4-1.5mm, interposition: 1.6-2.6mm; p<.001) with significant correlation between the total JSSF score (r=.40; p=.001). Conclusion: Combining medial capsule interposition with modified scarf osteotomy significantly improved mid-term clinical outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effectiveness of add-on iguratimod (IGU) in patients with rheumatoid arthritis (RA) who showed an inadequate response to tocilizumab (TCZ), especially patients who were intolerant of an effective dose of methotrexate (MTX). Methods: Thirty-one patients with RA (22 women, age 62.4 years, disease duration 13.8 years, prior TCZ duration 35.7 months, 25 intravenous [8 mg/kg/4 weeks] and 6 subcutaneous [162 mg/2 weeks] TCZ treatments, concomitant MTX 8.5 mg/week [35.5%], and prednisolone (PSL) 4.3 mg/day [25.8%]) who showed an inadequate response to TCZ (disease activity score assessing 28 joints with C-reactive protein [DAS28-CRP] 2.9, clinical disease activity index [CDAI] 15.0, 28 secondary inadequate responders) were treated with additional IGU (final dose 41.7 mg/day) and enrolled in this 24-week, multicenter, retrospective study. Results: Twenty-nine patients (93.5%) continued the treatment for 24 weeks (one dropped out for pneumonia and one for digestive symptoms). The TCZ and the concomitant dose and rate of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) (MTX, salazosulfapyridine [SASP], and tacrolimus [TAC]) were not significantly changed during this period. Outcome measures improved significantly, as follows: DAS28-CRP from 2.9 to 1.7 (p < .001); CDAI from 15.0 to 6.0 (p < .001); modified Health Assessment Questionnaire (mHAQ) from 0.8 to 0.6 (p < .05); and rheumatoid factor (RF) from 382.1 to 240.3 IU/mL (p < .001). Using the EULAR criteria, 64.5% achieved a moderate response, and 51.6% achieved ACR 20 at 24 weeks. Conclusion: Adding IGU to inadequate responders to TCZ may be a promising and safe complementary treatment option. [ABSTRACT FROM AUTHOR]

Xanthogranuloma is a benign disease represented as histiocytosis with lipoid deposition which usually occurs in children, but rarely in adults. We report a case of an adult patient with multiple subcutaneous xanthogranuloma at juxta-articular sites with bone cystic changes, manifesting similar clinical profiles to rheumatoid arthritis. Although very rare, we should consider the possibility of xanthogranulomatosis in the diagnosis of rheumatoid arthritis, especially in atypical cases. [ABSTRACT FROM AUTHOR]

Objectives: Advances in drug therapy for rheumatoid arthritis (RA) have been encouraging us to preserve the metatarsopharangeal (MTP) joint in correction of forefoot deformities, and original metatarsal shortening offset osteotomy was recommended as one of the conventional surgical options for forefoot deformities in RA cases. The objective of this study was to evaluate short-to mid-term outcomes of modified metatarsal shortening offset osteotomy. Methods: A retrospective observational study was completed for 80 RA cases (mean follow-up period: 3.2 years) who underwent modified metatarsal shortening offset osteotomy. Both lesser toe scales and RA foot ankle scales were administered using the Japanese Society for Surgery of the Foot (JSSF) standard rating system, and a postoperative self-administered foot evaluation questionnaire (SAFE-Q) at final follow-up was also checked to evaluate clinical outcomes. Results: This procedure significantly improved clinical scores of both the JSSF [lesser toes and RA foot and ankle] scales. Of 80 feet, 24 (30%) showed recurrence of MTP joint subluxation/dislocation. Furthermore, the feet in the recurrence group showed significant varus hindfoot. On the other hand, valgus foot in the recurrence group more frequently included midfoot bony ankyloses. All of the affected feet showed the limitation of MTP joints (<70°) after surgery. Conclusions: Modified metatarsal shortening offset osteotomy was recommended for RA forefoot disorders as one of the joint preservation surgeries in short- to mid-term follow-up. However, some modifications to avoid limitation of ROM in the MTP joint are required. It must be borne in mind that varus hindfoot and/or bony ankyloses in the mid-hindfoot can cause recurrence of dorsal dislocation/subluxation of the lesser toe MTP joint. [ABSTRACT FROM AUTHOR]

Objectives: To clarify the difference of patient-based outcome between joint-preserving arthroplasty and resection-replacement arthroplasty in forefoot surgery for patients with rheumatoid arthritis (RA). Methods: A total of 63 feet of 49 RA patients who underwent forefoot surgery were asked to answer pre-operative and post-operative self-administered foot evaluation questionnaire (SAFE-Q). Patients were treated with either (1) metatarsal head resection-replacement arthroplasty (28 feet, post-operative mean age 63.8 years, follow-up 4.2 years, DAS28-CRP 2.2) or (2) metatarsophalangeal joint-preserving arthroplasty (35 feet, post-operative mean age 63.1 years, follow-up 3.6 years, DAS28-CRP 2.1) at each surgeon's discretion. Results: Mean pre-operative and post-operative subscale scores of SAFE-Q of group (1) and (2) were as follows. Pain and pain-related [(1) pre-op 36.8 to post-op 75.0 vs. (2) pre-op 42.2 to post-op 82.6], physical functioning and daily-living [(1) 43.2-68.8 vs. (2) 52.778.1], social functioning [(1) 44.3-72.0 vs. (2) 52.5-81.9], general health and well-being [(1) 48.4-68.4 vs. (2) 45.5-84.4], and shoe-related [(1) 30.1-50.3 vs. (2) 30.6-64.4]. Both general health and well-being subscale scores (p<0.05) and shoe-related subscale scores (p<0.05) were significantly more improved in group (2) compared with group (1). Conclusions: Joint-preserving arthroplasty resulted in better patient-based outcomes than resectionreplacement arthroplasty. [ABSTRACT FROM AUTHOR]

Objective: To compare the influences of tocilizumab (TCZ) and TNF inhibitors (TNFi) on the angiogenesis in synovial tissues of rheumatoid arthritis (RA). Methods: Synovial tissues were obtained during joint operations from 13 RA patients treated with TCZ for at least 4 months with or without previous use of TNFi, from 13 RA patients with TNFi alone and from 10 RA patients with only conventional synthetic DMARDs (csDMARDs). Synovial tissues were evaluated by hematoxylin and eosin stain as well as by immunohistological staining with anti-CD31 in which the microvessel densities (MVD) were quantitated. Synovial histopathology was scored for various components. Results: The most remarkable change in the synovium with TCZ was reduced angiogenesis as well as degeneration of lining layers irrespective of the previous use of TNFi. Thus, MVD in patients treated with TCZ with or without previous TNFi were significantly decreased compared with those in patients with TNFi alone or with csDMARDs. Moreover, MVD was significantly correlated with lining layer proliferation, but not with synovial stromal proliferation or inflammatory changes. Conclusions: These results demonstrated that inhibition of angiogenesis is a unique action of TCZ. Moreover, the data also suggest that lining layers proliferation might be closely associated with angiogenesis. [ABSTRACT FROM AUTHOR]

Objective: To elucidate the incidence and risk factors for cervical lesions in patients with rheumatic arthritis (RA) under the current pharmacologic treatment paradigm. Methods: Of patients with RA onset after 2000, 151 who introduced biologic agents (BAs) because of high disease activity and underwent cervical radiography more than 5 years after onset were included. Incidence of those with cervical lesions and predictors of cervical lesions were analyzed. Mean disease duration was 8.5 years. The radiographic definitions of cervical lesions were as follows: atlantoaxial subluxation (AAS), atlantodental interval43 mm; vertical subluxation (VS), Ranawat value513 mm; and subaxial subluxation (SS), and listhesis42 mm. Results: Radiographic evaluation indicated AAS in 43 cases (28%), VS in 10 (7%), and SS in 6 (4%). The incidence of those with any cervical lesion was 32% (48/151). Univariate analysis showed that disease duration, time from onset to BA use, and onset before 2005 were significant predictors of cervical lesions, while multivariate regression analysis showed that disease duration and Steinbrocker stage were predictors. Conclusion: The incidence of cervical lesions in patients with RA onset after 2000 was still high (32%). In addition, disease duration and Steinbrocker stage were predictors of cervical lesions. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether preoperative pain intensity in callosities of the lesser toe metatarsopharangeal (MTP) joint was associated with the grade of fore-mid-hindfoot deformities, because rheumatoid arthritis (RA) foot deformity includes the whole part of foot, and curiously differences between cases in the pain intensity of MTP joint callosities are often observed. Methods: We evaluated 24 feet that had undergone forefoot surgery [August, 2014 - December, 2015] for painful lesser toe MTP joint deformity (callosities) in RA cases. A preoperative self-administered foot evaluation questionnaire (SAFE-Q) and pressure distribution information for foot function were also investigated. X-rays of the whole lower extremities and foot at weight-bearing were used to check fore-mid-hindfoot deformities. Results: Group M (mild) [n = 9] included patients with the pain visual analog scale (VAS) less than 40 mm, while group S (severe) [n=15] included patients whose VAS was over 40 mm. Group M showed stronger hindfoot valgus and pronated (abducted) deformity, and group M showed higher pressure on the first MTP joint compared with group S. Conclusions: These observations reconfirm that hindfoot valgus deformity and/or pronated (abducted) foot deformity affects the forefoot loading distribution, subsequently the pain of callosities in lesser toe MTP joints could be decreased. [ABSTRACT FROM AUTHOR]

Objectives: Tocilizumab (TCZ) shows good retention in patients with rheumatoid arthritis (RA), but no previous reports demonstrated hopeful treatment options against inadequate response to TCZ. Tacrolimus (TAC) has proved to show efficacy against inadequate response to tumor necrosis factor alpha inhibitors, yet its add-on effects on TCZ remain unknown. Methods: Twenty patients with RA (17 women, age 58.6 years, disease duration 12.1 years, prior TCZ duration 2.6 years, 18 intravenous [8 mg/kg/month] and 2 subcutaneous [324 mg/month] TCZ treatments, methotrexate 6.1 mg/week [70.0%]) who showed an inadequate response to TCZ (clinical disease activity index [CDAI]≤5.8, 18 secondary non-responders) were additionally treated with TAC (1.1 mg/day), and enrolled in this 24-week, prospective study. Results: Seventeen patients (85.0%) continued the treatment for 24 weeks. Statistically significant decreases in outcome measures were as follows: disease activity score based on 28 joints with C-reactive protein (DAS28-CRP) from 3.3 at baseline to 2.1 at week 24 (p50.001), CDAI from 17.7 to 7.6 (p50.001), and serum matrix metalloproteinase-3 levels from 232.8 to 66.2 ng/ml (p50.001). About 15 patients (75%) achieved low disease activity or remission (DAS28-CRP ≥ 2.7 or CDAI ≥ 10) at week 24. Conclusions: Adding low-dose TAC to inadequate responders to TCZ may be a promising complementary treatment option. [ABSTRACT FROM AUTHOR]

Control of rheumatoid arthritis (RA) disease activity is an important factor related to the development of hallux valgus (HV) deformity. Furthermore, if valgus hindfoot remains and/or appears after HV surgery, the affected foot is at risk of recurrence of HV deformity. We experienced a case suggesting the possibility that hindfoot valgus deformity appeared after HV surgery because of poor control of RA disease activity, and the HV deformity recurred in the very early period after surgery. [ABSTRACT FROM AUTHOR]

Hallux valgus (HV) deformity is associated with hindfoot valgus deformity. We experienced a case that suggests the possibility that valgus correction for varus hindfoot with bony ankylosis of the subtalar joint by total ankle arthroplasty may have caused a forefoot HV deformity, despite adequate valgus correction. [ABSTRACT FROM AUTHOR]

Objective. To clarify the three-dimensional (3D) morphometric characteristics of the spine in patients with degenerative spondylolisthesis (DS). Methods. 3D morphometric analyses of laminae and facets were performed and compared for a DS group, an age-matched spinal canal stenosis (LCS) group, and a control group of young persons without spinal disease. 3D facet sagittal angles (3D-FSAs), 3D facet axial angle (3D-FAAs), and 3D-FAA tropism at L3 and at L4 were measured by extracting the 3D inferior articular process. The 3D lamina inclination angles (3D-LIAs) of L3 and L4 were also measured by extracting the ventral surface of the laminae. Results. The 3D-FSAs at L4 in the DS group were significantly higher than for the other groups, but the difference in 3D-FSAs at L3 was not statistically significant among the groups. The 3D-FAAs at L4 in the DS group were significantly lower than in the control group. There was no significant difference in other factors. Conclusions. 3D morphometric analysis clarified that DS is significantly correlated with horizontalization (higher 3D-FSA), but is not correlated with sagittalization (lower 3D-FAA) and tropism (3D-FAA tropism) of facet joints or horizontalization of laminae (3D-LIA). There were no morphometric characteristics at the cranial adjacent segment of DS. [ABSTRACT FROM AUTHOR]

Intraoperative extracorporeal autogeneous irradiated bone grafting (IORBG) after femoral tumor resection ultimately sometimes will fail in patients achieving long-term survival. There are several alternative surgical approaches for revision of these reconstructions. In 2002 and 2005, two patients with femoral intercalary resection of malignant tumor (synovial sarcoma and MFH) underwent IORBG reconstruction with intramedullary nail or plate. At 32 and 96 months after IORBG reconstruction, both patients had failed IORBG (pathological fracture) in the femur. We used custom-made endoprostheses in these two patients to reconstruct femoral diaphyseal bone defect after excision of failed IORBG. Follow-up of the patients averaged 40.5 months (range, 39-42 months) after endoprosthetic revision. Musculoskeletal Tumor Society scores averaged 75% (66-83%). When used to salvage massive IORBG failure from fractures, intercalary endoprosthetic revision preserves limb function with minimal complications. [ABSTRACT FROM AUTHOR]