IntroductionReal-world evidence of the effectiveness of pharmacological thromboprophylaxis for venous thromboembolism (VTE) is limited. Our objective was to assess the effectiveness and safety of thromboprophylactic regimens in Japanese patients undergoing joint replacement in a real-world setting.MethodOverall, 1,294 patients (1,073 females and 221 males) who underwent total knee arthroplasty (TKA) and 868 patients (740 females and 128 males) who underwent total hip arthroplasty (THA) in 34 Japanese national hospital organization (NHO) hospitals were enrolled. The primary efficacy outcome was the incidence of deep vein thrombosis (DVT) detected by mandatory bilateral ultrasonography up to post-operative day (POD) 10 and pulmonary embolism (PE) up to POD28. The main safety outcomes were bleeding (major or minor) and death from any cause up to POD28.ResultsPatients undergoing TKA (n = 1,294) received fondaparinux (n = 360), enoxaparin (n = 223), unfractionated heparin (n = 72), anti-platelet agents (n = 45), or no medication (n = 594). Patients undergoing THA (n = 868) received fondaparinux (n = 261), enoxaparin (n = 148), unfractionated heparin (n = 32), anti-platelet agents (n = 44), or no medication (n = 383). The incidence rates of sonographically diagnosed DVTs up to POD10 were 24.3% in patients undergoing TKA and 12.6% in patients undergoing THA, and the incidence rates of major bleeding up to POD28 were 1.2% and 2.3%, respectively. Neither fatal bleeding nor fatal pulmonary embolism occurred. Significant risk factors for postoperative VTE identified by multivariate analysis included gender (female) in both TKA and THA groups and use of a foot pump in the TKA group. Only prophylaxis with fondaparinux reduced the occurrence of VTE significantly in both groups. Propensity score matching analysis (fondaparinux versus enoxaparin) showed that the incidence of DVT was lower (relative risk 0.70, 95% confidence interval (CI) 0.58 to 0.85, P = 0.002 in TKA and relative risk 0.73, 95% CI 0.53 to 0.99, P = 0.134 in THA) but that the incidence of major bleeding was higher in the fondaparinux than in the enoxaparin group (3.4% versus 0.5%, P = 0.062 in TKA and 4.9% versus 0%, P = 0.022 in THA).ConclusionsThese findings indicate that prophylaxis with fondaparinux, not enoxaparin, reduces the risk of DVT but increases bleeding tendency in patients undergoing TKA and THA.Trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry: UMIN000001366. Registered 11 September 2008.

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Objective. Recent studies have shown the importance of proteasome function in the regulation of apoptosis. This study examined whether inhibition of proteasome function mediates apoptosis of synovial cells, and whether cytokines modulate this process.Methods. Type B synovial cells (fibroblast-like synovial cells) were cultured with tumor necrosis factor ␣ (TNF␣) or transforming growth factor ␤1 (TGF␤1), and further incubated in the presence of variable concentrations of Z-Leu-Leu-Leu-aldehyde (LLL-CHO), a proteasome inhibitor. During this process, apoptosis of synovial cells was determined by Hoechst 33258 dye staining and 51 Cr release assay.

SummaryA 36-month observational study compared the incidence of unaffected side hip fracture in Japanese female osteoporosis patients with a history of hip fracture between 173 patients receiving risedronate and 356 risedronate-untreated controls. New hip fractures were significantly less frequent in the risedronate group, suggesting a preventive effect in high-risk patients.IntroductionThe purpose of this study was to investigate the preventive effect of risedronate on second hip fracture immediately following a first hip fracture in Japanese female osteoporosis patients with unilateral hip fracture.MethodsWe conducted a prospective matched cohort study in 184 patients treated with risedronate and 445 patients not receiving risedronate after discharge from hospital. Both groups were followed-up for 36 months, and the incidence of unaffected side hip fracture and the frequency of adverse events were assessed.ResultsEfficacy could be investigated in 173 patients from the risedronate group and 356 patients from the control group. Hip fracture was detected in 5 and 32 patients, respectively. Kaplan–Meier estimates of the 36-month fracture incidence were 4.3% in the risedronate group and 13.1% in the control group (P = 0.010, log-rank test). The hazard ratios (95% confidence intervals) obtained by univariate and multivariate analysis were 0.310 (0.121–0.796) and 0.218 (0.074–0.639), respectively, indicating a significantly lower incidence of unaffected side hip fracture in the risedronate group. Adverse events occurred in 38 patients (48 events) from the risedronate group and 94 patients (108 events) from the control group, with serious adverse events in 21 patients (26 events) and 78 patients (88 events), respectively.ConclusionsNo significant differences were observed between the two groups. The incidence of unaffected side hip fracture was significantly lower in the risedronate group. Accordingly, risedronate may have a preventive effect on hip fracture in high-risk Japanese female osteoporosis patients for fracture with a history of unilateral hip fracture.

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