Long-Term Safety and Efficacy of Subcutaneous Tanezumab Versus Nonsteroidal Antiinflammatory Drugs for Hip or Knee Osteoarthritis: A Randomized Trial.

OBJECTIVE: To assess the long-term safety and 16-week efficacy of subcutaneous tanezumab in patients with hip or knee osteoarthritis (OA). METHODS: This was a phase III randomized, double-blind, active treatment-controlled (using nonsteroidal antiinflammatory drugs [NSAIDs] as the active treatment control) safety trial of tanezumab (56-week treatment/24-week posttreatment follow-up) in adults who were receiving stable-dose NSAID therapy at the time of screening and who had Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function scores of ≥5; patient global assessment (PtGA) of OA of fair, poor, or very poor; history of inadequate pain relief with standard analgesics; and no history or radiographic evidence of prespecified bone/joint conditions beyond OA. Patients received oral naproxen, celecoxib, or diclofenac twice daily (NSAID group; n = 996) or tanezumab 2.5 mg (n = 1,002) or 5 mg (n = 998) subcutaneously every 8 weeks. Coprimary efficacy end points at week 16 were changes in WOMAC pain and physical function scores and changes in PtGA. The primary joint safety end point over 80 weeks comprised adjudicated rapidly progressive OA type 1 or 2, primary osteonecrosis, subchondral insufficiency fracture, or pathologic fracture. Mean values, least squares mean values, and least squares mean differences between groups (with 95% confidence intervals [95% CIs]) were calculated. RESULTS: Of 3,021 randomized patients, 2,996 received ≥1 treatment dose. Adverse events (AEs) were similar between patients treated with tanezumab 2.5 mg and those treated with NSAIDs, and were more prevalent in those treated with tanezumab 5 mg. Composite joint safety events were significantly more prevalent with tanezumab 2.5 mg and tanezumab 5 mg than with NSAIDs (observation time-adjusted rate/1,000 patient-years 38.3 [95% CI 28.0, 52.5] and 71.5 [95% CI 56.7, 90.2], respectively, versus 14.8 [95% CI 8.9, 24.6]; P = 0.001 for tanezumab 2.5 mg versus NSAIDs; P < 0.001 for tanezumab 5 mg versus NSAIDs). Tanezumab 5 mg significantly improved pain and physical function but did not improve PtGA at week 16 when compared to NSAIDs; corresponding differences between the tanezumab 2.5 mg and NSAID groups were not statistically significant. CONCLUSION: In patients previously receiving a stable dose of NSAIDs, tanezumab administered subcutaneously resulted in more joint safety events than continued NSAIDs, with differences being dose dependent. Pain and physical function improved with both doses of tanezumab compared to NSAIDs, reaching statistical significance with tanezumab 5 mg at 16 weeks.

Effect of eldecalcitol on muscle function and fall prevention in Japanese postmenopausal women: A randomized controlled trial.

BACKGROUD: Exercises and vitamin D interventions have shown to improve muscle function and balance, and prevent falls in postmenopausal healthy women and in patients with osteoporosis. However, the effects of eldecalcitol on these factors remain undetermined. The present open-label, randomized, controlled study aimed to investigate the effects of eldecalcitol treatment in reducing falls in postmenopausal women, and improving muscle function and balance. METHODS: The study population included 226 Japanese postmenopausal women with osteoporosis. Patients were randomly divided into two groups on the basis of treatment with or without eldecalcitol (0.75 µg/day). Treatment continued for 6 months. Participants in both groups were instructed to perform back extensor muscle exercise. Isometric back extensor and leg extensor strength, grip power, ten-meter walking speed, timed up and go test and time of single leg standing were measured at baseline and 24 weeks. Patients were asked to record the number of falls during the 24-week period. RESULTS: The percentage increase in average bilateral quadriceps muscle strength was significantly higher in the eldecalcitol group compared with the non-eldecalcitol group (right, p = 0.041; left, p = 0.042). In contrast, there were no significant differences in the strength of back muscles and grip power and the parameters of balance and walking abilities between the groups. There was no significant difference in the number of falls between the groups. CONCLUSIONS: A 24-week intervention of eldecalcitol improves the strength of the quadriceps muscles in postmenopausal women with osteoporosis. However, eldecalcitol neither improve balance and walking abilities nor reduce the number of falls.

Correction to: Effectiveness of monthly intravenous ibandronate on the low responders to oral bisphosphonate: the MOVEMENT study.

In the original publication of the article, the Figures 2 and 3 were published incorrectly. The corrected figures are given below.

Effectiveness of monthly intravenous ibandronate on the low responders to oral bisphosphonate: the MOVEMENT study.

The MOVEMENT study was designed to assess the effectiveness of monthly intravenous ibandronate on bone mineral density (BMD) in daily clinical practice in Japanese patients with primary osteoporosis whose lumbar spine BMD did not increase despite oral bisphosphonate therapy. This study was a multicenter, prospective, interventional study (52 sites; August 2015 to March 2018). Patients aged ≥ 50 years with primary osteoporosis, evaluated as low responders to oral bisphosphonate treatment for 1-3 years, continued on their existing oral bisphosphonate or switched to monthly intravenous ibandronate (1 mg) for 12 months. The primary endpoint was change in lumbar spine BMD from baseline to 12 months in the intravenous ibandronate group (IV IBN). A total of 240 and 141 patients were enrolled in the IV IBN and oral bisphosphonate groups (OBP), respectively. At 12 months, a significant increase in mean percent change from baseline in lumbar spine BMD was observed in the IV IBN (2.70%). This change was also significant at 6 months (1.92%). Similarly, the change in total hip BMD showed a significant increase at 12 months (0.78%). In the IV IBN, the responder rate, percentage of patient whose change from baseline of lumbar spine BMD has greater than 0%, for lumbar spine BMD was high at both 6 (72.3%, 141/195 patients) and 12 (78.0%, 145/186 patients) months. No new safety concerns were observed in either treatment group. Treatment with intravenous ibandronate significantly increased lumbar spine BMD without any new safety concerns in Japanese patients with osteoporosis who showed low response to existing oral bisphosphonates.

Prediction of pathological fracture of the femoral shaft with an osteolytic lesion using a computed tomography-based nonlinear three-dimensional finite element method.

BACKGROUND: Physicians radiologically estimate the reduction in bone strength based on the size or location of bone tumors. The goal of this study was to clarify the relationship between the size or location of a bony defect and its mechanical strength using a computed tomography-based three-dimensional finite element method. METHODS: Computed tomography data of the right femur from two volunteers (one healthy male and one female patient with primary osteoporosis) were used for the present study. A spherical defect of various sizes and locations at the level of the isthmus of the femoral shaft was created on the three-dimensional finite element models to simulate the osteolytic bone tumor. We classified these defects into three types: inner erosion, cortical disruption, and outer erosion. Two types of mechanical testing were performed: axial compression and torsion. RESULTS: In the axial compression testing of the healthy male subject, the correlation coefficients between the defect rate and the failure load in the cortical disruption type, inner erosion type, and outer erosion type were -0.916, -0.358, and -0.106, respectively. In the torsion testing, they were -0.8744, -0.9001, and -0.8907, respectively. In the axial compression testing of the osteoporotic female subject, the correlation coefficients in the cortical disruption type, inner erosion type, and outer erosion type were -0.754, -0.621, and -0.158, respectively. In the torsion testing, they were -0.9199, -0.5098, and -0.8363, respectively. In both tests, the defect rate of the cortex increased and the bone strength decreased, especially in the cortical disruption type. CONCLUSION: The results of the present study demonstrate that osteolytic bone tumors can weaken the bone strength, particularly when perforation of the cortex occurs via tumor invasion. These results may be useful for risk assessment of pathological fractures due to primary and metastatic osteolytic bone tumors in clinical practice.

Repeated hemarthrosis with massive rotator cuff tear.

An 80-year-old woman with repeated hemarthrosis of the right shoulder was examined and treated arthroscopically. Plain radiographs indicated narrowing of the acromiohumeral interval (3 mm) with large acromial spur. Under fluoroscopic visualization, the impingement between the humeral head and the medial edge of the acromion was seen at 50 degrees abduction. The area of impingement of the humeral head seemed to be just medial to the greater tuberosity. Arthroscopically, a crater formation was seen at this site. Active bleeding was seen at the center of the crater, which was interpreted as the principal cause of intra-articular hemorrhaging. The undersurface of the acromion was irregular because of the presence of osteophyte. At 50 degrees abduction, the crater impinged with the medial edge of the acromion. We assume that both the presence of osteophyte and the instability caused by the massive rotator cuff tear might contribute to the attrition of the humeral head. In this patient, intra-articular hemorrhaging was successfully treated arthroscopically by coagulation of the bleeding point with minimal abrasion of the undersurface of the acromion. We believe that the arthroscopy facilitated the clinical management of the repeated hemarthrosis with massive rotator cuff tear.