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The positive link between osteoporosis and hypercholesterolemia has been documented, and bone resorption inhibitors, such as nitrogen-containing bisphosphonates (N-BP) and selective estrogen receptor modulators (SERMs), are known to reduce serum cholesterol levels. However, the relationship between the baseline cholesterol level and incident fracture rate under the treatment using the bone resorption inhibitors has not been documented. We investigated the relation between vertebral fracture incident and the baseline cholesterol levels and cholesterol-lowering effect of N-BP and SERM in osteoporosis through a prospective randomized open-label study design. Patients with osteoporosis (n = 3986) were allocated into two groups based on the drug used for treatment: minodronic acid (MIN) (n = 1624) as an N-BP and raloxifene (RLX) as an SERM (n = 1623). Serum levels of cholesterol and incidence of vertebral fracture were monitored for 2 years. The vertebral fracture rates between the two groups were compared using the pre-specified stratification factors. The patients receiving MIN with baseline low-density lipoprotein (LDL)-cholesterol level of ≥ 140 mg/dL, high-density lipoprotein cholesterol level p = 0.001], 0.25 [95% CI 0.09 0.65, p = 0.005], 0.71 [95% CI 0.56 0.91, p = 0.006], 0.47 [95% CI 0.30 0.75, p = 0.0012], respectively). The cholesterol-lowering effect was stronger in the RLX group than in the MIN group, regardless of prior statin use. These results indicated that MIN treatment was more effective in reducing fracture risk in patients with higher LDL cholesterol levels, although its cholesterol-lowering ability was lesser than the RLX treatment.Trial registration University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR), No. UMIN000005433; date: April 13, 2011.

Eribulin therapy has been reported to prolong overall survival (OS) but not progression-free survival, probably because it prevents the development of metastatic lesions; however, this effect has not yet been confirmed.We reviewed the medical charts of 50 patients with metastatic breast cancer who underwent eribulin monotherapy at our hospital between 2014 and 2019. Patients were divided into two groups, namely, those who discontinued eribulin because of disease progression due to development of new lesions (NL group) and those who discontinued eribulin for other reasons, such as lesion growth and unacceptable side effects (non-NL group). Survival times were estimated for both groups and we investigated if eribulin-mediated suppression of new metastasis increased OS.Median OS for all patients, from eribulin initiation, was 14.4 months (range 1.2-60.1), whereas it was 4.6 months (range 1.7-24.7) in the NL group and 16.8 months (range 1.2-60.1) in the non-NL group. OS was significantly poorer in the NL group than in the non-NL group (p0.05).Eribulin monotherapy-mediated suppression of new metastatic lesions results in a better prognosis in patients with metastatic breast cancer.

To identify predictors for incident fractures in patients on pharmaceutical treatment for osteoporosis by a secondary analysis of the Japanese Osteoporosis Intervention Trial protocol number 4 (JOINT-04), which was a 2-year, randomized, parallel-group, controlled trial of minodronate and raloxifene in women with primary osteoporosis. This was a prospective, observational study using JOINT-04 data, in which biomarkers, such as undercarboxylated osteocalcin (ucOC), N-telopeptide of type 1 collagen, tartrate-resistant acid phosphatase 5b (TRACP-5b), bone alkaline phosphatase, homocysteine, and pentosidine in blood, and physical functions, such as the timed up and go test and one-leg standing test with eyes open (OLST), and the fall risk index, were measured. The relationships of incident morphometric vertebral fractures during the treatment period, as well as prevalent vertebral fractures, and baseline data were analyzed. The full analysis set of the JOINT-04 included 3247 patients (1623 in the minodronate group and 1624 in the raloxifene group). The hazard ratio (95% confidence interval) for incident vertebral fractures over 2 years of pharmacotherapy, adjusted for confounders, was 0.93 (0.90–0.96) for ucOC, 1.15 (1.08–1.23) for TRACP-5b, 1.02 (1.01–1.03) for pentosidine, 0.91 (0.88–0.94) for the OLST, and 1.27 (1.01–1.60) for the fall risk index, which were all independent predictors. Evaluating fracture risk for patients with osteoporosis considering these potential risk factors for fracture in addition to the established risk factors may be useful when starting pharmaceutical treatment.

In this randomized, controlled trial, sequential therapy with once-weekly subcutaneous injection of teriparatide for 72 weeks, followed by alendronate for 48 weeks resulted in a significantly lower incidence of morphometric vertebral fracture than monotherapy with alendronate for 120 weeks in women with osteoporosis at high risk of fracture.To determine whether the anti-fracture efficacy of sequential therapy with teriparatide, followed by alendronate is superior to that of monotherapy with alendronate, a prospective, randomized, open-label, blinded-endpoint trial was performed.Japanese women aged at least 75 years were eligible for the study, if they had primary osteoporosis and if they were at high risk of fracture. Patients were randomly assigned (1:1) to receive the sequential therapy (once-weekly subcutaneous injection of teriparatide 56.5 μg for 72 weeks, followed by alendronate for 48 weeks) or monotherapy with alendronate for 120 weeks. The primary endpoint in the final analysis was the incidence of morphometric vertebral fracture during the 120-week follow-up period.Between October 2014 and June 2020, 505 patients in the sequential therapy group and 506 in the monotherapy group were enrolled. Of these, 489 and 496, respectively, were included in the main analysis. The incidence of morphometric vertebral fracture during the 120-week follow-up period in the sequential therapy group (64 per 627.5 person-years, annual incidence rate 0.1020) was significantly lower than that in the monotherapy group (126 per 844.2 person-years, annual incidence rate 0.1492), with a rate ratio of 0.69 (95% confidence interval 0.54 to 0.88, P 0.01). After 72 weeks, no patient had a severe adverse event that was considered related to the study drug.Once-weekly injection of teriparatide, followed by alendronate resulted in a significantly lower incidence of morphometric vertebral fracture than alendronate monotherapy in women with osteoporosis who were at high risk of fracture. TRIAL REGISTRATION NUMBER, DATE OF REGISTRATION: jRCTs031180235 and UMIN000015573, March 12, 2019.

CAM software is generally used to generate tool paths for 5-axis controlled machining. However, adjusting its several parameters and settings is difficult. We propose a system for tool path generation to be applied to 5-axis controlled machining. The system allows machining movements to be established by manipulating haptic devices in a virtual environment. Therefore, the cutter location for 5-axis machining can be easily controlled by operating a virtual cutting tool. The contact between the cutting tool and the target shape is reflected to the user through the haptic device. The generated path can be converted into a numerical control program for the actual machining of the target object. We detail the implementation of the proposed interface using two haptic devices and a method of tool path generation that improves rough cutting by smoothing the generated cutting points and simplifying the tool postures. The effectiveness of the developed system is confirmed through machining simulations.

Despite advances in drug treatment, the optimal treatment strategy for severe osteoporosis remains uncertain. This article reports the design and rationale for the Japanese Osteoporosis Intervention Trial-05 (JOINT-05), a randomized, controlled trial that compares the efficacy and safety of teriparatide followed by alendronate with alendronate monotherapy for severe osteoporosis. Postmenopausal women aged at least 75 years were eligible for the study if they were at high risk of fracture. Patients were recruited from 113 institutions in Japan between October 2014 and December 2017. They were randomly assigned in a 1:1 ratio to the sequential therapy arm (once-weekly subcutaneous injections of teriparatide 56.5 μg for 72 weeks followed by alendronate for 48 weeks) or monotherapy arm (alendronate for 120 weeks). The regimens for alendronate are 5 mg (orally administered once daily), 35 mg (orally administered once weekly), or 900 μg (intravenously administered once every 4 weeks). The primary endpoint is the incidence of morphometric vertebral fracture at 72 weeks. The secondary endpoints include the incidence of morphometric vertebral fracture at 120 weeks; incidence of morphometric vertebral or non-vertebral fractures at 72 and 120 weeks; incidence of clinical vertebral fracture at 72 and 120 weeks; changes in bone mineral density, quality of life scores (EuroQol 5 Dimensions and the Japanese Osteoporosis Quality of Life Questionnaire short form), and a visual analog scale for back pain; and adverse events. We reported the design and rationale for the JOINT-05. The trial is registered with the Japan Registry of Clinical Trials (jRCTs031180235) and the University Hospital Medical Information Network-Clinical Trials Registry (UMIN000015573).

Background: Surgical treatment of breast cancer patients aged 85 years or older is still controversial. Methods: A series of surgically treated breast cancer patients aged 85 years or older was evaluated. The clinicopathological features and outcomes of these patients were compared with the features and outcomes of breast cancer patients in the same age group who were managed without surgery. Results: A total of 45 patients (75%) received surgical treatment, and 15 patients (25%) were managed without surgery. The differences between ages, tumor status, nodal status, stage and immunopathological status of the patients undergoing and not undergoing surgery were not significant. Significantly more patients treated by surgery underwent systemic treatment than patients managed without surgery (P=0.004). The three-year disease-free survival rate of patients treated by surgery was higher than that of the patients managed without surgery (90.6% vs 67.5%, respectively; PConclusions: The surgical treatment of breast cancer patients aged 85 years or older is warranted. This outcome was achieved with the use of hormonal therapy.

Japanese postmenopausal women with symptomatic periodontal disease had a significantly smaller increase in the T-score for total hip bone density than those without periodontal disease during medication therapy for osteoporosis. Intervention to treat symptomatic periodontal disease before and/or during osteoporosis therapy could maintain the effect of osteoporosis medications.Women with periodontal disease may be more likely to develop osteoporosis. We evaluated whether the presence of symptomatic periodontal disease can influence changes in skeletal bone mineral density (BMD) during medication therapy for osteoporosis in Japanese postmenopausal women.A total of 4,258 postmenopausal women participated in the Japanese Osteoporosis Intervention Trial protocol number 4 (JOINT-04 trial) and number 5 (JOINT-05 trial), which were multi-center, open-label, randomized controlled trials in Japan. Of these, 3,670 non-edentulous subjects participated in the study. Subjects who had self-reported symptoms of periodontal disease at baseline were defined as having periodontal disease. The study outcome was the difference in BMD changes during the study between subjects with and without periodontal disease. Mixed models for repeated measures after adjusting for covariates were used to investigate the difference in the BMD changes during the study between subjects with and without periodontal disease.Subjects with periodontal disease had significantly lower T-scores for total hip (p = 0.035) and metacarpal (p = 0.048) BMD than those without periodontal disease at baseline. During medication therapy for osteoporosis, subjects with periodontal disease had a significantly smaller increase in T-score for total hip BMD than those without periodontal disease (p = 0.021), although no significant differences were observed in the changes in T-scores for other skeletal BMD measurements between subjects with and without periodontal disease.The presence of self-reported symptoms of periodontal disease may be associated with a decrease in the effect of osteoporosis medications in Japanese postmenopausal women.

Background: The impact of the neutrophil–lymphocyte ratio (NLR) on the survival outcomes of patients with early-stage breast cancer is controversial. Methods: We reviewed a series of 115 breast cancer patients who received neoadjuvant chemotherapy followed by surgical treatment. The NLR was calculated using a blood sample obtained before neoadjuvant chemotherapy. The relationships of disease-free survival with the NLR as well as other clinicopathological factors were assessed.Results: There was no significant association between the NLR and disease-free survival in these patients. On the other hand, negative estrogen receptor and progesterone receptor statuses, extended nodal involvement, and advanced TNM stage were significant predictors of shorter disease-free survival.Conclusions: The NLR has little impact on the survival of early-stage breast cancer patients treated with neoadjuvant chemotherapy followed by surgical treatment.

Summary In this randomized, controlled trial, treatment with once-weekly subcutaneous injection of teriparatide for 72 weeks was found to be associated with a significant reduction in the incidence of morphometric vertebral fractures compared with alendronate in women with primary osteoporosis who were at high risk of fracture. Introduction To determine whether the anti-fracture efficacy of teriparatide is superior to that of alendronate, a prospective, randomized, open-label, blinded-endpoint trial was performed. Methods Japanese women aged at least 75 years were eligible for the study if they had primary osteoporosis and were at high risk of fracture. Patients were randomly assigned in a 1:1 ratio to receive sequential therapy (once-weekly subcutaneous injection of teriparatide 56.5 μg for 72 weeks followed by alendronate for 48 weeks) or monotherapy with alendronate for 120 weeks. The primary endpoint was the incidence of morphometric vertebral fractures at 72 weeks (at the end of teriparatide treatment). Results Between October 2014 and December 2017, 1011 patients (505 in the teriparatide group and 506 in the alendronate group) were enrolled. Of these, 778 patients (351 and 427, respectively) were included in the primary analysis. The incidence of morphometric vertebral fractures was significantly lower in the teriparatide group (56 per 419.9 person-years, annual incidence rate 0.1334) than in the alendronate group (96 per 553.6 person-years, annual incidence rate 0.1734), with a rate ratio of 0.78 (95% confidence interval 0.61 to 0.99, P = 0.04). In both groups, adverse events were most frequently reported in the following system organ classes: infections and infestations, gastrointestinal disorders, and musculoskeletal and connective tissue disorders. Conclusion Once-weekly subcutaneous injection of teriparatide significantly reduced the incidence of morphometric vertebral fractures compared with alendronate in women with primary osteoporosis who were at high risk of fracture. Trial registration jRCTs031180235 and UMIN000015573, March 12, 2019 Supplementary Information The online version contains supplementary material available at 10.1007/s00198-021-05996-2.

Background: Data on the postoperative outcomes of extremely elderly patients with breast cancer are lacking. Methods: We evaluated a series of 46 breast cancer patients aged 85 years or older (mean age: 87.4 years) who underwent surgical treatment, accumulated over the past 10 years. Results: The most common comorbidity was hypertension. Sixteen patients (34.8%) did not receive axillary treatment. The mean hospital stay was 12.8 days, and no in-hospital deaths were recorded. The 5-year overall survival rate was 78.2% (95% confidence interval: 63.5–96.3) over a median follow-up of 41 months.Conclusions: Surgical treatment of breast cancer patients aged 85 years or older is warranted.

We conducted a head-to-head randomized trial of minodronate, a bisphosphonate, and raloxifene, a selective estrogen receptor modulator, to obtain clinical evidence and information about their efficacy and safety. The Japanese Osteoporosis Intervention Trial protocol number 4 (JOINT-04) trial is a multi-center, open-labeled, blinded endpoints, head-to-head randomized trial of minodronate and raloxifene. Ambulatory elderly women with osteoporosis (age, >60 years) were randomly allocated to the raloxifene or minodronate group by central registration. The co-primary endpoints included any one of osteoporotic fractures (vertebral, humeral, femoral, and radial fractures), vertebral fractures, and major osteoporotic fractures (clinical vertebral, humeral, femoral, and radial fractures). The biological effects of each drug, patients’ quality of life, and drug safety were assessed based on the secondary outcomes. This study was registered at the University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) under trial identification number UMIN000005433. A total of 3896 patients were randomized to the minodronate and raloxifene groups, and drug efficacy assessments were performed for 3247 patients (1623 and 1624 patients, respectively). Among these patients, 1176 and 1187 patients received allocated treatment for 2 years. The incidence rate ratios for osteoporotic, vertebral, and major osteoporotic fractures in the minodronate group were 0.94 (95% CI: 0.78–1.13, p = .494), 0.86 (95% CI: 0.70–1.05, p = .147), and 1.22 (95% CI: 0.86–1.74, p = .274), respectively. Compared to the raloxifene group, the minodronate group showed significantly increased bone mineral density of the lumbar spine for each visit (6 months: p = .007, 12 months: p = .0003, 24 months: p Overall, there were no statistical differences in the incidence rates of osteoporotic, vertebral, or major osteoporotic fractures between the two groups. Serious adverse reactions were rare in both groups.

A Mn-Zn-Fe ferrite layer, several hundred nanometers thick, was deposited on the surface of Fe-3.5Si-4.5Cr (mass%) powder particles as an insulating material by an ultrasonic enhanced ferrite plating method. The compositions of the Mn-Zn-Fe ferrite layer were Mn0.18Zn0.27Fe2.55O4, Mn0.38Zn0.25Fe2.37O4, and Mn0.54Zn0.24Fe2.22O4. The core loss (Pcv) performances of the compacted cores and magnetic properties of the core-shell structured powders were evaluated. All the ferrite-coated cores exhibited a saturation flux density (Bs) in the range of 1.54–1.56 T derived from their soft magnetic metal and ferrite composition. All ferrite-coated cores annealed at 773 K exhibited a constant permeability µ′ in the frequency range up to 50 MHz owing to the insulating effect of the ferrite layer, and the Mn0.54Zn0.24Fe2.22O4 ferrite-coated core exhibited the highest real permeability µ′ of 56 at 50 MHz. The core loss of the Mn-Zn-Fe ferrite-coated Fe-3.5Si-4.5Cr cores was 604–738 kW/m3 at 100 kHz and 50 mT, which was much smaller than that obtained for the Fe-3.5Si-4.5Cr core without a ferrite layer (3617 kW/m3). The eddy-current loss (Pe) of the Mn-Zn-Fe ferrite-coated Fe-3.5Si-4.5Cr cores considerably decreased compared with those of the non-coated Fe-3.5Si-4.5Cr core owing to the insulating properties of the ferrite layer.

Background The Japanese Orthopaedic Association (JOA) has been surveying approximately 3000 orthopedic surgery hospitals and clinics with inpatient facilities nationwide to collect information on atypical femoral fractures (AFFs) and patient characteristics since 2010. The present study aims to examine radiographic images and clarify the relationship between radiographic and patient characteristics of patients with AFF and treatment status. Methods The study involved 1996 facilities certified as clinical training sites by the JOA and 912 clinics with inpatient facilities affiliated with the Japanese Clinical Orthopaedic Association (JCOA). Additional clinical data collection and radiographic image review were performed in patients aged 35 years or older who met the American Society for Bone and Mineral Research (ASBMR) case definition for AFF and received treatment at participating facilities registered with JOA in 2013. Radiographic images were evaluated in accordance with the ASBMR case definition. Results Radiographic images of 304 fractures in 304 patients were collected. Among them, 230 fractures were determined to be AFFs. The fracture site was the proximal third in 70 AFFs (30.4%), middle third in 157 AFFs (68.3%), and distal third in 3 AFFs (1.3%). Among patients with AFFs, 173 (75.2%) were treated with bisphosphonates (BPs) and 45 patients (19.6%) were not (unknown in 12 patients). Duration of use was three years or longer in 103 patients (59.5%) and between one and three years in 24 patients (13.9%). Radiographic beaking was observed in 149 fractures (86.1%) in patients treated with BPs and 17 fractures (37.8%) in patients who were not treated with BPs (odds ratio 11.3, 95% CI 5.7–22.3). Conclusions Radiographic beaking was observed more frequently in patients treated with BPs than in patients not treated with BPs.

Background A nationwide survey of hip fractures by the Japanese Orthopaedic Association (JOA) from 1998 to 2008 found a drastic increase in incidence. The aims of this study were to elucidate the status of hip fractures from 2009 to 2014 and to survey the causes for delayed surgery. Methods A tally of all hip fractures that occurred in patients from 2009 to 2014 was conducted in hospitals authorized by the JOA or in clinics with inpatient facilities of the Japanese Clinical Orthopaedic Association (JCOA). A survey of the causes for delay in surgery was conducted at 849 sites and 526 sites participated. Results A total of 488,759 hip fractures were registered. Increases in incidence from 2009 to 2014 were prominent in the 90–94-year-old age group among women and the 85–89-year-old age group among men. More trochanteric fractures than neck fractures occurred; however, the neck/trochanter ratio increased over time. The mean duration of preoperative hospital stay was 4.8 and 4.5 days, and the mean duration of hospitalization was 40.5 and 36.8 days in 2009 and 2014, respectively. There were significant differences between patients who waited for surgery up to 3 days and those who waited longer than 3 days in date of hospitalization, fracture type, comorbidities, anticoagulant use, surgical procedure, type of physician who administered anesthesia, type of anesthesia, and operating room schedule. Physicians in charge of each patient who waited for surgery for more than 3 days most frequently cited difficulties in securing operating rooms as the cause for delayed surgery. Conclusion A drastic increase occurred in the number of patients with hip fractures with time in Japan. One problem in the treatment of hip fractures is the long waiting time from hospitalization to surgery resulting from difficulties in securing operating rooms.

A 75-year-old man noted an elastic hard tumor under his left areola.Mammography showed a microlobulated mass, so he was diagnosed with category Ⅳ breast cancer.Ultrasonography showed a circular hypo-echoic mass that was 21mm in diameter with a moderately indistinct border.Based on core needle biopsy, the tumor was diagnosed as invasive ductal carcinoma.We performed a whole-body check-up, and he was diagnosed with T1N0M0, StageⅠ breast cancer.The patient underwent mastectomy and sentinel lymph node biopsy.The pathological diagnosis based on the resected surgical specimen was invasive ductal carcinoma, positive for ER and negative for PgR and HER2/neu protein expression, and the Ki-67 positive cell index was 20%.The surgical margins were negative, and there was no metastasis in the sentinel lymph nodes.He was administered endocrine therapy as adjuvant therapy.Two years after the surgery, he remains well without metastases.