A crossover comparison of patient satisfaction with two teriparatide regimens: primary results of the Japanese Osteoporosis Intervention Trial 06 (JOINT-06).

INTRODUCTION: This study aimed to compare treatment satisfaction with two dosing regimens (two teriparatide [TPTD] self-injection systems) in osteoporosis patients at high risk of fracture. MATERIALS AND METHODS: In this open-label crossover randomized trial comparing self-injected once-daily (1/D)-TPTD with self-injected twice-weekly (2/W)-TPTD, three satisfaction variables were evaluated by questionnaire for 2 years. The primary endpoint was overall satisfaction and secondary endpoints were satisfaction with treatment effectiveness and with utility of the self-injection device. Changes in quality of life (QOL) assessed by EuroQol-5 Dimension, pain assessed by visual analogue scale (VAS), and anthropometric parameters were also analyzed. Safety was evaluated based on the incidence and severity of adverse events (AEs). RESULTS: The 1/D-TPTD and 2/W-TPTD groups consisted of 180 (75.9 ± 7.3 years) and 179 (age: 75.5 ± 6.9 years) patients, respectively. After 26 weeks of treatment, no significant between-group difference in the persistence rate (79.4% vs 72.6% in the 1/D-TPTD and 2/W-TPTD groups, respectively), distributions of overall satisfaction scores, and satisfaction with treatment (p > 0.05) were observed. However, several items of satisfaction with the utility of the injection device were significantly higher in the 2/W-TPTD group (p < 0.05). Statistical improvements from baseline values were observed in QOL and pain VAS in both groups (p < 0.05). No serious AEs were reported. CONCLUSION: The between-group similarity of overall treatment satisfaction and effectiveness scores and between-group difference in satisfaction with the utility of the self-injection device was useful information for real-world treatment of osteoporosis. Both medication regimens were well tolerated.

Bone parameters of elite athletes with oligomenorrhea and prevalence seeking medical attention: a cross-sectional study.

INTRODUCTION: Since the definition of secondary amenorrhea is cessation of regular menses for more than 3 months, it is likely that athletes with irregular menstrual cycles, including oligomenorrhea, do not consider the condition as serious. However, the consequences of untreated oligomenorrhea have not been investigated in elite track and field athletes. MATERIALS AND METHODS: The cohort consisted of 91 elite-level track and field athletes. Body compositions, including bone parameters and bone turnover markers (BTMs), were measured. RESULTS: Among the 91 participants, 52 were eumenorrheic and 33 were oligomenorrheic. The eumenorrheic athletes had significantly higher bone mineral density (BMD) and bone mineral content (BMC) of the lumbar spine, lower extremities, and whole body than had the oligomenorrheic athletes (p < 0.01). There were no significant differences in BTMs between the two groups, but oligomenorrheic athletes had significantly lower percent body fat. CONCLUSION: More than 40% of the elite-level female track and field athletes in this study reported menstrual disorders with oligomenorrhea as the most common. However, none sought medical attention. As compared to the eumenorrheic athletes, the oligomenorrheic athletes had lower BMC and BMD. Hence, if an athlete is oligomenorrheic, bone parameter measurements are considerably important.

Bone Metabolism, Bone Mineral Content, and Density in Elite Late Teen Female Sprinters.

With intensive training, bone injuries are a major concern for athletes. To assess bone condition, we often measure bone turnover markers, bone mineral content and density; however, in junior athletes, it is not easy to distinguish changes caused by bone injuries from those caused by growth, because the metabolism is increased in both cases. Moreover, although some studies have examined female endurance athletes, knowledge regarding changes in static and dynamic bone conditions in late teen athletes is limited. In this study, we measured the bone mineral content and density, as well as bone turnover markers, in 40 elite female sprinters in their late teens. Whole body mode dual-energy X-ray absorptiometry was performed to measure bone mineral content and density. Blood samples were collected to determine bone resorption and formation markers at the end of track season in 2016 and during the same period of the following year. Body weight and bone mineral content significantly increased, and tartrate-resistant acid phosphatase type 5b, bone-type alkaline phosphatase, and osteocalcin significantly decreased after a year. Furthermore, the rate of change in bone mineral content was higher in younger athletes, indicating that bone growth approaches completion in the late teen years and that bone metabolism accordingly decreases.

Retraction Note to: Effect of whole-body vibration exercise on lumbar bone mineral density, bone turnover, and chronic back pain in post-menopausal osteoporotic women treated with alendronate.

The Editor-in-Chief has retracted this article [1] because an investigation by Keio University has concluded that there are inaccuracies in the data reported.

Treatment status and radiographic features of patients with atypical femoral fractures.

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.

Survey of hip fractures in Japan: Recent trends in prevalence and treatment.

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.

[Calcium and bone metabolism across women's life stages. Exercise and sport to increase bone strength in accordance with female lifecycle.]

Among females who require the strategies for preventing osteoporosis, appropriate exercise and sport through all their life are important to increase or maintain bone mass. However, the type of exercise and sport applied to females is different in accordance with the lifecycle. Jumping exercise increases bone mineral content(BMC)in prepubescent children(premenarcheal girls). Bone mineral density(BMD)is higher in adolescent athletes who are engaged in weight-bearing activities. Jumping exercise, muscle strengthening exercise, and weight-bearing plus muscle strengthening exercises increase BMD in young adults and premenopausal women. Walking, aerobic weight-bearing exercise, muscle strengthening exercise, and weight-bearing plus muscle strengthening exercises maintain or increase BMD in postmenopausal women. Thus, appropriate exercise and sport in accordance with the lifecycle are important strategies for preventing osteoporosis in females.

[A role of exercise and sports in the prevention of osteoporosis.]

Physical activity plays an important role in maintaining or enhancing bone health. Jumping exercise increases bone mineral content(BMC)in prepubescent children(premenarcheal girls). Bone mineral density(BMD)is higher in adolescent athletes who are engaged in weight-bearing activities. Jumping exercise, muscle strengthening exercise, and weight-bearing plus muscle strengthening exercises increase BMD in young adults and premenopausal women. Walking, aerobic weight-bearing exercise, muscle strengthening exercise, and weight-bearing plus muscle strengthening exercises maintain or increase BMD in postmenopausal women. Proper exercise and sports activity at each life stage are important strategies for preventing osteoporosis.

[The Effects of Exercising in Childhood on Bone Health.]

In contemporary Japan, there is a polarizing trend in children who exercise more than 1,800 minutes a week and those who exercise less than 60 minutes a week. Quite a lot of girls in particular hate exercise,and therefore they don't get enough of it. Osteoporosis is a preventable disease from childhood. It is crucial for girls to exercise and to provide appropriate stimulation to bones before menarche, which increases bone mineral content. Exercise and sports in childhood are characterized as the ways to the lifelong prevention strategies against osteoporosis and fractures. It is hoped that all children practice appropriate exercise program based on scientific evidence to promote bone health. In this review article, the effects of exercising in childhood on bone health, and the points to be noted regarding childhood sports are described.

Influence of Teriparatide and Ibandronate on Cortical Bone in New Zealand White Rabbits: A HR-QCT Study.

Teriparatide (TPTD) is known to increase the cortical thickness and porosity. The purpose of the present study was to determine whether switching from TPTD to ibandronate (IBN) would be useful for improving cortical bone parameters as assessed using high-resolution quantitative computed tomography (HR-QCT) analyses in mature rabbits. Forty-two female New Zealand white rabbits (18-22 weeks old) were randomized into six groups of 7 animals each as follows: 4-week vehicle administration group, 4-week TPTD administration group (20 µg/kg, subcutaneously [s.c.], daily), 12-week vehicle administration group, 4-week TPTD administration + 8-week vehicle administration group, 4-week TPTD administration + 8-week lower-dose IBN administration group (20 µg/kg, s.c., every 4 weeks), and 4-week TPTD administration + 8-week higher-dose IBN administration group (100 µg/kg, s.c., every 4 weeks). After the 4- or 12-week experimental period, the cortical bone of the distal femoral diaphysis was processed for HR-QCT analysis. The 4-week TPTD administration increased the pore ratio, number, and density as well as the cortical area, thickness, and bone mineral content (BMC), without significant influencing the volumetric bone mineral density (BMD). The 4-week TPTD administration + 8-week vehicle administration decreased the pore ratio, number, and density as well as the cortical area and thickness, compared with the 4-week TPTD administration, but the pore ratio, cortical area, and thickness were still higher compared with the 12-week vehicle administration. The 4-week TPTD administration + 8-week higher-dose IBN administration, but not the 4-week TPTD administration + 8-week lower-dose IBN administration, increased the cortical area, thickness, BMC, and volumetric BMD and decreased the pore ratio, but not the pore number or density, compared with the 4-week TPTD administration + 8-week vehicle administration. These results suggest that higher-dose IBN after TPTD therapy has a beneficial effect on the BMC, volumetric BMD, cortical area, thickness, and porosity in mature rabbits.

Patient preference for monthly bisphosphonate versus weekly bisphosphonate in a cluster-randomized, open-label, crossover trial: Minodroate Alendronate/Risedronate Trial in Osteoporosis (MARTO).

Minodronate is a potent nitrogen-containing bisphosphonate that can be administered according to a monthly (every 4 weeks) dosing regimen. A 6-month, cluster-randomized, open-label, multicenter, crossover trial was conducted to test the preference of Japanese patients with osteoporosis for monthly bisphosphonate versus weekly bisphosphonate. One hundred and forty-seven patients (postmenopausal women and men) with primary osteoporosis were recruited at eight outpatient clinics. The clinics were randomized into two groups according to the dosing protocol-monthly minodronate followed by weekly alendronate or risedronate for a total of 24 weeks, or weekly alendronate or risedronate followed by monthly minodronate for 24 weeks. Patient preference for either the monthly or weekly bisphosphonate regimen was evaluated using a preference questionnaire. One hundred and fifteen patients (78.2 %) who completed the trial were processed for the analyses. Significantly more patients preferred the monthly bisphosphonate regimen (65.2 %) than the weekly bisphosphonate regimen (15.7 %) (P = 0.007). 'Dosing schedule fits lifestyle better' was the most common reason given for the patient preference for both the monthly (32.0 %) and weekly bisphosphonate (33.3 %) regimens. Significantly more patients found the monthly bisphosphonate regimen to be more convenient (73.0 %) than the weekly bisphosphonate regimen (13.9 %) (P < 0.0001). The safety profiles of the two regimens were similar. The present trial demonstrated a strong patient preference for and the convenience of the monthly bisphosphonate regimen over the weekly bisphosphonate regimen in Japanese patients with osteoporosis.

Effect of Combined Teriparatide and Monthly Risedronate Therapy on Cancellous Bone Mass in Orchidectomized Rats: A Bone Histomorphometry Study.

This study investigated the effects of combined teriparatide (an anabolic agent) and monthly risedronate (an anti-resorptive agent) therapy on cancellous bone mass in orchidectomized (ORX) rats. Fifty 14-week-old male Sprague-Dawley rats were randomized into five groups of ten animals each: sham-operation + vehicle; ORX + vehicle; ORX + risedronate (90 µg/kg subcutaneous, every 4 weeks); ORX + teriparatide (30 µg/kg subcutaneous, three times per week); and ORX + risedronate + teriparatide. After the 12-week experimental period, cancellous bone in the tibial proximal metaphysis was examined by static and dynamic histomorphometric analyses. ORX decreased bone volume per total volume (BV/TV) and trabecular number (Tb.N), and increased trabecular separation (Tb.Sp). Risedronate increased BV/TV and Tb.N above the sham control values, while teriparatide prevented the ORX-induced decrease in BV/TV and increased trabecular width (Tb.Wi) above sham control levels. Risedronate decreased Tb.Sp below control values, while teriparatide prevented the ORX-induced increase in Tb.Sp. The combination of teriparatide and risedronate further increased BV/TV and Tb.N and decreased Tb.Sp as a result of suppression of bone remodeling, compared with teriparatide alone. These results suggest that teriparatide and monthly risedronate exert different effects on cancellous bone structure and thus have additive effects on cancellous bone mass in ORX rats.

Survey of the utility of once-monthly bisphosphonate treatment for improvement of medication adherence in osteoporosis patients in Japan.

Prescription of a bisphosphonate (BP) with monthly dosing has recently been approved in Japan. The value of this approach for improvement of medication adherence was investigated in patients undergoing drug therapy for osteoporosis. A questionnaire was distributed to patients receiving treatment for osteoporosis at 8 medical facilities (5 orthopedic, 2 gynecology, and one internal medicine). Responses were collected from 1,300 patients. After exclusion of those who missed an item on the questionnaire or took drugs other than oral drugs, responses from 1,151 patients were analyzed. The most frequently used drug for treatment of osteoporosis was a once-weekly BP. Of the 1,151 patients, 38.4 % reported forgetting to take their current drug. The most frequent concern was 'I cannot feel an effect', but 73.2 % answered 'I have no concerns'. Regarding the most appropriate dosing regimen for long-term treatment, 60.3 % selected once-weekly and 24 % selected once every 4 weeks. Based on a recommendation by a physician of a drug to be taken monthly, 32.5 % wanted to switch, 31.8 % were undecided, and 35.7 % wanted to continue with their current drug. The desire for a change was higher among patients currently taking a once-weekly BP (52.3 %) than among patients taking a daily BP (29.5 %) or a SERM (19.4 %). This survey revealed patients' preferences in osteoporosis drug therapy. It is important to select a drug for osteoporosis based on the efficacy and the drug regimen preferred by the individual patient.

Five-year experience with risedronate therapy for patients with increased fracture risk: a practice-based observational study.

The purpose of this practice-based observational study was to examine the effects of long-term treatment with risedronate in patients with an increased fracture risk. Seventy patients (4 men and 66 postmenopausal women; mean age, 68.0 years) with osteoporosis or osteopenia and clinical risk factors for fractures were treated with risedronate at either 2.5 mg/d or 17.5 mg/week for 5 years. The bone mineral density (BMD) of the lumbar spine and proximal femur, and the structural geometric parameters of the proximal femur were evaluated by dual-energy X-ray absorptiometry with advanced hip assessment software at baseline and after each year of treatment. The lumbar spine BMD rapidly increased during the first year of the treatment and steadily increased throughout the 5-year treatment period. The BMD of the femoral neck and total hip also significantly increased during the first 3 and 2 years of treatment, respectively, then gradually declined and reached the baseline level after 5 years of treatment. The cross-sectional moment of inertia, cross-sectional area, and mean width of the femoral neck region of interest significantly increased during the first 2 years, and these increases were maintained throughout the 5-year treatment period. The femur strength index and section modulus also significantly increased following time courses similar to those of the above three parameters. These results suggest that risedronate produced both a sustained increase in the lumbar spine BMD and improvement in the femoral structural geometric parameters for 5 years of treatment.

[Treatment of bone disease caused by gastrectomy].

Gastrectomy is undergone mainly in patients with gastric cancer. Bone diseases(osteoporosis and osteomalacia)caused by gastractomy are associated with weight loss, calcium and vitamin D inadequancy, and malnutrition. Most patients after gastrectomy have multile risk factors of bone diseases and subsequently are at a higher risk for fractures. In particular, sex hormone deficiency and aging enhance the risk for fractures. The management of bone diseases caused by gastraectomy include adequet intake of calcium, vitamin D and protein, sunlight exposure, and regular weight-bearing exercise, as well as non-smoking and avoiding excess alcohol drinking. The patients at a high risk for fractures shoud be treated with bisphosphonates.

Camphor induces cold and warm sensations with increases in skin and muscle blood flow in human.

Application of camphor to the skin has been empirically thought to improve blood circulation. However, camphor's effects on blood circulation to the skin and on thermal sensation have not been well elucidated. In this study, we examined its effects on the quality of sensation as well as on skin and muscle blood flow in human. Nine adults (average age 37±9.4 years) participated in the study. Petroleum jelly containing 5%, 10%, 20% camphor, or 2% menthol was separately applied to the skin on the medial side of one forearm of each subject. Just after the application, camphor at each concentration induced a cold sensation in a dose-dependent manner. Within 10 min, each subject reported that the cold sensation had faded, after which it was replaced by a warm sensation. As reported previously, a cold sensation was induced by application of 2% menthol, but the subjects did not adapt to that sensation. In addition, menthol did not induce a warm sensation at all. Application of menthol has been shown to increase blood flow in the skin. Finally, we measured blood flow in skin and muscle after the application of camphor or menthol. Application of camphor or menthol separately induced increases in local blood flow in the skin and muscle. The present results indicate that camphor induces both cold and warm sensations and improves blood circulation.

Effect of intermittent administration of hPTH(1-34) on cortical bone geometry in rats treated with high-dose glucocorticoids.

High-dose glucocorticoids reduce cortical bone gain in rats. The aim of the present study was to examine the effect of the intermittent administration of human parathyroid hormone (1-34) (hPTH[1-34]) on cortical bone in rats treated with high-dose prednisolone (PSL). Twenty-five female Sprague-Dawley rats (6 weeks old) were randomized into the following three groups: a vehicle administration (control) group, a PSL (10 mg/kg s.c., 5 times a week) administration group, and a PSL + hPTH(1-34) (30 µg/kg s.c., 3 times a week) administration group. After 8 weeks of treatment, the bone mineral density (BMD) of the femoral diaphysis was determined using peripheral quantitative computed tomography, and a static bone histomorphometric analysis was performed on the tibial diaphysis. PSL administration induced a decrease in the BMD of the femoral diaphysis, compared with the control group, as well as decreases in the total tissue area, cortical area, percent cortical area, and periosteal perimeter and increases in the marrow area, percent marrow area, and endocortical perimeter of the tibial diaphysis, compared with the control group. The intermittent administration of hPTH(1-34) to PSL-treated rats attenuated PSL-related changes in the BMD of the femoral diaphysis and the percent cortical area, marrow area, percent marrow area, and endocortical perimeter of the tibial diaphysis. The findings of the present study suggest that the intermittent administration of hPTH(1-34) improves cortical BMD, acts on the endocortical bone surface, and improves cortical bone geometry, in rats treated with highdose PSL.