Bridging analysis of the efficacy and safety of bazedoxifene in Japanese and global populations of postmenopausal women with osteoporosis.

This study examined whether the global clinical data for bazedoxifene could be extrapolated to a Japanese population by evaluating the results of a phase 2 study in postmenopausal Japanese women with osteoporosis as compared to those of a pivotal, phase 3 study. The efficacy of bazedoxifene 20 and 40 mg versus placebo on lumbar spine bone mineral density (BMD), bone turnover markers, lipid profile, incidence of fractures, and safety parameters was compared between the Japanese phase 2 study (N = 429) and the global phase 3 study (N = 7,492) during a 2-year period. In the primary population for assessment of bridging, differences in the mean percent change from baseline in lumbar spine BMD at 2 years relative to placebo were greater for women treated with bazedoxifene 20 and 40 mg in the phase 2 study than in the phase 3 study. BMD changes in the bazedoxifene groups were confirmed to be similar between the phase 2 study population and a subset of the phase 3 study population with similar baseline characteristics. The effects of bazedoxifene on incidence of fractures, bone turnover markers, and lipid metabolism were similar between studies. There were no major differences in safety parameters between studies. The greater improvement in lumbar spine BMD and similar results in bone turnover markers, fracture incidence, and safety profile observed with bazedoxifene in the phase 2 study compared with the phase 3 study confirmed the feasibility of extrapolating the global clinical data to a Japanese population.

[Basic Strategy for Pain Control in Rehabilitation].

Rehabilitation medicine regards pain as one disorder of whole human character and handles pain through multilateral approaches. When only the pain is treated it will not be relieved easily. Chronic pain can be more effectively handled if pain is considered as one obstacle of the whole human character and handled using many skills of rehabilitation medicine. We should apply physiotherapy including functional treatment, physical treatment and exercise from early stages of acute pain and approach chronic pain. This could improve the effectiveness of treatment for many kinds of acute pain and chronic pain disorders.

Detective value of historical height loss and current height/knee height ratio for prevalent vertebral fracture in Japanese postmenopausal women.

Vertebral fracture (VFx) is associated with various co-morbidities and increased mortality. In this paper, we have studied the detective value of height loss for VFx using two indices; historical height loss (HHL) which is the difference between the maximal height, and the current height (CH), and CH/knee height (KH) ratio. One-hundred and fifty-one postmenopausal women visiting the outpatient clinic of orthopaedics were studied for their CH, self-reported maximal height, KH, and radiographically diagnosed VFx number(s). VFx was present in 41.1 % of the subjects. Multiple regression analyses revealed that the number of prevalent fractures was a significant predictor of HHL and CH/KH ratio. Receiver operator characteristic curve analysis has shown that for HHL, the area under the curve (AUC) with their 95 %CI in the parentheses was 0.84 (0.77, 0.90), 0.88 (0.83, 0.94), and 0.91 (0.86, 0.96) for ≥ 1, ≥ 2, and ≥ 3 fractures, respectively. For the presence of ≥ 1 VFx, the cut-off value was 4.0 cm (specificity 79 %; sensitivity 79 %). Regarding the CH/KH ratio, AUC was 0.73 (0.65, 0.82), 0.85 (0.78, 0.93), and 0.91 (0.86, 0.96) for ≥ 1, ≥ 2, and ≥ 3 fractures, respectively. For the presence of ≥ 1 VFx, the cut-off value was 3.3 (specificity 47 %; sensitivity 91 %). Both cut-off values for HHL and CH/KH ratio had high negative predictivity across the wide range of theoretical VFx prevalence. Thus, HHL and CH/KH were both good detectors of VFx. Our data would be the basis to determine the cut-off value for the screening or case finding of subjects with VFx.

Responsiveness of the Japanese Osteoporosis Quality of Life questionnaire in women with postmenopausal osteoporosis.

BACKGROUND: The Japanese Osteoporosis Quality of Life (JOQOL) questionnaire measures quality of life in Japanese patients with osteoporosis. However, several important aspects of the psychometric properties of individual domains, including responsiveness, have not been addressed to enable valid clinical application. This analysis examined the internal and external responsiveness of the JOQOL questionnaire. METHODS: This was a post hoc analysis of a 24-week prospective postmarketing study of raloxifene (60 mg/day) administered to postmenopausal Japanese women with osteoporosis (JapicCTI-070465). Internal responsiveness was assessed using Standardized Response Mean (SRM) statistics and changes in JOQOL domain scores. Patients were also stratified into those who did or did not achieve a minimal clinically important change (MCIC) in pain, assessed by a visual analogue scale for pain (VAS pain): comparisons were made between treated patients who achieved VAS pain reduction ≥ 20 mm versus VAS pain reduction < 20 mm. External responsiveness was assessed using Pearson's correlation coefficient (r) for changes in JOQOL domain scores with Short Form-8 Health Survey and European Quality of Life Instrument scores. RESULTS: Of 506 patients analyzed, 421 had a baseline value for VAS pain; of these, 152 patients (36.1%) had a MCIC, whereas 264 patients (62.7%) did not. The JOQOL domains pain, overall health, and falls/psychological factors had small to moderate SRM values (0.3-0.5) in all patients, but consistently showed significantly larger changes in patients whose pain score changes exceeded the MCIC. Together, these findings suggest some degree of internal responsiveness for these domains. However, activities of daily living domain had a SRM value as low as 0.2, and recreation/social activities and posture/physique domains had SRM values close to 0. Moderate correlation (defined as r ≥ 0.4 to < 0.6) was noted between the domains pain, activities of daily living, and overall health and some Short Form-8 Health Survey subscales and the European Quality of Life total score, suggesting external responsiveness of these domains. CONCLUSIONS: The inconsistent responsiveness among individual JOQOL domains in treated patients suggests the need for improving several JOQOL domains, especially the activities of daily living, recreation/social activities and posture/physique domains, before application to clinical research.

Efficacy, tolerability, and safety of risedronate in Japanese patients with Paget's disease of bone.

This study evaluated the clinical efficacy of treatment with oral risedronate (17.5 mg once daily) for 8 weeks in 11 Japanese patients with Paget's disease of bone (PDB). Risedronate suppressed the excessive bone turnover associated with PDB and improved several biochemical markers, including serum alkaline phosphatase (ALP), serum bone-specific ALP (BALP), urinary deoxypyridinoline (DPD), and urinary cross-linked N-telopeptide of type 1 collagen (NTX). These markers began to decrease within about 2 weeks after the initiation of treatment in most patients, and the response persisted for up to 40 weeks after the cessation of treatment. Risedronate reduced pain by week 24 in most patients. According to quantitative bone scintigraphy, the lesion with the highest radioisotope (RI) uptake showed a decrease of uptake from 12.7 +/- 6.8 to 6.0 +/- 2.3 (mean +/- SD) in week 24, although each lesion of patients with polyostotic disease had a different scintigraphic response. Overall, risedronate at a dose of 17.5 mg once daily was well tolerated by patients with PDB, even though the dosage was seven times higher than that approved for the treatment of osteoporosis in Japan (2.5 mg once daily). In conclusion, treatment with high-dose risedronate for 8 weeks resulted in clinically significant and sustained improvement of biochemical markers of bone turnover for 48 weeks in patients with PDB, and this improvement was associated with a decrease of RI uptake by Paget's bone lesions and with reduced pain.

Results of total hip arthroplasty for dialysis arthropathy in long-term hemodialysis patients.

BACKGROUND: The number of hemodialysis patients has progressively increased in Japan. Among the orthopedic complications in this population, chronic hip arthropathy associated with long-term hemodialysis is one of the most devastating problems. Total hip arthroplasty (THA) is often indicated. However, varying results have been reported for THA in these patients. This study was undertaken to assess the risk-benefit ratio of THA performed in patients with dialysis hip arthropathy. METHODS: We evaluated 17 patients (19 hips) with dialysis hip arthropathy who underwent THA. The duration of hemodialysis before surgery ranged from 10 to 27 years. Histological examination of the tissue samples revealed accumulation of amyloid deposits in all cases. Three patients died within 2 years after operation; the remaining 14 patients (16 hips) were followed for a minimum of 3 years. RESULTS: The cumulative survival rate of the prostheses in these 16 hips up to the latest follow-up was 94%. Regarding surgery-related complications, deep infection occurred in one hip, and revision THA was required in one patient with recurrent dislocation and aseptic loosening. CONCLUSIONS: THA for dialysis hip arthropathy in long-term hemodialysis patients is associated with substantial local and general risks. Despite the substantial risk, THA for this patient population seems to afford reasonably satisfactory results.

[Infant bone quantity measurement. --Hoping for the growth of smooth bone].

As a method for measuring the bone mass of the children, we the measurement board for the measurement is improved so that the children may can be correspond ultrasonic wave bone density measuring apparatus CM100 made by FURUNO ELECTRIC Co., and the bone density of 11,418 pupils has been measured from 4 years old to 20 (male infants of 5,939 and female infants of 5,479) . And the evaluation system in each age is completed and we could put the ultrasonic wave measuring device on CM200. Then, it is proposed in order to hoping for the growth of the smooth bone of children in the developing time, and in order to utilize these measuring method and evaluations to the school education.

[Diabetes mellitus and exercise].

Diabetes mellitus is one of the most important life-style related diseases. As for the type 2 diabetes mellitus in particular, lack of exercise has a large influence on the onset and disease progress. We can improve glucose tolerance by exercising. Exercise is the most important fundamental treatment in diabetes mellitus. Continuation and safety become important to let exercise therapy succeed. It is important with a diabetic that a lot of patients without exercise habit should start to gain exercise habit. When we expect an exercise effect, we should take consideration of intensity and volume in exercise for performing. We should consider each contraindication matter even if we put it to have many complications with a diabetic when we perform exercise therapy. A case-by-case exercise treatment in diabetic patient is required.

[Provision for fragility of bone and its risk factors].

Fractures in osteoporosis patients have been affected by not only low bone density but also many factors like bone quality, shape of bone, soft part tissue, nutrition, ability of exercise, fall etc.. There are a lot of risk factors in fragility of osteoporotic bone. As for some factors, there is impossible of improvement like a genetic factor, but there are some factors like nutrition, exercise, environment which can improve the fragility of bones in osteoporotic patients. Provision for fragility of bone is improvement for each risk factor.

[Improvement of QOL in osteoporotic patients by calcitonin treatment].

Quality of life (QOL) is impaired in patients with osteoporosis, to which bodily pain greatly contributes. The presence of vertebral fractures detrimentally affects the patients' QOL in a dose-dependent manner. Calcitonin, with its potent analgesic action, markedly improves the various aspects of patients' QOL. Efficacy for the treatment of osteoporosis should be evaluated in terms of QOL also, in addition to the increase in bone mineral density and fracture prevention.

[Infant bone quantity measurement by the ultrasonic].

It seems that the maximum bone quantity in the young people will influence osteoporosis development in the later age. This study is to clarify the age-related change in the adolescence and the relations between bone density and exercise habit or diet habit, ultrasonic-measured bone density, physical capacity test and questionnaire survey were used. The values of SOS tended to increase along with the increase of age in both sexes when they were in the primary and middle school, but a decreased tendency was observed when they were in the high school. And the peak values were found in 17 - 18-year-old boys and 16-year-old girls. SOS correlated significantly with weight, and showed greater value in the exercise group compared with the sedentary group. And finally, the questionnaire survey showed that the regular diets were beneficial to increase SOS.

Quality of life in raloxifene-treated Japanese women with postmenopausal osteoporosis: a prospective, postmarketing observational study.

OBJECTIVE: To assess changes in quality of life (QOL) and pain in raloxifene-treated Japanese women with postmenopausal osteoporosis. RESEARCH DESIGN AND METHODS: This prospective, postmarketing observational study was conducted at 60 Japanese hospitals from September 2007 to February 2009 and included Japanese women with postmenopausal osteoporosis who were new to standard treatment with raloxifene (60 mg/day). Primary outcome measures (QOL and pain) were assessed using the Short Form-8 (SF-8), European Quality of Life Instrument (EQ-5D), osteoporosis-specific Japanese Osteoporosis Quality of Life Questionnaire (JOQOL), a visual analogue scale (VAS-pain), and a pain frequency survey. Assessments were performed at baseline and 8 (except JOQOL) and 24 weeks after first administration of raloxifene. Adverse drug reactions were recorded. Japan Pharmaceutical Information Center registration number: JapicCTI-070465. RESULTS: A total of 506 participants, mean (±standard deviation [SD]) age = 70.7 ± 8.7 years, completed ≥1 follow-up assessment and were included in the analyses. All QOL scores increased from baseline during follow-up. All SF-8 domain scores increased significantly from baseline after 8 and 24 weeks (P < 0.001). Mean (±SD) EQ-5D scores increased significantly from baseline (0.70 ± 0.17) by 0.05 ± 0.15 after 8 weeks and 0.07 ± 0.17 after 24 weeks (P < 0.001). The mean (±SD) total JOQOL score increased significantly from baseline (66.8 ± 16.5) by 3.8 ± 11.3 after 24 weeks (P < 0.001). The percentage of participants with a ≥20 mm reduction in VAS-pain was 32.6% (120/368) and 39.5% (115/291) after 8 and 24 weeks, respectively. The frequency of pain reported by participants decreased after 8 and 24 weeks. Forty adverse drug reactions were reported by 34 participants. LIMITATIONS: Limitations include the lack of a control group, the possibility of the changes being due to the natural disease course, and potential selection bias. CONCLUSIONS: Our findings suggest that standard treatment with raloxifene improves QOL and relieves pain in Japanese women with postmenopausal osteoporosis in a real-world clinical setting.

Effects of bazedoxifene on bone mineral density, bone turnover, and safety in postmenopausal Japanese women with osteoporosis.

This randomized, double-blind, placebo-controlled, dose-response late phase 2 study evaluated the efficacy and safety of bazedoxifene in postmenopausal Japanese women 85 years of age or younger with osteoporosis. Eligible subjects received daily treatment with oral doses of bazedoxifene 20 or 40 mg or placebo for 2 years. Efficacy assessments included bone mineral density (BMD) at the lumbar spine and other skeletal sites, bone turnover marker levels, lipid parameters, and incidence of new fractures. Of 429 randomized subjects, 387 were evaluable for efficacy, and 423 were included in the safety analyses (mean age, 64 years). At 2 years, the mean percent changes from baseline in lumbar spine BMD were significantly greater with bazedoxifene 20 and 40 mg (2.43% and 2.74%, respectively) than with placebo (-0.65%, p < .001 for both). Both bazedoxifene doses significantly improved BMD at the total hip, femoral neck, and greater trochanter compared with placebo (p < .001 for all). Decreases in bone turnover markers were observed with bazedoxifene 20 and 40 mg as early as 12 weeks (p < .05 for all) and were sustained throughout the study. Total and low-density lipoprotein cholesterol levels were significantly decreased from baseline with both bazedoxifene doses compared with placebo (p < .05 for all). Incidences of new vertebral and nonvertebral fractures were similar among the bazedoxifene and placebo groups. Overall, the incidence of adverse events with bazedoxifene 20 and 40 mg was similar to that with placebo. Bazedoxifene significantly improved BMD, reduced bone turnover, and was well tolerated in postmenopausal Japanese women with osteoporosis.

Bone graft for large bone cysts of the femoral neck in patients on hemodialysis.

Pathologic fracture of the femoral neck from an amyloid bone cyst in patients on long-term hemodialysis causes substantial morbidity. For patients with a bone cyst occupying more than 1/2 of the neck width, we have performed prophylactic internal fixation with an autogenous iliac bone graft. We describe our surgical technique and present clinical results from consecutively surgically treated patients. We determined whether our procedure successfully induced healing of the bone cyst, thus preventing a problematic sequel of fracture. From 1990 to 2003, 14 hips in 12 patients were treated, and the clinical results from these patients were retrospectively reviewed. One patient died 3 months after surgery; the remaining patients were followed for at least 3 years. In those 11 patients, bony healing was achieved in all cases with no recurrence of the cystic lesion. Considering the comparatively unsatisfactory results of internal fixation for pathologic fracture and THA for patients receiving long-term hemodialysis, our procedure gives surgeons another option for treating this difficult problem.