Effect of coordinator-based osteoporosis intervention on quality of life in patients with fragility fractures: a prospective randomized trial.

We examined the effects of the coordinator-based intervention on quality of life (QOL) in the aftermath of a fragility fracture, as well as factors predictive of post-fracture QOL. The coordinator-based interventions mitigated the decrease in QOL. Secondary fracture after primary fracture, however, was a significant predictor of lower QOL. PURPOSE: This study aimed to determine the effects of the coordinator-based intervention on QOL in the aftermath of a fragility fracture, as well as factors predictive of post-fracture QOL, in an Asian population. METHODS: Patients with new fractures in the intervention group received the coordinator-based intervention by a designated nurse certified as a coordinator, within 3 months of injury. QOL was evaluated using the Japanese version of the EuroQol 5 Dimension 5 Level (EQ-5D-5L) scale  before the fracture (through patient recollections) and at 0.5, 1, and 2 years after the primary fracture. RESULTS: Data for 141 patients were analyzed: 70 in the liaison intervention (LI) group and 71 in the non-LI group. Significant intervention effects on QOL were observed at 6 months after the fracture; the QOL score was 0.079 points higher in the LI group than in the non-LI group (p=0.019). Further, the LI group reported significantly less pain/discomfort at 2 years after the fracture, compared to the non-LI group (p=0.037). In addition, secondary fractures were found to significantly prevent improvement and maintenance of QOL during the recovery period (p=0.015). CONCLUSION: Short-term intervention effects were observable 6 months after the primary fracture, with the LI group mitigated the decrease in QOL. Few patients in the LI group reported pain/discomfort 2 years after the fracture, but there is uncertainty regarding its clinical significance. Secondary fracture after initial injury was a significant predictor of lower QOL after a fracture.

A randomized, controlled trial of once-weekly teriparatide injection versus alendronate in patients at high risk of osteoporotic fracture: primary results of the Japanese Osteoporosis Intervention Trial-05.

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.

Efficiency of coordinator-based osteoporosis intervention in fragility fracture patients: a prospective randomized trial.

We examined the effectiveness of coordinators' interventions to prevent secondary fractures in patients with fragility fractures. These coordinator-based interventions improved bone density assessment implementation and treatment rates, and enhanced treatment persistence rates in the early stages following fractures. INTRODUCTION: This study aimed to determine the efficiency of coordinator-based osteoporosis intervention in fragility fracture patients during a 2-year period. METHODS: A prospective intervention randomized control study was conducted at seven medical facilities from January 2015 to March 2017. Postmenopausal women and men over 50 years old with fragility fractures were randomly divided into the coordinator intervention (LI; 70 patients) and without intervention (non-LI; 71 patients) groups. The osteoporosis treatment rate, osteoporosis treatment persistence rate, fall rate, fracture incidence rate, and bone density measurement rate 3 months, 6 months, 1 year, and 2 years after registration were compared between the two groups. Non-parametric tests were used to analyze data at each inspection period. RESULTS: The osteoporosis treatment initiation rate was significantly higher in the LI group than in the non-LI group (85.7% vs. 71.8%; p = 0.04). The LI group had significantly higher bone density assessment implementation rates than the non-LI group at the time of registration (90.0% vs. 69.0%; p = 0.00) and 6 months after registration (50.0% vs. 29.6%; p = 0.01), but not 1 or 2 years after registration. In addition, no significant differences in fall or fracture incidence rates were found between the two groups. CONCLUSION: The coordinator-based interventions for fragility fractures improved bone density assessment implementation and treatment rates and enhanced treatment persistence rates in the early stages following bone fractures. The findings suggest that liaison intervention may help both fracture and osteoporosis physicians for the evaluation of osteoporosis and initiation and continuation of osteoporosis medication.

Cost effectiveness of romosozumab versus teriparatide for severe postmenopausal osteoporosis in Japan.

This study assessed the cost effectiveness of romosozumab versus teriparatide, both sequenced to alendronate, for the treatment of severe postmenopausal osteoporosis in Japan, using bone mineral density (BMD) efficacy data. Results show that romosozumab/alendronate produces greater health benefits at a lower cost than teriparatide/alendronate. INTRODUCTION: This study aims to assess the cost effectiveness of romosozumab versus teriparatide, both sequenced to alendronate, for the treatment of severe postmenopausal osteoporosis in Japanese women previously treated with bisphosphonates. METHODS: A Markov model was used to assess the relative cost effectiveness of 1 year of romosozumab versus 2 years of teriparatide, both sequenced to alendronate for a total treatment duration of 5 years. Outcomes for a cohort of women with a mean age of 78 years, a T-score ≤-2.5 and a previous fragility fracture were simulated over a lifetime horizon. The analysis was conducted from the perspective of the Japanese healthcare system and used a discount rate of 2% per annum. To inform relative fracture incidence, the bone mineral density (BMD) advantage of romosozumab over teriparatide was translated into relative risks of fracture, using relationships provided by a meta-regression of osteoporosis therapy trials. Outcomes were assessed in terms of lifetime costs (2020 US dollars) and quality-adjusted life years (QALYs). RESULTS: Base case results showed that, compared with teriparatide/alendronate, romosozumab/alendronate reduced costs by $5134 per patient and yielded 0.045 additional QALYs. Scenario analyses and probabilistic sensitivity analysis confirmed that results are robust to uncertainty in model assumptions and inputs. CONCLUSION: Results show that romosozumab/alendronate produces greater health benefits at a lower total cost than teriparatide/alendronate.

FRAX score and recent fall history predict the incidence for sarcopenia in community-dwelling older adults: a prospective cohort study.

We hypothesized that the baseline FRAX score and previous falls would predict the incidence of sarcopenia in community-dwelling older adults who received medical check-ups. The FRAX score (hazard ratio [HR] = 1.087, 95% CI 1.014-1.167) and previous falls (HR = 5.181, 95% CI 1.002-26.777) were determined to be independent risk factors for the incidence of sarcopenia. PURPOSE: This prospective study was performed to elucidate the prevalence and incidence of sarcopenia in community-dwelling older adults who received medical check-ups, and to determine whether FRAX score and fall history predict the incidence of sarcopenia. METHODS: Participants were recruited from a group of individuals who had registered for an annual town-sponsored medical check-up. Study inclusion criteria were aged older than 60 years, living independently, and ability to walk without assistance. Individuals who received nursing care were excluded from the study. A total of 426 residential participants were analyzed. Demographic information, fall history of the previous year, and FRAX score without bone mineral density were assessed. The assessment for sarcopenia was based on the recommendations of the Asian Working Group for Sarcopenia. RESULTS: The final sample for the assessment of sarcopenia incidence comprised 258 participants. The mean follow-up time was 2.92 years. The rate of sarcopenia was 1.06 cases per 100 person-years at risk. The Cox multivariate logistic regression model in our analysis was adjusted for age, gender, muscle mass, and covariates and showed that the FRAX score (HR = 1.087, 95% CI 1.014-1.167) and recent history of falls (HR = 5.181, 95% CI 1.002-26.777) were independent risk factors for the incidence of sarcopenia. CONCLUSION: FRAX and history of falling can be a simple screening tool to raise awareness of the prevention of osteoporosis and sarcopenia in clinical settings.

A multicenter, randomized, rater-blinded, parallel-group, phase 3 study to compare the efficacy, safety, and immunogenicity of biosimilar RGB-10 and reference once-daily teriparatide in patients with osteoporosis.

The efficacy and safety of RGB-10 and reference teriparatide were evaluated in a randomized 52-week study in 250 patients with osteoporosis at high risk of fracture. RGB-10 was equivalent to reference teriparatide in efficacy and had a comparable safety profile. INTRODUCTION: RGB-10 is the first biosimilar teriparatide authorized in the European Union. This multicenter, randomized, rater-blinded, parallel-group phase 3 study evaluated equivalence in efficacy and compared safety between RGB-10 and reference teriparatide in patients with osteoporosis at high risk of fracture for registration in Japan. METHODS: Ambulatory postmenopausal women and men (≥ 55 years of age) with osteoporosis at high risk of fracture were randomized 1:1 to receive either RGB-10 or reference teriparatide 20 µg once daily via subcutaneous self-injection for 52 weeks. The primary efficacy endpoint was the percent change from baseline to 52 weeks in lumbar spine (L2-L4) bone mineral density (BMD). Safety outcomes and immunogenicity were also assessed. RESULTS: In total, 250 patients (125 in each group) were randomized. The percent change from baseline to 52 weeks in lumbar spine (L2-L4) BMD (mean ± standard deviation) was 8.94% ± 6.19% in the RGB-10 group and 9.65% ± 6.22% in the reference teriparatide group. The estimated between-group difference (95% confidence interval) was - 0.65% (- 2.17% to - 0.87%) within the pre-specified equivalence margin (± 2.8%), which indicates equivalence in efficacy between the two groups. Changes in BMD at lumbar spine (L1-L4), femoral neck, and total hip and serum procollagen type I amino-terminal propeptide were also similar between the groups. Safety profiles, including immunogenicity, were comparable. CONCLUSIONS: The therapeutic equivalence of RGB-10 to reference teriparatide was demonstrated. RGB-10 had comparable safety profile to that of reference teriparatide.

Study of twice-weekly injections of Teriparatide by comparing efficacy with once-weekly injections in osteoporosis patients: the TWICE study.

A 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial (the TWICE study) conducted in Japanese primary osteoporosis patients with a high risk of fractures demonstrated that a 28.2-µg twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-µg once-weekly regimen of teriparatide, while also improving safety. INTRODUCTION: While a 56.5-µg once-weekly regimen of teriparatide has high efficacy for osteoporosis, treatment continuation rates are low, with one of the major causes being adverse drug reactions such as nausea or vomiting. The TWICE study was therefore conducted to investigate whether a twice-weekly regimen with 28.2-µg teriparatide can provide comparable efficacy to the 56.5-µg once-weekly regimen while improving safety. METHODS: A 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial was conducted in Japan. Patients with primary osteoporosis aged ≥ 65 years at high risk of fractures (n = 553) were randomly allocated to the 28.2-µg twice-weekly group (n = 277) or the 56.5-µg once-weekly group (n = 276). The primary endpoint was the percentage change in lumbar spine (L2-L4) bone mineral density (BMD) at final follow-up. RESULTS: The percentage changes in lumbar spine (L2-L4) BMD at final follow-up in the 28.2-µg twice-weekly and 56.5-µg once-weekly groups were 7.3% and 5.9%, respectively; the difference (95% confidence interval [CI]) in percentage change was 1.3% (0.400-2.283%). Since the lower limit of the 95% CI was above the pre-specified non-inferiority margin (- 1.6%), non-inferiority of the 28.2-µg twice-weekly group was demonstrated. Adverse drug reactions were significantly less frequent in the 28.2-µg twice-weekly group (39.7% vs 56.2%; p < 0.01); the incidence of major adverse drug reactions was lower, and the number of subjects who discontinued due to adverse drug reactions was less in the 28.2-µg twice-weekly group. CONCLUSIONS: A 28.2-µg twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-µg once-weekly regimen while improving safety. CLINICAL TRIAL REGISTRATION: JapicCTI-163477 .

Influence of backrest angle on swallowing musculature activity and physical strain during the head lift exercise in elderly women compared with young women.

The head lift exercise (HLE) is the most common exercise for strengthening the swallowing musculature in clinical situations. This study investigated whether a change in the backrest angle of a bed influences swallowing musculature activity and physical strain during the HLE and whether it can generate an appropriate exercise load for swallowing musculature activity for older women compared with younger women. Participants were 10 elderly women and 10 young women, each of whom performed the HLE with a backrest randomly angled at 0°, 15°, 30° and 45°. The activity of the suprahyoid, infrahyoid and sternocleidomastoid muscles was assessed with electromyography. The perception of fatigue was measured with the Borg Rating of Perceived Exertion Scale. The activity of the infrahyoid and sternocleidomastoid muscles in elderly women was significantly lower when the angle of the backrest was raised to 45° vs 0°. In both groups, the Borg rating decreased significantly at the 30° and 45° backrest positions vs the 0° and 15° positions. The activity required for the suprahyoid and infrahyoid muscles in elderly women at a 30° backrest position was almost equal to the activity required by these muscles in young women at a 0° backrest position. In elderly women, it is possible that the HLE with the backrest at a 30° angle may be easier and provide a more appropriate exercise load for strengthening the swallowing muscles.

Cost-effectiveness analysis of once-yearly injection of zoledronic acid for the treatment of osteoporosis in Japan.

Model-based economic evaluation was performed to assess the cost-effectiveness of zoledronic acid. Although zoledronic acid was dominated by alendronate, the incremental quality-adjusted life year (QALY) was quite small in extent. Considering the advantage of once-yearly injection of zoledronic acid in persistence, zoledronic acid might be a cost-effective treatment option compared to once-weekly oral alendronate. INTRODUCTION: The purpose of this study was to estimate the cost-effectiveness of once-yearly injection of zoledronic acid for the treatment of osteoporosis in Japan. METHODS: A patient-level state-transition model was developed to predict the outcome of patients with osteoporosis who have experienced a previous vertebral fracture. The efficacy of zoledronic acid was derived from a published network meta-analysis. Lifetime cost and QALYs were estimated for patients who had received zoledronic acid, alendronate, or basic treatment alone. The incremental cost-effectiveness ratio (ICER) of zoledronic acid was estimated. RESULTS: For patients 70 years of age, zoledronic acid was dominated by alendronate with incremental QALY of -0.004 to -0.000 and incremental cost of 430 USD to 493 USD. Deterministic sensitivity analysis indicated that the relative risk of hip fracture and drug cost strongly affected the cost-effectiveness of zoledronic acid compared to alendronate. Scenario analysis considering treatment persistence showed that the ICER of zoledronic acid compared to alendronate was estimated to be 47,435 USD, 27,018 USD, and 10,749 USD per QALY gained for patients with a T-score of -2.0, -2.5, or -3.0, respectively. CONCLUSION: Although zoledronic acid is dominated by alendronate, the incremental QALY is quite small in extent. Considering the advantage of annual zoledronic acid treatment in compliance and persistence, zoledronic acid may be a cost-effective treatment option compared to alendronate.

Health state utility values and patient-reported outcomes before and after vertebral and non-vertebral fractures in an osteoporosis clinical trial.

We assessed the health state utility value (HSUV) reductions associated with vertebral fractures using data collected in the Japanese Osteoporosis Intervention Trial-03 (JOINT-03). Our analysis revealed that assessment of HSUVs after morphometric vertebral fracture is important to capture the burden of vertebral fractures. INTRODUCTION: Evaluation of the HSUV after fracture is important to calculate the quality-adjusted life years (QALYs) of osteoporosis patients, which is essential information in the context of health economic evaluation. METHODS: JOINT-03 study patients were aged ≥65 years and treated with risedronate and vitamin K2 or risedronate alone. Radiographic information and patient-reported outcomes measured by EQ-5D and a visual analogue scale (VAS) were assessed at registration and followed up after 6, 12, and 24 months. According to differences among the dates of these assessments and the radiographic information, we classified the follow-up HSUVs calculated based on EQ-5D results into before or after fracture categories regardless of clinical symptoms. RESULTS: Among 2922 follow-up HSUVs, 201 HSUVs were categorized as HSUVs that were observed after incident vertebral fractures on X-ray films. The median time from the detection of an incident vertebral fracture until the EQ-5D assessment was 53 days (25th percentile, 0 day; 75th percentile, 357 days). The impact of incident vertebral fractures on HSUVs was quantified as -0.03. Among the five health profile domains on the EQ-5D, an incident vertebral fracture had significant effects on anxiety/depression, self-care, and usual activities. CONCLUSIONS: The results suggest that incident morphometric vertebral fracture was associated with impairment of the HSUV for patients with osteoporosis not only immediately but also several months after the fracture.

Efficacy and safety of once-yearly zoledronic acid in Japanese patients with primary osteoporosis: two-year results from a randomized placebo-controlled double-blind study (ZOledroNate treatment in Efficacy to osteoporosis; ZONE study).

In a 2-year randomized, placebo-controlled study of 665 Japanese patients with primary osteoporosis, once-yearly administration of zoledronic acid (5 mg) reduced the risk of new morphometric vertebral fractures. INTRODUCTION: The purpose of this study was to determine the efficacy and safety of once-yearly intravenous infusion of ZOL in Japanese patients with primary osteoporosis. METHODS: This was a two-year multicenter, randomized, placebo-controlled, double-blind, parallel-group comparative study (ZONE Study). Subjects were 665 Japanese patients between the ages of 65 and 89 years who had prevalent vertebral fracture. Subjects were randomly assigned to receive once-yearly intravenous infusion of 5 mg of ZOL or placebo at baseline and 12 months. RESULTS: The 2-year incidence of new morphometric vertebral fracture was 3.0 % (10/330 subjects) in the ZOL group and 8.9 % (29/327) in the placebo group (p = 0.0016). The 24-month cumulative incidence of new morphometric vertebral fracture was 3.3 % in the ZOL group versus 9.7 % in the placebo group (log-rank test: p = 0.0029; hazard ratio: 0.35; 95 % confidence interval: 0.17-0.72). The cumulative incidence of any clinical fracture, clinical vertebral fracture, and non-vertebral fracture was significantly reduced in the ZOL group by 54, 70, and 45 %, respectively, compared to the placebo group. At 24 months, ZOL administration increased bone mineral density in the lumbar spine, femoral neck, and total hip (t test: p < 0.0001). No new adverse events or osteonecrosis of the jaw were observed in this study. CONCLUSIONS: Once-yearly administration of ZOL 5 mg to Japanese patients with primary osteoporosis reduced the risk of new morphometric vertebral fractures and was found to be safe.

Epidemiology of fragility fractures in Sakaiminato, Japan: incidence, secular trends, and prognosis.

UNLABELLED: We investigated the incidence of fragility fractures from 2010 to 2012 in Sakaiminato, Japan. The incidence rates of limb fractures in Sakaiminato were lower than in Caucasian populations but had increased relative to data obtained in Japan in the 1990s. Clinical vertebral fractures occurred at higher rates in Sakaiminato than in Caucasian populations. INTRODUCTION: To elucidate the incidence and prognosis of fragility fractures in Sakaiminato, Japan. METHODS: A survey of all hip, distal radius, proximal humerus, and clinical vertebral fractures was performed from 2010 to 2012 in patients aged 50 or older in Sakaiminato city, Tottori prefecture, Japan. The age- and gender-specific incidence rates (per 100,000 person-years) were calculated based on the population of Sakaiminato city each year. The incidence rates of hip, distal radius, and proximal humerus fractures were compared with previous reports. We conducted a follow-up study assessing patients within 1 year following their initial treatment at two Sakaiminato hospitals. RESULTS: The age-adjusted incidence rates in population aged 50 years or older (per 100,000 person-years) of hip, distal radius, proximal humerus, and clinical vertebral fractures were, respectively, 217, 82, 26, and 412 in males and 567, 432, 96, and 1229 in females. Age-specific incidence rates of hip, distal radius, and proximal humerus fractures all increased since the 1990s. Our study also revealed that anti-osteoporotic pharmacotherapy was prescribed 1 year post-fracture at rates of 29, 20, 30, and 50 % for patients with hip, distal radius, proximal humerus, and clinical vertebral fractures, respectively. CONCLUSIONS: The incidence rates of limb fractures in Sakaiminato were substantially lower than Caucasian populations in northern Europe but had increased relative to data obtained in Japan in the 1990s. Unlike upper and lower limb fractures, clinical vertebral fractures occurred at higher rates in our study population than in other Asian and North European countries.

Inadequate management for secondary fracture prevention in patients with distal radius fracture by trauma surgeons.

UNLABELLED: We evaluated the secondary fracture prevention in 1445 patients with distal radius fracture by trauma surgeons. The rate of patients with distal radius fracture who underwent bone mineral density (BMD) examination was low, suggesting that appropriate treatment for osteoporosis by trauma surgeons is not performed at present. INTRODUCTION: To clarify the status of osteoporosis interventions after distal radial fractures by trauma surgeons who play the main role in treatment for these fractures, we performed a survey involving multiple institutions in Japan. METHODS: We asked 155 board members of the Japanese Society for Fracture Repair for their cooperation and performed a survey in 48 institutions with which members who gave cooperation were affiliated. The subjects consisted of consecutive patients with distal radial fractures occurring between January and December 2012. The presence or absence of a diagnosis of osteoporosis and bone mineral density examination after fracture was investigated. RESULTS: A total of 1445 patients with distal radial fractures were evaluated in this study. BMD examination for diagnosis and treatment for osteoporosis after fracture was performed respectively in 126 (8.7 %) and 193 (13.4 %) of 1445 patients. Treatment for osteoporosis was performed in 93 (73.8 %) of 126 patients who underwent BMD examination after fracture and 100 (8.2 %) of 1219 who did not undergo BMD examination. Of the 126 patients who underwent BMD examination after fracture, 89 showed a BMD <80 % of the young adult mean as a criterion for the initiation of drug treatment for osteoporosis in Japan and 77 (86.5 %) of the 89 patients were treated with drugs. CONCLUSIONS: The rate of patients with distal radial fractures who underwent BMD examination was low, suggesting that appropriate treatment for osteoporosis by trauma surgeons is not performed at present.

Clinical efficacy and safety of monthly oral ibandronate 100 mg versus monthly intravenous ibandronate 1 mg in Japanese patients with primary osteoporosis.

UNLABELLED: The MOVEST study evaluated the efficacy and safety of monthly oral ibandronate versus licensed monthly IV ibandronate in Japanese osteoporotic patients. Relative BMD gains after 12 months were 5.22 % oral and 5.34 % IV, showing non-inferiority of oral to IV ibandronate (primary endpoint). No new safety concerns were identified. INTRODUCTION: The randomized, phase 3, double-blind MOVEST (Monthly Oral VErsus intravenouS ibandronaTe) study evaluated the efficacy and safety of monthly oral ibandronate versus the licensed monthly intravenous (IV) ibandronate regimen in Japanese patients with osteoporosis. METHODS: Ambulatory patients aged ≥ 55 years with primary osteoporosis were randomized to receive oral ibandronate 100 mg/month plus monthly IV placebo, or IV ibandronate 1 mg/month plus monthly oral placebo. The primary endpoint was non-inferiority of oral versus IV ibandronate with respect to bone mineral density (BMD) gains at the lumbar spine after 12 months of treatment. RESULTS: Four hundred twenty-two patients were enrolled with 372 patients in the per-protocol set (183 and 189 in the oral and IV ibandronate groups, respectively). The relative change from baseline in lumbar spine BMD values for the oral and IV ibandronate groups, respectively, was 5.22 % (95 % confidence interval [CI] 4.65, 5.80) and 5.34 % (95 % CI 4.78, 5.90). The least squares mean difference between the two groups was -0.23 % (95 % CI -0.97, 0.51), showing non-inferiority of oral ibandronate to IV ibandronate (non-inferiority limit = -1.60). Changes in BMD values at other sites, and bone turnover marker levels in the oral ibandronate group, were comparable with those of the IV group. The safety profile was similar to that previously demonstrated; no new safety concerns were identified. CONCLUSIONS: This study demonstrated the non-inferiority of oral ibandronate 100 mg/month to IV ibandronate 1 mg/month (licensed dose in Japan) in increasing lumbar spine BMD in Japanese patients with primary osteoporosis.

Effect of low-frequency rTMS on motor neuron excitability after stroke.

OBJECTIVES: The purpose of this study was to test the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) over the non-lesional hemisphere on motor neuron excitability of the paretic upper limb in post-stroke patients by electrophysiological examination. MATERIALS AND METHODS: Thirteen post-stroke patients with spastic upper limb hemiparesis were studied (age, 57.5 ± 11.1 years; time after stroke, 55.2 ± 51.4 months). Low-frequency rTMS of 1 Hz was applied for 20 min to the motor cortex of the non-lesional hemisphere. The M-response amplitude and F-wave parameters were recorded in the abductor pollicis brevis muscle following stimulation of the median nerve in both the affected and unaffected upper limbs. The F-wave frequency, F-max/M ratio (ratio of maximum F-wave amplitude to M-response amplitude), and F-mean/M ratio (the ratio of mean F-wave amplitude to the M-response amplitude) were measured before and after the 20-min rTMS, analyzed for both limbs. RESULTS: Application of low-frequency rTMS did not result in significant changes in the frequency of F-wave and F-max/M ratio in both upper limbs, but significantly decreased F-mean/M ratio in the affected upper limb (P < 0.005), but not in the unaffected limb. CONCLUSIONS: Low-frequency rTMS applied to the non-lesional hemisphere might be potentially useful therapeutically for post-stroke patients with spastic upper limb hemiparesis.

Efficacy and safety of monthly oral minodronate in patients with involutional osteoporosis.

UNLABELLED: Monthly minodronate at 30 or 50 mg had similar efficacy as 1 mg daily in terms of change in bone mineral density (BMD) and bone turnover markers with similar safety profiles. This new regimen provides patients with a new option for taking minodronate. INTRODUCTION: Minodronate at a daily oral dose of 1 mg has been proven to have antivertebral fracture efficacy. In the present study, the efficacy and safety of oral minodronate at monthly doses of either 30 mg or 50 mg were compared with a daily dose of 1 mg. METHODS: A total of 692 patients with involutional osteoporosis were randomized to receive minodronate at either 30 or 50 mg monthly or a daily dose of 1 mg. The primary endpoint was the percent change from baseline in lumbar spine (LS) BMD at 12 months. Total hip BMD, bone turnover markers, serum calcium (Ca), and parathyroid hormone (PTH) levels were also evaluated. RESULTS: Minodronate at monthly doses of 30 or 50 mg were noninferior to the 1 mg daily dose in terms of change in LS-BMD. Changes in total hip BMD were also comparable. Although a transient decrease in serum Ca and increase in PTH levels were observed in all three groups at slightly different magnitudes and time courses, changes in bone turnover markers were comparable among the different dosage groups with a similar time course. Safety profiles were also comparable. CONCLUSION: Minodronate at monthly doses of 30 or 50 mg has similar efficacy to the daily 1 mg dose in terms of BMD and bone turnover markers with similar tolerability.

Incidence and risk factors of falling in ambulatory patients with rheumatoid arthritis: a prospective 1-year study.

UNLABELLED: A prospective 1-year study showed that fall incidence was 50% in women with rheumatoid arthritis. Multivariate analysis identified swollen joint count, use of antihypertensives or diuretics, one-leg standing time, and sway area measured by stabilometer as significant parameters associated with falls. INTRODUCTION: Patients with rheumatoid arthritis (RA) may be at increased risk of falling because they frequently experience muscle weakness and stiff or painful joints. The aim of this study was to use a prospective design to determine the incidence of falls and their risk factors in women with RA. METHODS: Eighty-four women aged 50 and over who had RA were enrolled. The mean age was 64.1 years. We evaluated postural stability, physical performance related to falls, disease activity, muscle volume, and bone density. The occurrence of falls was assessed every month for 1 year. Among 84 patients, 80 completed a 1-year observation. RESULTS: Forty patients (50.0%) reported one or more falls, and two of them (5.0%) had fractures during the follow-up period. The fall group had more swollen joints and took more antihypertensives and/or diuretics. The fall group also had lower postural stability and tended to have reduced physical performance. The one-leg standing time was shorter, and the step-up-and-down test score was lower in the fall group. The sway area was larger in the fall group. DISCUSSION: Multiple logistic regression analysis identified that number of swollen joints, use of antihypertensives or diuretics, shorter time standing on one foot, and the sway area were the most significant parameters associated with falls. CONCLUSION: We concluded that fall rates in RA patients were higher than in the general population and that balance impairment or side effects of drugs may play a role in increasing the risk of falls.

Recent trends in the incidence and lifetime risk of hip fracture in Tottori, Japan.

SUMMARY: Hip fracture incidence from 2004 to 2006 in the Tottori prefecture of Japan was investigated and compared with previously reported rates. The age- and gender-specific incidence of hip fracture in the Tottori prefecture has not plateaued, as has been reported for populations in Northern Europe or North America. INTRODUCTION: Recent data from Northern Europe and North America indicate that the incidence of hip fracture has plateaued, whereas most reports from Asia indicate that the incidence is increasing. The aims of this study were to investigate the recent incidence of hip fracture in the Tottori prefecture, Japan, and to compare it with previous reports. METHODS: All hip fractures in patients aged 35 years and older occurring between 2004 and 2006 were surveyed in all of the hospitals from the Tottori prefecture. The age- and gender-specific incidence rates were then calculated. Using these and previously reported data, the estimated number of hip fracture patients was determined using the age- and gender-specific incidence rates in each year from 1986 to 2006. RESULTS: The survey identified 851, 906, and 1,059 patients aged 35 years and older, in 2004, 2005, and 2006 respectively. The residual lifetime risk of hip fracture for individuals at 50 years of age was estimated to be 5.6% for men and 20.0% for women. The estimated number of patients from 1986 to 2006 showed a significant increase over time for both genders. CONCLUSIONS: The age- and gender-specific incidence of hip fracture in the Tottori prefecture, Japan has not plateaued for either gender.