Achieving osteoporosis treat-to-target goals with teriparatide or alendronate: sub-analysis of Japanese Osteoporosis Intervention Trial-05 (JOINT-05).

INTRODUCTION: The purpose of this study was to evaluate whether bone mineral density (BMD) ≥ -2.5 SD could be used as the treat-to-target (T2T) goal when treating osteoporosis with teriparatide (TPTD) and alendronate (ALN), and to investigate the relationship with incident vertebral fracture by re-analyzing data from a randomized, controlled trial (JOINT-05) involving postmenopausal Japanese women at high fracture risk. MATERIALS AND METHODS: Participants received sequential therapy with once-weekly TPTD for 72 weeks, followed by ALN for 48 weeks (TPTD-ALN group) or ALN monotherapy for 120 weeks (ALN group). BMDs were measured at the lumbar spine (L2-4), total hip, and femoral neck at 0, 24, 48, 72, and 120 weeks by dual-energy X-ray absorptiometry. The T2T goal was BMD ≥ -2.5 SD, and the endpoint was the proportion of participants with baseline BMD < -2.5 SD in three measurement sites achieving BMD ≥ -2.5 SD. RESULTS: A total of 559 participants were selected. BMD ≥ -2.5 SD at 120 weeks in the L2-4, total hip, and femoral neck sites was achieved in 20.5%, 23.1%, and 5.9%, respectively, in the TPTD-ALN group and 22.2%, 11.7%, and 7.3%, respectively, in the ALN group. Incident vertebral fractures occurred in areas of both lower and high BMD. CONCLUSION: During the 1.5-year treatment period, more than 20% of participants achieved BMD ≥ -2.5 SD as a T2T goal at L2-4. Since the achievement level differed depending on the BMD measurement site, the appropriate site should be selected according to the baseline BMD level.

Characteristics of patients presenting with concomitant carpal tunnel syndrome at the initial diagnosis with rheumatoid arthritis.

OBJECTIVE: To investigate the clinical characteristics of patients who presented with concomitant carpal tunnel syndrome (CTS) at the initial diagnosis with rheumatoid arthritis (RA). METHODS: We analyzed patients with newly diagnosed RA at a single institution between 2012 and 2021. Patient demographic and laboratory data, the 2010 ACR/EULAR classification criteria, and the duration from the initial visit to RA diagnosis were compared between RA patients with concomitant CTS (RA with CTS group) and those without CTS (RA without CTS group). RESULTS: The study included 235 patients (157 females), of which 11 patients (4.7%) presented with CTS at the initial diagnosis with RA. In the RA with CTS group, the age was significantly higher (P = .033), all patients were female, and anti-cyclic citrullinated peptide antibody (ACPA) was negative, and the duration to RA diagnosis was longer than in the RA without CTS group. Among all RA with CTS patients, ultrasonography showed power Doppler signal-positive tenosynovitis in the carpal tunnel, which is not usually detected in idiopathic CTS. CONCLUSIONS: Patients with concomitant CTS at the initial diagnosis with RA were characterized by old age, female sex, and negative ACPA. Patients with symptoms of CTS should undergo ultrasonography for early diagnosis of RA.

Urinary pentosidine level is associated with the risk of fracture in community-dwelling older adults: a prospective observational study.

A history of fracture in adulthood and urinary pentosidine levels were independently and significantly associated with fracture occurrence in this prospective observational study of community-dwelling older adults. PURPOSE: This prospective observational study aimed to determine the factors associated with fragility fractures in community-dwelling older adults. METHODS: Overall, 254 older adults who were participants of the Good Aging and Intervention Against Nursing Care and Activity Decline study in 2016 were included in this study. Grip strength, muscle mass, gait speed, calcaneal bone density, and the levels of parathyroid hormone, osteocalcin, 25-hydroxyvitamin D, total procollagen type I N-terminal propeptide, insulin-like growth factor-1 (IGF-1), tartrate-resistant acid phosphatase-5b, and urinary pentosidine were measured at baseline. Participants were classified as fracture ( +) or fracture (-) based on the data collected during a 5-year follow-up period. RESULTS: Excluding those who were lost to follow-up during the observation period, 182 participants (64 men and 118 women, mean age: 74.2 years, range: 47-99 years) were included in the analysis. During the observation period, 23 patients experienced 24 new fractures. In univariate analysis, sex, height, weight, history of fracture in adulthood, baseline grip strength, muscle mass, bone density, and the levels of urinary pentosidine and IGF-1 at baseline were significantly different between patients who developed a fracture during follow-up and those who did not. In multivariate analysis, a history of fracture in adulthood and urinary pentosidine levels were independently and significantly associated with fracture occurrence. CONCLUSION: High urine pentosidine levels and a history of fracture in adulthood are independent risk factors for fracture occurrence in community-dwelling older adults.

Sequential therapy with once-weekly teriparatide injection followed by alendronate versus monotherapy with alendronate alone in patients at high risk of osteoporotic fracture: final results of the Japanese Osteoporosis Intervention Trial-05.

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. PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Effect of Bone Resorption Inhibitors on Serum Cholesterol Level and Fracture Risk in Osteoporosis: Randomized Comparative Study Between Minodronic Acid and Raloxifene.

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 < 40 mg/dL, age group of ≥ 75 years, and T score of BMD ≥ -3 SD had significantly lower vertebral fracture rates than those receiving RLX (incidence rate ratios (IRR) 0.45 [95% confidence interval (CI) 0.30 0.75, 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.

Cooperation between physicians and dentists for osteonecrosis of the jaw: a 2022 Japanese survey.

INTRODUCTION: A 2015 survey of the Japan Osteoporosis Society (JOS) on medication-related osteonecrosis of the jaw (MRONJ) revealed that cooperation between physicians and dentists was poor. Discontinuation of antiresorptive agents before tooth extraction was found to increase adverse events without preventing MRONJ. We compared this 2015 survey with a new survey conducted in 2022 to investigate cooperation between physicians and dentists for MRONJ. MATERIALS AND METHODS: A web-based structured questionnaire including 13 key queries was sent to 3813 physicians who were members of JOS, and 1227 (32.2%) responses were received. RESULTS: Of the 1227 respondents, 909 (74.1%) had complied with a discontinuation request from a dentist before tooth extraction, although 25.4% of medications were not related to the incidence of MRONJ. Of these, 177 respondents reported 252 adverse events including 10 (1.3%) cases of MRONJ. The prevalence of fractures increased from 4.8% in 2015 to 8.2% in 2022. The rates of respondents who requested oral health care by a dentist before antiresorptive agent therapy and reported cooperation between physicians and dentists were 72.7% and 42.4% in 2022 compared with 32.9% and 24.8% in 2015, respectively. The rates of cooperation among the 47 prefectures in Japan were significantly different, ranging from 10.0 to 83.3% (p = 0.02). CONCLUSION: This study confirmed increased cooperation between physicians and dentists for MRONJ in Japan. However, a more equal distribution of cooperation across Japan is necessary to optimally manage MRONJ. Discontinuation of antiresorptive agents is no longer necessary because fractures during discontinuation continue to increase in Japan.

Reliability of early stage symptoms/clinical findings of osteonecrosis of the jaw: Japanese Osteoporosis Intervention Trial-05 (JOINT-05).

INTRODUCTION: To investigate the differences in the incidence rates of suspected stage 0/1 osteonecrosis of the jaw (ONJ) and incidence risk of relevant clinical findings of suspected stage 0 ONJ between patients treated with sequential therapy comprising weekly teriparatide for 72 weeks followed by alendronate for 48 weeks vs. those who received monotherapy with alendronate for 120 weeks. MATERIALS AND METHODS: Suspected stage 0/1 ONJ was defined by non-specific symptoms. Tooth mobility and periodontal symptoms (gingival bleeding, swelling, and/or pain) were selected as clinical findings of suspected stage 0 ONJ. Poisson regression models were applied to calculate the incidence rate ratios of suspected stage 0/1 between the teriparatide group (TG) and alendronate group (AG). Generalized linear models were used to calculate the risk ratios of clinical findings between groups. RESULTS: Two hundred and sixty-one participants in the TG and 344 in the AG answered a structured questionnaire on oral health and were included in this study. There were no significant differences between the groups in the incidence rate of suspected stage 0/1 ONJ at both 72 and 120 weeks. The risk ratio of the TG to AG for tooth mobility was 0.34 (95% confidence interval [CI] 0.13-0.88, p = 0.02) at 72 weeks and 0.90 (95% CI 0.40-2.03, p = 0.83) at 120 weeks. The incidence rate of tooth mobility related to periodontal symptoms decreased in the TG and increased in the AG during the study. CONCLUSION: Tooth mobility accompanied by clinical periodontal symptoms may be a useful early sign of stage 0 ONJ.

Antiresorptive Drugs and the Risk of Femoral Shaft Fracture in Men and Women With Osteoporosis: A Cohort Study Using the National Database of Health Insurance Claims of Japan.

BACKGROUND: This cohort study aimed to estimate incidence rates of femoral shaft fracture in patients who were treated with antiresorptive drugs. METHODS: We used data from the National Database of Health Insurance Claims of Japan from April 2009 and October 2016. All patients with new use of an antiresorptive drug, prescription-free period of ≥3 months, and no prior femoral fractures were included. Femoral shaft fractures were identified using a validated definition based on International Classification of Diseases, 10th revision (ICD-10) codes. Incidence rate ratios were estimated using Poisson regression, with adjustment for sex, age, and the Charlson Comorbidity Index. RESULTS: We identified 7,958,655 patients (women: 88.4%; age ≥75 years: 51.2%). Femoral shaft fractures were identified in 22,604 patients. Incidence rates per 100,000 person-years were 74.8 for women, 30.1 for men, 30.1 for patients aged ≤64 years, 47.7 for patients aged 65-74 years, and 99.0 for patients aged ≥75 years. Adjusted incidence rate ratios in patients taking versus not taking each type of antiresorptive drug were 1.00 (95% confidence interval [CI], 0.98-1.03) for bisphosphonates, 0.46 (95% CI, 0.44-0.48) for selective estrogen receptor modulators, 0.24 (95% CI, 0.18-0.32) for estrogens, 0.75 (95% CI, 0.71-0.79) for calcitonins, and 0.93 (95% CI, 0.84-1.03) for denosumab. The adjusted incidence rate ratio for alendronate was 1.18 (95% CI, 1.14-1.22). CONCLUSION: The incidence rates of femoral shaft fracture varied across patients treated with different antiresorptive drugs. Further research on a specific antiresorptive drug can increase understanding of the risk of femoral shaft fracture.

Walking speed is associated with postoperative pain catastrophizing in patients with lumbar spinal stenosis: a prospective observational study.

BACKGROUND: The purpose of this study was to investigate whether walking speed is associated with postoperative pain catastrophizing in patients with lumbar spinal stenosis. METHODS: In this prospective observational study, consecutive patients with clinically and radiologically defined lumbar spinal stenosis underwent surgical treatment (decompression, or posterolateral or transforaminal lumbar interbody fusion) at Tottori University Hospital, between October 2015 and April 2018. The pain catastrophizing scale, walking speed, leg and back pain (numerical rating scale), and Japanese Orthopaedic Association score were evaluated preoperatively and at 3, 6, and 12 months postoperatively. Correlations between the pain catastrophizing scale and each variable were analyzed at each evaluation time point. The effect of walking speed on the pain catastrophizing scale was analyzed using mixed-effect models for repeated measurements. RESULTS: Ninety-four patients were included at baseline, and 83, 88, and 82 patients were analyzed at 3, 6, and 12 months postoperatively, respectively. The pain catastrophizing scale was significantly correlated with walking speed, leg pain, back pain, and the Japanese Orthopaedic Association score at all evaluation time points. The pain catastrophizing scale was associated with walking speed at all evaluation time points. CONCLUSIONS: Our results suggest that changes in postoperative pain catastrophizing after lumbar spine surgery are associated with walking speed. Thus, walking speed is a necessary assessment for the management of pain catastrophizing and associated pain and disability in patients after lumbar spine surgery.

Total knee arthroplasty in the past three decades: Trends in patient characteristics and implant survivorship.

OBJECTIVE: To explore the trends in patient characteristics and implant survivorship (IS) for primary total knee arthroplasty (TKA) over the past three decades. METHODS: This retrospective study enrolled a total of 635 knees who underwent TKA from 1985 to 2014. They were divided into three groups: group A, 125 knees in 1985-1994; group B, 203 knees in 1995-2004; and group C, 307 knees A in 2005-2014. The patient characteristics and IS were compared. RESULTS: The mean age of patients undergoing TKA was getting older: 65.3 ± 9.7, 69.1 ± 10.0, and 74.6 ± 8.4 years, in groups A, B, and C, respectively (p = .001). The proportion of patients <60 years old with RA decreased (p < .001), whereas that of patients ≥ 80 years old with OA increased dramatically, it was 7.0%, 14.5%, and 32.0% in groups A, B, and C, respectively (p < .001). The IS free from infection was over 98% in all groups. Alternatively, the IS free from aseptic loosening become better, it was 83.7%, 95.2%, and 98.2% in groups A, B, and C, respectively (p = .014). CONCLUSIONS: From these trends, we can estimate that the number of patients undergoing TKA will further increase in the future in an aging society.

Impact of high-load resistance training on bone mineral density in osteoporosis and osteopenia: a meta-analysis.

INTRODUCTION: This study aimed to examine the effect of high-load resistance training (HLRT) on bone mineral density (BMD) in patients with osteoporosis and osteopenia using a meta-analysis. MATERIALS AND METHODS: We searched for randomized controlled trials (RCTs) on HLRT in patients with osteoporosis and osteopenia from medical databases. Our meta-analysis was performed with the primary endpoints being the standardized mean difference (SMD) of the change in BMD of the lumbar spine (LS), femoral neck (FN), and total hip (TH). The robustness of the results was assessed by subgroup analysis. Heterogeneity factors were examined by meta-regression. Publication bias was evaluated using a funnel plot. RESULTS: We selected nine RCTs, with 259 patients in the HLRT group (women, 55.2%) and 236 patients in the control group (women, 62.7%). The HLRT group showed a significant increase in BMD in the LS [SMD = 1.40, 95% confidence interval (CI) = 0.68-2.12, p < 0.001, I2 = 90%], the FN (SMD = 0.86, 95% CI = 0.05-1.67, p = 0.04, I2 = 92%), and the TH (SMD = 1.26, 95% CI = 0.45-2.08, p = 0.002, I2 = 91%). Subgroup analysis confirmed the robustness of the results only in LS. Total sessions and a high risk of bias were identified as the factors of heterogeneity in FN and TH (p < 0.05). The funnel plot showed asymmetry in all measurement sites. CONCLUSION: This study suggested that HLRT can be effective in increasing BMD, mainly of LS, in patients with osteoporosis and osteopenia. However, due to high heterogeneity and publication bias, additional studies with a low risk of bias should be conducted to generalize our findings.

Risk factors for incident vertebral fractures in osteoporosis pharmacotherapy: a 2-year, prospective, observational study.

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Urinary pentosidine level is associated with grip strength and gait speed in community-dwelling adults: a cross-sectional study.

BACKGROUND: Muscle and bone interactions might be associated with osteoporosis and sarcopenia. Urinary pentosidine and serum 25-hydroxyvitamin D (25(OH)D) might affect muscle and bone interactions. It is unclear whether these biomarkers are affected by age and sex or play a role in muscle and physical functions. We aimed to investigate the association between urinary pentosidine and serum 25(OH)D levels with muscle mass, muscle strength, and physical performance in community-dwelling adults. METHODS: Two-hundred and fifty-four middle-aged and elderly adults were enrolled. There was no significant difference in age between 97 men (75.0 ± 8.9 years) and 157 women (73.6 ± 8.1 years). The skeletal muscle mass index (SMI), grip strength, and gait speed were assessed. The urinary pentosidine level was measured. We evaluated the association of urinary pentosidine and serum 25(OH)D levels with age and sex (student's t-test) and correlations between biomarker and each variable (Pearson's correlation coefficients). Multiple regression analysis was performed with grip strength and gait speed as dependent variables and with age, height, weight, body mass index (BMI), speed of sound (SOS), SMI, glycated hemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), 25(OH)D, and pentosidine as independent variables using the stepwise method. RESULTS: The urinary pentosidine level was negatively correlated with grip strength, gait speed, eGFR, and insulin-like growth factor-1 (IGF-1) in men and with SOS, grip strength, and gait speed in women. The serum 25(OH)D level was positively correlated with IGF-1 in women and grip strength in men. Grip strength was associated with age, height, and pentosidine in men and height and pentosidine in women. Gait speed was associated with age, BMI, and pentosidine in men and age, height, and pentosidine in women. CONCLUSION: Urinary pentosidine levels are significantly associated with grip strength and gait speed and may serve as a biomarker of muscle and bone interactions.

Design of a randomized trial of teriparatide followed by alendronate: Japanese Osteoporosis Intervention Trial-05 (JOINT-05).

INTRODUCTION: Despite advances in drug treatment, the optimal treatment strategy for severe osteoporosis remains uncertain. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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).

Minodronate combined with alfacalcidol versus alfacalcidol alone for glucocorticoid-induced osteoporosis: a multicenter, randomized, comparative study.

INTRODUCTION: This study compared the clinical usefulness of minodronate (50 mg/4 weeks) plus alfacalcidol (1 µg/day) (Group M) with that of alfacalcidol alone (1 µg/day) (Group A) for treating glucocorticoid-induced osteoporosis. MATERIALS AND METHODS: The primary endpoints were the changes from baseline in lumbar spine (LS) bone mineral density (BMD) and the cumulative incidence of vertebral fracture at 24 months; secondary endpoints included the changes from baseline in total hip (TH) BMD and bone turnover markers. RESULTS: Of 164 patients enrolled, 152 (Group M, n = 75; Group A, n = 77) were included in the analysis of efficacy. At each time point and at 24 months, LS BMD and TH BMD were significantly higher in Group M than in Group A. The 152 patients were divided into two subgroups that were previously treated with glucocorticoids for ≤ 3 months or > 3 months. In both subgroups, the changes from baseline in LS BMD and TH BMD from baseline at 24 months had increased more in Group M than in Group A. There were no differences found in the incidence of vertebral fracture between the groups, because the number of enrolled patients was lesser than that initially expected. In Group M, both bone formation and resorption markers significantly decreased from baseline at 3 months and maintained at 6, 12, and 24 months. CONCLUSIONS: Minodronate plus alfacalcidol was more effective than alfacalcidol alone in increasing BMD and was effective in increasing BMD for both prevention and treatment. Therefore, minodronate can be a good candidate drug for the treatment of glucocorticoid-induced osteoporosis.

Phase II/III, randomized, double-blind, parallel-group study of monthly delayed-release versus daily immediate-release risedronate tablets in Japanese patients with involutional osteoporosis.

Absorption of oral immediate-release (IR) risedronate tablets is reduced by food intake, thus a delayed-release (DR) tablet has been developed to overcome the necessity of taking IR tablets under fasting conditions. This randomized, double-blind, phase II/III study compared efficacy and safety of risedronate IR once-daily (QD) and DR once-monthly (QM) tablets in Japanese patients with involutional osteoporosis. Patients received 2.5 mg IR on awakening QD, or 25 or 37.5 mg DR on awakening, following breakfast, or 30 min after breakfast, QM for 12 months. Primary endpoint was non-inferiority in mean percent change from baseline to end of study (month 12, last observation carried forward [M12, LOCF]) in mean lumbar spine (L2-L4) bone mineral density (BMD) between risedronate IR on awakening and DR following breakfast. Mean percent changes in (L2-L4) BMD at M12, LOCF were 5.07% (IR at awakening, n = 190), 3.36% (25 mg DR following breakfast, n = 194), and 4.11% (37.5 mg DR following breakfast, n = 181). Mean percent change in (L2-L4) BMD was numerically lower in the DR following breakfast groups versus the respective on awakening and 30 min after breakfast DR groups. Overall incidences of treatment-emergent adverse events (TEAEs) were comparable between groups. In the DR groups, 1.5-4.0% of patients reported TEAEs potentially associated with acute-phase reactions versus 0% in the IR group. In this study, non-inferiority could not be declared for 37.5 or 25 mg DR following breakfast QM (p = 0.1346 or p = 0.6711, respectively) versus 2.5 mg IR on awakening QD.

Executive summary of clinical practice guide on fracture risk in lifestyle diseases.

Accumulating evidence has shown that patients with lifestyle diseases such as type 2 diabetes mellitus, chronic kidney disease, and chronic obstructive pulmonary disease are at increased risk of osteoporotic fracture. Fractures deteriorate quality of life, activities of daily living, and mortality as well as a lifestyle disease. Therefore, preventing fracture is an important issue for those patients. Although the mechanism of the lifestyle diseases-induced bone fragility is still unclear, not only bone mineral density (BMD) reduction but also bone quality deterioration are involved in it. Because fracture predictive ability of BMD and FRAX® is limited, especially for patients with lifestyle diseases, the optimal management strategy should be established. Thus, when the intervention of the lifestyle diseases-induced bone fragility is initiated, the deterioration of bone quality should be taken into account. We here review the association between lifestyle diseases and fracture risk and proposed an algorism of starting anti-osteoporosis drugs for patients with lifestyle diseases.

Preoperative low muscle mass is a predictor of falls within 12 months of surgery in patients with lumbar spinal stenosis.

BACKGROUND: Patients with lumbar spinal stenosis (LSS) may be at high risk of falls due to various factors. No effective fall risk assessments or fall prevention measures have been performed for patients with LSS because only a few studies have evaluated falls in these patients. This study aimed to evaluate the incidence and preoperative predictors of falls within 12 months of surgery in patients with LSS. METHODS: In this prospective study of 82 consecutive preoperative patients with LSS, preoperative demographic data, previous fall history, leg pain, low back pain, Japanese Orthopaedic Association (JOA) score, Hospital Anxiety and Depression Scale (HADS) scores, lower extremity muscle strength, walking speed, grip strength, and muscle mass were assessed at baseline. Falls were assessed at 3, 6, 9, and 12 months after surgery. Participants were categorized as fallers and non-fallers and baseline variables were compared. Binomial logistic regression was used to identify predictors of falls within 12 months of surgery. RESULTS: Seventy-four patients (90.2%) completed the 12-month follow-up after surgery, of whom 24 patients (32.4%) experienced falls. A higher proportion of fallers were female and had a history of falls compared to non-fallers. Fallers had a significantly lower JOA score and a higher HADS-depression score compared to non-fallers. Fallers had significantly lower tibialis anterior muscle strength, gait speed, grip strength, and skeletal muscle mass index. Fallers had a higher prevalence of low muscle mass compared with non-fallers. The presence of low muscle mass was significantly predictive of falls within 12 months of surgery (odds ratio, 4.46; 95% confidence interval, 1.02-19.63). CONCLUSIONS: Patients with LSS have a high incidence of falls after surgery and preoperative low muscle mass may be a predictor of postoperative falls.

Age-related changes in muscle elasticity around the shoulder joint in young male baseball players: A prospective longitudinal study.

BACKGROUND: Longitudinal changes of elasticity in the muscle tissues around the shoulder joint during the growth period have not been assessed using shear wave elastography. METHODS: This study enrolled male students aged 13-18 years who played baseball or rubber baseball as an extra-curricular activity during junior high or high school or on a baseball team outside of school. The exclusion criterion was a history of surgery for athletic injury. One hundred and twenty-one boys were included in the study. The elasticity of the superior part of the trapezius, the supraspinatus, and the infraspinatus were measured by ultrasound. The shear elastic modulus (SEM), which is the ratio of the strain ratio (SR) in the acoustic coupler to the SR of each muscle, was calculated as a representative value. Six months after the baseline assessment, subjects were evaluated regarding any newly developed pain in the joint of the throwing shoulder, and categorized into either the non-pain group or the pain group. RESULTS: Although all muscle SEMs tended to increase in both the throwing and non-throwing shoulders, no significant difference was observed in the prevalence of shoulder joint pain between ages (p = 0.541). The results of a binominal logistic regression analysis, adjusted for age, body mass index, playing position in baseball, frequency of baseball practice, shoulder range of motion, and muscle strength showed that a decrease in SEM values of the supraspinatus was a risk factor for the development of new pain (odds ratio: 0.056; 95% confidence interval 0.011-0.299; p = 0.001). CONCLUSIONS: The elasticity of muscle tissues around the throwing shoulder increased with age, and low tissue elasticity of the supraspinatus of the throwing shoulder was a factor that triggered pain during throwing motions.

Changes in quality of life in patients with postmenopausal osteoporosis receiving weekly bisphosphonate treatment: a 2-year multicenter study in Japan.

We investigated changes in quality of life (QOL), including pain, in Japanese women aged ≥ 55 years who were diagnosed as having osteoporosis at 265 centers across Japan and treated continuously with once-weekly bisphosphonates for 24 months. In 2650 evaluable patients, a significant improvement in QOL was observed from 3 months after enrollment onward and maintained throughout the 2-year observation period. A significant improvement in scores was observed for all domains of the Euro QOL 5 Dimension (EQ-5D), and the "pain", "health perception", and "posture, figure" domains of the Japanese Osteoporosis QOL Questionnaire (JOQOL). Factors identified as significantly contributing to QOL change were "fractures within the year before enrollment", "presence of spondylosis deformans", "presence of osteoarthritis", "use of activated vitamin D3", and "age" based on the JOQOL, and "presence of spondylosis deformans", "use of activated vitamin D3", and "age" based on the EQ-5D. The results suggested that the patients' perception of treatment effects, such as improvement in pain, contributes to treatment continuation. Osteoporosis patients should be informed that continuous treatment with once-weekly bisphosphonates can lead to a significant improvement in QOL regardless of concomitant locomotor diseases, to encourage them to remain on treatment. In conclusion, continuous bisphosphonate treatment improved the QOL even in patients with locomotor diseases, and the concomitant use of activated vitamin D3 may also facilitate further improvement in QOL.