The 2023 Guidelines for the management and treatment of glucocorticoid-induced osteoporosis.

INTRODUCTION: Although synthetic glucocorticoids (GCs) are commonly used to treat autoimmune and other diseases, GC induced osteoporosis (GIOP) which accounts for 25% of the adverse reactions, causes fractures in 30-50% of patients, and markedly decreases their quality of life. In 2014, the Japanese Society for Bone and Mineral Research (JSBMR) published the revised guidelines for the management and treatment of steroid-induced osteoporosis, providing the treatment criteria based on scores of risk factors, including previous fractures, age, GC doses, and bone mineral density, for patients aged ≥18 years who are receiving GC therapy or scheduled to receive GC therapy for ≥3 months. MATERIALS AND METHODS: The Committee on the revision of the guidelines for the management and treatment of GIOP of the JSBMR prepared 17 clinical questions (CQs) according to the GRADE approach and revised the guidelines for the management and treatment of GIOP through systematic reviews and consensus conferences using the Delphi method. RESULTS: Bisphosphonates (oral and injectable formulations), anti-RANKL antibody teriparatide, eldecalcitol, or selective estrogen receptor modulators are recommended for patients who has received or scheduled for GC therapy with risk factor scores of ≥3. It is recommended that osteoporosis medication is started concomitantly with the GC therapy for the prevention of fragility fractures in elderly patients. CONCLUSION: The 2023 guidelines for the management and treatment of GIOP was developed through systematic reviews and consensus conferences using the Delphi method.

Reliability, stability during long-term storage, and intra-individual variation of circulating levels of osteopontin, osteoprotegerin, vascular endothelial growth factor-A, and interleukin-17A.

BACKGROUND: Studies in many populations have reported associations between circulating cytokine levels and various physiological or pathological conditions. However, the reliability of cytokine measurements in population studies, which measure cytokines in multiple assays over a prolonged period, has not been adequately examined; nor has stability during sample storage or intra-individual variation been assessed. METHODS: We assessed (1) analytical reliability in short- and long-term repeated measurements; (2) stability and analytical reliability during long-term sample storage, and (3) variability within individuals over seasons, of four cytokines-osteopontin (OPN), osteoprotegerin (OPG), vascular endothelial growth factor-A (VEGF-A), and interleukin-17A (IL-17A). Measurements in plasma or serum samples were made with commercial kits according to standard procedures. Estimation was performed by fitting a random or mixed effects linear model on the log scale. RESULTS: In repeated assays over a short period, OPN, OPG, and VEGF-A had acceptable reliability, with intra- and inter-assay coefficients of variation (CV) less than 0.11. Reliability of IL-17A was poor, with inter- and intra-assay CV 0.85 and 0.43, respectively. During long-term storage, OPG significantly decayed (- 33% per year; 95% confidence interval [- 54, - 3.7]), but not OPN or VEGF-A (- 0.3% or - 6.3% per year, respectively). Intra- and inter-assay CV over a long period were comparable to that in a short period except for a slight increase in inter-assay CV of VEGF-A. Within-individual variation was small for OPN and VEGF-A, with intra-class correlations (ICC) 0.68 and 0.83, respectively, but large for OPG (ICC 0.11). CONCLUSIONS: We conclude that OPN and VEGF-A can be reliably measured in a large population, that IL-17A is suitable only for small experiments, and that OPG should be assessed with caution due to degradation during storage and intra-individual variation. The overall results of our study illustrate the need for validation under relevant conditions when measuring circulating cytokines in population studies.

A meta-analysis of previous falls and subsequent fracture risk in cohort studies.

The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. INTRODUCTION: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). METHODS: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. RESULTS: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51) and men (HR 1.53, 95% CI 1.41-1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27-1.84) in men vs. HR 1.32 (95% CI 1.20-1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men. CONCLUSIONS: A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.

Patients' preferences for fracture risk communication: the Risk Communication in Osteoporosis (RICO) study.

The RICO study indicated that most patients would like to receive information regarding their fracture risk but that only a small majority have actually received it. Patients globally preferred a visual presentation of fracture risk and were interested in an online tool showing the risk. PURPOSE: The aim of the Risk Communication in Osteoporosis (RICO) study was to assess patients' preferences regarding fracture risk communication. METHODS: To assess patients' preferences for fracture risk communication, structured interviews with women with osteoporosis or who were at risk for fracture were conducted in 11 sites around the world, namely in Argentina, Belgium, Canada at Hamilton and with participants from the Osteoporosis Canada Canadian Osteoporosis Patient Network (COPN), Japan, Mexico, Spain, the Netherlands, the UK, and the USA in California and Washington state. The interviews used to collect data were designed on the basis of a systematic review and a qualitative pilot study involving 26 participants at risk of fracture. RESULTS: A total of 332 women (mean age 67.5 ± 8.0 years, 48% with a history of fracture) were included in the study. Although the participants considered it important to receive information about their fracture risk (mean importance of 6.2 ± 1.4 on a 7-point Likert scale), only 56% (i.e. 185/332) had already received such information. Globally, participants preferred a visual presentation with a traffic-light type of coloured graph of their FRAX® fracture risk probability, compared to a verbal or written presentation. Almost all participants considered it important to discuss their fracture risk and the consequences of fractures with their healthcare professionals in addition to receiving information in a printed format or access to an online website showing their fracture risk. CONCLUSIONS: There is a significant communication gap between healthcare professionals and patients when discussing osteoporosis fracture risk. The RICO study provides insight into preferred approaches to rectify this communication gap.

Incidence and trend of antiresorptive agent-related osteonecrosis of the jaw from 2016 to 2020 in Kure, Japan.

We investigated the incidence/trend of osteonecrosis of the jaw by antiresorptive agent dose over a 5-year period in Kure city, Japan. The incidence was 24 times higher among osteoporosis patients with low-dose agents and 421 times higher among cancer patients with high-dose agents than in the population without agents. PURPOSE: We launched the registry system of osteonecrosis of the jaw (ONJ) cases in 2015 to investigate the trend in ONJ incidence. The purpose of our study was to estimate the ONJ incidence among patients with antiresorptive agent use by dosage and people without antiresorptive agent use in Kure and its trend from 2016 to 2020. METHODS: From 2016 to 2021, 98 eligible ONJ patients were enrolled. Medication-related ONJ (MRONJ) was diagnosed based on the American Association of Oral and Maxillofacial Surgeons criteria. The annual number of those with and without antiresorptive agents was obtained from the claims database. Antiresorptive agents used for cancer and osteoporosis patients were defined as high- and low-dose medications, respectively. RESULTS: The annual incidence of high-dose MRONJ was 2305.8 per 100,000 and that of low-dose MRONJ was 132.5 per 100,000, while the ONJ incidence among people without antiresorptive agents was 5.1 per 100,000. The incidence ratio was 23.6 (p < 0.001, 95% confidence interval (CI) 13.3-41.8) among osteoporosis patients who used low-dose antiresorptive agents and 420.6 (p < 0.001, 95% CI 220.8-801.4) among cancer patients who used high-dose agents compared with people who did not use these agents. MRONJ incidence increased from 2016 to 2020, but the incidence of high-dose MRONJ decreased, although this was nonsignificant. CONCLUSION: We demonstrated the incidence and trend of ONJ by antiresorptive agent dose over a 5-year period in Kure after launching the multiprofession study. This collaborative study for the early detection and prevention of ONJ will continue.

Prevalence of osteoporosis and incidence of related fractures in developed economies in the Asia Pacific region: a systematic review.

Robust data on osteoporosis in the Asia Pacific region could improve healthcare decision-making. Osteoporosis affects 10-30% of women aged 40 + , and up to 10% of men in 7 developed economies in Asia Pacific. Fractures affect 500-1000 adults aged 50 + per 100,000 person-years. Policymakers and clinicians must address this problem. PURPOSE: Osteoporosis and associated fractures result in considerable morbidity, loss of productivity, early mortality, and increased healthcare expenses. Many countries in the Asia Pacific (AP) region, especially middle- and higher-income economies, are faced with aging and increasingly sedentary populations. It is critical to consolidate and analyze the available information on the prevalence and incidence of the disease in these countries. METHODS: We systematically reviewed articles and gray literature for Australia, China, Hong Kong, Japan, Singapore, South Korea, and Taiwan. We searched PubMed, ScienceDirect, JSTOR, Cochrane, Google Scholar, and other databases for data published 2009-2018. We included articles with prevalence or incidence estimates for adults with osteoporosis or related fractures. RESULTS: All locations had data available, but of widely varying quantity and quality. Most estimates for osteoporosis prevalence ranged from 10 to 30% for women ages 40 and older, and up to 10% for men. Osteoporotic fracture incidence typically ranged between 500 and 1000 per 100,000 person-years among adults aged 50 and older. Both outcomes typically increased with age and were more common among women. CONCLUSION: Osteoporosis and associated fractures affect significant portions of the adult population in developed economies in the AP region. Governments and healthcare systems must consider how best to prevent and diagnose osteoporosis, and manage affected individuals, to reduce healthcare costs and mortality associated with fractures.

Real-world evaluation of osteoporotic fractures using the Japan Medical Data Vision database.

In Japanese patients who experienced an osteoporotic fracture, 10.8% and 18.6% had a subsequent fracture within 1 and 2 years of follow-up, respectively. Although the burden of hip and vertebral fractures has been reported widely, we found that patients with non-hip non-vertebral (NHNV) fractures had a 26% higher risk of subsequent fracture than patients with hip fractures; therefore, NHNV fractures should also be considered an important risk factor for subsequent fracture. INTRODUCTION: To investigate imminent risk and odds of subsequent osteoporotic fractures and associated risk factors in patients who experienced an initial osteoporotic fracture. METHODS: Patients aged ≥ 50 years with ≥ 1 osteoporotic fracture were analyzed from Japan's Medical Data Vision (MDV) database of claims from acute-care hospitals (January 2012-January 2017). Multivariable models were constructed to explore the impact of key comorbidities and medications on the subsequent fracture risk: Cox proportional hazards model for time to subsequent fracture and logistic regression models for odds of subsequent fracture within 1 and 2 years from index fracture. RESULTS: In total, 32,926 patients were eligible with a median follow-up duration of 12.3 months. The percentage of patients experiencing subsequent fractures was 14.1% across the study duration, and 10.8% and 18.6% in patients with 1 and 2 years of follow-up, respectively. In the Cox proportional hazards model, patients with vertebral or NHNV index fractures had a higher subsequent fracture risk than patients with a hip index fracture (adjusted hazard ratio [aHR] 1.11 and 1.26, respectively); subsequent fracture risk was lower in males than females (aHR 0.89). Patients with baseline claims for tranquilizers and glucocorticoids had a higher subsequent fracture risk than those without (aHR 1.14 and 1.08, respectively). Additionally, baseline claims for anti-Parkinson's medications, alcoholism, and stage 4/5 chronic kidney disease were significantly associated with higher odds of subsequent fracture in the logistic regression models. CONCLUSION: Several clinical and demographic factors were associated with a higher risk and odds of subsequent fracture. This may help to identify patients who should be prioritized for osteoporosis treatment.

Incidence of Diabetes in the Atomic Bomb Survivors: 1969-2015.

CONTEXT: Recent epidemiological studies have shown increased risk of diabetes among childhood cancer survivors who received high therapeutic doses of radiation, particularly to the total body or to the abdomen. However, the effect of low-to-moderate dose radiation (<4 Gy) on the risk of diabetes is still unknown. OBJECTIVES: To investigate the radiation effect on diabetes incidence among atomic bomb (A-bomb) survivors, and whether the dose response is modified by other factors including city, sex, and age at time of bombing (ATB). METHODS: 9131 participants without diabetes at baseline were observed through biennial clinical exams from 1969 to 2015. A Cox proportional hazards model was used to estimate hazard ratios (HR) to evaluate the dose response for diabetes incidence. RESULTS: During the study period, 1417 incident diabetes cases were identified. The overall crude incidence rate was 7.01/103 person-years. Radiation dose was significantly associated with diabetes incidence, with effect modification by city and age ATB. In Hiroshima, at ages 10 and 30 ATB, the HRs at 1 Gy of pancreatic radiation dose were 1.47 (95% CI, 1.31-1.66) and 1.13 (95% CI, 0.97-1.31), respectively. However, no significant radiation dose response was observed at these ages in Nagasaki. The HR for radiation dose was higher among those who were younger ATB and decreased 1% for each additional year of age. CONCLUSIONS: Among A-bomb survivors, a radiation association was suggested for incidence of diabetes. Results were inconsistent by city and age ATB, which could indicate potential confounding of the radiation association with diabetes.

Differences in the effects of BMI on bone microstructure between loaded and unloaded bones assessed by HR-pQCT in Japanese postmenopausal women.

OBJECTIVES: The relationship between weight-related load and bone mineral density (BMD)/bone microstructure under normal load conditions using high-resolution peripheral quantitative computed tomography (HR-pQCT) remains unconfirmed. The study aims to investigate the differences in effect of body mass index (BMI) on BMD/bone microstructure of loaded and unloaded bones, respectively, in Japanese postmenopausal women. METHODS: Fifty-seven postmenopausal women underwent HR-pQCT on the tibia and radius. Correlation analysis, principal component (PC) analysis, and hierarchical multiple regression were performed to examine the relationship between BMI and HR-pQCT parameters. RESULTS: Several microstructural parameters of the tibia and radius correlated with BMI through a simple correlation analysis, and these relationships remained unchanged even with an age-adjusted partial correlation analysis. PC analysis was conducted using seven bone microstructure parameters. The first PC (PC1) reflected all parameters of trabecular and cortical bone microstructures, except for cortical porosity, whereas the second PC (PC2) reflected only cortical bone microstructure. Hierarchical multiple regression analysis indicated that BMI was more strongly related to BMD/bone microstructure in the tibia than in the radius. Furthermore, BMI was associated with trabecular/cortical BMD, and PC1 (not PC2) of the tibia and radius. Thus, BMI was strongly related to the trabecular bone microstructure rather than the cortical bone microstructure. CONCLUSIONS: Our data confirmed that BMI is associated with volumetric BMD and trabecular bone microstructure parameters in the tibia and radius. However, although BMI may be more related to HR-pQCT parameters in the tibia than in the radius, the magnitude of association is modest.

Incidence of fractures among patients receiving medications for type 2 diabetes or chronic obstructive pulmonary disease and glucocorticoid users according to the National Claims Database in Japan.

According to information from the National Health Insurance and Claims database, the risk for hip, radius, and clinical vertebral fractures was higher among patients receiving medication for type 2 diabetes, COPD, or glucocorticoids than among the whole Japanese population after middle age. PURPOSE: The aim of this study was to determine the incidence of fractures among patients receiving medications for type 2 diabetes or chronic obstructive pulmonary disease (COPD) and using glucocorticoids (GC) according to the National Database of Health Insurance Claims (NDB) in Japan. METHODS: We obtained data on the number of fractures and patients receiving medications for type 2 diabetes, COPD, or GC from the NDB. The claims data included sex, age group, injury/illness name, hospitalization, outpatient, surgery/medical treatment, and drugs used between January and December 2017. RESULTS: The risk of hip fracture was higher among patients receiving medications for diabetes or COPD and GC users than in the Japanese population, with standardized incidence ratios (SIRs) of 1.71 (95% confidence interval [CI]1.6-1.75), 1.35 (95% CI 1.28-1.42), and 1.62 (95% CI 1.53-1.71) in men and 1.81 (95% CI 1.79-1.84), 1.67 (95% CI 1.54-1.80), and 1.71 (95% CI 1.66-1.76) in women, respectively. There was also a significantly higher incidence of radial fractures in women and clinical vertebral fractures in both men and women. A greater risk of hip fracture was found among diabetic patients starting in their late 40 s. CONCLUSIONS: Real-world data revealed that the incidence of hip, radius, and clinical vertebral fractures was significantly higher among patients receiving medications for diabetes or COPD and GC users than in the Japanese population after middle age.

Radiation effects on atherosclerosis in atomic bomb survivors: a cross-sectional study using structural equation modeling.

Past reports indicated that total-body irradiation at low to moderate doses could be responsible for cardiovascular disease risks, but the mechanism remains unclear. The purpose of this study was to investigate the association between radiation exposure and atherosclerosis, an underlying pathology of cardiovascular diseases, in the Japanese atomic bomb survivors. We performed a cross-sectional study measuring 14 clinical-physiological atherosclerosis indicators during clinical exams from 2010 to 2014 in 3274 participants of the Adult Health Study cohort. Multivariable analyses were performed by using a structural equation model with latent factors representing underlying atherosclerotic pathologies: (1) arterial stiffness, (2) calcification, and (3) plaque　as measured with indicators chosen a priori on the basis of clinical-physiological knowledge. Radiation was linearly associated with calcification (standardized coefficient per Gy 0.15, 95 % confidence interval: CI [0.070, 0.23]) and plaque (0.11, 95 % CI [0.029, 0.20]), small associations that were comparable to about 2 years of aging per Gy of radiation exposure, but not with arterial stiffness (0.036, 95 % CI [- 0.025, 0.095]). The model fitted better and had narrower confidence intervals than separate ordinary regression models explaining individual indicators independently. The associations were less evident when the dose range was restricted to a maximum of 2 or 1 Gy. By combining individual clinical-physiological indicators that are correlated because of common, underlying atherosclerotic pathologies, we found a small, but significant association of radiation with atherosclerosis.

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.

Modifying Effect of Chronic Atrophic Gastritis on Radiation Risk for Noncardia Gastric Cancer According to Histological Type.

The findings from previously published studies have suggested that radiation exposure is associated with increased mortality and incidence of gastric cancer. However, few cohort studies have incorporated risk factors such as Helicobacter pylori (H. pylori) infection or chronic atrophic gastritis (CAG). The current study is aimed at evaluating the modifying effect of CAG on radiation risk of noncardia gastric cancer by histological type, by reanalyzing data from a nested case-control study conducted within the longitudinal clinical cohort of atomic bomb survivors. The analysis was restricted to 297 intestinal- or diffuse-type noncardia cases and 873 controls rematched to the cases on gender, age, city, and time and type of serum storage, and countermatched on radiation dose. Multivariable-adjusted relative risks [95% confidence interval (CI)] of noncardia gastric cancer were 3.9 (2.1-7.2) for H. pylori IgG seropositivity with cytotoxin-associated gene A (CagA) IgG low titer, 2.6 (1.9-3.6) for CAG, 1.9 (1.3-2.8) for current smoking, and 1.4 (1.1-1.9) for 1 Gy irradiation. Among subjects without CAG, the relative risk (95% CI) of noncardia gastric cancer at 1 Gy was 2.3 (1.4-3.7), whereas relative risk (95% CI) at 1 Gy was 1.1 (0.8-1.5) among subjects with CAG (for the overall interaction, P = 0.012). By histological type, the risk at 1 Gy was high for diffuse type without CAG, with adjusted relative risk (95% CI) of 3.8 (2.0-7.6), but was not high for diffuse type with CAG or for intestinal-type irrespective of CAG status. The results indicate that radiation exposure is associated with increased risk of diffuse-type noncardia gastric cancer without CAG, and this association exists despite adjustment for H. pylori infection and smoking habit.

Incidence of clinical vertebral fractures and hip fractures of the elderly (65 years or over) population-large-scale data analysis using claim database in Kure City, Hiroshima, Japan.

Using the claim database, we investigated the incidence rate of clinical vertebral fractures per 1,000 in the elderly residents, over 65 years of age, in Kure city. The incidence rate, of clinical vertebral fractures, was 15.58 (7.29 male, 21.17 female, 2.90 female/male ratio). PURPOSE: To elucidate the incidence of clinical vertebral and hip fractures using the claim database, in those over 65 years of age in Kure city, and to compare with the previous reports. METHODS: We used, for residents in 2015, the medical care information of the National Health Insurance or Senior Elderly Care System in Kure City (Hiroshima Prefecture, Japan). Those with vertebral fractures as disease name, and either treatment/operation/hospitalization were defined as clinical vertebral fractures. Among the claim database, we extracted the clinical vertebral fracture and investigated the number of occurrences and the incidence rate per 1,000. We also investigated the incidence rate of hip fractures and compared those to the clinical vertebral fractures. RESULT: The incidence rate of clinical vertebral fractures of the elderly population (65 years or over) per 1,000 was 15.58 (7.29 male, 21.17 female, 2.90 female/male ratio). In both men and women, the incidence rate increased with aging. The incidence rate of hip fractures per 1,000 was 9.17 (3.55 male, 12.96 female, 3.65 male/female ratio). Clinical vertebral fractures were more frequent than hip fractures, and the ratio of incidence rate of vertebral fractures to hip fractures was 1.70 (male, 2.05, female, 1.63). For both fractures, the incidence rate increases with age, apart from the women where the incidence of vertebral fracture reduces slightly in the older age group CONCLUSION: This is the first report that investigated the incidence rate of the clinical vertebral fractures using the claim database, which covered almost the whole number of 230,000 population area.

Efficacy of non-steroidal anti-inflammatory drugs on zoledronic acid-induced acute-phase reactions: randomized, open-label, Japanese OZ study.

INTRODUCTION: Zoledronic acid infusion is used to treat osteoporosis but patients, especially Japanese patients, often experience acute-phase reactions (APRs). In this multicenter, randomized, open-label, parallel-group study, we examined the efficacy of the most commonly used non-steroidal anti-inflammatory drug loxoprofen in Japan in reducing the incidence rate of zoledronic acid-induced APRs and body temperature, and investigated risk/protective factors for APRs in this population. MATERIALS AND METHODS: Patients aged ≥ 60 years with primary osteoporosis (n = 368) were allocated randomly to zoledronic acid plus loxoprofen (ZOL + LOX) or zoledronic acid alone (ZOL). All patients received 5-mg zoledronic acid infusion on day 1, and patients in the ZOL + LOX group also received 120 mg and 180 mg of oral loxoprofen on days 1 and 2, respectively. Adverse events and body temperature were recorded during the 7-day observation period. RESULTS: The incidence rates of APRs were 34.4% (64/186 patients) and 47.8% (87/182 patients) in the ZOL + LOX and ZOL groups, respectively (P = 0.0109). The proportions of patients with increased body temperature (≥ 1 °C and ≥ 37.5 °C) were similar in both groups (P = 0.1186). Past bisphosphonate users had a significantly lower incidence rate of APRs than treatment-naïve patients (odds ratio 0.444, 95% confidence interval 0.285-0.692, P = 0.0003). CONCLUSIONS: Zoledronic acid-induced APRs appeared to be suppressed by loxoprofen. Known risk/protective factors, including prior osteoporosis treatment, were applicable to Japanese patients.

Executive summary of the Japan Osteoporosis Society Guide for the Use of Bone Turnover Markers in the Diagnosis and Treatment of Osteoporosis (2018 Edition).

With the aging of society, the number of osteoporosis-related fractures is increasing. Prevention of osteoporosis and maintenance of the quality of life of osteoporosis patients require early diagnosis, effective treatment, and highly precise treatment monitoring. Although bone biopsy is clinically one of the essential techniques for diagnosis of osteoporosis, it is invasive and difficult to perform in general clinical practice. Bone mineral density measurement is another essential technique available in clinical practice that provides good precision. However, it is not effective for determining the appropriate treatment options or evaluating short-term treatment efficacy. On the other hand, bone turnover markers (BTMs) have gained attention because they provide information that is valuable for both the selection of treatment and short-term monitoring. BTMs are now positioned to become a tool for clinically assessing bone turnover outcomes. Since the Japan Osteoporosis Society issued its Guidelines for the Use of Bone Turnover Markers in the Diagnosis and Treatment of Osteoporosis in 2012, new drugs, drug formulations, and combination drug therapies have been approved; therefore, we updated the 2012 guidelines in the Guide for the Use of Bone Turnover Markers in the Diagnosis and Treatment of Osteoporosis (2018 Edition).

Disease burden of fractures among patients with osteoporosis in Japan: health-related quality of life, work productivity and activity impairment, healthcare resource utilization, and economic costs.

Osteoporosis remains undertreated in Japan, and bone fractures are the most frequent complications imposing heavy burden on individuals and the community. This paper investigates the clinical and economic burden of fractures among osteoporosis patients in Japan. The Japan National Health and Wellness Survey 2012-2014 database was used for analysis. Respondents aged ≥ 50 years and indicated a physician diagnosis of osteoporosis (N = 1107) were categorized into three subgroups: no prior fracture (N = 693), single fracture (N = 242), and multiple (≥ 2) fractures (N = 172). Health-related quality of life (HRQoL), work productivity and activity impairment, healthcare resource utilization and associated direct and indirect costs were compared across three fracture subgroups adjusting for respondents' sociodemographic and clinical characteristics using generalized linear regression models. The estimated fracture prevalence among respondents with osteoporosis who were ≥ 50 years was 37.4%, of whom 41.5% had multiple fractures. Relative to osteoporosis respondents with no fracture and with single fracture, those with multiple fractures reported significant higher disability in HRQoL, more healthcare resource utilization, and were associated with higher direct costs. Improved treatment of fractures among osteoporosis patients is necessary and may help reduce the clinical and economic burden in this osteoporosis population.

Reduction of Hip and Other Fractures in Patients Receiving Teriparatide in Real-World Clinical Practice: Integrated Analysis of Four Prospective Observational Studies.

The phase 3 teriparatide Fracture Prevention Trial showed significant reductions in vertebral (VF) and nonvertebral (NVF) fractures; however, patient exposure was insufficient for full analysis of low-incidence fractures, including hip. We assessed fracture results in pooled data from four prospective, observational teriparatide studies. Ambulatory women and men with osteoporosis received subcutaneous teriparatide 20 µg/day for up to 24 months per routine clinical practice. Fracture rates were compared between 6-month periods, using 0 to 6 months of treatment as the reference period. Analyses used a piecewise exponential model for first fracture. Hip, NVF, clinical VF (CVF), any clinical, and wrist fractures were assessed. For 8828 patients analyzed, mean age was 71 years; mean (SD) treatment duration was 17.4 (8.6) months. The rate of hip fracture decreased significantly for the > 12 to 18-month (- 47.7%) and > 18-month periods (-85.2%) versus the first 6 months of therapy, and for the > 18 versus the > 6 to 12-month period. NVF, CVF, and all clinical fractures were all significantly decreased in each post-reference period, with maximum decreases (> 18-month period) of 52.7%, 69.4%, and 61.2%, respectively, versus 0 to 6 months. No significant reduction was seen for rates of wrist fracture. Teriparatide treatment was associated with statistically significant decreases in hip fracture rate, particularly for > 18 months of treatment, and in NVF, CVF, and all clinical fracture rate in real-world patients. These results should be interpreted in the context of the non-controlled design of the source studies.

Association Between Prevalence of Peripheral Artery Disease and Radiation Exposure in the Atomic Bomb Survivors.

Background Past reports suggested that total-body irradiation at 0.5 to 1.0 Gy could be responsible for atherosclerosis. Peripheral artery disease ( PAD ) is a manifestation of systematic atherosclerosis. Whether the consequences of a low-to-moderate dose of radiation include increased risk of PAD remains to be determined. The purpose of this study was to examine the association between radiation exposure and prevalence of PAD among Japanese atomic bomb survivors. Methods and Results Radiation exposure from the atomic bombing was assessed in 3476 participants (41.1% men, mean age 74.8 years with SD 6.4 years) with a cross-sectional survey in 2010 to 2014. Left- and right-side ankle-brachial indexes and upstroke time ( UT ) were obtained using oscillometric VP -2000. PAD was defined as an ankle-brachial index of 1.0 or less or a prior history related to revascularization. UT was considered a sensitive marker of early-stage PAD . Association between radiation exposure and PAD or UT was assessed using multivariable regression analyses with adjustment for potential confounding factors. Of 3476 participants, 79 (2.3%) were identified as having prevalent PAD . Multivariate logistic regression analysis indicated that radiation dose was unrelated to PAD prevalence (odds ratio, 0.83; 95% confidence interval [0.57-1.21]). UT appeared to increase with radiation dose, but the increase was not statistically significant (1.09 ms/Gy; 95% confidence interval [-0.17 to 2.36]). Conclusions We found no clear association of radiation dose with PAD , but it remains to be determined whether UT is associated with radiation dose.