Journal of Bone and Mineral Metabolism最新文献

{"title":"Increased complications of proximal femur fractures during the COVID-19 pandemic: a nationwide medical claims database study in Japan.","authors":"Hidetatsu Tanaka, Kunio Tarasawa, Yu Mori, Kiyohide Fushimi, Kenji Fujimori, Toshimi Aizawa","doi":"10.1007/s00774-025-01611-0","DOIUrl":"https://doi.org/10.1007/s00774-025-01611-0","url":null,"abstract":"<p><strong>Introduction: </strong>Coronavirus disease 2019 (COVID-19) is a worldwide pandemic, and mortality increases in elderly patients with comorbidities. This study aims to examine the in-hospital complications and mortality for elderly patients with proximal femur fractures during the COVID-19 pandemic or countermeasure periods.</p><p><strong>Materials and methods: </strong>The proximal femur fractures undergoing surgery during the COVID-19 pandemic or countermeasure period were compared with the pre-pandemic in a Japanese national inpatient data. The assessed outcomes were the development of pneumonia, deep vein thrombosis (DVT), pulmonary embolism (PE), and mortality during hospitalization in two periods, and those for COVID-19-positive patients.</p><p><strong>Results: </strong>A total of 284,922 proximal femur fractures aged over 65 years were included. In the COVID-19 pandemic period compared to the pre-pandemic, the odds of pneumonia, DVT, PE, and mortality decreased to 0.942 (95% confidence interval [CI]: 0.901 - 0.986, P = 0.0102) and 0.839 (95% CI: 0.745 - 0.946, P = 0.004), increased to 1.153 (95% CI: 1.112 - 1.195, P < 0.001), and 1.048 (95% CI: 0.982 - 1.118, P = 0.1554), respectively. For COVID-19 positivity at admission, the odds of PE increased significantly to 12.95 (95% CI: 8.795 - 19.06, P < 0.001). For COVID-19 positivity during hospitalization, the odds of pneumonia and mortality were increased to 2.896 (95% CI: 1.820 - 4.608, P < 0.001) and 6.303 (95% CI: 3.440 - 11.55, P < 0.001), respectively.</p><p><strong>Conclusion: </strong>These findings alert healthcare professionals and patients to the elevated complications, especially PE rate for proximal femoral fracture with COVID-19 positive.</p>","PeriodicalId":15116,"journal":{"name":"Journal of Bone and Mineral Metabolism","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the genetic interconnection between sarcopenia and osteoporosis: SCD1.","authors":"Yan Lv, Yong-Jun Du, Jia-Mian Liu, Jian-Qing Liao, Cheng-Jie Ma, Rui Xu, Jun-Hua Fang, Lv Zhao, Shao-Quan Pu, Sheng Lu","doi":"10.1007/s00774-025-01612-z","DOIUrl":"https://doi.org/10.1007/s00774-025-01612-z","url":null,"abstract":"<p><strong>Introduction: </strong>Sarcopenia is closely related to osteoporosis, but the causal direction of these associations remains unclear. This study aims to explore these potential causal associations from the perspective of gene regulation.</p><p><strong>Materials and methods: </strong>Differentially expressed genes between sarcopenia and control, were identified as exposure factors, with osteoporosis serving as outcome variable, to identify key genes that had potential causal association with osteoporosis. Further analysis was conducted to investigate the causal links between key genes and sarcopenia-related characteristics. Moreover, enrichment analyses, ceRNA and Gene-Gene Interaction network were studied.</p><p><strong>Results: </strong>Only SCD1 demonstrated a potential causal association with osteoporosis (OR = 0.9970, P = 0.0217), acting as a protective factor against the disease. The potential causal links between SCD1 and sarcopenia-related characteristics are executed. SCD1 was identified as a risk factor for low hand grip strength (OR = 1.1397, P = 0.0290), while being pinpointed as a protective factor for appendicular lean mass (OR = 0.8777, P = 0.0147), usual walking pace (OR = 0.9834, P = 0.0290), whole body fat-free mass (OR = 0.9412, P = 0.0227), and trunk fat-free mass (OR = 0.9425, P = 0.0257). All analyses passed Steiger directional test, indicating a unidirectional causal association. Moreover, indicated that SCD1 was significantly associated with metabolic pathways related to lipid biosynthesis and regulation.</p><p><strong>Conclusion: </strong>SCD1 was identified as a protective factor for osteoporosis and a risk factor for sarcopenia. This research provides new insights for the study of sarcopenia and osteoporosis, and offers theoretical backing for the positive effects of exercise in the elderly.</p>","PeriodicalId":15116,"journal":{"name":"Journal of Bone and Mineral Metabolism","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to \"Comment on 'Associations between hormones, metabolic markers, and bone mass in perimenopausal and postmenopausal women'\".","authors":"Bingru Lu, Qunxiao Han, Shiyu Zhao, Shan Ding, Guolin Bao, Yiqing Liu","doi":"10.1007/s00774-025-01614-x","DOIUrl":"https://doi.org/10.1007/s00774-025-01614-x","url":null,"abstract":"","PeriodicalId":15116,"journal":{"name":"Journal of Bone and Mineral Metabolism","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Locomotive syndrome and increased musculoskeletal disorder incidence in older adults: a prospective study.","authors":"Yuki Kitsuda, Hiromi Matsumoto, Chika Tanimura, Takashi Wada, Shinji Tanishima, Chikako Takeda, Mari Osaki, Hideki Nagashima, Hiroshi Hagino","doi":"10.1007/s00774-025-01607-w","DOIUrl":"https://doi.org/10.1007/s00774-025-01607-w","url":null,"abstract":"<p><strong>Introduction: </strong>With the population aging, musculoskeletal disorders increasingly impair older adults' quality of life and escalating healthcare costs, necessitating effective prevention strategies. Locomotive syndrome (LS), characterized by mobility decline due to musculoskeletal dysfunction, is closely linked to these disorders. However, its role in predicting future musculoskeletal conditions remains unclear. This study examined the association between LS and the incidence of newly diagnosed musculoskeletal disorders.</p><p><strong>Material and methods: </strong>This prospective study included 367 community-dwelling adults aged ≥ 40 years who were independent in daily activities. LS was assessed using the five-question Geriatric Locomotive Function Scale (GLFS-5). The primary outcome was the incidence of musculoskeletal disorders, including osteoarthritis, lumbar spinal stenosis, and osteoporosis. Cox proportional hazards regression analyzed associations between LS and future diagnoses, while receiver operating characteristic (ROC) analysis determined the GLFS-5 cutoff score for risk prediction.</p><p><strong>Results: </strong>At baseline, 19.1% of participants had LS. Over four years, musculoskeletal disorders occurred more frequently in participants with LS than in those without (22.2 vs. 8.8 per 100 person-years, p < 0.001). After adjusting for covariates, LS remained a significant risk factor (hazard ratio 1.98, 95% confidence interval 1.16-3.36, p = 0.011). ROC analysis identified a GLFS-5 cutoff score of 2 (sensitivity: 62.0%, specificity: 62.0%).</p><p><strong>Conclusions: </strong>LS nearly doubled the risk of musculoskeletal disorders, with a GLFS-5 score ≥ 2 serving as an early risk indicator. Proactive screening and targeted interventions may mitigate this risk in aging populations.</p>","PeriodicalId":15116,"journal":{"name":"Journal of Bone and Mineral Metabolism","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A scoring system and seven factors associated with certification for Japanese long-term care insurance in older people.","authors":"Keisuke Takahashi, Katsumasa Ideo, Masaru Uragami, Yuko Fukuma, Takehiro Koga, Kazuhiro Yoshiura, Shuken Boku, Naoto Kajitani, Minoru Takebayashi, Takeshi Miyamoto","doi":"10.1007/s00774-025-01606-x","DOIUrl":"https://doi.org/10.1007/s00774-025-01606-x","url":null,"abstract":"<p><strong>Introduction: </strong>The increase in the older population is a serious concern in developed countries, and how to maintain independence of these individuals is now an urgent issue. Various factors are known to put older people at risk for needing long-term care, but it is not clear to what extent each factor is associated with that need.</p><p><strong>Materials and methods: </strong>In a cohort of 1577 community-dwelling older persons, we excluded 40 persons whose long-term care insurance certification was unknown and then divided the remaining 1537 into two groups: dependent group (134 persons) certified as requiring assistance or long-term care, and an independent group (1403 persons). We extracted 7 factors and created a scoring system from these factors based on regression coefficients.</p><p><strong>Results: </strong>Among 92 factors initially evaluated, 7 were significantly associated with the need for assistance or long-term care, namely walking speed, age, grip strength, mobility (EQ5D), ability to use public transportation by oneself (IADL), ability to perform usual activities (EQ5D), and serum albumin levels. Based on these 7, we constructed a scoring system and calculated a cutoff value of 8 points with an area under curve as high as 0.949.</p><p><strong>Conclusion: </strong>We determined the cutoff value for dependency risk to be 8, but no single factor scored 8 or higher, suggesting that a combination of these factors promotes the need for nursing care in older people.</p>","PeriodicalId":15116,"journal":{"name":"Journal of Bone and Mineral Metabolism","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bisphosphonates with high bone-resorption-capacity promote osteonecrosis of the jaw development after tooth extraction in mice.","authors":"Ryuta Kubo, Rui Tajiri, Hibiki Yamada, Hideki Nakayama, Takeshi Miyamoto","doi":"10.1007/s00774-025-01608-9","DOIUrl":"https://doi.org/10.1007/s00774-025-01608-9","url":null,"abstract":"<p><strong>Introduction: </strong>Medication-Related Osteonecrosis of the Jaw (MRONJ) is a condition marked by osteonecrosis of the jaw bone and other symptoms seen following invasive surgical procedures in patients administered bone-modifying agents. Once disease develops, a patient's ADL levels are significantly compromised. However, the pathogenesis of this disease is not clearly understood. Bisphosphonates (BPs) are bone resorption inhibitors commonly used to treat osteoporosis. Although not confirmed, it is generally believed that MRONJ risk is higher in the presence of injectable rather than oral formulations. Here, we assessed risk of developing ONJ in mice in the presence of 3 different BPs-zoledronate, ibandronate, or alendronate-that are administered clinically intravenously or via infusion.</p><p><strong>Materials and methods: </strong>Eight-week-old wild-type mice were administered zoledronate, alendronate, ibandronate or PBS vehicle subcutaneously once a week for 2 weeks. Then the right first molars in the mandible were extracted. Six-weeks later, osteonecrosis development was analyzed by histochemistry.</p><p><strong>Results: </strong>Among mice administered BPs, mice treated with zoledronate exhibited the highest frequency of osteocytes exhibiting osteonecrosis. Bone mineral density was higher in mice receiving zoledronate, alendronate, or ibandronate than in PBS control mice, but effects of the 3 drugs were comparable. Moreover, formation of multi-nuclear osteoclasts in vitro was most strongly inhibited by zoledronate, followed by alendronate and ibandronate.</p><p><strong>Conclusion: </strong>Administration of BPs with high osteoclastogenesis inhibitory potential, such as zoledronate, increases risk of ONJ development after tooth extraction more than treatment with other agents tested, even at equivalent dosage.</p>","PeriodicalId":15116,"journal":{"name":"Journal of Bone and Mineral Metabolism","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spexin-induced MC3T3-E1 cell-derived exosomes enhance osteoblast differentiation.","authors":"Freshet Assefa, Eui Kyun Park","doi":"10.1007/s00774-025-01604-z","DOIUrl":"https://doi.org/10.1007/s00774-025-01604-z","url":null,"abstract":"<p><strong>Introduction: </strong>The roles of exosomes in osteoblast differentiation has been widely investigated. Low exosome production from donor cells constitutes the greatest challenges in exosome-based therapies. Spexin (SPX) is a neuropeptide that is involved in various biological activities including osteogenic differentiation and bone regeneration. Therefore, the purpose of this study was to investigate the effects of SPX on exosome production in osteogenic medium (OM)-treated MC3T3-E1 cells and SPX induced MC3T3-E1 cell-derived exosomes (OM + SPX-Exos) on osteoblast differentiation.</p><p><strong>Materials and methods: </strong>To evaluate exosome yield, MC3T3-E1 cells were treated with SPX. Exosome marker expression and particle number were validated via reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) and nanoparticle tracking analysis (NTA), respectively. MC3T3-E1 cells were then treated with various concentrations of OM + SPX-Exos and osteogenic medium treated MC3T3-E1 derived exosomes (OM-Exos). Cell proliferation, osteogenic differentiation marker expression, alkaline phosphatase (ALP) activity, and mineralization were evaluated using the CCK-8 assay, RT-qPCR, ALP staining, and alizarin red S staining, respectively.</p><p><strong>Results: </strong>SPX significantly increased exosome production and the expression of the exosome markers; Cd63, Rab27a and Alix in MC3T3E1 cells. Furthermore, OM + SPX-Exos significantly increased in the expression of runt-related transcription factor 2 (Runx2), alkaline phosphatase, biomineralized associated (Alpl), collagen type I alpha 1 (Col1a1), secreted phosphoprotein 1 (Spp1) and Integrin-binding sialoprotein (Ibsp) at a concentration of 5 µg/ml. ALP staining and alizarin red S staining also revealed that OM + SPX-Exos (5 µg/ml) resulted in more ALP-positive cells and markedly promoted mineralization, respectively.</p><p><strong>Conclusion: </strong>In general, these results indicate that SPX stimulates exosome production. OM + SPX-Exos enhances MC3T3-E1 cells proliferation, osteogenic differentiation and mineralization.</p>","PeriodicalId":15116,"journal":{"name":"Journal of Bone and Mineral Metabolism","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Higher systemic immune-inflammation index associates with vertebral marrow proton density fat fraction in postmenopausal women.","authors":"Li Lu, Zheng Xu, Zeyang Miao, Xiaoyong Zuo, Dan Shi, Shixin Chang, Peng Luo, Guanwu Li","doi":"10.1007/s00774-025-01609-8","DOIUrl":"https://doi.org/10.1007/s00774-025-01609-8","url":null,"abstract":"<p><strong>Introduction: </strong>The systemic immune-inflammation index (SII) may influence bone homeostasis through inflammatory modulation. Although bone marrow adipocytes regulate bone metabolism via adipokine secretion, their interaction with SII remains unexplored. We investigated the SII-marrow adiposity relationship in postmenopausal women.</p><p><strong>Materials and methods: </strong>This retrospective study included 187 postmenopausal women. Lumbar spine MRI using chemical shift encoding generated proton density fat fraction (PDFF) maps, with bone mineral density (BMD) measured by dual x-ray absorptiometry. The relationship between SII and marrow PDFF was evaluated through multivariable-adjusted linear regression, smooth curve fittings, and threshold analysis.</p><p><strong>Results: </strong>The results revealed a negative correlation between marrow PDFF values and BMD (r = - 0.438, P < 0.001). After accounting for age, time since menopause, body mass index, physical activity, C-reactive protein, interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and BMD in the regression analysis, each unit increase in SII was found to be inked to an increase of 0.247 (β = 0.247; 95% confidence interval [CI], 0.212 to 0.281; P <0.001) in PDFF. After converting SII to a categorical variable (quartiles), participants in the highest SII quartile had a 16.8% higher vertebral marrow PDFF than those in the lowest SII quartile (β = 16.753, 95% CI: 11.036-18.522, P <0.001). Furthermore, a curvilinear relationship and threshold effect were also identified. Turning point was identified at the SII value of 441 on the adjusted smooth curve.</p><p><strong>Conclusions: </strong>SII levels were positively associated with marrow adiposity in postmenopausal women.</p>","PeriodicalId":15116,"journal":{"name":"Journal of Bone and Mineral Metabolism","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the fracture prevention effects of teriparatide and alendronate in patients with frailty: a sub-analysis of the Japanese osteoporosis intervention trial-05.","authors":"Tatsuya Hosoi, Makoto Yunoki, Shiro Tanaka, Hiroshi Hagino, Satoshi Mori, Satoshi Soen, Sumito Ogawa","doi":"10.1007/s00774-025-01610-1","DOIUrl":"https://doi.org/10.1007/s00774-025-01610-1","url":null,"abstract":"<p><strong>Introduction: </strong>The fracture prevention effects of teriparatide (TPTD) and alendronate (ALN) were evaluated in frail patients using data from the JOINT-05 trial. In addition, predictors of adherence-related treatment discontinuation were evaluated for TPTD and ALN.</p><p><strong>Materials and methods: </strong>Japanese women aged ≥ 75 years with primary osteoporosis and high fracture risk were randomized to either sequential therapy (TPTD for 72 weeks followed by ALN for 48 weeks) or ALN monotherapy for 120 weeks. Cognitive frailty was defined as an MMSE score ≤ 27, and physical frailty as requiring support or nursing care. Vertebral, non-vertebral, and all fractures were assessed. Adherence-related discontinuations were identified, and baseline predictors were analyzed using multiple regression to calculate odds ratios.</p><p><strong>Results: </strong>A total of 514 patients with cognitive frailty (254 with TPTD, 260 with ALN) and 204 patients with physical frailty (109 with TPTD, 95 with ALN) were identified. In patients with cognitive frailty, vertebral fracture incidence tended to be lower with TPTD (rate ratio 0.72), but not significantly. In patients with physical frailty, the incidence was significantly lower with TPTD (rate ratio 0.50, p < 0.01). Dyslipidemia and serum calcium levels were significant predictors of TPTD discontinuation, whereas cognitive impairment and dyslipidemia were predictors for ALN discontinuation.</p><p><strong>Conclusion: </strong>In patients with physical frailty, TPTD reduced vertebral fractures significantly more than ALN. However, in cases with cognitive impairment, the results of the JOINT-05 study may not necessarily apply. Assessing the presence of dyslipidemia and cognitive decline may be useful for predicting adherence-related discontinuation.</p><p><strong>Trial registration: </strong>jRCTs031180235 and UMIN000015573, March 12, 2019.</p>","PeriodicalId":15116,"journal":{"name":"Journal of Bone and Mineral Metabolism","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Masafumi Fukagawa, MD, PhD : November 8, 1958 to November 9, 2024.","authors":"Hirotaka Komaba","doi":"10.1007/s00774-025-01602-1","DOIUrl":"https://doi.org/10.1007/s00774-025-01602-1","url":null,"abstract":"","PeriodicalId":15116,"journal":{"name":"Journal of Bone and Mineral Metabolism","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}