Journal of Bone and Mineral Research最新文献

{"title":"Preterm birth and risk of bone fractures during childhood and early adulthood.","authors":"Suvi Alenius, Maija E Miettinen, Markku Nurhonen, Samuli Salmi, Pieta Näsänen-Gilmore, Peija Haaramo, Marjaana Tikanmäki, Marja Vääräsmäki, Mika Gissler, Outi Mäkitie, Petteri Hovi, Eero Kajantie","doi":"10.1093/jbmr/zjaf011","DOIUrl":"10.1093/jbmr/zjaf011","url":null,"abstract":"<p><p>People born preterm have reduced BMD, subnormal peak bone mass, and an increased risk of osteoporosis. Whether this translates to increased risk of bone fractures is uncertain. We assessed fracture risk from childhood to early adulthood in relation to gestational age and sex by conducting a nationwide register-linkage cohort study comprising all 223 615 liveborn (January 1987-September 1990) singletons (9161, 4.1%; preterm) in Finland. Cox regression models provided hazard ratios (HRs) for fracture diagnosis in public specialty health care in both first and recurrent event settings during the whole follow-up (0-29 years) and during different age periods (0-4, 5-9, 10-29 years). Gestational age was considered categorical (full-term, 39-41 weeks; reference). A total of 39 223 (17.5%) children or young adults had at least 1 fracture. In analyses not stratified by sex, only extremely preterm birth (<28 completed weeks' gestation) was associated with risk of bone fracture at 0-29 years (adjusted HR [aHR]: 0.46; 95% CI: 0.28-0.74) compared with those born full-term. Among females, gestational age was unrelated to fracture risk at 0-29 years. Among males, extremely and very preterm (28-31 weeks) birth was associated with lower risk of fracture at 0-29 years compared with those born full-term (aHR: 0.38 [95% CI: 0.21-0.71] and 0.75 [95% CI: 0.59-0.95], respectively). Restricting the analyses to the individuals without severe medical condition(s) attenuated the associations. However, the fracture risk varied according age and sex: at 10-29 years, moderately preterm (32-33 weeks) females and extremely and very preterm males had a lower risk (aHR: 0.63 [0.43-0.94], 0.35 [0.17-0.69], and 0.74 [0.57-0.95], respectively), while late-preterm birth (34-36 weeks) was associated with a 1.6-fold higher risk among females at 0-5 years, and a 1.4-fold risk among males at 5-10 years. Analyses on recurrent fractures showed a similar pattern. Children and young adults, in particular males, born extremely or very preterm may have fewer bone fractures; this is partly explained by severe medical conditions in this group.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"382-395"},"PeriodicalIF":5.1,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of femoral neck width and hip axis length on incident hip fracture risk: a registry-based cohort study.","authors":"Fatima Zarzour, Sajjad Aftabi, William D Leslie","doi":"10.1093/jbmr/zjaf019","DOIUrl":"10.1093/jbmr/zjaf019","url":null,"abstract":"<p><p>BMD measured with DXA is widely used in clinical practice to assess fracture risk and guide management. DXA can also assess hip geometry, including femoral neck width (FNW) and hip axis length (HAL), which have both been associated with increased risk for hip fracture independently from BMD. Our objective was to assess if FNW predicts hip fracture independently from other factors including HAL. We performed a retrospective cohort study using the Province of Manitoba BMD registry. The study population comprised 75 095 individuals (90.8% women), mean age 64.7 yr, with baseline hip BMD and hip geometry parameters. Linked health records were used to ascertain subsequent hospitalization with hip fracture as a primary diagnosis. During a mean follow-up of 8.3 (SD 5.1) yr, 2341 incident hip fractures were recorded. Each SD increase in age- and sex-adjusted FNW was associated with incident hip fracture (HR 1.15, 95% CI 1.10-1.19), which was unchanged after adjustment for height, weight, FN BMD, and clinical risk factors. However, FNW showed a significant positive correlation with HAL (r = 0.68). When further adjusted for HAL, FNW was no longer associated with increased risk for hip fracture (HR 0.98, 95% CI 0.94-1.03). A similar pattern was seen for FN, and intertrochanteric and non-hip fractures. In contrast, increased risk of hip fracture was consistently seen with each SD increase in HAL even after adjustment for all covariates including FNW (HR 1.35, 95% CI 1.28-1.42). In conclusion, FNW is a risk factor for hip fracture before but not after adjustment for HAL. HAL, on the other hand, robustly and independently predicts hip fracture, including both FN and trochanteric fractures.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"332-338"},"PeriodicalIF":5.1,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Individuals with heterogenous trabecular bone texture by clinical magnetic resonance imaging have lower bone strength and stiffness by quantitative computed tomography-based finite element analysis.","authors":"Alexander S Dash, Ryan Breighner, Fernando Quevedo Gonzalez, Olivia Blumberg, Matthew F Koff, Emma Billings, Alison Heilbronner, Jeri Nieves, Emily M Stein","doi":"10.1093/jbmr/zjae207","DOIUrl":"10.1093/jbmr/zjae207","url":null,"abstract":"<p><p>Opportunistic screening is essential to improve the identification of individuals with osteoporosis. Our group has utilized image texture features to assess bone quality using clinical MRIs. We have previously demonstrated that greater heterogeneity of MRI texture related to history of fragility fractures, lower bone density, and worse microarchitecture. The present study investigated relationships between MRI-based texture features and biomechanical properties of bone using CT-based finite element analyses (FEAs). We hypothesized that individuals with greater texture heterogeneity would have lower stiffness and failure load. Thirty individuals included in this prospective study had CT and MRI of L1 and L2 vertebrae. Using T1-weighted MR images, a gray-level co-occurrence matrix was generated to characterize the distribution and spatial organization of voxelar signal intensities to derive the following texture features: contrast (variability), entropy (disorder), angular second moment (ASM; uniformity), and inverse difference moment (IDM; homogeneity). Features were calculated in five directions relative to the image plane. Whole-bone stiffness and failure load were calculated from phantom-calibrated lumbar QCT. Mean age of subjects was 59 ± 11 yr (57% female). Individuals with lower vertebral stiffness had greater texture heterogeneity; specifically, higher contrast (r = -0.54, p < .01), higher entropy (r = -0.52, p < .01), lower IDM (r = 0.54, p < .01) and lower ASM (r = 0.51, p < .01). Lower vertebral failure load and lower vBMD were similarly associated with greater texture heterogeneity. Relationships were unchanged when using the average of texture in all directions or the vertical direction in isolation. In summary, individuals with more heterogeneous MRI-based trabecular texture had lower stiffness and failure load by FEA, and lower vBMD by central quantitative CT. These results-the first relating MRI-based texture features and biomechanical properties of bone-provide further support that MRI-based texture measurements can be used to opportunistically detect skeletal fragility.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"339-347"},"PeriodicalIF":5.1,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the effects of immune checkpoint inhibitors on bone utilizing machine learning-assisted opportunistic quantitative computed tomography.","authors":"Bryn E Matheson, Jacob L Jaremko, Alexandra Dowhanik, Jasmine Gill, Cassandra Gallant, John Walker, Nathan Armani, William D Leslie, Michael Kolinsky, Steven K Boyd, Carrie Ye","doi":"10.1093/jbmr/zjaf009","DOIUrl":"10.1093/jbmr/zjaf009","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) are widely used in cancer treatment, yet their impact on bone health remains unclear. This study aimed to perform a retrospective cohort study utilizing routine CT scans from patients with melanoma to perform opportunistic QCT analysis to investigate the effects of ICI treatment on skeletal health, including volumetric BMD (vBMD) measurements and osteoarthritis (OA) parameters. A previously established machine learning-assisted opportunistic QCT pipeline was used to estimate lumbar spine vBMD from baseline and 12-mo follow-up CT scans in patients with melanoma treated with ICI therapy and those not treated with ICI therapy. Facet joint OA, osteophyte formation, and endplate sclerosis were also graded. Independent and paired t tests were used to determine any differences in vBMD and OA parameters between ICI users and non-ICI users. Multivariable linear regression models were used to control for confounding variables. Non-ICI users had a significant decrease in vBMD of -6.96 mg/cm3 from baseline to follow-up, whereas the ICI users had no significant change. There was a significant difference in change in vBMD from baseline to follow-up between the 2 groups, with the non-ICI users experiencing a 11.22 mg/cm3 larger decrease in vBMD. After adjusting for baseline age, sex, baseline vBMD, and change in OA parameters, this difference remained significant at -13.04 mg/cm3. Among the ICI users, those who had a decline in vBMD had a lower baseline vBMD compared with those who had increased vBMD. Neither group showed a significant change in OA parameters over the follow-up period, nor a difference in change between ICI and non-ICI users, even after adjusting for sex, age, and baseline OA parameters. While the effects of ICI treatment on vBMD may vary based on baseline bone health, ICIs do not significantly impact OA parameters in the short term.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"396-403"},"PeriodicalIF":5.1,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating CD34-positive cells are associated with prolonged time to fracture in people with Duchenne muscular dystrophy on chronic glucocorticoids.","authors":"Angela Sadlowski, Julia See, Sonum Bharill, Weixin Zhang, Arryn Otte, Emely Loscalzo, Nazanin Yousefzadeh, Ethan Gough, Tricia Nilles, Sisir Barik, Malinda Wu, Janet L Crane","doi":"10.1093/jbmr/zjaf041","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf041","url":null,"abstract":"<p><p>In murine models, glucocorticoids decrease preosteoclast (POC) platelet-derived growth factor type BB (PDGF-BB), reducing migration of endothelial precursor and osteoprogenitor cells, impairing skeletal angiogenesis and osteogenesis. To explore translation to humans, we conducted a case-control study on Duchenne Muscular Dystrophy (DMD) youth treated with chronic glucocorticoids with or without osteoporosis relative to healthy controls. We quantified factors from serum (PDGF-BB, VEGF, angiogenin) by ELISA and peripheral blood mononuclear cell (PBMC) subpopulations as surrogates of POCs (CD14+/Stro-1-/CD105-), osteoprogenitor cells (Stro-1+/CD105+/CD14-/CD45-), and endothelial/hematopoietic progenitor cells (CD34+/CD14-/Stro-1-/CD105-) by flow cytometry to determine association with fractures. The mean fluorescence intensity (MFI) of CD140b (PDGF receptor beta) was also quantitated. People with DMD, aged 8-20-years, were stratified by fractures, including prior and subsequent fractures relative to biospecimen collection date. Healthy controls were age- and sex-matched. Differences between groups were assessed with one-way ANOVA with post-hoc Tukey's test, simple linear regression correlation between factors, retrospective fractures by Kendall Tau correlation, and prospective fractures by bivariable and multivariable accelerated time failure (AFT) models. Baseline characteristics between groups were similar, though people with DMD were shorter relative to healthy controls, and in the DMD groups, those with prior fractures had a longer duration of glucocorticoid therapy. We noted decreased concentrations of serum PDGF-BB and percentages of circulating POCs, SPCs, and CD34+ cells in people with DMD treated with chronic glucocorticoids relative to healthy controls. Circulating CD34+ cell percentage positively correlated with PDGF-BB concentration, similar to murine models. A lower percentage of circulating SPCs and CD140b MFI was associated with increased number of retrospective fractures by Kendall Tau correlation. After a mean follow-up of 2.23 years, 19 of the 24 people with DMD sustained a subsequent fracture. A higher PDGF-BB concentration, and percent of POC, SPCs, and CD34+ cells were associated with a longer time to next fracture by AFT bivariable models. After controlling for covariates potentially associated with fracture risk, the percentage of CD34+ cells continued to be associated with a prolonged time to next fracture. Circulating CD34+ cells may thus be a potential biomarker to predict acute fracture risk in young people with DMD on chronic glucocorticoids.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heme metabolism mediates RANKL-induced osteoclastogenesis via mitochondrial oxidative phosphorylation.","authors":"Heng Qiu, Haiming Jin, Jiansen Miao, Hui Li, Junchun Chen, Xiaohong Yang, Xiaojun Chen, Benjamin H Mullin, Kai Chen, Ronghe Gu, An Qin, Scott G Wilson, Jiake Xu","doi":"10.1093/jbmr/zjaf040","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf040","url":null,"abstract":"<p><p>Bone undergoes life-long remodelling, in which disorders of bone remodelling could occur in many pathological conditions including osteoporosis. Understanding the cellular metabolism of osteoclasts is key to developing new treatments for osteoporosis, a disease that affects over 200 million women worldwide per annum. We found that human osteoclast differentiation from peripheral blood mononuclear cells (PBMCs) derived from 8 female patients is featured with a distinct gene expression profile of mitochondrial biogenesis. Elevated mitochondrial membrane potential (MMP, Δψm) was also observed in RANKL-induced osteoclasts. Interestingly, the gene pathways of heme synthesis and metabolism were activated upon RANKL stimulation, featured by a transcriptomic profiling in murine cells at a single-cell resolution, which revealed a stepwise expression pattern of heme-related genes. The real-world human data also divulges potential links between heme-related genes and bone mineral density. Heme is known to have a role in the formation of functional mitochondrial complexes that regulate MMP. Disruption of heme biosynthesis via genetically silencing Ferrochelatase or a selective inhibitor, N-methyl Protoporphyrin IX (NMPP), demonstrated potent inhibition of osteoclast differentiation, with a dose-dependent effect observed in NMPP treatment and a substantial efficacy even at a single dose. In vivo study further showed the protective effect of NMPP on ovariectomy-induced bone loss in female mice. Collectively, we found that RANKL-mediated signaling regulated mitochondrial formation and heme metabolism to synergistically support osteoclastogenesis. Inhibition of heme synthesis impaired osteoclast formation and reversed excessive bone loss, representing a new therapeutic target for metabolic skeletal disorders.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brittle, but not boring: a fresh look at osteogenesis imperfecta type V.","authors":"Mathieu Ferron, Jean Vacher","doi":"10.1093/jbmr/zjaf035","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf035","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Denosumab discontinuation in the clinic: implications of rebound bone turnover and emerging strategies to prevent bone loss and fractures.","authors":"Shejil Kumar, Mawson Wang, Albert S Kim, Jacqueline R Center, Michelle M Mcdonald, Christian M Girgis","doi":"10.1093/jbmr/zjaf037","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf037","url":null,"abstract":"<p><p>Denosumab is a highly effective treatment for osteoporosis, and its long-term use is associated with incremental gains in bone mineral density (BMD) and sustained fracture risk reduction. Stopping denosumab, however, results in rebound increase in bone turnover, loss of treatment-associated BMD gains, and in the worst case, spontaneous vertebral fractures (VFs). Insights into the risk factors and the underlying mechanisms for rebound-associated bone loss and true incidence of rebound VFs are emerging. Conventional strategies using bisphosphonates to mitigate post-denosumab rebound display mixed success. Bisphosphonates may preserve bone density following short-term denosumab but the optimal sequential approach after longer-term denosumab remains elusive. Patients at particular risk of are those with prevalent VFs or greater on-treatment BMD gains. To greater understand these risks and strategies to preserve bone after denosumab, an emerging body of translational and pre-clinical work is shedding new light on the biology of RANKL inhibition and withdrawal. Discovering an effective \"exit strategy\" to control rebound bone turnover and avoid bone loss after denosumab will improve confidence amongst patients and clinicians in this highly effective and otherwise safe treatment for osteoporosis. This perspective characterizes the clinical problem of post-denosumab rebound, provides a comprehensive update on human studies examining the use of bisphosphonates following denosumab and explores mechanistic insights from pre-clinical studies that will be critical in the design of definitive human trials.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143583899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Control of alveolar bone development, homeostasis, and socket healing by salt inducible kinases.","authors":"Nicha Tokavanich, Byron Chan, Katelyn Strauss, Christian D Castro Andrade, Yuki Arai, Mizuki Nagata, Marc Foretz, Daniel J Brooks, Noriaki Ono, Wanida Ono, Marc N Wein","doi":"10.1093/jbmr/zjaf038","DOIUrl":"10.1093/jbmr/zjaf038","url":null,"abstract":"<p><p>Alveolar bone supports and anchors teeth. The parathyroid hormone-related protein (PTHrP) pathway plays a key role in alveolar bone biology. Salt inducible kinases (SIKs) are important downstream regulators of PTH/PTHrP signaling in the appendicular skeleton, where SIK inhibition increases bone formation and trabecular bone mass. However, the function of these kinases in alveolar bone remains unknown. Here, we report a critical role for SIK2/SIK3 in alveolar bone development, homeostasis, and socket healing after tooth extraction. Inducible SIK2/SIK3 (Ubq-creERt;Sik2f/f;Sik3f/f) deletion led to dramatic alveolar bone defects without changes in tooth eruption. Ablating these kinases impairs alveolar bone formation due to disrupted osteoblast maturation, a finding associated with ectopic periostin expression by fibrous cells in regions of absent alveolar bone at steady state and following molar extraction. Notably, this phenotype is the opposite of the increased trabecular bone mass observed in long bones following SIK2/SIK3 deletion. Distinct phenotypic consequences of SIK2/SIK3 deletion in appendicular versus craniofacial bones prompted us to identify a specific transcriptomic signature in alveolar versus long bone osteoblasts. Thus, SIK2/SIK3 deletion illuminates a key role for these kinases in alveolar bone biology and highlights the emerging concept that different osteoblast subsets utilize unique genetic programs. (192/300).</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143583898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D and disease prevention in 2024: commentary on recent Endocrine Society recommendations.","authors":"Catherine M Gordon, Meryl S LeBoff","doi":"10.1093/jbmr/zjaf036","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf036","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}