Pub Date : 2024-09-07DOI: 10.1016/j.bone.2024.117251
Natalia M. Castoldi , Dermot O'Rourke , Maria Antico , Vittorio Sansalone , Laura Gregory , Peter Pivonka
This work focuses on the growth patterns of the human fourth lumbar vertebra (L4) in a paediatric population, with specific attention to sexual dimorphism. The study aims to understand morphological and density changes in the vertebrae through age-dependent statistical shape and statistical appearance models, which can describe full three-dimensional anatomy. Results show that the main growth patterns are associated with isotropic volumetric vertebral growth, a decrease in the relative size of the vertebral foramen, and an increase in the length of the transverse processes. Moreover, significant sexual dimorphism was demonstrated during puberty. We observe significant age and sex interaction in the anterior vertebral body height (P = 0.005), where females exhibited an earlier increase in rates of vertebral height evolution. Moreover, we also observe an increase in cross-sectional area (CSA) with age (P = 0.020), where the CSA is smaller in females than in males (significant sex effect P = 0.042). Finally, although no significant increase in trabecular bone density with age is observed (P = 0.363), a trend in the statistical appearance model suggests an increase in density with age.
这项研究的重点是人类第四腰椎(L4)在儿科人群中的生长模式,特别关注性别二态性。研究旨在通过与年龄相关的统计形状和统计外观模型来了解椎骨的形态和密度变化,这些模型可以描述完整的三维解剖结构。结果表明,主要的生长模式与各向同性的椎体体积增长、椎孔相对大小的减小以及横突长度的增加有关。此外,青春期还表现出明显的性别二态性。在椎体前部高度方面,我们观察到了明显的年龄和性别交互作用(P = 0.005),其中雌性的椎体高度进化率增长较早。此外,我们还观察到横截面积(CSA)随着年龄的增长而增加(P = 0.020),其中女性的横截面积小于男性(显著性别效应 P = 0.042)。最后,虽然没有观察到骨小梁密度随年龄的增长而明显增加(P = 0.363),但统计外观模型中的趋势表明密度会随着年龄的增长而增加。
{"title":"Assessment of age-dependent sexual dimorphism in paediatric vertebral size and density using a statistical shape and statistical appearance modelling approach","authors":"Natalia M. Castoldi , Dermot O'Rourke , Maria Antico , Vittorio Sansalone , Laura Gregory , Peter Pivonka","doi":"10.1016/j.bone.2024.117251","DOIUrl":"10.1016/j.bone.2024.117251","url":null,"abstract":"<div><p>This work focuses on the growth patterns of the human fourth lumbar vertebra (L4) in a paediatric population, with specific attention to sexual dimorphism. The study aims to understand morphological and density changes in the vertebrae through age-dependent statistical shape and statistical appearance models, which can describe full three-dimensional anatomy. Results show that the main growth patterns are associated with isotropic volumetric vertebral growth, a decrease in the relative size of the vertebral foramen, and an increase in the length of the transverse processes. Moreover, significant sexual dimorphism was demonstrated during puberty. We observe significant age and sex interaction in the anterior vertebral body height (<em>P</em> = 0.005), where females exhibited an earlier increase in rates of vertebral height evolution. Moreover, we also observe an increase in cross-sectional area (CSA) with age (<em>P</em> = 0.020), where the CSA is smaller in females than in males (significant sex effect <em>P</em> = 0.042). Finally, although no significant increase in trabecular bone density with age is observed (<em>P</em> = 0.363), a trend in the statistical appearance model suggests an increase in density with age.</p></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S8756328224002400/pdfft?md5=326eea364020ae4b2ddeef656abe33d9&pid=1-s2.0-S8756328224002400-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142169567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-07DOI: 10.1016/j.bone.2024.117253
Jiaying Li , Hongyu Jia , Zhenqiu Liu , Kelin Xu
Low bone mineral density (LBMD) remains a global public health concern. To provide deeper insights, we retrieved and calibrated LBMD death and Disability-Adjusted Life Years (DALYs) data from the Global Burden of Disease 2021 (GBD 2021) database. We calculated the age-standardized rate (ASR) and estimated annual percentage change (EAPC) to delineate LBMD trends across sexes, age groups, Sociodemographic Index (SDI) regions, and countries. Spearman rank order correlation analysis was used to explore the relationship between SDI and ASR. Additionally, we constructed Bayesian age-period-cohort (BAPC) models to predict future trends in LBMD up to 2030, with the mean absolute percentage error (MAPE) used to evaluate prediction accuracy. Our analyses revealed that global deaths related to LBMD nearly doubled, from 250,930 in 1990 to 463,010 in 2021, and are projected to rise to 473,690 by 2030. However, the ASR exhibited an opposite trend, decreasing from 17.91 per 100,000 in 1990 to 15.77 per 100,000 in 2021, and is expected to further decline to 13.64 per 100,000 by 2030. The EAPC indicated descending trends in 1990–2021 and 2022–2030. Trends in LBMD varied across different subgroups by sex, age, and location. Males are projected to continue experiencing higher death numbers than females, though the gap is narrowing. The 90 to 94 age group consistently had the highest ASR from 1990 to 2030. Lower SDI remains a critical factor contributing to the higher burden of LBMD. Spearman rank order correlation analysis showed a negative correlation between SDI and ASR. We categorized 6 distinct trends in ASR across different countries, with most expected to experience a decline by 2030. The MAPE value (0.038 < 0.1) indicated that the BAPC model produced reliable predictions even under the COVID-19 pandemic.
{"title":"Global, regional and national trends in the burden of low bone mineral density from 1990 to 2030: A Bayesian age-period-cohort modeling study","authors":"Jiaying Li , Hongyu Jia , Zhenqiu Liu , Kelin Xu","doi":"10.1016/j.bone.2024.117253","DOIUrl":"10.1016/j.bone.2024.117253","url":null,"abstract":"<div><p>Low bone mineral density (LBMD) remains a global public health concern. To provide deeper insights, we retrieved and calibrated LBMD death and Disability-Adjusted Life Years (DALYs) data from the Global Burden of Disease 2021 (GBD 2021) database. We calculated the age-standardized rate (ASR) and estimated annual percentage change (EAPC) to delineate LBMD trends across sexes, age groups, Sociodemographic Index (SDI) regions, and countries. Spearman rank order correlation analysis was used to explore the relationship between SDI and ASR. Additionally, we constructed Bayesian age-period-cohort (BAPC) models to predict future trends in LBMD up to 2030, with the mean absolute percentage error (MAPE) used to evaluate prediction accuracy. Our analyses revealed that global deaths related to LBMD nearly doubled, from 250,930 in 1990 to 463,010 in 2021, and are projected to rise to 473,690 by 2030. However, the ASR exhibited an opposite trend, decreasing from 17.91 per 100,000 in 1990 to 15.77 per 100,000 in 2021, and is expected to further decline to 13.64 per 100,000 by 2030. The EAPC indicated descending trends in 1990–2021 and 2022–2030. Trends in LBMD varied across different subgroups by sex, age, and location. Males are projected to continue experiencing higher death numbers than females, though the gap is narrowing. The 90 to 94 age group consistently had the highest ASR from 1990 to 2030. Lower SDI remains a critical factor contributing to the higher burden of LBMD. Spearman rank order correlation analysis showed a negative correlation between SDI and ASR. We categorized 6 distinct trends in ASR across different countries, with most expected to experience a decline by 2030. The MAPE value (0.038 < 0.1) indicated that the BAPC model produced reliable predictions even under the COVID-19 pandemic.</p></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-04DOI: 10.1016/j.bone.2024.117252
Daria Masztalerz-Kozubek, Monika A. Zielinska-Pukos, Jadwiga Hamulka
Lifestyle factors have the potential to influence bone health in various ways, whether positively or negatively. As osteoporosis is believed to originate in early years, it is therefore essential to indicate factors that may positively affect bone health during childhood. The aim of our study was to investigate the effects of early and current diet, vitamin D supplementation, and BMI z-score on bone properties in a group of children aged 3–7 years. A cross-sectional sample of 205 preschoolers and their parents participated in the study. Dietary assessment was made using a modified version of the Polish-adapted Mediterranean Diet score (MVP-aMED) on the basis of the data from food frequency questionnaire (FFQ), filled out by the parents. Quantitative ultrasound (QUS) was used in the assessment of bone properties. In the sex-stratified analysis, significant associations were observed between MVP-aMED score (β = 0.193, 95 % CI: 0.005, 0.237; p = 0.04), BMI z-score (β = −0.318, 95 % CI: −1.455, −0.039; p = 0.04) and QUS z-score, exclusively among girls. After adjustment, only the relationship with diet remained significant (β = 0.209, 95 % CI: 0.007, 0.255; p = 0.04), suggesting that a higher adherence to the Mediterranean Diet may be associated with better bone properties in girls aged 3–7 years old. Our results emphasize the importance of fostering healthy dietary habits and maintaining proper weight in children in order to promote optimal bone development.
生活方式因素有可能以各种方式对骨骼健康产生积极或消极的影响。由于骨质疏松症被认为起源于幼年时期,因此有必要指出可能对儿童时期骨骼健康产生积极影响的因素。我们的研究旨在调查早期和当前饮食、维生素 D 补充剂以及体重指数 z 分数对 3-7 岁儿童骨骼特性的影响。共有 205 名学龄前儿童及其家长参与了这项横断面样本研究。根据家长填写的食物频率问卷(FFQ)数据,使用波兰改良版地中海饮食评分(MVP-aMED)进行饮食评估。定量超声(QUS)用于评估骨骼特性。在性别分层分析中,观察到 MVP-aMED 评分(β = 0.193,95 % CI:0.005,0.237;p = 0.04)、体重指数 z 评分(β = -0.318,95 % CI:-1.455,-0.039;p = 0.04)与 QUS z 评分之间存在显著关联,且仅限于女孩。经过调整后,只有与饮食的关系仍然显著(β = 0.209, 95 % CI: 0.007, 0.255; p = 0.04),这表明更多坚持地中海饮食可能与 3-7 岁女孩更好的骨骼特性有关。我们的研究结果表明,培养儿童健康的饮食习惯和保持适当的体重对促进骨骼的最佳发育非常重要。
{"title":"Sex-specific effects of a Mediterranean diet on lower limb bone strength in Polish children","authors":"Daria Masztalerz-Kozubek, Monika A. Zielinska-Pukos, Jadwiga Hamulka","doi":"10.1016/j.bone.2024.117252","DOIUrl":"10.1016/j.bone.2024.117252","url":null,"abstract":"<div><p>Lifestyle factors have the potential to influence bone health in various ways, whether positively or negatively. As osteoporosis is believed to originate in early years, it is therefore essential to indicate factors that may positively affect bone health during childhood. The aim of our study was to investigate the effects of early and current diet, vitamin D supplementation, and BMI z-score on bone properties in a group of children aged 3–7 years. A cross-sectional sample of 205 preschoolers and their parents participated in the study. Dietary assessment was made using a modified version of the Polish-adapted Mediterranean Diet score (MVP-aMED) on the basis of the data from food frequency questionnaire (FFQ), filled out by the parents. Quantitative ultrasound (QUS) was used in the assessment of bone properties. In the sex-stratified analysis, significant associations were observed between MVP-aMED score (β = 0.193, 95 % CI: 0.005, 0.237; <em>p</em> = 0.04), BMI z-score (β = −0.318, 95 % CI: −1.455, −0.039; p = 0.04) and QUS z-score, exclusively among girls. After adjustment, only the relationship with diet remained significant (β = 0.209, 95 % CI: 0.007, 0.255; <em>p</em> = 0.04), suggesting that a higher adherence to the Mediterranean Diet may be associated with better bone properties in girls aged 3–7 years old. Our results emphasize the importance of fostering healthy dietary habits and maintaining proper weight in children in order to promote optimal bone development.</p></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S8756328224002412/pdfft?md5=ccc822044a6438f81f7dc3081e001aa6&pid=1-s2.0-S8756328224002412-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To investigate which joint microarchitectural parameters measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) serve as imaging markers for rheumatoid arthritis (RA).
Methods
The second and third metacarpophalangeal (MCP) joints of 50 patients with RA and 50 healthy controls (HCs) (aged 50–79 years, all females) were scanned using a HR-pQCT. Joint space, trabecular bone microarchitecture, and erosion were measured and compared between RA patients and HCs.
Results
There were no differences in joint space parameters between RA patients and HCs.
For bone microarchitecture, RA patients had lower trabecular bone mineral density (127 vs. 167 mg/cm3), thinner trabecular thickness (0.20 vs. 0.21 mm), fewer trabecular number (1.49 vs. 1.55 /mm), more rod-like structure (1.68 vs. 1.23), and poorer trabecular connectivity (4.51 vs. 5.72 /mm3) than HCs.
Regarding erosion, RA patients had a higher number of erosions per joint (36/100 vs. 18/100), larger volume (4.62 vs. 1.89 mm3), and longer width (2.40 vs. 1.82 mm) and longer length (2.34 vs. 1.64 mm) than HCs.
Most of the erosions in HCs were <5 mm3 in volume (95 %) and located on the radial side (85 %). When erosions <5 mm3 were compared between RA patients and HCs, there were no differences in their location or morphology.
Conclusions
Deterioration of bone microarchitecture and existences of erosions >5 mm3 in the MCP joints are sensitive imaging markers of RA. Erosions <5 mm3 in RA patients may include not only early pathological erosion but also physiological erosion because even HCs can have erosions <5 mm3.
目的:研究高分辨率外周定量计算机断层扫描(HR-pQCT)测量的哪些关节微结构参数可作为类风湿性关节炎(RA)的影像学标记:研究通过高分辨率外周定量计算机断层扫描(HR-pQCT)测量的哪些关节微结构参数可作为类风湿性关节炎(RA)的影像学标记:使用 HR-pQCT 扫描了 50 名 RA 患者和 50 名健康对照者(HCs)(年龄在 50-79 岁之间,均为女性)的第二和第三掌指关节(MCP)。对关节间隙、骨小梁微结构和侵蚀情况进行了测量,并对 RA 患者和 HCs 进行了比较:结果:RA 患者和 HCs 的关节间隙参数没有差异。在骨微结构方面,与 HCs 相比,RA 患者的骨小梁骨矿物质密度较低(127 vs. 167 mg/cm3),骨小梁厚度较薄(0.20 vs. 0.21 mm),骨小梁数量较少(1.49 vs. 1.55 /mm),杆状结构较多(1.68 vs. 1.23),骨小梁连接性较差(4.51 vs. 5.72 /mm3)。在侵蚀方面,RA 患者每个关节的侵蚀数量(36/100 对 18/100)、体积(4.62 对 1.89 mm3)、宽度(2.40 对 1.82 mm)和长度(2.34 对 1.64 mm)均高于 HC 患者。HCs 中的大多数糜烂体积为 3(95%),位于桡侧(85%)。当对RA患者和HC患者的侵蚀3进行比较时,其位置和形态均无差异:结论:骨微结构的恶化和 MCP 关节中大于 5 mm3 的侵蚀是 RA 的敏感影像学标志。RA患者的侵蚀3不仅包括早期病理侵蚀,还可能包括生理性侵蚀,因为即使是HCs也可能存在侵蚀3。
{"title":"Microarchitectural analysis of the metacarpophalangeal joint using HR-pQCT in patients with rheumatoid arthritis: A comparison with healthy controls","authors":"Kounosuke Watanabe , Ko Chiba , Kazuteru Shiraishi , Takeshi Iida , Naoki Iwamoto , Akihiko Yonekura , Atsushi Kawakami , Makoto Osaki","doi":"10.1016/j.bone.2024.117250","DOIUrl":"10.1016/j.bone.2024.117250","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate which joint microarchitectural parameters measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) serve as imaging markers for rheumatoid arthritis (RA).</p></div><div><h3>Methods</h3><p>The second and third metacarpophalangeal (MCP) joints of 50 patients with RA and 50 healthy controls (HCs) (aged 50–79 years, all females) were scanned using a HR-pQCT. Joint space, trabecular bone microarchitecture, and erosion were measured and compared between RA patients and HCs.</p></div><div><h3>Results</h3><p>There were no differences in joint space parameters between RA patients and HCs.</p><p>For bone microarchitecture, RA patients had lower trabecular bone mineral density (127 vs. 167 mg/cm<sup>3</sup>), thinner trabecular thickness (0.20 vs. 0.21 mm), fewer trabecular number (1.49 vs. 1.55 /mm), more rod-like structure (1.68 vs. 1.23), and poorer trabecular connectivity (4.51 vs. 5.72 /mm<sup>3</sup>) than HCs.</p><p>Regarding erosion, RA patients had a higher number of erosions per joint (36/100 vs. 18/100), larger volume (4.62 vs. 1.89 mm<sup>3</sup>), and longer width (2.40 vs. 1.82 mm) and longer length (2.34 vs. 1.64 mm) than HCs.</p><p>Most of the erosions in HCs were <5 mm<sup>3</sup> in volume (95 %) and located on the radial side (85 %). When erosions <5 mm<sup>3</sup> were compared between RA patients and HCs, there were no differences in their location or morphology.</p></div><div><h3>Conclusions</h3><p>Deterioration of bone microarchitecture and existences of erosions >5 mm<sup>3</sup> in the MCP joints are sensitive imaging markers of RA. Erosions <5 mm<sup>3</sup> in RA patients may include not only early pathological erosion but also physiological erosion because even HCs can have erosions <5 mm<sup>3</sup>.</p></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-28DOI: 10.1016/j.bone.2024.117242
T.S. Pinto , B.C. van der Eerden , M. Schreuders-Koedam , J. van de Peppel , I. Ayada , Q. Pan , M.M. Verstegen , L.J. van der Laan , G.M. Fuhler , W.F. Zambuzzi , M.P. Peppelenbosch
As obesity rates continue to rise, the prevalence of metabolic dysfunction and alcohol-associated steatotic liver disease (MetALD), a new term for Nonalcoholic Fatty Liver Disease (NAFLD), also increases. In an aging population, it is crucial to understand the interplay between metabolic disorders, such as MetALD, and bone health. This understanding becomes particularly significant in the context of implant osseointegration. This study introduces an in vitro model simulating high lipogenesis through the use of human Mesenchymal Stroma Cells-derived adipocytes, 3D intrahepatic cholangiocyte organoids (ICO), and Huh7 hepatocytes, to evaluate the endocrine influence on osteoblasts interacting with titanium. We observed a significant increase in intracellular fat accumulation in all three cell types, along with a corresponding elevation in metabolic gene expression compared to the control groups. Notably, osteoblasts undergoing mineralization in this high-lipogenesis environment also displayed lipid vesicle accumulation. The study further revealed that titanium surfaces modulate osteogenic gene expression and impact cell cycle progression, cell survival, and extracellular matrix remodeling under lipogenic conditions. These findings provide new insights into the challenges of implant integration in patients with obesity and MetALD, offering a deeper understanding of the metabolic influences on bone regeneration and implant success.
{"title":"Interaction of high lipogenic states with titanium on osteogenesis","authors":"T.S. Pinto , B.C. van der Eerden , M. Schreuders-Koedam , J. van de Peppel , I. Ayada , Q. Pan , M.M. Verstegen , L.J. van der Laan , G.M. Fuhler , W.F. Zambuzzi , M.P. Peppelenbosch","doi":"10.1016/j.bone.2024.117242","DOIUrl":"10.1016/j.bone.2024.117242","url":null,"abstract":"<div><p>As obesity rates continue to rise, the prevalence of metabolic dysfunction and alcohol-associated steatotic liver disease (MetALD), a new term for Nonalcoholic Fatty Liver Disease (NAFLD), also increases. In an aging population, it is crucial to understand the interplay between metabolic disorders, such as MetALD, and bone health. This understanding becomes particularly significant in the context of implant osseointegration. This study introduces an <em>in vitro</em> model simulating high lipogenesis through the use of human Mesenchymal Stroma Cells-derived adipocytes, 3D intrahepatic cholangiocyte organoids (ICO), and Huh7 hepatocytes, to evaluate the endocrine influence on osteoblasts interacting with titanium. We observed a significant increase in intracellular fat accumulation in all three cell types, along with a corresponding elevation in metabolic gene expression compared to the control groups. Notably, osteoblasts undergoing mineralization in this high-lipogenesis environment also displayed lipid vesicle accumulation. The study further revealed that titanium surfaces modulate osteogenic gene expression and impact cell cycle progression, cell survival, and extracellular matrix remodeling under lipogenic conditions. These findings provide new insights into the challenges of implant integration in patients with obesity and MetALD, offering a deeper understanding of the metabolic influences on bone regeneration and implant success.</p></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142089667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-23DOI: 10.1016/j.bone.2024.117241
Jennifer C. Coulombe , Brittany N. Bozzini , Katelyn I. Guerriere , Stephen A. Foulis , Marinaliz Reynoso , Leila A. Walker , Jeffery S. Staab , Mary L. Bouxsein , Julie M. Hughes , Kristin L. Popp
Importance
U.S. Army Basic Combat Training (BCT) improves tibial volumetric bone mineral density (BMD) and structure in most, but not all soldiers. Few studies have investigated whether changes in serum bone biomarkers during BCT are associated with changes in tibial BMD and bone structure following BCT.
Objective
To characterize bone biomarker changes during BCT and to investigate the relationship between changes in bone biomarkers and changes in tibial BMD and bone structure.
Methods
We enrolled 235 trainees entering BCT in this ten-week prospective observational study. Trainees provided fasted blood samples and questionnaires weekly throughout BCT. Procollagen type 1 N-terminal propeptide (PINP) and C-terminal telopeptide of type 1 collagen (CTX) were measured by enzyme-linked immunoabsorbent assays every two weeks during BCT. We evaluated body composition and mass via dual-energy X-ray absorptiometry and bone structure, microarchitecture, and mineral density at the distal tibia via high-resolution peripheral quantitative computed tomography at baseline and post-BCT.
Results
Both male (n = 110) and female trainees (n = 125) were young (20.9 ± 3.7 and 20.7 ± 4.3 years, respectively), with normal to overweight BMIs (25.2 ± 4.1 and 24.2 ± 3.6 kg/m2, respectively). In female trainees, PINP increased during and post-BCT compared to baseline, with the greatest increase in PINP at week four (45.4 % ± 49.6, p < 0.0001), whereas there were no changes in CTX. PINP also increased in male trainees, but only at weeks two and four (21.9 % ± 24.5, p = 0.0027 and 35.9 % ± 35.8, p < 0.0001, respectively). Unlike female trainees, in males, CTX was lower than baseline at weeks four, eight, and post-BCT. The change in PINP from baseline to week four of BCT was positively associated with changes in tibial BMD, Tb.BMD, Tb.Th, Tb.BV/TV, Ct.Th, Ct.Ar, and Ct.Po from the baseline to post-BCT.
Conclusion
The bone formation marker PINP increases during U.S. Army BCT, especially during the first four weeks. Increases in PINP, but not CTX, were correlated with improved BMD and bone structure in the distal tibia.
{"title":"Association between changes in serum bone metabolism markers and bone microarchitecture changes during basic combat training – The ARMI study","authors":"Jennifer C. Coulombe , Brittany N. Bozzini , Katelyn I. Guerriere , Stephen A. Foulis , Marinaliz Reynoso , Leila A. Walker , Jeffery S. Staab , Mary L. Bouxsein , Julie M. Hughes , Kristin L. Popp","doi":"10.1016/j.bone.2024.117241","DOIUrl":"10.1016/j.bone.2024.117241","url":null,"abstract":"<div><h3>Importance</h3><p>U.S. Army Basic Combat Training (BCT) improves tibial volumetric bone mineral density (BMD) and structure in most, but not all soldiers. Few studies have investigated whether changes in serum bone biomarkers during BCT are associated with changes in tibial BMD and bone structure following BCT.</p></div><div><h3>Objective</h3><p>To characterize bone biomarker changes during BCT and to investigate the relationship between changes in bone biomarkers and changes in tibial BMD and bone structure.</p></div><div><h3>Methods</h3><p>We enrolled 235 trainees entering BCT in this ten-week prospective observational study. Trainees provided fasted blood samples and questionnaires weekly throughout BCT. Procollagen type 1 N-terminal propeptide (PINP) and C-terminal telopeptide of type 1 collagen (CTX) were measured by enzyme-linked immunoabsorbent assays every two weeks during BCT. We evaluated body composition and mass via dual-energy X-ray absorptiometry and bone structure, microarchitecture, and mineral density at the distal tibia via high-resolution peripheral quantitative computed tomography at baseline and post-BCT.</p></div><div><h3>Results</h3><p>Both male (<em>n</em> = 110) and female trainees (<em>n</em> = 125) were young (20.9 ± 3.7 and 20.7 ± 4.3 years, respectively), with normal to overweight BMIs (25.2 ± 4.1 and 24.2 ± 3.6 kg/m<sup>2</sup>, respectively). In female trainees, PINP increased during and post-BCT compared to baseline, with the greatest increase in PINP at week four (45.4 % ± 49.6, <em>p</em> < 0.0001), whereas there were no changes in CTX. PINP also increased in male trainees, but only at weeks two and four (21.9 % ± 24.5, <em>p</em> = 0.0027 and 35.9 % ± 35.8, <em>p</em> < 0.0001, respectively). Unlike female trainees, in males, CTX was lower than baseline at weeks four, eight, and post-BCT. The change in PINP from baseline to week four of BCT was positively associated with changes in tibial BMD, Tb.BMD, Tb.Th, Tb.BV/TV, Ct.Th, Ct.Ar, and Ct.Po from the baseline to post-BCT.</p></div><div><h3>Conclusion</h3><p>The bone formation marker PINP increases during U.S. Army BCT, especially during the first four weeks. Increases in PINP, but not CTX, were correlated with improved BMD and bone structure in the distal tibia.</p></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-23DOI: 10.1016/j.bone.2024.117240
Bruno Magalhães de Castro , Thiago dos Santos Rosa , Thaís Branquinho de Araújo , Hugo de Luca Corrêa , Lysleine Alves de Deus , Rodrigo Vanerson Passos Neves , Andrea Lucena Reis , Rafael Lavarini dos Santos , Jéssica Mycaelle da Silva Barbosa , Fernando de Sousa Honorato , Vitória Marra da Motta Vilalva Mestrinho , Milton Rocha de Moraes , Carmen Tzanno-Martins , Jonato Prestes
Chronic kidney disease (CKD) is associated with a series of mineral bone disturbances due to increased production of parathormone which increases the activity of osteoclasts, removing calcium and phosphorous from the bones. However, the literature lacks investigations on the feasibility of different resistance training (RT) methods, such as cluster-sets, in this population. Thus, the aim of the present study was to compare traditional versus cluster-set RT protocols on bone mineral density (BMD) T-score, BMD Total, femur BMD, L3-L4 BMD, femoral neck BMD, Klotho, FGF23, Klotho - FGF23 ratio, Sclerostin, vitamin D, phosphorous and calcium in older subjects with CKD. Seventy-eight older subjects (age: 57.55 ± 4.06 years, body mass: 72.26 ± 13.96 kg, body mass index: 26.73 ± 2.97 kg/m2) with CKD undergoing maintenance hemodialysis were randomly divided into control group (CG, n = 26), traditional RT (RT, n = 26) and cluster-set RT (RT-CS, n = 26) groups. Subjects completed 24 weeks of RT three times per week, 1 h and 30 min before the hemodialysis session, and each training lasted around 60 to 80 min. There was a group×time interaction for total BMD, femur BMD, L3-L4 BMD, and femoral neck BMD, revealed by improvements for RT and RT-CS groups (pre versus post). Only femur BMD displayed differences as compared with the CG. Minimum clinically important difference (MCID) values revealed more responsive subjects in the RT-CS group for total BMD, femur BMD, klotho, FGF23, sclerostin, Vitamin D and calcium. In conclusion, RT can be used as a non-pharmacological complementary strategy for the treatment of CKD. RT-CS may be useful for these subjects as more responders were found for this type of training.
{"title":"Effects of cluster set resistance training on bone mineral density and markers of bone metabolism in older hemodialysis subjects: A pilot study","authors":"Bruno Magalhães de Castro , Thiago dos Santos Rosa , Thaís Branquinho de Araújo , Hugo de Luca Corrêa , Lysleine Alves de Deus , Rodrigo Vanerson Passos Neves , Andrea Lucena Reis , Rafael Lavarini dos Santos , Jéssica Mycaelle da Silva Barbosa , Fernando de Sousa Honorato , Vitória Marra da Motta Vilalva Mestrinho , Milton Rocha de Moraes , Carmen Tzanno-Martins , Jonato Prestes","doi":"10.1016/j.bone.2024.117240","DOIUrl":"10.1016/j.bone.2024.117240","url":null,"abstract":"<div><p>Chronic kidney disease (CKD) is associated with a series of mineral bone disturbances due to increased production of parathormone which increases the activity of osteoclasts, removing calcium and phosphorous from the bones. However, the literature lacks investigations on the feasibility of different resistance training (RT) methods, such as cluster-sets, in this population. Thus, the aim of the present study was to compare traditional versus cluster-set RT protocols on bone mineral density (BMD) T-score, BMD Total, femur BMD, L3-L4 BMD, femoral neck BMD, Klotho, FGF23, Klotho - FGF23 ratio, Sclerostin, vitamin D, phosphorous and calcium in older subjects with CKD. Seventy-eight older subjects (age: 57.55 ± 4.06 years, body mass: 72.26 ± 13.96 kg, body mass index: 26.73 ± 2.97 kg/m2) with CKD undergoing maintenance hemodialysis were randomly divided into control group (CG, <em>n</em> = 26), traditional RT (RT, n = 26) and cluster-set RT (RT-CS, n = 26) groups. Subjects completed 24 weeks of RT three times per week, 1 h and 30 min before the hemodialysis session, and each training lasted around 60 to 80 min. There was a group×time interaction for total BMD, femur BMD, L3-L4 BMD, and femoral neck BMD, revealed by improvements for RT and RT-CS groups (pre versus post). Only femur BMD displayed differences as compared with the CG. Minimum clinically important difference (MCID) values revealed more responsive subjects in the RT-CS group for total BMD, femur BMD, klotho, FGF23, sclerostin, Vitamin D and calcium. In conclusion, RT can be used as a non-pharmacological complementary strategy for the treatment of CKD. RT-CS may be useful for these subjects as more responders were found for this type of training.</p></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.1016/j.bone.2024.117239
Ningxin Gao , Yue Zhuang , Yi Zheng , Yucan Li , Yawen Wang , Sibo Zhu , Min Fan , Weizhong Tian , Yanfeng Jiang , Yingzhe Wang , Mei Cui , Chen Suo , Tiejun Zhang , Li Jin , Xingdong Chen , Kelin Xu
Osteoporosis is a complex metabolic bone disease that severely undermines the quality of life and overall health of the elderly. While previous studies have established a close relationship between gut microbiome and host bone metabolism, the role of genetic factors has received less scrutiny. This research aims to identify potential taxa associated with various bone mineral density states, incorporating assessments of genetic factors. Fecal microbiome profiles from 605 individuals (334 females and 271 males) aged 55–65 from the Taizhou Imaging Study with osteopenia (n = 270, 170 women) or osteoporosis (n = 94, 85 women) or normal (n = 241, 79 women) were determined using shotgun metagenomic sequencing. The linear discriminant analysis was employed to identify differentially enriched taxa. Utilizing the Kyoto Encyclopedia of Genes and Genomes for annotation, functional pathway analysis was conducted to identify differentially metabolic pathways. Polygenic risk score for osteoporosis was estimated to represent genetic susceptibility to osteoporosis, followed by stratification and interaction analyses. Gut flora diversity did not show significant differences among various bone mineral groups. After multivariable adjustment, certain species, such as Clostridium leptum, Fusicatenibacter saccharivorans and Roseburia hominis, were enriched in osteoporosis patients. Statistically significant interactions between the polygenic risk score and taxa Roseburia faecis, Megasphaera elsdenii were observed (P for interaction = 0.005, 0.018, respectively). Stratified analyses revealed a significantly negative association between Roseburia faecis and bone mineral density in the low-genetic-risk group (β = −0.045, P < 0.05), while Turicimonas muris was positively associated with bone mineral density in the high-genetic-risk group (β = 4.177, P < 0.05) after multivariable adjustments. Functional predictions of the gut microbiome indicated an increase in pathways related to structural proteins in high-genetic-risk patients, while low-genetic-risk patients exhibited enrichment in enzyme-related pathways. This study emphasizes the association between gut microbes and bone mass, offering new insights into the interaction between genetic background and gut microbiome.
{"title":"Investigating the link between gut microbiome and bone mineral density: The role of genetic factors","authors":"Ningxin Gao , Yue Zhuang , Yi Zheng , Yucan Li , Yawen Wang , Sibo Zhu , Min Fan , Weizhong Tian , Yanfeng Jiang , Yingzhe Wang , Mei Cui , Chen Suo , Tiejun Zhang , Li Jin , Xingdong Chen , Kelin Xu","doi":"10.1016/j.bone.2024.117239","DOIUrl":"10.1016/j.bone.2024.117239","url":null,"abstract":"<div><p>Osteoporosis is a complex metabolic bone disease that severely undermines the quality of life and overall health of the elderly. While previous studies have established a close relationship between gut microbiome and host bone metabolism, the role of genetic factors has received less scrutiny. This research aims to identify potential taxa associated with various bone mineral density states, incorporating assessments of genetic factors. Fecal microbiome profiles from 605 individuals (334 females and 271 males) aged 55–65 from the Taizhou Imaging Study with osteopenia (<em>n</em> = 270, 170 women) or osteoporosis (<em>n</em> = 94, 85 women) or normal (<em>n</em> = 241, 79 women) were determined using shotgun metagenomic sequencing. The linear discriminant analysis was employed to identify differentially enriched taxa. Utilizing the Kyoto Encyclopedia of Genes and Genomes for annotation, functional pathway analysis was conducted to identify differentially metabolic pathways. Polygenic risk score for osteoporosis was estimated to represent genetic susceptibility to osteoporosis, followed by stratification and interaction analyses. Gut flora diversity did not show significant differences among various bone mineral groups. After multivariable adjustment, certain species, such as <em>Clostridium leptum</em>, <em>Fusicatenibacter saccharivorans</em> and <em>Roseburia hominis,</em> were enriched in osteoporosis patients. Statistically significant interactions between the polygenic risk score and taxa <em>Roseburia faecis, Megasphaera elsdenii</em> were observed (<em>P</em> for interaction = 0.005, 0.018, respectively). Stratified analyses revealed a significantly negative association between <em>Roseburia faecis</em> and bone mineral density in the low-genetic-risk group (β = −0.045, <em>P</em> < 0.05), while <em>Turicimonas muris</em> was positively associated with bone mineral density in the high-genetic-risk group (β = 4.177, <em>P</em> < 0.05) after multivariable adjustments. Functional predictions of the gut microbiome indicated an increase in pathways related to structural proteins in high-genetic-risk patients, while low-genetic-risk patients exhibited enrichment in enzyme-related pathways. This study emphasizes the association between gut microbes and bone mass, offering new insights into the interaction between genetic background and gut microbiome.</p></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-17DOI: 10.1016/j.bone.2024.117237
Seigo Mitsutake , Reidar P. Lystad , Janet C. Long , Jeffrey Braithwaite , Rebecca Mitchell
Purpose
There is limited evidence regarding the impact of public health restrictions on hip fracture hospitalization by place of fracture occurrence. This study aimed to examine the impact of COVID-19 public health restrictions on fall-related hip fracture hospitalization rates by place of occurrence.
Methods
This retrospective cohort study was conducted using hospitalization data in New South Wales, Australia, between January 2014 and June 2022. Older adults aged ≥65 years admitted to hospital following a fall-related hip fracture. An interrupted time-series analysis using autoregressive integrated moving average models evaluated the impact of public health restrictions on fall-related hip fracture hospitalization by place of fracture occurrence (home/residence, residential aged care facility (RACF), or away from usual residence).
Results
The mean observed fall-related hip fracture hospitalization rate during COVID-19 public health restrictions (36.3 per 100,000 people per month) was 13.4 % lower than the forecasted rate (41.1 per 100,000 people per month). The mean observed hospitalization rates for fall-related hip fractures at home/residence, at a RACF, and away from the usual residence were 3.8 %, 18.5 %, and 40.1 % lower than the forecasted rates, respectively. Level changes in the fall-related hip fracture hospitalization rates at RACFs and away from usual residences were −0.9 per 100,000 people per month (95 % CI −1.6 to −0.2) and −1.7 per 100,000 people per month (95 % CI −2.5 to −0.9), respectively.
Conclusions
There was a decline in fall-related hip fracture hospitalization rates among older adults, where the fracture occurred at RACFs and away from a person's usual residence during COVID-19 public health restrictions.
{"title":"Impact of COVID-19 public health restrictions on fall-related hip fracture hospitalizations: An interrupted time series analysis","authors":"Seigo Mitsutake , Reidar P. Lystad , Janet C. Long , Jeffrey Braithwaite , Rebecca Mitchell","doi":"10.1016/j.bone.2024.117237","DOIUrl":"10.1016/j.bone.2024.117237","url":null,"abstract":"<div><h3>Purpose</h3><p>There is limited evidence regarding the impact of public health restrictions on hip fracture hospitalization by place of fracture occurrence. This study aimed to examine the impact of COVID-19 public health restrictions on fall-related hip fracture hospitalization rates by place of occurrence.</p></div><div><h3>Methods</h3><p>This retrospective cohort study was conducted using hospitalization data in New South Wales, Australia, between January 2014 and June 2022. Older adults aged ≥65 years admitted to hospital following a fall-related hip fracture. An interrupted time-series analysis using autoregressive integrated moving average models evaluated the impact of public health restrictions on fall-related hip fracture hospitalization by place of fracture occurrence (home/residence, residential aged care facility (RACF), or away from usual residence).</p></div><div><h3>Results</h3><p>The mean observed fall-related hip fracture hospitalization rate during COVID-19 public health restrictions (36.3 per 100,000 people per month) was 13.4 % lower than the forecasted rate (41.1 per 100,000 people per month). The mean observed hospitalization rates for fall-related hip fractures at home/residence, at a RACF, and away from the usual residence were 3.8 %, 18.5 %, and 40.1 % lower than the forecasted rates, respectively. Level changes in the fall-related hip fracture hospitalization rates at RACFs and away from usual residences were −0.9 per 100,000 people per month (95 % CI −1.6 to −0.2) and −1.7 per 100,000 people per month (95 % CI −2.5 to −0.9), respectively.</p></div><div><h3>Conclusions</h3><p>There was a decline in fall-related hip fracture hospitalization rates among older adults, where the fracture occurred at RACFs and away from a person's usual residence during COVID-19 public health restrictions.</p></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S8756328224002266/pdfft?md5=8b49ebfd16a64d1489873e83f5c1f234&pid=1-s2.0-S8756328224002266-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-15DOI: 10.1016/j.bone.2024.117238
Cassandra Smith , Xuzhu Lin , Lewan Parker , Bu B. Yeap , Alan Hayes , Itamar Levinger
Understanding the mechanisms involved in whole body glucose regulation is key for the discovery of new treatments for type 2 diabetes (T2D). Historically, glucose regulation was largely focused on responses to insulin and glucagon. Impacts of incretin-based therapies, and importance of muscle mass, are also highly relevant. Recently, bone was recognized as an endocrine organ, with several bone proteins, known as osteokines, implicated in glucose metabolism through their effects on the liver, skeletal muscle, and adipose tissue. Research efforts mostly focused on osteocalcin (OC) as a leading example. This review will provide an overview on this role of bone by discussing bone turnover markers (BTMs), the receptor activator of nuclear factor kB ligand (RANKL), osteoprotegerin (OPG), sclerostin (SCL) and lipocalin 2 (LCN2), with a focus on OC. Since 2007, some, but not all, research using mostly OC genetically modified animal models suggested undercarboxylated (uc) OC acts as a hormone involved in energy metabolism. Most data generated from in vivo, ex vivo and in vitro models, indicate that exogenous ucOC administration improves whole-body and skeletal muscle glucose metabolism. Although data in humans are generally supportive, findings are often discordant likely due to methodological differences and observational nature of that research. Overall, evidence supports the concept that bone-derived factors are involved in energy metabolism, some having beneficial effects (ucOC, OPG) others negative (RANKL, SCL), with the role of some (LCN2, other BTMs) remaining unclear. Whether the effect of osteokines on glucose regulation is clinically significant and of therapeutic value for people with insulin resistance and T2D remains to be confirmed.
{"title":"The role of bone in energy metabolism: A focus on osteocalcin","authors":"Cassandra Smith , Xuzhu Lin , Lewan Parker , Bu B. Yeap , Alan Hayes , Itamar Levinger","doi":"10.1016/j.bone.2024.117238","DOIUrl":"10.1016/j.bone.2024.117238","url":null,"abstract":"<div><p>Understanding the mechanisms involved in whole body glucose regulation is key for the discovery of new treatments for type 2 diabetes (T2D). Historically, glucose regulation was largely focused on responses to insulin and glucagon. Impacts of incretin-based therapies, and importance of muscle mass, are also highly relevant. Recently, bone was recognized as an endocrine organ, with several bone proteins, known as osteokines, implicated in glucose metabolism through their effects on the liver, skeletal muscle, and adipose tissue. Research efforts mostly focused on osteocalcin (OC) as a leading example. This review will provide an overview on this role of bone by discussing bone turnover markers (BTMs), the receptor activator of nuclear factor kB ligand (RANKL), osteoprotegerin (OPG), sclerostin (SCL) and lipocalin 2 (LCN2), with a focus on OC. Since 2007, some, but not all, research using mostly OC genetically modified animal models suggested undercarboxylated (uc) OC acts as a hormone involved in energy metabolism. Most data generated from in vivo, ex vivo and in vitro models, indicate that exogenous ucOC administration improves whole-body and skeletal muscle glucose metabolism. Although data in humans are generally supportive, findings are often discordant likely due to methodological differences and observational nature of that research. Overall, evidence supports the concept that bone-derived factors are involved in energy metabolism, some having beneficial effects (ucOC, OPG) others negative (RANKL, SCL), with the role of some (LCN2, other BTMs) remaining unclear. Whether the effect of osteokines on glucose regulation is clinically significant and of therapeutic value for people with insulin resistance and T2D remains to be confirmed.</p></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S8756328224002278/pdfft?md5=2d7b60dc412ed76cc740d21422101b7e&pid=1-s2.0-S8756328224002278-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141997076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}