JBMR Plus最新文献

{"title":"Sex- and Age Group-Specific Fracture Incidence Rates Trends for Type 1 and 2 Diabetes Mellitus","authors":"Mohamad I Nasser,&nbsp;Annika Vestergaard Kvist,&nbsp;Peter Vestergaard,&nbsp;Richard Eastell,&nbsp;Andrea M Burden,&nbsp;Morten Frost","doi":"10.1002/jbm4.10836","DOIUrl":"https://doi.org/10.1002/jbm4.10836","url":null,"abstract":"<p>The incidence of major osteoporotic fractures has declined in men and women in Western countries over the last two decades. Although fracture risk is higher in persons with diabetes mellitus, trends of fractures remain unknown in men and women with diabetes. We investigated the trends in fracture incidence rates (IRs) in men and women with type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D) in Denmark between 1997 and 2017. We identified men and women aged 18+ years who sustained a fracture (excluding skull and facial fractures) between 1997 and 2017 using the Danish National Patient Registry. We calculated sex-specific IRs of fractures per 10,000 person-years separately in persons with T1D, T2D, or without diabetes. Furthermore, we compared median IRs of the first 5 years (1997–2002) to the median IRs of the last 5 years (2012–2017). We identified 1,235,628 persons with fractures including 4863 (43.6% women) with T1D, 65,366 (57.5% women) with T2D, and 1,165,399 (54.1% women) without diabetes. The median IRs of fractures declined 20.2%, 19.9%, and 7.8% in men with T1D, T2D, and without diabetes, respectively (<i>p</i>-trend &lt;0.05). The median IRs decreased 6.4% in women with T1D (<i>p</i>-trend = 0.35) and 25.6% in women with T2D (<i>p</i>-trend &lt;0.05) but increased 2.3% in women without diabetes (<i>p</i>-trend = 0.08). Fracture IRs decreased in men with both diabetes types and only in women with T2D, highlighting the need for further attention behind the stable trend observed in women with T1D. © 2023 The Authors. <i>JBMR Plus</i> published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"7 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://asbmr.onlinelibrary.wiley.com/doi/epdf/10.1002/jbm4.10836","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134814826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacologic Inhibition of Myostatin With a Myostatin Antibody Improves the Skeletal Muscle and Bone Phenotype of Male Insulin-Deficient Diabetic Mice","authors":"R Clay Bunn,&nbsp;Reuben Adatorwovor,&nbsp;Rebecca R Smith,&nbsp;Philip D Ray,&nbsp;Sarah E Fields,&nbsp;Alexander R Keeble,&nbsp;Christopher S Fry,&nbsp;Sasidhar Uppuganti,&nbsp;Jeffry S Nyman,&nbsp;John L Fowlkes,&nbsp;Evangelia Kalaitzoglou","doi":"10.1002/jbm4.10833","DOIUrl":"https://doi.org/10.1002/jbm4.10833","url":null,"abstract":"<p>Type 1 diabetes (T1D) is associated with low bone and muscle mass, increased fracture risk, and impaired skeletal muscle function. Myostatin, a myokine that is systemically elevated in humans with T1D, negatively regulates muscle mass and bone formation. We investigated whether pharmacologic myostatin inhibition in a mouse model of insulin-deficient, streptozotocin (STZ)-induced diabetes is protective for bone and skeletal muscle. DBA/2J male mice were injected with low-dose STZ (diabetic) or vehicle (non-diabetic). Subsequently, insulin or palmitate Linbits were implanted and myostatin (REGN647-MyoAb) or control (REGN1945-ConAb) antibody was administered for 8 weeks. Body composition and contractile muscle function were assessed in vivo. Systemic myostatin, P1NP, CTX-I, and glycated hemoglobin (HbA1c) were quantified, and gastrocnemii were weighed and analyzed for muscle fiber composition and gene expression of selected genes. Cortical and trabecular parameters were analyzed (micro-computed tomography evaluations of femur) and cortical bone strength was assessed (three-point bending test of femur diaphysis). In diabetic mice, the combination of insulin/MyoAb treatment resulted in significantly higher lean mass and gastrocnemius weight compared with MyoAb or insulin treatment alone. Similarly, higher raw torque was observed in skeletal muscle of insulin/MyoAb-treated diabetic mice compared with MyoAb or insulin treatment. Additionally, muscle fiber cross-sectional area (CSA) was lower with diabetes and the combination treatment with insulin/MyoAb significantly improved CSA in type II fibers. Insulin, MyoAb, or insulin/MyoAb treatment improved several parameters of trabecular architecture (eg, bone volume fraction [BV/TV], trabecular connectivity density [Conn.D]) and cortical structure (eg, cortical bone area [Ct. Ar.], minimum moment of inertia [Imin]) in diabetic mice. Lastly, cortical bone biomechanical properties (stiffness and yield force) were also improved with insulin or MyoAb treatment. In conclusion, pharmacologic myostatin inhibition is beneficial for muscle mass, muscle function, and bone properties in this mouse model of T1D and its effects are both independent and additive to the positive effects of insulin. © 2023 The Authors. <i>JBMR Plus</i> published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"7 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://asbmr.onlinelibrary.wiley.com/doi/epdf/10.1002/jbm4.10833","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134814448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of Quantitative and Qualitative Muscle Parameters With Second Hip Fracture Risk in Older Women: A Prospective Cohort Study","authors":"Wenshuang Zhang,&nbsp;Yufeng Ge,&nbsp;Yandong Liu,&nbsp;Yi Yuan,&nbsp;Jian Geng,&nbsp;Fengyun Zhou,&nbsp;Pengju Huang,&nbsp;Jia Shi,&nbsp;Kangkang Ma,&nbsp;Zitong Cheng,&nbsp;Glen M. Blake,&nbsp;Minghui Yang,&nbsp;Xinbao Wu,&nbsp;Xiaoguang Cheng,&nbsp;Ling Wang","doi":"10.1002/jbm4.10834","DOIUrl":"10.1002/jbm4.10834","url":null,"abstract":"<p>Older women with a first hip fracture exhibit heightened susceptibility and incidence of second fracture and potentially severe consequences. This prospective study was to compare the predictive power of qualitative and quantitative muscle parameters for a second hip fracture in older women with a first hip fracture. A total of 206 subjects were recruited from the longitudinal Chinese Second Hip Fracture Evaluation study. Hip computed tomography (CT) scans were obtained immediately after the first fracture. Muscle fat infiltration was assessed according to the Goutallier classification qualitatively. Quantitative parameters included cross-sectional area and density of gluteus maximus (G.MaxM) and gluteus medius and minimus (G.Med/MinM) muscles. CT X-ray absorptiometry was used to measure the areal bone mineral density (aBMD) of the contralateral femur. Cox proportional hazards models were used to compute hazard ratios (HR) of second hip fracture risk. The mean age of subjects was 74.9 (±9.5) years at baseline. After 4.5 years, 35 had a second hip fracture, 153 without a second hip fracture, and 18 died. Except for the combined G.MinM Goutallier grade 3 and 4 groups before adjustment for covariates (HR = 5.83; 95% confidence interval [CI] 1.49–22.83), there were no significant HRs for qualitative classification to predict a second hip fracture. Among quantitative metrics, after adjustment for covariates, G.Med/MinM density was significant in the original (HR = 1.44; CI 1.02–2.04) and competing risk analyses (HR = 1.46; CI 1.02–2.07). After additional adjustment for femoral neck (FN) aBMD, G.Med/MinM density remained borderline significant for predicting a second hip fracture in competing risk analysis (HR = 1.43; CI 0.99–2.06; <i>p</i> = 0.057). Our study revealed that Goutallier classification was less effective than quantitative muscle metrics for predicting hip second fracture in this elderly female cohort. After adjustment for FN aBMD, G.Med/MinM density is a borderline independent predictor of second hip fracture risk. © 2023 The Authors. <i>JBMR Plus</i> published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"7 12","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://asbmr.onlinelibrary.wiley.com/doi/epdf/10.1002/jbm4.10834","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135166877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Palovarotene Action Against Heterotopic Ossification Includes a Reduction of Local Participating Activin A-Expressing Cell Populations","authors":"Christina Mundy,&nbsp;Lutian Yao,&nbsp;Kelly A. Shaughnessy,&nbsp;Cheri Saunders,&nbsp;Eileen M. Shore,&nbsp;Eiki Koyama,&nbsp;Maurizio Pacifici","doi":"10.1002/jbm4.10821","DOIUrl":"10.1002/jbm4.10821","url":null,"abstract":"<p>Heterotopic ossification (HO) consists of extraskeletal bone formation. One form of HO is acquired and instigated by traumas or surgery, and another form is genetic and characterizes fibrodysplasia ossificans progressiva (FOP). Recently, we and others showed that activin A promotes both acquired and genetic HO, and in previous studies we found that the retinoid agonist palovarotene inhibits both HO forms in mice. Here, we asked whether palovarotene's action against HO may include an interference with endogenous activin A expression and/or function. Using a standard mouse model of acquired HO, we found that activin A and its encoding RNA (<i>Inhba</i>) were prominent in chondrogenic cells within developing HO masses in untreated mice. Single-cell RNAseq (scRNAseq) assays verified that <i>Inhba</i> expression characterized chondroprogenitors and chondrocytes in untreated HO, in addition to its expected expression in inflammatory cells and macrophages. Palovarotene administration (4 mg/kg/d/gavage) caused a sharp inhibition of both HO and amounts of activin A and <i>Inhba</i> transcripts. Bioinformatic analyses of scRNAseq data sets indicated that the drug had reduced interactions and cross-talk among local cell populations. To determine if palovarotene inhibited <i>Inhba</i> expression directly, we assayed primary chondrocyte cultures. Drug treatment inhibited their cartilaginous phenotype but not <i>Inhba</i> expression. Our data reveal that palovarotene markedly reduces the number of local <i>Inhba</i>-expressing HO-forming cell populations. The data broaden the spectrum of HO culprits against which palovarotene acts, accounting for its therapeutic effectiveness. © 2023 The Authors. <i>JBMR Plus</i> published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"7 12","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://asbmr.onlinelibrary.wiley.com/doi/epdf/10.1002/jbm4.10821","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135780151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Classification of Fracture Risk in Fallers Using Dual-Energy X-Ray Absorptiometry (DXA) Images and Deep Learning-Based Feature Extraction","authors":"Damith Senanayake,&nbsp;Sachith Seneviratne,&nbsp;Mahdi Imani,&nbsp;Christel Harijanto,&nbsp;Myrla Sales,&nbsp;Peter Lee,&nbsp;Gustavo Duque,&nbsp;David C. Ackland","doi":"10.1002/jbm4.10828","DOIUrl":"10.1002/jbm4.10828","url":null,"abstract":"<p>Dual-energy X-ray absorptiometry (DXA) scans are one of the most frequently used imaging techniques for calculating bone mineral density, yet calculating fracture risk using DXA image features is rarely performed. The objective of this study was to combine deep neural networks, together with DXA images and patient clinical information, to evaluate fracture risk in a cohort of adults with at least one known fall and age-matched healthy controls. DXA images of the entire body as, well as isolated images of the hip, forearm, and spine (1488 total), were obtained from 478 fallers and 48 non-faller controls. A modeling pipeline was developed for fracture risk prediction using the DXA images and clinical data. First, self-supervised pretraining of feature extractors was performed using a small vision transformer (ViT-S) and a convolutional neural network model (VGG-16 and Resnet-50). After pretraining, the feature extractors were then paired with a multilayer perceptron model, which was used for fracture risk classification. Classification was achieved with an average area under the receiver-operating characteristic curve (AUROC) score of 74.3%. This study demonstrates ViT-S as a promising neural network technique for fracture risk classification using DXA scans. The findings have future application as a fracture risk screening tool for older adults at risk of falls. © 2023 The Authors. <i>JBMR Plus</i> published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"7 12","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://asbmr.onlinelibrary.wiley.com/doi/epdf/10.1002/jbm4.10828","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135780264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone Structure and Turnover in Postmenopausal Women With Long-Standing Type 1 Diabetes","authors":"Viral N Shah,&nbsp;Shijing Qui,&nbsp;Jason Stoneback,&nbsp;Lubna Qamar,&nbsp;Virginia L Ferguson,&nbsp;Wendy M Kohrt,&nbsp;Janet K Snell-Bergeon,&nbsp;Sudhaker D Rao","doi":"10.1002/jbm4.10831","DOIUrl":"https://doi.org/10.1002/jbm4.10831","url":null,"abstract":"<p>Compromised bone structural and mechanical properties are implicated in the increased fracture risk in type 1 diabetes (T1D). We investigated bone structure and turnover by histomorphometry in postmenopausal women with T1D and controls without diabetes using tetracycline double-labeled transiliac bone biopsy. After in vivo tetracycline double labeling, postmenopausal women with T1D of at least 10 years and without diabetes underwent transiliac bone biopsy. An expert blinded to the study group performed histomorphometry. Static and dynamic histomorphometry measurements were performed and compared between the two groups. The analysis included 9 postmenopausal women with T1D (mean age 58.4 ± 7.1 years with 37.9 ± 10.9 years of diabetes and HbA1c 7.1% ± 0.4%) and 7 postmenopausal women without diabetes (mean age 60.9 ± 3.3 years and HbA1c 5.4% ± 0.2%). There were no significant differences in serum PTH (38.6 ± 8.1 versus 51.9 ± 23.9 pg/mL), CTX (0.4 ± 0.2 versus 0.51 ± 0.34 ng/mL), or P1NP (64.5 ± 26.2 versus 87.3 ± 45.3 ng/mL). Serum 25-hydroxyvitamin D levels were higher in T1D than in controls (53.1 ± 20.8 versus 30.9 ± 8.2 ng/mL, <i>p</i> &lt; 0.05). Bone structure metrics (bone volume, trabecular thickness, trabecular number, and cortical thickness) were similar between the groups. Indices of bone formation (osteoid volume, osteoid surface, and bone formation rate) were 40% lower in T1D and associated with lower activation frequency. However, the differences in bone formation were not statistically significant. Long-standing T1D may affect bone turnover, mainly bone formation, without significantly affecting bone structure. Further research is needed to understand bone turnover and factors affecting bone turnover in people with T1D. © 2023 The Authors. <i>JBMR Plus</i> published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"7 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://asbmr.onlinelibrary.wiley.com/doi/epdf/10.1002/jbm4.10831","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134806581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tensile Mechanical Properties of Dry Cortical Bone Extracellular Matrix: A Comparison Among Two Osteogenesis Imperfecta and One Healthy Control Iliac Crest Biopsies","authors":"Michael Indermaur,&nbsp;Daniele Casari,&nbsp;Tatiana Kochetkova,&nbsp;Bettina M. Willie,&nbsp;Johann Michler,&nbsp;Jakob Schwiedrzik,&nbsp;Philippe Zysset","doi":"10.1002/jbm4.10826","DOIUrl":"10.1002/jbm4.10826","url":null,"abstract":"<p>Osteogenesis imperfecta (OI) is a genetic, collagen-related bone disease that increases the incidence of bone fractures. Still, the origin of this brittle mechanical behavior remains unclear. The extracellular matrix (ECM) of OI bone exhibits a higher degree of bone mineralization (DBM), whereas compressive mechanical properties at the ECM level do not appear to be inferior to healthy bone. However, it is unknown if collagen defects alter ECM tensile properties. This study aims to quantify the tensile properties of healthy and OI bone ECM. In three transiliac biopsies (healthy <i>n</i> = 1, OI type I <i>n</i> = 1, OI type III <i>n</i> = 1), 23 microtensile specimens (gauge dimensions 10 × 5 × 2 μm³) were manufactured and loaded quasi-statically under tension in vacuum condition. The resulting loading modulus and ultimate strength were extracted. Interestingly, tensile properties in OI bone ECM were not inferior compared to controls. All specimens revealed a brittle failure behavior. Fracture surfaces were graded according to their mineralized collagen fibers (MCF) orientation into axial, mixed, and transversal fracture surface types (FST). Furthermore, tissue mineral density (TMD) of the biopsy cortices was extracted from micro–computed tomogra[hy (μCT) images. Both FST and TMD are significant factors to predict loading modulus and ultimate strength with an adjusted <i>R</i>² of 0.556 (<i>p</i> = 2.65e−05) and 0.46 (<i>p</i> = 2.2e−04), respectively. The influence of MCF orientation and DBM on the mechanical properties of the neighboring ECM was further verified with quantitative polarized Raman spectroscopy (qPRS) and site-matched nanoindentation. MCF orientation and DBM were extracted from the qPRS spectrum, and a second mechanical model was developed to predict the indentation modulus with MCF orientation and DBM (<i>R</i>² = 67.4%, <i>p</i> = 7.73e−07). The tensile mechanical properties of the cortical bone ECM of two OI iliac crest biopsies are not lower than the one from a healthy and are primarily dependent on MCF orientation and DBM. © 2023 The Authors. <i>JBMR Plus</i> published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"7 12","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://asbmr.onlinelibrary.wiley.com/doi/epdf/10.1002/jbm4.10826","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136213616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zucker Diabetic-Sprague Dawley Rats Have Impaired Peri-Implant Bone Formation, Matrix Composition, and Implant Fixation Strength","authors":"Kyle D Anderson,&nbsp;Christian Beckmann,&nbsp;Saskia Heermant,&nbsp;Frank C Ko,&nbsp;Bryan Dulion,&nbsp;Imad Tarhoni,&nbsp;Jeffrey A Borgia,&nbsp;Amarjit S Virdi,&nbsp;Markus A Wimmer,&nbsp;D Rick Sumner,&nbsp;Ryan D Ross","doi":"10.1002/jbm4.10819","DOIUrl":"https://doi.org/10.1002/jbm4.10819","url":null,"abstract":"<p>An increasing number of patients with type 2 diabetes (T2DM) will require total joint replacement (TJR) in the next decade. T2DM patients are at increased risk for TJR failure, but the mechanisms are not well understood. The current study used the Zucker Diabetic-Sprague Dawley (ZDSD) rat model of T2DM with Sprague Dawley (SPD) controls to investigate the effects of intramedullary implant placement on osseointegration, peri-implant bone structure and matrix composition, and fixation strength at 2 and 10 weeks post-implant placement. Postoperative inflammation was assessed with circulating MCP-1 and IL-10 2 days post-implant placement. In addition to comparing the two groups, stepwise linear regression modeling was performed to determine the relative contribution of glucose, cytokines, bone formation, bone structure, and bone matrix composition on osseointegration and implant fixation strength. ZDSD rats had decreased peri-implant bone formation and reduced trabecular bone volume per total volume compared with SPD controls. The osseointegrated bone matrix of ZDSD rats had decreased mineral-to-matrix and increased crystallinity compared with SPD controls. Osseointegrated bone volume per total volume was not different between the groups, whereas implant fixation was significantly decreased in ZDSD at 2 weeks but not at 10 weeks. A combination of trabecular mineral apposition rate and postoperative MCP-1 levels explained 55.6% of the variance in osseointegration, whereas cortical thickness, osseointegration mineral apposition rate, and matrix compositional parameters explained 69.2% of the variance in implant fixation strength. The results support the growing recognition that both peri-implant structure and matrix composition affect implant fixation and suggest that postoperative inflammation may contribute to poor outcomes after TJR surgeries in T2DM patients. © 2023 The Authors. <i>JBMR Plus</i> published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"7 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://asbmr.onlinelibrary.wiley.com/doi/epdf/10.1002/jbm4.10819","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134805109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interrogating Causal Effects of Body Composition and Puberty-Related Risk Factors on Adolescent Idiopathic Scoliosis: A Two-Sample Mendelian Randomization Study","authors":"Faegheh Ghanbari,&nbsp;Nao Otomo,&nbsp;Isabel Gamache,&nbsp;Takuro Iwami,&nbsp;Yoshinao Koike,&nbsp;Anas M. Khanshour,&nbsp;Shiro Ikegawa,&nbsp;Carol A. Wise,&nbsp;Chikashi Terao,&nbsp;Despoina Manousaki","doi":"10.1002/jbm4.10830","DOIUrl":"10.1002/jbm4.10830","url":null,"abstract":"<p>Adolescent idiopathic scoliosis (AIS) is the most common form of pediatric musculoskeletal disorder. Observational studies have pointed to several risk factors for AIS, but almost no evidence exists to support their causal association with AIS. Here, we applied Mendelian randomization (MR), known to limit bias from confounding and reverse causation, to investigate causal associations between body composition and puberty-related exposures and AIS risk in Europeans and Asians. For our two-sample MR studies, we used single nucleotide polymorphisms (SNPs) associated with body mass index (BMI), waist-hip ratio, lean mass, childhood obesity, bone mineral density (BMD), 25-hydroxyvitamin D (25OHD), age at menarche, and pubertal growth in large European genome-wide association studies (GWAS), and with adult osteoporosis risk and age of menarche in Biobank Japan. We extracted estimates of the aforementioned SNPs on AIS risk from the European or Asian subsets of the largest multiancestry AIS GWAS (<i>N</i> = 7956 cases/88,459 controls). The results of our inverse variance-weighted (IVW) MR estimates suggest no causal association between the aforementioned risk factors and risk of AIS. Pleiotropy-sensitive MR methods yielded similar results. However, restricting our analysis to European females with AIS, we observed a causal association between estimated BMD and the risk of AIS (IVW odds ratio for AIS = 0.1, 95% confidence interval 0.01 to 0.7, <i>p</i> = 0.02 per SD increase in estimated BMD), but this association was no longer significant after adjusting for BMI, body fat mass, and 25OHD and remained significant after adjusting for age at menarche in multivariable MR. In conclusion, we demonstrated a protective causal effect of BMD on AIS risk in females of European ancestry, but this effect was modified by BMI, body fat mass, and 25OHD levels. Future MR studies using larger AIS GWAS are needed to investigate small effects of the aforementioned exposures on AIS. © 2023 The Authors. <i>JBMR Plus</i> published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"7 12","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://asbmr.onlinelibrary.wiley.com/doi/epdf/10.1002/jbm4.10830","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135482349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstracts from the 50th International Musculoskeletal Biology Workshop, July 22 – 27, 2023, Midway, Utah","authors":"","doi":"10.1002/jbm4.10827","DOIUrl":"https://doi.org/10.1002/jbm4.10827","url":null,"abstract":"<p>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"7 S7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm4.10827","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50119383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}