The amino acid sensor Eif2ak4/GCN2 is required for proliferation of osteoblast progenitors in mice
AbstractSkeletal stem/progenitor cells (SSPC) are critical regulators of bone homeostasis by providing a continuous supply of osteoblasts throughout life. In response to inductive signals, SSPC proliferate prior to osteoblast differentiation. Proliferation requires the duplication of all cellular components prior to cell division. This imposes a unique biosynthetic requirement for amino acids that can be used for biomass production. Thus, the ability to sense and respond to amino acid availability is likely a major determinant for proliferation. Using a cellular and genetic approach, we demonstrate the amino acid sensor GC...
Source: Journal of Bone and Mineral Research - May 26, 2020 Category: Orthopaedics Authors: Guoli Hu, Yilin Yu, Yuning J. Tang, Colleen Wu, Fanxin Long, Courtney M. Karner Tags: Original Article Source Type: research

Disruption of BMP signaling prevents hyperthyroidism ‑induced bone loss in male mice
AbstractThyroid hormones (TH) are key regulators of bone health, and TH excess in mice causes high bone turnover ‐mediated bone loss. However, the underlying molecular mechanisms of TH actions on bone remain poorly defined. Here, we tested the hypothesis whether TH mediate their effects via the pro‐osteogenic bone morphogenetic protein (BMP) signaling pathwayin vitro andin vivo. Primary murine osteoblasts treated with 3,3 ’,5‐triiodo‐L‐thyronine (T3) showed an enhanced differentiation potential, which was associated with activated canonical BMP/SMAD signaling reflected by SMAD1/5/8 phosphorylation. Blocking...
Source: Journal of Bone and Mineral Research - May 26, 2020 Category: Orthopaedics Authors: Franziska Lademann, Heike Weidner, Elena Tsourdi, Ravi Kumar, Eddy Rijntjes, Josef K öhrle, Lorenz C. Hofbauer, Martina Rauner Tags: Original Article Source Type: research

Unique, gender ‐dependent serum microRNA profile in PLS3 gene‐related osteoporosis
ABSTRACTPlastin 3 (PLS3), encoded byPLS3, is a newly recognized regulator of bone metabolism and mutations in the encoding gene result in severe childhood ‐onset osteoporosis. Since an X chromosomal gene,PLS3 mutation ‐positive males are typically more severely affected while females portray normal to increased skeletal fragility. Despite the severe skeletal pathology, conventional metabolic bone markers tend to be normal and are thus insufficient in diagnosing or monitoring patients. Our study aimed to explore serum microRNA (miRNA) concentrations in subjects with defective PLS3 function to identify novel markers that...
Source: Journal of Bone and Mineral Research - May 26, 2020 Category: Orthopaedics Authors: Riikka E. M äkitie, Matthias Hackl, Moritz Weigl, Amelie Frischer, Anders Kämpe, Alice Costantini, Johannes Grillari, Outi Mäkitie Tags: Original Article Source Type: research

T ‐Score as an Indicator of Fracture Risk During Treatment With Romosozumab or Alendronate in the ARCH Trial
ABSTRACTIn the Active ‐Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) clinical trial (NCT01631214), 1 year of romosozumab followed by alendronate reduced the risk of vertebral and nonvertebral fractures compared to alendronate alone in women with prevalent fracture. We perform ed post hoc analyses of data from patients in ARCH (romosozumab,n =  1739; alendronate,n =  1726) who had a baseline BMD measurement and received at least one open‐label alendronate dose. We evaluated 1‐year mean BMD and correspondingT‐score changes; proportions of patients achievi...
Source: Journal of Bone and Mineral Research - May 22, 2020 Category: Orthopaedics Authors: Felicia Cosman, E Michael Lewiecki, Peter R Ebeling, Eric Hesse, Nicola Napoli, Toshio Matsumoto, Daria B Crittenden, Maria Rojeski, Wenjing Yang, Cesar Libanati, Serge Ferrari Tags: Original Article Source Type: research

Circulating Osteocalcin ‐Positive Cells as a Novel Diagnostic Biomarker for Bone Metastasis in Breast Cancer Patients
ABSTRACTCurrent diagnosis of bone metastasis (BM) in breast cancer relies on structural changes of bone that occur only in the advanced stage. A sensitive biomarker for detecting early progression of bone metastasis is urgently required. We performed clinical and preclinical studies to investigate diagnostic value of circulating osteocalcin ‐positive cells (cOC) in breast cancer bone metastasis. Metastatic breast cancer patients (n =  92) with or without bone metastasis (ie, BM+ or BM–) were enrolled, and cOC were measured at enrollment. Patients were followed up for bone metastasis progression for 18 &thins...
Source: Journal of Bone and Mineral Research - May 20, 2020 Category: Orthopaedics Authors: Kyung ‐Hun Lee, Kyoung Jin Lee, Tae‐Yong Kim, Febby Hutomo, Hyun Jin Sun, Gi Jeong Cheon, Serk In Park, Sun Wook Cho, Seock‐Ah Im Tags: Original Article Source Type: research

Intracellular accumulation of advanced glycation end ‐products induces osteoblast apoptosis via endoplasmic reticulum stress
This article is protected by copyright. All rights reserved. (Source: Journal of Bone and Mineral Research)
Source: Journal of Bone and Mineral Research - May 19, 2020 Category: Orthopaedics Authors: Ryusuke Suzuki, Yukio Fujiwara, Mitsuru Saito, Shoutaro Arakawa, Jun ‐ichi Shirakawa, Mikihiro Yamanaka, Yoshihiro Komohara, Keishi Marumo, Ryoji Nagai Tags: Original Article Source Type: research

Single cell rna sequencing of calvarial and long bone endocortical cells
This article is protected by copyright. All rights reserved. (Source: Journal of Bone and Mineral Research)
Source: Journal of Bone and Mineral Research - May 19, 2020 Category: Orthopaedics Authors: Ugur M. Ayturk, Joseph P. Scollan, Didem Goz Ayturk, Eun Sung Suh, Alexander Vesprey, Christina M. Jacobsen, Paola Divieti Pajevic, Matthew L. Warman Tags: Original Article Source Type: research

Intracellular accumulation of advanced glycation end ‐products induces osteoblast apoptosis via endoplasmic reticulum stress
This article is protected by copyright. All rights reserved. (Source: Journal of Bone and Mineral Research)
Source: Journal of Bone and Mineral Research - May 19, 2020 Category: Orthopaedics Authors: Ryusuke Suzuki, Yukio Fujiwara, Mitsuru Saito, Shoutaro Arakawa, Jun ‐ichi Shirakawa, Mikihiro Yamanaka, Yoshihiro Komohara, Keishi Marumo, Ryoji Nagai Tags: Original Article Source Type: research

Single cell rna sequencing of calvarial and long bone endocortical cells
This article is protected by copyright. All rights reserved. (Source: Journal of Bone and Mineral Research)
Source: Journal of Bone and Mineral Research - May 19, 2020 Category: Orthopaedics Authors: Ugur M. Ayturk, Joseph P. Scollan, Didem Goz Ayturk, Eun Sung Suh, Alexander Vesprey, Christina M. Jacobsen, Paola Divieti Pajevic, Matthew L. Warman Tags: Original Article Source Type: research

Bone ‐Specific Drugs and Osteonecrosis of Sites Other Than the Jaw: A Nationwide Cohort Study
ABSTRACTBone ‐specific drugs (BSDs) increase the risk of osteonecrosis of the jaw (ONJ), but whether they increase the risk of osteonecrosis at other sites is not known. Two studies, a cohort study and a case–control study, were conducted using registry data on everyone who was residing in Sweden on December 31, 2005, and who was 50 years of age or older at the time (n =  3,523,912). In the cohort study, individuals prescribed a BSD during the period 2006–2017 (n =  217,387) were 1:1 matched with nonusers on birth year, sex, hip fracture status, and Swedish or foreign origin. In the case&...
Source: Journal of Bone and Mineral Research - May 18, 2020 Category: Orthopaedics Authors: Peter Nordstr öm, Jonathan Bergman, Marcel Ballin, Sabine Björk, Anna Nordström Tags: Original Article Source Type: research

Scientific Editing in the COVID ‐19 Era – Personal Vignettes from the JBMR Editors
Journal of Bone and Mineral Research, Accepted Article. (Source: Journal of Bone and Mineral Research)
Source: Journal of Bone and Mineral Research - May 15, 2020 Category: Orthopaedics Authors: Roberto Civitelli Tags: Editorial Source Type: research

Osteoporosis Management in the Era of COVID ‐19
AbstractOsteoporosis is a chronic condition which reflects reduced bone strength and an associated increased risk for fracture. As a chronic condition, osteoporosis generally requires sustained medical intervention(s) to limit the risks for additional bone loss, compromise of skeletal integrity, and fracture occurrence. Further complicating this issue is the fact that the abrupt cessation of some therapies can be associated with an increased risk for harm. It is in this context that the COVID ‐19 pandemic has brought unprecedented disruption to the provision of healthcare globally, including near universal requirements f...
Source: Journal of Bone and Mineral Research - May 14, 2020 Category: Orthopaedics Authors: Elaine W Yu, Elena Tsourdi, Bart L Clarke, Douglas C Bauer, Matthew T Drake Tags: Perspective Source Type: research

The Effect Of Fall Biomechanics On Risk For Hip Fracture In Older Adults: A Cohort Study Of Video ‐Captured Falls In Long‐Term Care
ABSTRACTOver 95% of hip fractures in older adults are caused by falls, yet only 1 –2% of falls result in hip fracture. Our current understanding of the types of falls that lead to hip fracture is based on reports by the faller or witness. We analyzed videos of real‐life falls in long‐term care to provide objective evidence on the factors that separate falls that result in h ip fracture from falls that do not. Between 2007–2018, we video‐captured 2377 falls by 646 residents in two long‐term care facilities. Hip fracture was documented in 30 falls. We analyzed each video with a structured questionnaire, a...
Source: Journal of Bone and Mineral Research - May 13, 2020 Category: Orthopaedics Authors: Yijian Yang, Vicki Komisar, Nataliya Shishov, Bryan Lo, Alexandra MB Korall, Fabio Feldman, Stephen N Robinovitch Tags: Original Article Source Type: research

Bone mass, bone microstructure and biomechanics in patients with hand osteoarthritis
AbstractBackgroundThe impact of primary hand osteoarthritis (HOA) on bone mass, microstructure and biomechanics in the affected skeletal regions is largely unknown.MethodsHOA patients and healthy controls (HC) underwent high ‐resolution peripheral quantitative computed tomography (HR‐pQCT). We measured total, trabecular and cortical volumetric bone mineral densities (vBMD), microstructural attributes and performed micro‐finite element analysis for bone strength. Failure load and scaled multivariate outcome matrice s from distal radius and 2nd metacarpal (MCP 2) head measurements were analyzed using multiple linear re...
Source: Journal of Bone and Mineral Research - May 12, 2020 Category: Orthopaedics Authors: David Simon, Koray Tascilar, Sara Unbehend, Sara Bayat, Andreas Berlin, Anna ‐Maria Liphardt, Timo Meinderink, Juergen Rech, Axel J Hueber, Georg Schett, Arnd Kleyer Tags: Original Article Source Type: research

Bone microarchitecture assessed by Trabecular Bone Score is independent of mobility level or height in pediatric patients with cerebral palsy
AbstractBone strength and fracture risk do not only depend on bone density, but also on bone structure. The Trabecular Bone Score (TBS) evaluates homogeneity of bone microarchitecture indirectly by measuring gray ‐level variations of two‐dimensional DXA images. Although TBS is well‐established for adults, there have been only few publications in pediatrics. In this monocentric retrospective analysis, we investigated TBS in children and adolescents with Cerebral Palsy (CP), a patient group vulnerable to low bone mineral mass due to impaired mobility. The influence of different parameters on TBS and areal BMD (aBMD) we...
Source: Journal of Bone and Mineral Research - May 12, 2020 Category: Orthopaedics Authors: Mirko Rehberg, Manuela Azim, Kyriakos Martakis, Renaud Winzenrieth, Heike Hoyer ‐Kuhn, Eckhard Schoenau, Oliver Semler, Ibrahim Duran Tags: Original Article Source Type: research

Bone mass, bone microstructure and biomechanics in patients with hand osteoarthritis
AbstractBackgroundThe impact of primary hand osteoarthritis (HOA) on bone mass, microstructure and biomechanics in the affected skeletal regions is largely unknown.MethodsHOA patients and healthy controls (HC) underwent high ‐resolution peripheral quantitative computed tomography (HR‐pQCT). We measured total, trabecular and cortical volumetric bone mineral densities (vBMD), microstructural attributes and performed micro‐finite element analysis for bone strength. Failure load and scaled multivariate outcome matrice s from distal radius and 2nd metacarpal (MCP 2) head measurements were analyzed using multiple linear re...
Source: Journal of Bone and Mineral Research - May 12, 2020 Category: Orthopaedics Authors: David Simon, Koray Tascilar, Sara Unbehend, Sara Bayat, Andreas Berlin, Anna ‐Maria Liphardt, Timo Meinderink, Juergen Rech, Axel J Hueber, Georg Schett, Arnd Kleyer Tags: Original Article Source Type: research

Bone microarchitecture assessed by Trabecular Bone Score is independent of mobility level or height in pediatric patients with cerebral palsy
AbstractBone strength and fracture risk do not only depend on bone density, but also on bone structure. The Trabecular Bone Score (TBS) evaluates homogeneity of bone microarchitecture indirectly by measuring gray ‐level variations of two‐dimensional DXA images. Although TBS is well‐established for adults, there have been only few publications in pediatrics. In this monocentric retrospective analysis, we investigated TBS in children and adolescents with Cerebral Palsy (CP), a patient group vulnerable to low bone mineral mass due to impaired mobility. The influence of different parameters on TBS and areal BMD (aBMD) we...
Source: Journal of Bone and Mineral Research - May 12, 2020 Category: Orthopaedics Authors: Mirko Rehberg, Manuela Azim, Kyriakos Martakis, Renaud Winzenrieth, Heike Hoyer ‐Kuhn, Eckhard Schoenau, Oliver Semler, Ibrahim Duran Tags: Original Article Source Type: research

Issue Information ‐Declaration of Helsinki
Journal of Bone and Mineral Research, Volume 35, Issue 5, Page BMi-BMii, May 2020. (Source: Journal of Bone and Mineral Research)
Source: Journal of Bone and Mineral Research - May 11, 2020 Category: Orthopaedics Tags: Issue Information ‐Declaration of Helsinki Source Type: research

Ed Bd, Masthead, Comm List and TOC
Journal of Bone and Mineral Research, Volume 35, Issue 5, Page FMi-FMv, May 2020. (Source: Journal of Bone and Mineral Research)
Source: Journal of Bone and Mineral Research - May 11, 2020 Category: Orthopaedics Tags: Issue Information Source Type: research

Journal of Bone and Mineral Research: Volume 35, Number 5, May 2020
Journal of Bone and Mineral Research, Volume 35, Issue 5, Page C1-C1, May 2020. (Source: Journal of Bone and Mineral Research)
Source: Journal of Bone and Mineral Research - May 11, 2020 Category: Orthopaedics Tags: Cover Source Type: research

Ed Bd, Masthead, Comm List and TOC
Journal of Bone and Mineral Research, Volume 35, Issue 5, Page FMi-FMv, May 2020. (Source: Journal of Bone and Mineral Research)
Source: Journal of Bone and Mineral Research - May 11, 2020 Category: Orthopaedics Tags: Issue Information Source Type: research

Issue Information ‐Declaration of Helsinki
Journal of Bone and Mineral Research, Volume 35, Issue 5, Page BMi-BMii, May 2020. (Source: Journal of Bone and Mineral Research)
Source: Journal of Bone and Mineral Research - May 11, 2020 Category: Orthopaedics Tags: Issue Information ‐Declaration of Helsinki Source Type: research

Journal of Bone and Mineral Research: Volume 35, Number 5, May 2020
Journal of Bone and Mineral Research, Volume 35, Issue 5, Page C1-C1, May 2020. (Source: Journal of Bone and Mineral Research)
Source: Journal of Bone and Mineral Research - May 11, 2020 Category: Orthopaedics Tags: Cover Source Type: research

The Effect of Biochemical Remission on Bone Metabolism in Cushing's Syndrome: A 2 ‐Year Follow‐Up Study
This study shows that the phase immediately after surgical remission from endogenous CS is characterized by a high rate of bone turnover resulting in a striking net increase in bone mineral density in the majority of patients. © 2020 The Authors.Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research. (Source: Journal of Bone and Mineral Research)
Source: Journal of Bone and Mineral Research - May 8, 2020 Category: Orthopaedics Authors: Leah T Braun, Julia Fazel, Stephanie Zopp, Sarina Benedix, Andrea Osswald ‐Kopp, Anna Riester, German Rubinstein, Max Seidensticker, Felix Beuschlein, Michael Drey, Martin Bidlingmaier, Ralf Schmidmaier, Martin Reincke Tags: Original Article Source Type: research

Fgfr3 is a positive regulator of osteoblast expansion and differentiation during zebrafish skull vault development
AbstractGain or loss ‐of‐function mutations in fibroblast growth factor receptor 3 (FGFR3) result in cranial vault defects highlighting the protein’s role in membranous ossification. Zebrafish express high levels offgfr3 during skull development; in order to study FGFR3 ’s role in cranial vault development, we generated the firstfgfr3 loss ‐of‐function zebrafish(fgfr3lof/lof). The mutant fish exhibited major changes in the craniofacial skeleton, with a lack of sutures, abnormal frontal and parietal bones, and the presence of ectopic bones. Integrated analyses (in vivo imaging, and single ‐cell RNA seq...
Source: Journal of Bone and Mineral Research - May 7, 2020 Category: Orthopaedics Authors: Emilie Dambroise, Ivan Ktorza, Alessandro Brombin, Ghaith Abdessalem, Joanne Edouard, Marine Luka, Imke Fiedler, Olivia Binder, Olivier Pelle, E. Elizabeth Patton, Bj örn Busse, Mickaël Menager, Frederic Sohm, Laurence Legeai‐Mallet Tags: Original Article Source Type: research

Bone Specific Drugs and Osteonecrosis of Sites Other than the Jaw: A Nationwide Cohort Study
ABSTRACTBone specific drugs (BSDs) increase the risk of osteonecrosis of the jaw, but whether they increase the risk of osteonecrosis at other sites is not known. Two studies, a cohort study and a case –control study, were conducted using registry data on everyone who was residing in Sweden on December 31, 2005, and who was 50 years of age or older at the time (N = 3,523,912). In the cohort study, individuals prescribed a BSD during 2006–2017 (n = 217 387) were 1:1 matched with nonusers on birth year, sex, hip fracture status and Swedish or foreign origin. In the case–control st...
Source: Journal of Bone and Mineral Research - May 7, 2020 Category: Orthopaedics Authors: Peter Nordstr öm, Jonathan Bergman, Marcel Ballin, Sabine Björk, Anna Nordström Tags: Original Article Source Type: research

Circulating Osteocalcin ‐Positive Cells as a Novel Diagnostic Biomarker for Bone Metastasis in Breast Cancer Patients
ABSTRACTCurrent diagnosis of bone metastasis (BM) in breast cancer relies on structural changes of bone that occurs only in the advanced stage. A sensitive biomarker for detecting early progression of bone metastasis is urgently required. We performed clinical and pre ‐clinical studies to investigate diagnostic value of circulating osteocalcin‐positive cells (cOC) in breast cancer bone metastasis. Metastatic breast cancer patients (n = 92) with or without bone metastasis (i.e. BM+ or BM‐) were enrolled, and cOC were measured at enrollment. Patients were followed up for bone metastasis progression for 18&t...
Source: Journal of Bone and Mineral Research - May 7, 2020 Category: Orthopaedics Authors: Kyung ‐Hun Lee, Kyoung Jin Lee, Tae‐Yong Kim, Febby Hutomo, Hyun Jin Sun, Gi Jeong Cheon, Serk In Park, Sun Wook Cho, Seock‐Ah Im Tags: Original Article Source Type: research

Fgfr3 is a positive regulator of osteoblast expansion and differentiation during zebrafish skull vault development
AbstractGain or loss ‐of‐function mutations in fibroblast growth factor receptor 3 (FGFR3) result in cranial vault defects highlighting the protein’s role in membranous ossification. Zebrafish express high levels offgfr3 during skull development; in order to study FGFR3 ’s role in cranial vault development, we generated the firstfgfr3 loss ‐of‐function zebrafish(fgfr3lof/lof). The mutant fish exhibited major changes in the craniofacial skeleton, with a lack of sutures, abnormal frontal and parietal bones, and the presence of ectopic bones. Integrated analyses (in vivo imaging, and single ‐cell RNA seq...
Source: Journal of Bone and Mineral Research - May 7, 2020 Category: Orthopaedics Authors: Emilie Dambroise, Ivan Ktorza, Alessandro Brombin, Ghaith Abdessalem, Joanne Edouard, Marine Luka, Imke Fiedler, Olivia Binder, Olivier Pelle, E. Elizabeth Patton, Bj örn Busse, Mickaël Menager, Frederic Sohm, Laurence Legeai‐Mallet Tags: Original Article Source Type: research

Nitrates Do Not Affect Bone Density or Bone Turnover in Postmenopausal Women: A Randomized Controlled Trial
ABSTRACTOrganic nitrates have been reported to have significant effects on bone mineral density (BMD) and bone turnover in previous clinical trials. However, results are inconsistent and some trials with strikingly positive results have been retracted because of scientific misconduct. As preparation for a potential fracture prevention study, we set out to determine the lowest effective dose and the most effective and acceptable nitrate preparation. We undertook a 1 ‐year, double‐blind, randomized, placebo‐controlled trial of three different nitrate preparations and two different doses in osteopenic postmenopausal wom...
Source: Journal of Bone and Mineral Research - May 5, 2020 Category: Orthopaedics Authors: Mark J Bolland, Meaghan E House, Anne M Horne, Veronica Pinel, Greg D Gamble, Andrew Grey, Ian R Reid Tags: Clinical Trial Source Type: research

Mice carrying a ubiquitous R235W mutation of Wnt1 display a bone ‐specific phenotype
ABSTRACTSince a key function of Wnt1 in brain development was established early on through the generation of non ‐viableWnt1‐deficient mice, it was initially surprising thatWNT1 mutations were found to cause either early ‐onset osteoporosis (EOOP) or osteogenesis imperfecta type XV (OI‐XV). The deduced function of Wnt1 as an osteoanabolic factor has been confirmed in various mouse models with bone‐specific inactivation or over‐expression, but mice carrying disease‐causingWnt1 mutations have not yet been described. Triggered by the clinical analysis of EOOP patients carrying a heterozygousWNT1 mutation (p.R235...
Source: Journal of Bone and Mineral Research - May 5, 2020 Category: Orthopaedics Authors: Timur Alexander Yorgan, Tim Rolvien, Julian St ürznickel, Nele Vollersen, Fabiola Lange, Wenbo Zhao, Anke Baranowsky, Lana Rosenthal, Irm Hermans‐Borgmeyer, Ahmed Sharaf, Meliha Karsak, Jean‐Pierre David, Ralf Oheim, Michael Amling, Tho Tags: Original Article Source Type: research

Nitrates Do Not Affect Bone Density or Bone Turnover in Postmenopausal Women: A Randomized Controlled Trial
ABSTRACTOrganic nitrates have been reported to have significant effects on bone mineral density (BMD) and bone turnover in previous clinical trials. However, results are inconsistent and some trials with strikingly positive results have been retracted because of scientific misconduct. As preparation for a potential fracture prevention study, we set out to determine the lowest effective dose and the most effective and acceptable nitrate preparation. We undertook a 1 ‐year, double‐blind, randomized, placebo‐controlled trial of three different nitrate preparations and two different doses in osteopenic postmenopausal wom...
Source: Journal of Bone and Mineral Research - May 5, 2020 Category: Orthopaedics Authors: Mark J Bolland, Meaghan E House, Anne M Horne, Veronica Pinel, Greg D Gamble, Andrew Grey, Ian R Reid Tags: Clinical Trial Source Type: research

Mice carrying a ubiquitous R235W mutation of Wnt1 display a bone ‐specific phenotype
ABSTRACTSince a key function of Wnt1 in brain development was established early on through the generation of non ‐viableWnt1‐deficient mice, it was initially surprising thatWNT1 mutations were found to cause either early ‐onset osteoporosis (EOOP) or osteogenesis imperfecta type XV (OI‐XV). The deduced function of Wnt1 as an osteoanabolic factor has been confirmed in various mouse models with bone‐specific inactivation or over‐expression, but mice carrying disease‐causingWnt1 mutations have not yet been described. Triggered by the clinical analysis of EOOP patients carrying a heterozygousWNT1 mutation (p.R235...
Source: Journal of Bone and Mineral Research - May 5, 2020 Category: Orthopaedics Authors: Timur Alexander Yorgan, Tim Rolvien, Julian St ürznickel, Nele Vollersen, Fabiola Lange, Wenbo Zhao, Anke Baranowsky, Lana Rosenthal, Irm Hermans‐Borgmeyer, Ahmed Sharaf, Meliha Karsak, Jean‐Pierre David, Ralf Oheim, Michael Amling, Tho Tags: Original Article Source Type: research

LncRNA Neat1 Stimulates Osteoclastogenesis via Sponging miR ‐7
ABSTRACTIncreasing evidence uncover the essential role of lncRNAs in bone metabolism and the association of lncRNA with genetic risk of osteoporosis. However, whether lncRNA Neat1 is involved remains largely unknown. In the present study, we found that Neat1 is induced by osteoclastic differentiation stimuli. Knockdown of Neat1 attenuates osteoclast formation whereas overexpression of Neat1 accelerates osteoclast formation.In vivo evidence demonstrated that enhanced Neat1 expression stimulates osteoclastogenesis and reduces bone mass in mice. Mechanically, Neat1 competitively binds with miR ‐7 and blocks its function for...
Source: Journal of Bone and Mineral Research - April 30, 2020 Category: Orthopaedics Authors: Yan Zhang, Xiao ‐Feng Chen, Jing Li, Fang He, Xu Li, Yan Guo Tags: Original Article Source Type: research

Release of CXCL12 from Apoptotic Skeletal Cells Contributes to Bone Growth Defects Following Dexamethasone Therapy in Rats
Journal of Bone and Mineral Research, EarlyView. (Source: Journal of Bone and Mineral Research)
Source: Journal of Bone and Mineral Research - April 30, 2020 Category: Orthopaedics Authors: Qian Tang, Yu ‐Wen Su, Chia‐Ming Fan, Rosa Chung, Mohammadhossein Hassanshahi, Yaser Peymanfar, Cory J Xian Tags: Erratum Source Type: research

LncRNA Neat1 Stimulates Osteoclastogenesis via Sponging miR ‐7
ABSTRACTIncreasing evidence uncover the essential role of lncRNAs in bone metabolism and the association of lncRNA with genetic risk of osteoporosis. However, whether lncRNA Neat1 is involved remains largely unknown. In the present study, we found that Neat1 is induced by osteoclastic differentiation stimuli. Knockdown of Neat1 attenuates osteoclast formation whereas overexpression of Neat1 accelerates osteoclast formation.In vivo evidence demonstrated that enhanced Neat1 expression stimulates osteoclastogenesis and reduces bone mass in mice. Mechanically, Neat1 competitively binds with miR ‐7 and blocks its function for...
Source: Journal of Bone and Mineral Research - April 30, 2020 Category: Orthopaedics Authors: Yan Zhang, Xiao ‐Feng Chen, Jing Li, Fang He, Xu Li, Yan Guo Tags: Original Article Source Type: research

Release of CXCL12 from Apoptotic Skeletal Cells Contributes to Bone Growth Defects Following Dexamethasone Therapy in Rats
Journal of Bone and Mineral Research, EarlyView. (Source: Journal of Bone and Mineral Research)
Source: Journal of Bone and Mineral Research - April 30, 2020 Category: Orthopaedics Authors: Qian Tang, Yu ‐Wen Su, Chia‐Ming Fan, Rosa Chung, Mohammadhossein Hassanshahi, Yaser Peymanfar, Cory J Xian Tags: Erratum Source Type: research

Effects of High ‐Intensity Resistance Training on Osteopenia and Sarcopenia Parameters in Older Men with Osteosarcopenia—One‐Year Results of the Randomized Controlled Franconian Osteopenia and Sarcopenia Trial (FrOST)
ABSTRACTDynamic resistance exercise (DRT) might be the most promising agent for fighting sarcopenia in older people. However, the positive effect of DRT on osteopenia/osteoporosis in men has still to be confirmed. To evaluate the effect of low ‐volume/high‐intensity (HIT)‐DRT on bone mineral density (BMD) and skeletal muscle mass index (SMI) in men with osteosarcopenia, we initiated the Franconian Osteopenia and Sarcopenia Trial (FrOST). Forty‐three sedentary community‐dwelling older men (aged 73 to 91 years) with osteopenia/o steoporosis and SMI‐based sarcopenia were randomly assigned to a HIT‐RT exer...
Source: Journal of Bone and Mineral Research - April 28, 2020 Category: Orthopaedics Authors: Wolfgang Kemmler, Matthias Kohl, Michael Fr öhlich, Franz Jakob, Klaus Engelke, Simon Stengel, Daniel Schoene Tags: Clinical Trial Source Type: research

Visualization of mineral ‐targeted alkaline phosphatase binding to sites of calcification in vivo
ABSTRACTA mineral ‐targeted form of recombinant tissue‐nonspecific alkaline phosphatase (TNAP), asfotase alfa, was approved multi‐nationally as an enzyme replacement therapy for hypophosphatasia in 2015. Two reports to‐date have shown evidence of binding of this drug to mineralizing tissues using histochemist ry and immunohistochemistry. Here, we sought to expand on those earlier studies by directly visualizing thein vivo binding of asfotase alfa conjugated with AnaTag HiLyte Fluor 750 or Alexa Fluor 647 fluorescent dye to sites of skeletal/dental mineralization and ectopic calcification. We utilized 40 ‐day‐ol...
Source: Journal of Bone and Mineral Research - April 28, 2020 Category: Orthopaedics Authors: F. Amadeu de Oliveira, S. Narisawa, M. Bottini, J. L. Mill án Tags: Original Article Source Type: research

Effects of High ‐Intensity Resistance Training on Osteopenia and Sarcopenia Parameters in Older Men with Osteosarcopenia—One‐Year Results of the Randomized Controlled Franconian Osteopenia and Sarcopenia Trial (FrOST)
ABSTRACTDynamic resistance exercise (DRT) might be the most promising agent for fighting sarcopenia in older people. However, the positive effect of DRT on osteopenia/osteoporosis in men has still to be confirmed. To evaluate the effect of low ‐volume/high‐intensity (HIT)‐DRT on bone mineral density (BMD) and skeletal muscle mass index (SMI) in men with osteosarcopenia, we initiated the Franconian Osteopenia and Sarcopenia Trial (FrOST). Forty‐three sedentary community‐dwelling older men (aged 73 to 91 years) with osteopenia/o steoporosis and SMI‐based sarcopenia were randomly assigned to a HIT‐RT exer...
Source: Journal of Bone and Mineral Research - April 28, 2020 Category: Orthopaedics Authors: Wolfgang Kemmler, Matthias Kohl, Michael Fr öhlich, Franz Jakob, Klaus Engelke, Simon Stengel, Daniel Schoene Tags: Clinical Trial Source Type: research

Functional Characterization of PHEX Gene Variants in Children with X ‐linked Hypophosphatemic Rickets Shows no Evidence of Genotype‐Phenotype Correlation
AbstractX ‐linked hypophosphatemia (XLHR) is caused by loss‐of‐function mutations in the phosphate regulating endopeptidase homolog X‐linked (PHEX) gene. Considerable controversy exists regarding genotype‐phenotype correlations in XLHR. The present study describes the clinical features and molecular genetic bases of 53 pediatric patients with XLHR. Overall, 47 different mutations were identified, of which 27 were not previously described in the literature or entered in the HGMD. A high prevalence (72.34%) of truncating variants was observed in XLHR patients. The clinical presentation and sever ity of XLHR did not...
Source: Journal of Bone and Mineral Research - April 24, 2020 Category: Orthopaedics Authors: Bixia Zheng, Chunli Wang, Qiuxia Chen, Ruochen Che, Yugen Sha, Fei Zhao, Guixia Ding, Wei Zhou, Zhanjun Jia, Songming Huang, Ying Chen, Aihua Zhang Tags: Original Article Source Type: research

Thrombomodulin functional domains support osteoblast differentiation and bone healing in diabetes in mice
AbstractThrombomodulin (TM) is a transmembrane glycoprotein that contains five functional domains. Soluble TM (sTM), comprising extracellular domains TMD1 (lectin ‐like), TMD2 (EGF‐like repeat containing) and TMD3 (serine‐threonine rich), can be shed from cells by the intramembrane protease rhomboid‐like‐2 (RHBDL2). TM is expressed by osteoblasts, yet its role there has not been determined. Herein we aimed to investigate the properties of TM and its domains in osteoblast function and bone repair following injury in diabetes. In response to a scratch injury of cultured osteoblast‐like MG63 cells, expression of T...
Source: Journal of Bone and Mineral Research - April 24, 2020 Category: Orthopaedics Authors: Chung ‐Hwan Chen, Chao‐Han Lai, Yi‐Kai Hong, Jui‐Ming Lu, Sung‐Yen Lin, Tien‐Ching Lee, Lan‐Yun Chang, Mei‐Ling Ho, Edward M. Conway, Hua‐Lin Wu, Tsung‐Lin Cheng Tags: Original Article Source Type: research

Skeletal Changes Following Hematopoietic Stem Cell Transplantation in Osteopetrosis
AbstractOsteopetrosis is a rare skeletal dysplasia resulting from an osteoclast defect leading to increased bone mass and density. Hematopoietic stem cell transplantation can rescue the disease phenotype and prevent complications. However, little is known about the skeletal changes hematopoietic stem cell transplantation induces in patients with this disease. The purpose of this study was to describe the skeletal changes following hematopoietic stem cell transplantation in a retrospective cohort of patients diagnosed with osteopetrosis in one medical center over 13  years. For this purpose, all available epidemiolog...
Source: Journal of Bone and Mineral Research - April 24, 2020 Category: Orthopaedics Authors: Galina Shapiro, Jorge Fishleder, Polina Stepensky, Naum Simanovsky, Vladimir Goldman, Ron Lamdan Tags: Clinical Trial Source Type: research

Functional Characterization of PHEX Gene Variants in Children with X ‐linked Hypophosphatemic Rickets Shows no Evidence of Genotype‐Phenotype Correlation
AbstractX ‐linked hypophosphatemia (XLHR) is caused by loss‐of‐function mutations in the phosphate regulating endopeptidase homolog X‐linked (PHEX) gene. Considerable controversy exists regarding genotype‐phenotype correlations in XLHR. The present study describes the clinical features and molecular genetic bases of 53 pediatric patients with XLHR. Overall, 47 different mutations were identified, of which 27 were not previously described in the literature or entered in the HGMD. A high prevalence (72.34%) of truncating variants was observed in XLHR patients. The clinical presentation and sever ity of XLHR did not...
Source: Journal of Bone and Mineral Research - April 24, 2020 Category: Orthopaedics Authors: Bixia Zheng, Chunli Wang, Qiuxia Chen, Ruochen Che, Yugen Sha, Fei Zhao, Guixia Ding, Wei Zhou, Zhanjun Jia, Songming Huang, Ying Chen, Aihua Zhang Tags: Original Article Source Type: research

Thrombomodulin functional domains support osteoblast differentiation and bone healing in diabetes in mice
AbstractThrombomodulin (TM) is a transmembrane glycoprotein that contains five functional domains. Soluble TM (sTM), comprising extracellular domains TMD1 (lectin ‐like), TMD2 (EGF‐like repeat containing) and TMD3 (serine‐threonine rich), can be shed from cells by the intramembrane protease rhomboid‐like‐2 (RHBDL2). TM is expressed by osteoblasts, yet its role there has not been determined. Herein we aimed to investigate the properties of TM and its domains in osteoblast function and bone repair following injury in diabetes. In response to a scratch injury of cultured osteoblast‐like MG63 cells, expression of T...
Source: Journal of Bone and Mineral Research - April 24, 2020 Category: Orthopaedics Authors: Chung ‐Hwan Chen, Chao‐Han Lai, Yi‐Kai Hong, Jui‐Ming Lu, Sung‐Yen Lin, Tien‐Ching Lee, Lan‐Yun Chang, Mei‐Ling Ho, Edward M. Conway, Hua‐Lin Wu, Tsung‐Lin Cheng Tags: Original Article Source Type: research