Current Osteoporosis Reports最新文献

{"title":"Disorganization and Musculoskeletal Diseases: Novel Insights into the Enigma of Unexplained Bone Abnormalities and Fragility Fractures.","authors":"Roger Zebaze,&nbsp;Peter Robert Ebeling","doi":"10.1007/s11914-022-00759-2","DOIUrl":"https://doi.org/10.1007/s11914-022-00759-2","url":null,"abstract":"<p><strong>Purpose of review: </strong>Describe the potential contribution of disorganized tissue to the pathogenesis of bone abnormalities and fractures. Especially, fractures that are unexplained by bone loss (osteoporosis) or structural deterioration.</p><p><strong>Recent findings: </strong>Currently, bone fragility is primarily viewed as due to loss, or decay (osteoporosis). However, it is also acknowledged that this view is limited because it does not explain many fractures or abnormalities such as necrosis, sclerosis, or infarcts. Atypical femoral fractures (AFFs) during antiresorptive therapy are an example. Hence, it is proposed that another distinct mechanism is responsible for bone diseases. A remarkable bone property distinct from mass and decay is the organization (arrangement) of its components. Components must be perfectly assembled or well-stacked to ensure \"the right amount of bone, at the right place\". Disorganization is an aberration that is conspicuous in many diseases, more so in conditions poorly associated with bone mass and decay such as osteogenesis imperfecta, hypophosphatasia, and AFFs. However, despite the likely critical role of disorganization, this feature has received limited clinical attention. This review focuses on the potential contribution of disorganization to bone in health and diseases. Particularly, we propose that disorganization, by causing ineffective transfer of loads, may produce not only bone abnormalities (pain, necrosis, infarct, sclerosis, delayed healing) but also fractures, especially AFFs or stress fractures. A disorganized element is one that is where it shouldn't be (improperly stacked elements). Hence, disorganization can be measured by quantifying the extent to which a tissue (pixel within an image) is at an incorrect location.</p>","PeriodicalId":11080,"journal":{"name":"Current Osteoporosis Reports","volume":"21 2","pages":"154-166"},"PeriodicalIF":4.3,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9321707","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}

{"title":"Proceedings of the Post-Genome Analysis for Musculoskeletal Biology Workshop.","authors":"Cheryl Ackert-Bicknell,&nbsp;David Karasik","doi":"10.1007/s11914-023-00781-y","DOIUrl":"https://doi.org/10.1007/s11914-023-00781-y","url":null,"abstract":"<p><strong>Purpose of the review: </strong>Herein, we report on the proceedings of the workshop entitled \"Post-Genome analysis for musculoskeletal biology\" that was held in July of 2022 in Safed, Galilee, Israel. Supported by the Israel Science Foundation, the goal of this workshop was to bring together established investigators and their trainees who were interested in understanding the etiology of musculoskeletal disease, from Israel and from around the world.</p><p><strong>Recent findings: </strong>Presentations at this workshop spanned the spectrum from basic science to clinical studies. A major emphasis of the discussion centered on genetic studies in humans, and the limitations and advantages of such studies. The power of coupling studies using human data with functional follow-up studies in pre-clinical models such as mice, rats, and zebrafish was discussed in depth. The advantages and limitations of mice and zebrafish for faithfully modelling aspects of human disease were debated, specifically in the context of age-related diseases such as osteoporosis, osteoarthritis, adult-onset auto-immune disease, and osteosarcopenia. There remain significant gaps in our understanding of the nature and etiology of human musculoskeletal disease. While therapies and medications exist, much work is still needed to find safe and effective interventions for all patients suffering from diseases associated with age-related deterioration of musculoskeletal tissues. The potential of forward and reverse genetic studies has not been exhausted for diseases of muscles, joints, and bones.</p>","PeriodicalId":11080,"journal":{"name":"Current Osteoporosis Reports","volume":"21 2","pages":"184-192"},"PeriodicalIF":4.3,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9500649","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}

{"title":"Clinical Assessments of Fracture Healing and Basic Science Correlates: Is There Room for Convergence?","authors":"Luke A Lopas,&nbsp;Huaishuang Shen,&nbsp;Ning Zhang,&nbsp;Yohan Jang,&nbsp;Vivianne L Tawfik,&nbsp;Stuart B Goodman,&nbsp;Roman M Natoli","doi":"10.1007/s11914-022-00770-7","DOIUrl":"https://doi.org/10.1007/s11914-022-00770-7","url":null,"abstract":"<p><strong>Purpose of review: </strong>The purpose of this review is to summarize the clinical and basic science methods used to assess fracture healing and propose a framework to improve the translational possibilities.</p><p><strong>Recent findings: </strong>Mainstays of fracture healing assessment include clinical examination, various imaging modalities, and assessment of function. Pre-clinical studies have yielded insight into biomechanical progression as well as the genetic, molecular, and cellular processes of fracture healing. Efforts are emerging to identify early markers to predict impaired healing and possibly early intervention to alter these processes. Despite of the differences in clinical and preclinical research, opportunities exist to unify and improve the translational efforts between these arenas to develop and optimize our ability to assess and predict fracture healing, thereby improving the clinical care of these patients.</p>","PeriodicalId":11080,"journal":{"name":"Current Osteoporosis Reports","volume":"21 2","pages":"216-227"},"PeriodicalIF":4.3,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9506427","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}

{"title":"Impact of Cinacalcet and Etelcalcetide on Bone Mineral and Cardiovascular Disease in Dialysis Patients.","authors":"Julie Bernardor,&nbsp;Aurélie De Mul,&nbsp;Justine Bacchetta,&nbsp;Claus Peter Schmitt","doi":"10.1007/s11914-023-00782-x","DOIUrl":"https://doi.org/10.1007/s11914-023-00782-x","url":null,"abstract":"<p><strong>Purposes of review: </strong>With chronic kidney disease (CKD) progression, secondary hyperparathyroidism (sHPT) and mineral and bone metabolism disease (MBD) almost inevitably develop and result in renal osteodystrophy and cardiovascular disease (CVD). Together with active vitamin D, calcimimetics are the main therapy for sHPT in CKD. This review provides an overview of the therapeutic effects of oral cinacalcet and intravenous etelcalcetide on CKD-MBD and vascular disease, with a focus on pediatric dialysis patients.</p><p><strong>Recent findings: </strong>Randomized controlled trials in adults and children demonstrate efficient lowering of parathyroid hormone (PTH) by the calcimimetics together with a reduction in serum calcium and phosphate when combined with low-dose active vitamin D, while therapy with active vitamin D analogs alone increases serum calcium and phosphate. Cinacalcet and etelcalcetide both improve bone formation and correct adynamic bone, i.e., have a direct bone anabolic effect. They decrease serum calciprotein particles, which are involved in endothelial dysfunction, atherogenesis, and vascular calcification. Clinical trials in adults suggest a modest slowing of the progression of cardiovascular calcification with cinacalcet. Calcimimetic agents represent a major pharmacological tool for improved control of CKD-MBD, by efficiently counteracting sHPT and allowing for better control of calcium/phosphate and bone homeostasis. Albeit definite evidence is lacking, the beneficial effects of calcimimetics on CVD are promising. Routine use of cinacalcet has been suggested in children.</p>","PeriodicalId":11080,"journal":{"name":"Current Osteoporosis Reports","volume":"21 2","pages":"193-204"},"PeriodicalIF":4.3,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9512215","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}

{"title":"SP7: from Bone Development to Skeletal Disease.","authors":"Jialiang S Wang, Nicha Tokavanich, Marc N Wein","doi":"10.1007/s11914-023-00778-7","DOIUrl":"10.1007/s11914-023-00778-7","url":null,"abstract":"<p><strong>Purpose of review: </strong>The purpose of this review is to summarize the different roles of the transcription factor SP7 in regulating bone formation and remodeling, discuss current studies in investigating the causal relationship between SP7 mutations and human skeletal disease, and highlight potential therapeutic treatments that targeting SP7 and the gene networks that it controls.</p><p><strong>Recent findings: </strong>Cell-type and stage-specific functions of SP7 have been identified during bone formation and remodeling. Normal bone development regulated by SP7 is strongly associated with human bone health. Dysfunction of SP7 results in common or rare skeletal diseases, including osteoporosis and osteogenesis imperfecta with different inheritance patterns. SP7-associated signaling pathways, SP7-dependent target genes, and epigenetic regulations of SP7 serve as new therapeutic targets in the treatment of skeletal disorders. This review addresses the importance of SP7-regulated bone development in studying bone health and skeletal disease. Recent advances in whole genome and exome sequencing, GWAS, multi-omics, and CRISPR-mediated activation and inhibition have provided the approaches to investigate the gene-regulatory networks controlled by SP7 in bone and the therapeutic targets to treat skeletal disease.</p>","PeriodicalId":11080,"journal":{"name":"Current Osteoporosis Reports","volume":"21 2","pages":"241-252"},"PeriodicalIF":4.3,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10758296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10080971","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}

{"title":"Wnt/β-Catenin Signaling in Craniomaxillofacial Osteocytes.","authors":"Pedro L Cuevas,&nbsp;Fabiana Aellos,&nbsp;Isaiah M Dawid,&nbsp;Jill A Helms","doi":"10.1007/s11914-023-00775-w","DOIUrl":"https://doi.org/10.1007/s11914-023-00775-w","url":null,"abstract":"<p><strong>Purpose of review: </strong>There is a growing appreciation within the scientific community that cells exhibit regional variation. Whether the variation is attributable to differences in embryonic origin or anatomical location and mechanical loading has not been elucidated; what is clear, however, is that adult cells carry positional information that ultimately affects their functions. The purpose of this review is to highlight the functions of osteocytes in the craniomaxillofacial (CMF) skeleton as opposed to elsewhere in the body, and in doing so gain mechanistic insights into genetic conditions and chemically-induced diseases that particularly affect this region of our anatomy.</p><p><strong>Recent findings: </strong>In the CMF skeleton, elevated Wnt/β-catenin signaling affects not only bone mass and volume, but also mineralization of the canalicular network and osteocyte lacunae. Aberrant elevation in the Wnt/β-catenin pathway can also produce micropetrosis and osteonecrosis of CMF bone, presumably due to a disruption in the signaling network that connects osteocytes to one another, and to osteoblasts on the bone surface.</p>","PeriodicalId":11080,"journal":{"name":"Current Osteoporosis Reports","volume":"21 2","pages":"228-240"},"PeriodicalIF":4.3,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9338593","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}

{"title":"Copy Number Variation and Osteoporosis.","authors":"Nika Lovšin","doi":"10.1007/s11914-023-00773-y","DOIUrl":"10.1007/s11914-023-00773-y","url":null,"abstract":"<p><strong>Purpose of review: </strong>The purpose of this review is to summarize recent findings on copy number variations and susceptibility to osteoporosis.</p><p><strong>Recent findings: </strong>Osteoporosis is highly influenced by genetic factors, including copy number variations (CNVs). The development and accessibility of whole genome sequencing methods has accelerated the study of CNVs and osteoporosis. Recent findings include mutations in novel genes and validation of previously known pathogenic CNVs in monogenic skeletal diseases. Identification of CNVs in genes previously associated with osteoporosis (e.g. RUNX2, COL1A2, and PLS3) has confirmed their importance in bone remodelling. This process has been associated also with the ETV1-DGKB, AGBL2, ATM, and GPR68 genes, identified by comparative genomic hybridisation microarray studies. Importantly, studies in patients with bone pathologies have associated bone disease with the long non-coding RNA LINC01260 and enhancer sequences residing in the HDAC9 gene. Further functional investigation of genetic loci harbouring CNVs associated with skeletal phenotypes will reveal their role as molecular drivers of osteoporosis.</p>","PeriodicalId":11080,"journal":{"name":"Current Osteoporosis Reports","volume":"21 2","pages":"167-172"},"PeriodicalIF":4.3,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10105686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10035467","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}

{"title":"Multiple Mechanisms Explain Genetic Effects at the CPED1-WNT16 Bone Mineral Density Locus.","authors":"Arianna Ericka Gómez,&nbsp;Sumaya Addish,&nbsp;Kurtis Alvarado,&nbsp;Priscilla Boatemaa,&nbsp;Anne C Onyali,&nbsp;Emily G Ramirez,&nbsp;Maria F Rojas,&nbsp;Jyoti Rai,&nbsp;Kiana A Reynolds,&nbsp;W Joyce Tang,&nbsp;Ronald Young Kwon","doi":"10.1007/s11914-023-00783-w","DOIUrl":"https://doi.org/10.1007/s11914-023-00783-w","url":null,"abstract":"<p><strong>Purpose of review: </strong>Chromosome region 7q31.31, also known as the CPED1-WNT16 locus, is robustly associated with BMD and fracture risk. The aim of the review is to highlight experimental studies examining the function of genes at the CPED1-WNT16 locus.</p><p><strong>Recent findings: </strong>Genes that reside at the CPED1-WNT16 locus include WNT16, FAM3C, ING3, CPED1, and TSPAN12. Experimental studies in mice strongly support the notion that Wnt16 is necessary for bone mass and strength. In addition, roles for Fam3c and Ing3 in regulating bone morphology in vivo and/or osteoblast differentiation in vitro have been identified. Finally, a role for wnt16 in dually influencing bone and muscle morphogenesis in zebrafish has recently been discovered, which has brought forth new questions related to whether the influence of WNT16 in muscle may conspire with its influence in bone to alter BMD and fracture risk.</p>","PeriodicalId":11080,"journal":{"name":"Current Osteoporosis Reports","volume":"21 2","pages":"173-183"},"PeriodicalIF":4.3,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10202127/pdf/nihms-1894552.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10126232","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}

{"title":"Osteoimmunology in Periodontitis and Orthodontic Tooth Movement.","authors":"Bushra Alghamdi, Hyeran Helen Jeon, Jia Ni, Dongxu Qiu, Alyssia Liu, Julie J Hong, Mamoon Ali, Albert Wang, Michael Troka, Dana T Graves","doi":"10.1007/s11914-023-00774-x","DOIUrl":"10.1007/s11914-023-00774-x","url":null,"abstract":"<p><strong>Purpose of review: </strong>To review the role of the immune cells and their interaction with cells found in gingiva, periodontal ligament, and bone that leads to net bone loss in periodontitis or bone remodeling in orthodontic tooth movement.</p><p><strong>Recent findings: </strong>Periodontal disease is one of the most common oral diseases causing inflammation in the soft and hard tissues of the periodontium and is initiated by bacteria that induce a host response. Although the innate and adaptive immune response function cooperatively to prevent bacterial dissemination, they also play a major role in gingival inflammation and destruction of the connective tissue, periodontal ligament, and alveolar bone characteristic of periodontitis. The inflammatory response is triggered by bacteria or their products that bind to pattern recognition receptors that induce transcription factor activity to stimulate cytokine and chemokine expression. Epithelial, fibroblast/stromal, and resident leukocytes play a key role in initiating the host response and contribute to periodontal disease. Single-cell RNA-seq (scRNA-seq) experiments have added new insight into the roles of various cell types in the response to bacterial challenge. This response is modified by systemic conditions such as diabetes and smoking. In contrast to periodontitis, orthodontic tooth movement (OTM) is a sterile inflammatory response induced by mechanical force. Orthodontic force application stimulates acute inflammatory responses in the periodontal ligament and alveolar bone stimulated by cytokines and chemokines that produce bone resorption on the compression side. On the tension side, orthodontic forces induce the production of osteogenic factors, stimulating new bone formation. A number of different cell types, cytokines, and signaling/pathways are involved in this complex process. Inflammatory and mechanical force-induced bone remodeling involves bone resorption and bone formation. The interaction of leukocytes with host stromal cells and osteoblastic cells plays a key role in both initiating the inflammatory events as well as inducing a cellular cascade that results in remodeling in orthodontic tooth movement or in tissue destruction in periodontitis.</p>","PeriodicalId":11080,"journal":{"name":"Current Osteoporosis Reports","volume":"21 2","pages":"128-146"},"PeriodicalIF":4.3,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10696608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9509685","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}

{"title":"Genetics of Intervertebral Disc Degeneration.","authors":"David C Ou-Yang,&nbsp;Christopher J Kleck,&nbsp;Cheryl L Ackert-Bicknell","doi":"10.1007/s11914-022-00769-0","DOIUrl":"https://doi.org/10.1007/s11914-022-00769-0","url":null,"abstract":"<p><strong>Purpose of review: </strong>Intervertebral disc degeneration is a contributor to chronic back pain. While a part of the natural aging process, early or rapid intervertebral disc degeneration is highly heritable. In this review, we summarize recent progress towards unraveling the genetics associated with this degenerative process.</p><p><strong>Recent findings: </strong>Use of large cohorts of patient data to conduct genome-wide association studies (GWAS) for intervertebral disc disease, and to lesser extent for aspects of this process, such as disc height, has resulted in a large increase in our understanding of the genetic etiology. Genetic correlation suggests that intervertebral disc disease is pleiotropic with risk factors for other diseases such as osteoporosis. The use of Mendelian Randomization is slowly establishing what are the causal relationships between intervertebral disc disease and factors previously correlated with this disease. The results from these human genetic studies highlight the complex nature of this disease and have the potential to lead to improved clinical management of intervertebral disc disease. Much additional work should now be focused on characterizing the causative relationship various co-morbid conditions have with intervertebral disc degeneration and on finding interventions to slow or halt this disease.</p>","PeriodicalId":11080,"journal":{"name":"Current Osteoporosis Reports","volume":"21 1","pages":"56-64"},"PeriodicalIF":4.3,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9161855","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}