Review
Endocrinology & Metabolism
Qing-Chang Chen, Yan Zhang
Summary: Bone diseases are the main causes of disability and impaired quality of life. Neuropeptide Y plays important roles in bone tissue by regulating bone metabolism and disease progression through its receptors. This review provides a brief overview of recent progress in understanding the regulatory mechanism of bone physiology and pathological metabolism.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Ji Hyun Lee, JooYong Park, Jung Hee Kim, Ji-Yeob Choi, Hyung Jin Choi, Eu Jeong Ku, A. Ram Hong, Chan Soo Shin, Nam H. Cho
Summary: This Korean prospective cohort study found that decreasing waist circumference and lean muscle mass loss were significant risk factors for hip bone loss in both men and women. Other factors may have sex-specific or age-specific effects on hip bone loss. None of the genetic factors tested were associated with hip bone loss after multiple testing adjustments, indicating that modifiable factors may play a larger role in determining bone health.
Review
Endocrinology & Metabolism
Siwang Hu, Shuangshuang Wang
Summary: SIRT3 is an enzyme that regulates mitochondrial morphology and function, and it has been shown to play a role in many aging-related diseases. Osteoporosis, a common aging-related disease, is characterized by decreased bone mass and fragility fractures, but the specific effects and mechanisms of SIRT3 in osteoporosis are not yet clear.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Pharmacology & Pharmacy
Yuqi Xin, Anqun Tang, Shuting Pan, Jie Zhang
Summary: This review summarizes research on the endocannabinoid system (ECS) and bone diseases in the past twenty years, revealing the important role cannabinoids play in bone metabolism and highlighting their therapeutic potential in treating bone diseases.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biology
Mone Zaidi, Se-Min Kim, Mehr Mathew, Funda Korkmaz, Farhath Sultana, Sari Miyashita, Anisa Azatovna Gumerova, Tal Frolinger, Ofer Moldavski, Orly Barak, Anusha Pallapati, Satish Rojekar, John Caminis, Yelena Ginzburg, Vitaly Ryu, Terry F. Davies, Daria Lizneva, Clifford J. Rosen, Tony Yuen
Summary: Significant advances have been made in understanding skeletal homeostasis and the mechanisms of bone disease over the past decade. Identifying disease-causing mutations and modeling human bone disease in rodents have highlighted the integrative nature of skeletal physiology. Bone cells communicate and regulate each other's fate through various signaling pathways, and developmental pathways like BMP, NOTCH, and WNT play important roles in postnatal bone remodeling. The skeleton communicates with neighboring organs as well as vital organs, and has effects on energy homeostasis and other physiological processes. This article discusses the mechanisms controlling bone remodeling, communication between bone cells and other cell lineages, crosstalk between bone and vital organs, and potential treatments for bone diseases.
Article
Biochemistry & Molecular Biology
Kwang-Jin Kim, Jusung Lee, Weihong Wang, Yongjin Lee, Eunseok Oh, Kyu-Hyung Park, Chanyoon Park, Gee-Eun Woo, Young-Jin Son, Heonjoong Kang
Summary: Austalide K, isolated from the marine fungus Penicillium rudallenes, has dual activities in bone remodeling by inhibiting osteoclast differentiation and promoting osteoblast formation. It showed good efficacy in an in vivo bone loss model and may lead to new drug treatments for bone diseases like osteoporosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Plant Sciences
Reena Rai, Sudhir Kumar, Krishna Bhan Singh, Sonu Khanka, Yatendra Singh, K. R. Arya, Sanjeev Kanojiya, Rakesh Maurya, Divya Singh
Summary: The ethanolic extract and butanolic fraction of Musa paradisiaca flower show potential in preventing bone density loss and promoting bone regeneration, improving bone microarchitecture in postmenopausal conditions. Compounds isolated from the extract exhibit significant osteogenic effects.
Review
Medicine, General & Internal
Yevgeniya Kushchayeva, Iryna Pestun, Sergiy Kushchayev, Nataliia Radzikhovska, E. Michael Lewiecki
Summary: Osteoporosis and osteoarthritis, both age-related disorders, may require surgical treatment. Poor bone quality can negatively impact surgical outcomes. This review summarizes the pathophysiology of osteoporotic bone healing, the effect of fractures on bone turnover markers, the diagnosis of low bone mineral density before surgery, and the effectiveness of anti-osteoporosis treatment.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Chemistry, Multidisciplinary
Junjie Li, Ruizhi Zhang, Yawei Du, Gongwen Liu, Yu Dong, Miao Zheng, Wenguo Cui, Peng Jia, Youjia Xu
Summary: Osteoclast adhesion and bone resorption are the main causes of postmenopausal osteoporosis (PMOP). Hsa-miR-378i/mmu-miR-378a-3p has been identified as closely associated with PMOP. An osteophilic and dual-regulated antagomir@Aln-Lipo has been developed to effectively reverse bone loss by synergistically regulating osteoclastogenesis and bone resorption.
Article
Medicine, Research & Experimental
Biao Wu, Jie Shang, Shiyuan Lin, Ning Jiang, Baizhou Xing, Rong Peng, Xianghe Xu, Huading Lu
Summary: Increased bone resorption caused by excessive osteoclasts is the main cause of osteoporosis. The expression of RILP, a protein, is induced by receptor activator of NF-KB ligand, and its inhibition decreases the number and function of osteoclasts. Inhibition of RILP also reduces preosteoclast migration and bone resorption. The study suggests that RILP plays a crucial role in osteoclast formation and bone resorption, and could be a therapeutic target for bone diseases caused by excessive osteoclasts.
LABORATORY INVESTIGATION
(2023)
Review
Pediatrics
Silvia Ciancia, Rick R. van Rijn, Wolfgang Hoegler, Natasha M. Appelman-Dijkstra, Annemieke M. Boot, Theo C. J. Sas, Judith S. Renes
Summary: Early recognition of osteoporosis in children and adolescents is crucial for appropriate diagnosis and treatment. Genetic and acquired pediatric bone disorders are common and cause significant morbidity. Recent progress has been made in understanding the genetic and molecular mechanisms underlying bone fragility and identifying acquired causes of osteoporosis in children.
EUROPEAN JOURNAL OF PEDIATRICS
(2022)
Article
Engineering, Environmental
Yan Huang, Maowen Chen, Yiding Shen, Xinkun Shen, Menghuan Li, Yanan Li, Yuan Liu, Kaiyong Cai, Zhong Luo, Yan Hu
Summary: This study presents a bone-targeted nanoformulation based on CaCO3 nanomaterials, which can be activated in the acidic microenvironment of osteoporosis and regulate the activity of osteoclasts and osteoblasts to reverse bone deterioration. The study provides an effective approach for the treatment of osteoporosis in clinics.
CHEMICAL ENGINEERING JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Arne Martens, Pieter Hertens, Dario Priem, Vagelis Rinotas, Theodore Meletakos, Meropi Gennadi, Lisette Van Hove, Els Louagie, Julie Coudenys, Amelie De Muynck, Djoere Gaublomme, Mozes Sze, Jolanda van Hengel, Leen Catrysse, Esther Hoste, Jeffrey D. Zajac, Rachel A. Davey, Luc Van Hoorebeke, Tino Hochepied, Mathieu J. M. Bertrand, Marietta Armaka, Dirk Elewaut, Geert van Loo
Summary: The anti-inflammatory protein A20 plays a critical role in inhibiting NF-kappa B signaling and inflammation. Deficiency of A20 can lead to osteoporosis without causing inflammatory arthritis. A20 regulates RANK-induced NF-kappa B signaling through its specific domains, controlling osteoclast differentiation and bone development.
Article
Biochemistry & Molecular Biology
Hong Chen, Fangfang Song, Fanxin Long
Summary: Glucocorticoids are a common cause for osteoporosis and fractures, but current treatments are not effective due to side effects. This study shows that WNT7B can restore bone mass after glucocorticoid-induced bone loss by increasing osteoblast number and function. However, WNT7B overexpression does not improve abnormal fat accumulation.
Review
Medicine, Research & Experimental
Zhi-heng Luo, Jian-xiong Ma, Wei Zhang, Ai-xian Tian, Shu-wei Gong, Yan Li, Yu-xiao Lai, Xin-long Ma
Summary: The pathogenesis of osteoporosis involves multiple factors, and changes in the bone microenvironment play a crucial role. TRPV5, as a member of the TRPV family, exerts significant influence on bone through calcium regulation and response to hormones and agonists. This review focuses on the changes in the osteoporotic microenvironment and the specific effects of TRPV5 at various levels.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Endocrinology & Metabolism
Richard Eastell, Eric Vittinghoff, Li-Yung Lui, Charles E. McCulloch, Imre Pavo, Arkadi Chines, Sundeep Khosla, Jane A. Cauley, Bruce Mitlak, Douglas C. Bauer, Mary Bouxsein, Dennis M. Black
Summary: The surrogate threshold effect (STE) is defined as the minimum treatment effect on a surrogate that reliably predicts the treatment effect on the clinical outcome. This study aimed to validate the STE for change in total hip (TH) BMD as a surrogate for fracture risk reduction, finding that STE differs by fracture type and has been validated in trials not used to develop the approach.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Computer Science, Artificial Intelligence
Chen Zhao, Joyce H. Keyak, Jinshan Tang, Tadashi S. Kaneko, Sundeep Khosla, Shreyasee Amin, Elizabeth J. Atkinson, Lan-Juan Zhao, Michael J. Serou, Chaoyang Zhang, Hui Shen, Hong-Wen Deng, Weihua Zhou
Summary: In this study, we aimed to develop a deep-learning-based method for automatic proximal femur segmentation in quantitative computed tomography (QCT) images. We proposed a spatial transformation V-Net (ST-V-Net) that incorporates a shape prior into the segmentation network to improve model performance. Experimental results showed excellent performance of the proposed ST-V-Net for automatic proximal femur segmentation in QCT images.
COMPLEX & INTELLIGENT SYSTEMS
(2023)
Review
Endocrinology & Metabolism
Dominik Saul, Sundeep Khosla
Summary: More than 2.1 million age-related fractures occur in the United States annually, resulting in a significant socioeconomic burden. Age-related deterioration of bone structure is associated with impaired bone healing, which occurs in four stages: inflammation, angiogenesis and cartilage formation, soft callus development, and remodeling. Impaired fracture healing due to aging is related to detrimental changes at the cellular level, and recent studies show that clearing senescent cells enhances fracture repair.
Article
Endocrinology & Metabolism
Danielle E. Whittier, Elizabeth J. Samelson, Marian T. Hannan, Lauren A. Burt, David A. Hanley, Emmanuel Biver, Pawel Szulc, Elisabeth Sornay-Rendu, Blandine Merle, Roland Chapurlat, Eric Lespessailles, Andy Kin On Wong, David Goltzman, Sundeep Khosla, Serge Ferrari, Mary L. Bouxsein, Douglas P. Kiel, Steven K. Boyd
Summary: The prevalence of osteoporosis in older adults is high, but current clinical methods fail to detect most fragility fracture cases. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides additional information about bone density and structure, but interpretation is challenging. In this study, the authors identified common bone phenotypes associated with fracture risk using HR-pQCT data from a multinational cohort. They found that different phenotypes had significantly different fracture risks and identified imaging biomarkers for fractures within each phenotype.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Editorial Material
Endocrinology & Metabolism
Sundeep Khosla, Nicole C. Wright, Ann L. Elderkin, Douglas P. Kiel
LANCET DIABETES & ENDOCRINOLOGY
(2023)
Article
Geriatrics & Gerontology
Sara E. Espinoza, Sundeep Khosla, Joseph A. Baur, Rafael de Cabo, Nicolas Musi
Summary: The geroscience hypothesis suggests that targeting key hallmarks of aging can improve healthspan and prevent age-related diseases. Several pharmacological interventions, including senolytics, NAD(+) boosters, and metformin, are being studied for their potential benefits. Preclinical studies show that senolytic drugs improve healthspan in rodents, while increasing NAD(+) through supplementation appears to extend healthspan in model organisms. Metformin, on the other hand, has pleiotropic effects and is being examined for its potential to improve healthspan and prevent frailty in clinical trials. However, further research is needed to determine their efficacy, safety, target populations, and long-term outcomes.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Endocrinology & Metabolism
Japneet Kaur, Dominik Saul, Madison L. Doolittle, Joshua N. Farr, Sundeep Khosla, David G. Monroe
Summary: Aging is associated with an accumulation of senescent cells in various tissues, including bones. This study found that a specific miRNA, miR-19a-3p, decreases with age in mouse and human bones. Furthermore, inducing senescence in mouse bone marrow stromal cells also reduced the levels of miR-19a-3p. The study suggests that miR-19a-3p could be a potential therapeutic target for age-related bone loss.
Article
Endocrinology & Metabolism
Stefan Bartenschlager, Alexander Cavallaro, Tobias Pogarell, Oliver Chaudry, Michael Uder, Sundeep Khosla, Georg Schett, Klaus Engelke
Summary: Opportunistic screening is a promising technique for identifying individuals at high risk for osteoporotic fracture using CT scans. This study compared the performance of four existing phantomless calibration methods and found that precalibrated phantomless calibration methods performed well.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Madison L. Doolittle, Dominik Saul, Japneet Kaur, Jennifer L. Rowsey, Stephanie J. Vos, Kevin D. Pavelko, Joshua N. Farr, David G. Monroe, Sundeep Khosla
Summary: The article provides a detailed characterization of senescent skeletal cells in vivo, identifying a population of senescent cells associated with age and increased in late osteoblasts/osteocytes and CD24(high) osteolineage cells. The authors also establish CD24 as a marker for skeletal cells cleared by senolytics.
NATURE COMMUNICATIONS
(2023)
Article
Endocrinology & Metabolism
Madison L. Doolittle, Sundeep Khosla, Dominik Saul
Summary: The regulation of bone mineral density (BMD) is influenced by genetics and age. Genome-wide association studies (GWAS) have identified many genes associated with BMD, but their specific mechanisms in different cell types and during aging are still unclear. By analyzing age-related transcriptomics and single-cell RNA-sequencing (scRNA-seq) datasets, this study investigated the cell-specific expression of GWAS candidate genes and identified enrichment in various cells related to bone metabolism. The findings provide potential therapeutic targets for osteoporosis treatment.
Article
Endocrinology & Metabolism
Madison L. L. Doolittle, Brittany A. A. Eckhardt, Stephanie J. J. Vos, Sarah Grain, Jennifer L. L. Rowsey, Ming Ruan, Dominik Saul, Joshua N. N. Farr, Megan M. M. Weivoda, Sundeep Khosla, David G. G. Monroe
Summary: Estrogen plays a crucial role in regulating bone mass, primarily through its action on ERalpha. Recent studies have shown that estrogen action in osteocytes is more important than in osteoclasts, and the loss of ERalpha in specific cell types results in decreased bone volume and reduced bone formation rate.
Article
Endocrinology & Metabolism
Pamela Rufus-Membere, Kara L. Holloway-Kew, Adolfo Diez-Perez, Natasha M. Appelman-Dijkstra, Mary L. Bouxsein, Erik F. Eriksen, Joshua N. Farr, Sundeep Khosla, Mark A. Kotowicz, Xavier Nogues, Mishaela Rubin, Julie A. Pasco
Summary: Impact microindentation (IMI) is a novel technique for assessing bone material strength index (BMSi) in vivo. The aim of this study was to define the reference intervals for men and women by evaluating healthy adults from multiple countries. BMSi values ranged from 48 to 101, with mean values of 84.4 +/- 6.9 for men and 79.0 +/- 9.1 for women.
CALCIFIED TISSUE INTERNATIONAL
(2023)
Article
Cell Biology
Xu Zhang, Leena Habiballa, Zaira Aversa, Yan Er Ng, Ayumi E. E. Sakamoto, Davis A. A. Englund, Vesselina M. M. Pearsall, Thomas A. A. White, Matthew M. M. Robinson, Donato A. A. Rivas, Surendra Dasari, Adam J. J. Hruby, Anthony B. B. Lagnado, Sarah K. K. Jachim, Antoneta Granic, Avan A. A. Sayer, Diana Jurk, Ian R. R. Lanza, Sundeep Khosla, Roger A. A. Fielding, K. Sreekumaran Nair, Marissa J. J. Schafer, Joao F. Passos, Nathan K. K. LeBrasseur
Summary: This study comprehensively assesses cellular senescence in skeletal muscle of young and old mice using single-cell and bulk RNA sequencing, as well as imaging methods. The results demonstrate that a subpopulation of fibroadipogenic progenitors in old mice highly express p16(Ink4a) and multiple senescence-related genes, accompanied by DNA damage and chromatin reorganization. A senescence phenotype is also observed in isolated myofibers, governed by p21(Cip1). Treatment with a senotherapeutic intervention improves age-related molecular and morphological changes and enhances skeletal muscle strength in old mice. Furthermore, the senescence phenotype is conserved in skeletal muscle from older humans.
Meeting Abstract
Endocrinology & Metabolism
Danielle Whittier, Elizabeth Samelson, Marian Hannan, Emmanuel Biver, Pawel Szulc, Elisabeth Sornay-Rendu, Roland Chapurlat, David Goltzman, Sundeep Khosla, Serge Ferrari, Mary Bouxsein, Doug Kiel, Steven Boyd
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Review
Medicine, Research & Experimental
Sundeep Khosla, Joshua N. Farr, David G. Monroe
Summary: Cellular senescence is a key mechanism in aging, especially in the skeletal system, and targeting senescent cells shows promise in preventing age-related bone loss and fragility. Efforts are underway to develop senolytic drugs that specifically kill senescent cells while sparing normal cells, offering a potential treatment for multiple age-related comorbidities.
JOURNAL OF CLINICAL INVESTIGATION
(2022)