Bone最新文献

{"title":"Immune microenvironment of cancer bone metastasis","authors":"Toru Hiraga","doi":"10.1016/j.bone.2024.117328","DOIUrl":"10.1016/j.bone.2024.117328","url":null,"abstract":"<div><div>Bone is a common and frequent site of metastasis in cancer patients, leading to a significant reduction in quality of life and increased mortality. Bone marrow, the primary site of hematopoiesis, also serves as both a primary and secondary lymphoid organ. It harbors and supports a diverse array of immune cells, thereby creating a distinct immune microenvironment. These immune cells engage in a range of activities, including anti-tumor, pro-tumor, or a combination of both, which influence the development and progression of bone metastases. Rapid advances in cancer immunotherapy have underscored its potential to eradicate bone metastases. However, clinical outcomes have not yet met expectations. To improve the efficacy of immunotherapy, it is crucial to gain a comprehensive and in-depth understanding of the immune microenvironment within bone metastases. This review provides an overview of the current understanding of the role of different immune cells, their anti-tumor and pro-tumor activities, and their overall contribution to bone metastasis.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"191 ","pages":"Article 117328"},"PeriodicalIF":3.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645327","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":"Calorie restriction induces mandible bone loss by regulating mitochondrial function","authors":"Linyi Liu ,&nbsp;Phuong T. Le ,&nbsp;Victoria E. DeMambro ,&nbsp;Tiange Feng ,&nbsp;Hanghang Liu ,&nbsp;Wangyang Ying ,&nbsp;Roland Baron ,&nbsp;Clifford J. Rosen","doi":"10.1016/j.bone.2024.117326","DOIUrl":"10.1016/j.bone.2024.117326","url":null,"abstract":"<div><div>Caloric restriction (CR), commonly used as both a lifestyle choice and medical strategy, has been shown to adversely impact appendicular bone mass. However, its influence on alveolar bone health and the underlying mechanisms remain poorly understood. In this study, 8-week-old C57BL/6 J mice were fed with 30 % CR for 8 weeks. Micro-architecture, histologic parameters, and in vitro trajectories of osteoblast and adipocyte differentiation were examined. To further explore the underlying mechanisms, metabolic cages and in vitro bioenergetics were performed. Our results showed that 8 weeks of CR led to trabecular and cortical bone loss in the mandibles of female mice. CR in female mice decreased bone formation and bone resorption activities but induced adiposity in the mandibles. After CR, the adipogenesis in mesenchymal cells from orofacial bones (OMSCs) was greatly accelerated, whereas osteogenic differentiation was reduced in females. Undifferentiated CR OMSCs showed marked suppression in ATP production rates from mitochondria in female mice. ATP production rates decreased after osteogenesis but were upregulated during adipogenesis in female mice. Conversely, the generation of reactive oxygen species (ROS) was heightened during both osteoblastic and adipogenic differentiation in female CR groups. Collectively, our study indicated that CR could cause significant bone loss in the mandibles of female mice, almost certainly related to a reduced ATP supply and the unregulated generation of ROS.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117326"},"PeriodicalIF":3.5,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634349","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":"Innate immune response to bone fracture healing","authors":"Jane Burgan ,&nbsp;Maryam Rahmati ,&nbsp;Mark Lee ,&nbsp;Augustine Mark Saiz","doi":"10.1016/j.bone.2024.117327","DOIUrl":"10.1016/j.bone.2024.117327","url":null,"abstract":"<div><div>The field of osteoimmunology has primarily focused on fracture healing in isolated musculoskeletal injuries. The innate immune system is the initial response to fracture, with inflammatory macrophages, cytokines, and neutrophils arriving first at the fracture hematoma, followed by an anti-inflammatory phase to begin the process of new bone formation. This review aims to first discuss the current literature and knowledge gaps on the immune responses governing single fracture healing by encompassing the individual role of macrophages, neutrophils, cytokines, mesenchymal stem cells, bone cells, and other immune cells. This paper discusses the interactive effects of these cellular responses underscoring the field of osteoimmunology. The critical role of the metabolic environment in guiding the immune system properties will be highlighted along with some effective therapeutics for fracture healing in the context of osteoimmunology. However, compared to isolated fractures, which frequently heal well, long bone fractures in over 30 % of polytrauma patients exhibit impaired healing. Clinical evidence suggests there may be distinct physiologic and inflammatory pathways altered in polytrauma resulting in nonunion. Nonunion is associated with worse patient outcomes and increased societal healthcare costs. The dysregulated immunomodulatory/inflammatory response seen in polytrauma may lead to this increased nonunion rate. This paper will investigate the differences in immune response between isolated and polytrauma fractures. Finally, future directions for fracture studies are explored with consideration of the emerging roles of newly discovered immune cell functions in fracture healing, the existing challenges and conflicting results in the field, the translational potential of these studies in clinic, and the more complex nature of polytrauma fractures that can alter cell functions in different tissues.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117327"},"PeriodicalIF":3.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634270","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":"Tertiary hyperparathyroidism in two paediatric patients with X-linked hypophosphatemia during Burosumab treatment","authors":"Raja Padidela ,&nbsp;Lauren Rayner ,&nbsp;Annemieke M. Boot","doi":"10.1016/j.bone.2024.117324","DOIUrl":"10.1016/j.bone.2024.117324","url":null,"abstract":"<div><h3>Introduction</h3><div>Although secondary hyperparathyroidism is known in X-linked hypophosphatemia (XLH) patients receiving treatment, tertiary hyperparathyroidism with hypercalcemia is rare, especially in children. We report two paediatric XLH patients treated with Burosumab who developed this rare complication.</div></div><div><h3>Case descriptions</h3><div><strong>1:</strong> A female patient with XLH on conventional therapy (phosphate and active vitamin D) since one year of age was switched to Burosumab at 10 years. At 14 years of age, she developed tertiary hyperparathyroidism with hypercalcaemia. Burosumab was continued. Post-parathyroidectomy her hypercalcaemia resolved and 4 years post-surgery her calcium levels continue to remain normal.</div><div><strong>2:</strong> A female patient with XLH on conventional therapy since 4 months of age was switched to Burosumab at 4 years of age. At 7 years of age, she developed secondary hyperparathyroidism and within 6 months she developed tertiary hyperparathyroidism. Burosumab was discontinued at 7.5 years of age, and she was commenced on Cinacalcet but, hypercalcaemia failed to resolve. Post-parathyroidectomy her tertiary hyperparathyroidism resolved. However, within 2 weeks, PTH increased which normalised with Cinacalcet. Burosumab has been recommenced and she continues cinacalcet.</div></div><div><h3>Discussion</h3><div>The cause of tertiary hyperparathyroidism is not clear in these patients. Higher post-dose phosphate levels or a direct effect of <em>PHEX</em> mutation on the parathyroid gland could have triggered PTH secretion.</div></div><div><h3>Conclusion</h3><div>XLH patients treated with Burosumab can develop hyperparathyroidism and should be regularly monitored for the development of secondary and tertiary hyperparathyroidism.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117324"},"PeriodicalIF":3.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634354","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":"Exposure to fluoride and risk of primary bone cancer: A systematic review","authors":"Natalie Hajduga ,&nbsp;Murali Perumbakkam Subramanian ,&nbsp;Hannah Brown ,&nbsp;Richard McNally ,&nbsp;Vida Zohoori ,&nbsp;Vikki Rand","doi":"10.1016/j.bone.2024.117320","DOIUrl":"10.1016/j.bone.2024.117320","url":null,"abstract":"<div><div>Fluoride has long been considered essential in the prevention of dental caries, however, its relationship with bone cancer remains unclear. With little improvements in survival from primary bone cancers, it is important to understand the underlying drivers. The focus of this systematic review was, therefore, to assess the association between fluoride exposure and the development of primary bone cancer. The review was conducted as per the PRISMA guidelines and was registered on PROSPERO (CRD42021296109) with a search cut-off of March 2024. In total, 14 studies, involving 8680 participants across all age groups, were identified examining the effects of fluoride exposure on humans investigated for primary bone cancer. Of the 14 studies, only two reported a positive association between fluoride and primary bone cancer. One study including 88 participants reported a positive association between water fluoridation and osteosarcoma development (in young males between 0 and 20 years of age), and the second study, with an unreported number of participants, reported this positive association with bone cancers in males. No association between fluoridation and bone cancer development was reported in the remaining studies. Across all 14 studies, data was presented in a narrative synthesis with subgroup analysis conducted on study design, age, sex, fluoride level and quality score. Both studies reporting a positive association between fluoride and bone cancer identified this association in males, however, both studies concluded that further research is needed. Here we report the most comprehensive systematic review to date examining associations between fluoride exposure and primary bone cancer. We also highlight some of the methodological limitations of some studies, and identify the need, and opportunity, to conduct a large, prospective study to address this and other health issues associated with fluoride.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117320"},"PeriodicalIF":3.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607624","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":"Role of the PGAM5-CypD mitochondrial pathway in methylglyoxal-induced bone loss in diabetic osteoporosis","authors":"Wanying Jiang ,&nbsp;Xinyi Ma ,&nbsp;Bin Li ,&nbsp;Tianle Jiang ,&nbsp;Haopu Jiang ,&nbsp;Wenxia Chen ,&nbsp;Jia Gao ,&nbsp;Yixin Mao ,&nbsp;Xiaoyu Sun ,&nbsp;Zhou Ye ,&nbsp;Shufan Zhao ,&nbsp;Shengbin Huang ,&nbsp;Yang Chen","doi":"10.1016/j.bone.2024.117322","DOIUrl":"10.1016/j.bone.2024.117322","url":null,"abstract":"<div><div>Diabetic osteoporosis (DOP) is a skeletal complication with a high rate of disability. It results in a great burden to the patient's family and society. Methylglyoxal (MG) is a toxic by-product of the glycolytic process that occurs during diabetic conditions. It causes osteoblastic injury and con-tributes to the initiation and development of DOP. Disruption of mitochondrial homeostasis has been implicated as a cause of dysregulated osteo-blastogenesis, an essential step in bone formation. It is unclear whether mitochondrial dysfunction is involved in MG-induced osteoblast dysfunction. In this study, we showed that mitochondrial dysfunction contributes to MG-induced MC3T3-E1 cell apoptosis and impaired differentiation. A significant reduction of mitochondrial membrane potential (MMP) and ATP production occurred in MG-induced osteoblasts as well as increasing mitochondrial reactive oxygen species (mtROS) and intracellular Ca²⁺. Classical antioxidant N-Acetylcysteine (NAC) significantly attenuated mitochondrial dysfunction as well as osteoblast apoptosis and osteogenic differentiation damage induced by MG. More importantly, we found that activating phosphoglycerate mutase family member 5 (PGAM5) and cyclophilin D (CypD), which contributes to mitochondrial homeostasis, is involved in MG-induced osteoblast injury. Both PGAM5 and CypD knockdown effectively reversed osteoblast viability and function, whereas PGAM5 or CypD overexpression aggravated osteoblast injury caused by MG. Moreover, the result of co-transfection revealed that PGAM5 is an upstream signaling molecule of CypD. By constructing type I diabetes mouse models, we further found that the expression of PGAM5 and CypD were both increased in the femur along with a reduction of ATP and increased TUNEL-positive cells. These results, for the first time, suggest that MG-induced mitochondrial dysfunction induces osteoblast injury through the PGAM5-CypD pathway. This study provides insight into the prevention and treatment of DOP.</div></div><div><h3>Lay summary</h3><div>This study highlights the role of mitochondria in regulating osteoblast viability and function under conditions of diabetic osteoporosis (DOP). We found that the PGAM5-CypD mitochondrial pathway is activated following glycolytic by-product methylglyoxal (MG) treatment, which contributes to mitochondrial dysfunction and osteogenic dysfunction. This mechanism implicates mitochondria as a potential therapeutic target for osteoporosis.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117322"},"PeriodicalIF":3.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607626","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":"Extracellular vesicles from mouse bone marrow macrophages-derived osteoclasts treated with zoledronic acid contain miR-146a-5p and miR-322-3p, which inhibit osteoclast function","authors":"Sakura Minami ,&nbsp;Yasuyuki Fujii ,&nbsp;Yusuke Yoshioka ,&nbsp;Ayano Hatori ,&nbsp;Kotaro Kaneko ,&nbsp;Takahiro Ochiya ,&nbsp;Daichi Chikazu","doi":"10.1016/j.bone.2024.117323","DOIUrl":"10.1016/j.bone.2024.117323","url":null,"abstract":"<div><div>Medication-related osteonecrosis of the jaw (MRONJ) is an intractable form of osteonecrosis of the jaw that rarely occurs in patients using bone resorption inhibitors such as bisphosphonates (BPs). Then, extracellular vesicles (EVs) carry various signaling molecules, such as mRNAs, microRNAs (miRNAs), and proteins, and have attracted attention as intercellular communication tools. Recently, the role of EVs in communication between osteoclasts and surrounding bone cells has been confirmed. This study aimed to elucidate the effects of EVs derived from osteoclasts treated with zoledronic acid (ZA), one of the BPs on osteoclast function. EVs were isolated by ultracentrifugation of the culture supernatant of osteoclasts treated with ZA, and miRNAs were extracted from these EVs. Tartrate-resistant acid phosphatase staining of the ZA treated osteoclasts showed reduced osteoclastogenesis. In addition, pit assay showed that ZA significantly decreased the bone resorption capacity of osteoclasts. miRNA-seq analysis identified 11 upregulated and 5 downregulated differentially expressed genes (DEGs) in the miRNA of EVs derived from ZA-treated osteoclasts compared to EVs derived from osteoclasts not treated with ZA. qRT-PCR analysis confirmed the amount of these specific miRNAs, with miR-146a-5p, and miR-322-3p being significantly upregulated by ZA. Overexpression of miR-146a-5p in osteoclasts inhibited osteoclastogenesis and decreased the mRNA expression of osteoclast markers. In addition, <em>Traf6</em> was identified as a candidate target gene of miR-146a-5p in several miRNA databases. Indeed, the overexpression of miR-146a-5p decreased the expression level of <em>Traf6</em> in osteoclasts. Additionally, overexpression of miR-322-3p in the pre-osteoblast, MC3T3-E1 cells, resulted in a significant increase in the mRNA expression levels of <em>Sp7</em>. Our data indicate that BPs attenuate osteoclastogenesis by simultaneously altering the characteristics of osteoclast-derived EVs. Overexpression of miR-146a-5p and miR-322-3p influences osteoclast differentiation, and <em>Traf6</em> is a target gene of miR-146a-5p. On the other hand, Overexpression of miR-322-3p affects osteoblast differentiation. We suggest that ZA-treated osteoclast-derived EVs may play an important role in osteoclast function and bone resorption.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117323"},"PeriodicalIF":3.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607625","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":"Biomimetic periosteum-bone scaffolds with codelivery of BMP-2 and PDGF-BB for skull repair","authors":"Zihao Zhan ,&nbsp;Ran Li ,&nbsp;Yiang Wu ,&nbsp;Xiaotian Shen ,&nbsp;Dongming Fu ,&nbsp;Hao Han ,&nbsp;Pengrui Jing ,&nbsp;Bin Li ,&nbsp;Fengxuan Han ,&nbsp;Bin Meng","doi":"10.1016/j.bone.2024.117315","DOIUrl":"10.1016/j.bone.2024.117315","url":null,"abstract":"<div><div>Tissue engineering employs the use of bioactive materials to facilitate the filling and acceleration of bone defect healing, thereby introducing novel concepts to the field of <em>in situ</em> bone repair. Some studies have shown that periosteum plays an important role in bone regeneration and repair. In this study, biomimetic periosteum-bone scaffolds were prepared by depositing poly-L-lactic acid (PLLA) electrospun fibers on the surface of the gelatin/chitosan cryogel to mimic the bone and periosteum structure, respectively. To improve the bioactivity of the scaffold, bone morphogenetic protein-2 (BMP-2) was loaded into a loose porous mesh-like cryogel, while platelet-derived growth factor-BB (PDGF-BB) was encapsulated in the core of PLLA nanofibers with core-shell structure. Both of these two growth factors were released locally at the site of bone defect, where they exert a synergistic effect on osteogenesis, thereby greatly accelerating bone healing. The <em>in vitro</em> experiments demonstrated that the biomimetic periosteum-bone scaffolds exhibited favourable biocompatibility and osteogenesis ability. Furthermore, the <em>in vivo</em> experiments indicated that the composite scaffold repaired rat skull defects in a more rapid and effective manner. In conclusion, biomimetic periosteum-bone scaffolds with codelivery of BMP-2 and PDGF-BB shows significant potential for bone regeneration.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117315"},"PeriodicalIF":3.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592410","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":"Integrin α2β1 deficiency enhances osteogenesis via BMP-2 signaling for accelerated fracture repair","authors":"Daniel Kronenberg ,&nbsp;Melanie Brand ,&nbsp;Jens Everding ,&nbsp;Louisa Wendler ,&nbsp;Eric Kieselhorst ,&nbsp;Melanie Timmen ,&nbsp;Michael D. Hülskamp ,&nbsp;Richard Stange","doi":"10.1016/j.bone.2024.117318","DOIUrl":"10.1016/j.bone.2024.117318","url":null,"abstract":"<div><div>Previous studies have shown that the absence of the collagen-binding integrin α2β1 confers protection against osteoporosis, primarily by enhancing osteoblast-mediated matrix formation, with a particular increase in collagen type I production. This study aimed to elucidate the mechanism underlying this increased matrix production. Our findings demonstrate that osteoblasts lacking integrin α2 secrete a pro-osteogenic factor that activates both TGF-β and BMP signaling pathways. Among these, BMP-2 was identified as the key signaling protein responsible for this effect, as its expression was significantly upregulated during osteoblast differentiation. Moreover, integrin α2 deficiency led to earlier and elevated BMP-2 secretion at the cell surface during osteogenesis, which promoted accelerated osteoblast differentiation. This phenomenon likely contributes to enhanced matrix production in aging animals, providing a protective effect against osteoporosis.</div><div>To explore the broader implications of this phenotype, we utilized a fracture healing model. In integrin α2-deficient 12 weeks old female mice, elevated serum levels of BMP-2 were detected during the early stages of fracture repair. This upregulation of BMP signaling within the fracture callus accelerated the healing process, resulting in faster formation and mineralization of the cartilaginous callus. Additionally, the elevated BMP-2 levels facilitated earlier differentiation of chondrocytic cells, evidenced by the premature appearance of collagen type II- and type X-positive cells during endochondral ossification. Despite the accelerated healing, the overall biomechanical integrity of the repaired fractures remained uncompromised.</div><div>Thus, the modulation of integrin α2β1 presents a promising therapeutic target for enhancing fracture repair by regulating BMP-2 signaling in a physiologically relevant manner.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117318"},"PeriodicalIF":3.5,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585208","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":"HarDNet-based deep learning model for osteoporosis screening and bone mineral density inference from hand radiographs","authors":"Chan-Shien Ho ,&nbsp;Tzuo-Yau Fan ,&nbsp;Chang-Fu Kuo ,&nbsp;Tzu-Yun Yen ,&nbsp;Szu-Yi Chang ,&nbsp;Yu-Cheng Pei ,&nbsp;Yueh-Peng Chen","doi":"10.1016/j.bone.2024.117317","DOIUrl":"10.1016/j.bone.2024.117317","url":null,"abstract":"<div><h3>Purpose</h3><div>Osteoporosis, affecting over 200 million individuals, often remains unrecognized and untreated, increasing the risk of fractures in older adults. Osteoporosis is typically diagnosed with bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA). This study aims to develop DeepDXA-Hand, a deep learning model using the efficient CNN-based deep learning architecture, for opportunistic osteoporosis screening from hand radiographs.</div></div><div><h3>Methods</h3><div>DeepDXA-Hand utilizes a CNN-based, HarDNet, approach to predict BMD non-invasively. A total of 10,351 hand radiographs and DXA pairs were used for model training and validation. The model's interpretability was enhanced using GradCAM for hotspot analysis to determine the model's attention areas.</div></div><div><h3>Results</h3><div>The predicted and ground truth BMD were significantly correlated with a correlation coefficient of 0.745. For binary classification of osteoporosis, DeepDXA-Hand demonstrated a sensitivity of 0.73, specificity of 0.83, and accuracy of 0.80, indicating its clinical potential. The model mainly focused on the carpal bones, such as the capitate, trapezoid, hamate, triquetrum, and the head of the second metacarpal bone, suggesting these areas provide radiological features for inferring BMD.</div></div><div><h3>Conclusion</h3><div>DeepDXA-Hand shows potential for the early detection of osteoporosis with high sensitivity and specificity. Further studies should explore its utility in predicting fracture risks.</div></div><div><h3>Mini abstract</h3><div>Osteoporosis affects millions and often goes undetected and untreated. DeepDXA-Hand, a HarDNet-based deep learning model, predicted bone mineral density with a correlation of 0.745 and classified osteoporosis with 0.80 accuracy. This model enhances early detection and has significant clinical potential as osteoporosis opportunistic screening tool.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117317"},"PeriodicalIF":3.5,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585206","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}