Bone Research最新文献

Aging microenvironment in osteoarthritis focusing on early-stage alterations and targeted therapies. 骨关节炎的衰老微环境关注早期改变和靶向治疗。

IF 12.7 1区医学

Bone Research Pub Date : 2025-10-10 DOI: 10.1038/s41413-025-00465-6

Yifan Dang,Yuhang Liu,Bingjun Zhang,Xiaoling Zhang

{"title":"Aging microenvironment in osteoarthritis focusing on early-stage alterations and targeted therapies.","authors":"Yifan Dang,Yuhang Liu,Bingjun Zhang,Xiaoling Zhang","doi":"10.1038/s41413-025-00465-6","DOIUrl":"https://doi.org/10.1038/s41413-025-00465-6","url":null,"abstract":"Osteoarthritis (OA) is one of the most common degenerative and age-related diseases in joints, which affects 654 million people worldwide. Current therapies could not fundamentally reverse the pathologic process of OA due to the complex pathogenesis. Although OA mechanisms have been investigated on a large scale over the past decade, the OA pathology correlated with aging-associated changes is still largely unrevealed. Therefore, in-depth analysis of the aging microenvironment and aging-related molecular mechanisms in OA may offer additional strategies for clinical prevention and treatment. In this review, we discuss the potential pathogenesis of OA in light of aging-associated changes and summarize three main components of the aging microenvironment of the OA joint: immune homeostatic imbalance, cellular senescence, and stem cell exhaustion, which could be induced by aging and further exacerbate OA progression. Additionally, it is emphasized that immune homeostatic imbalance appears before established OA, which occurs in the early stage and is the therapeutic window of opportunity for better clinical outcomes. Importantly, we evaluate recent therapeutic targets and promising interventions against these components, as well as the challenges and prospects for precise and individualized therapies of OA patients, which we believe would guide the construction of novel combined strategies targeting aging-related factors against OA for better treatments in the future.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"121 1","pages":"84"},"PeriodicalIF":12.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Injured bone-triggered osteokines secretion promotes diabetic wound healing. 损伤骨触发的骨因子分泌促进糖尿病伤口愈合。

IF 12.7 1区医学

Bone Research Pub Date : 2025-10-02 DOI: 10.1038/s41413-025-00454-9

Tong Shen,Kai Dai,Shuang Zhang,Jing Wang,Changsheng Liu

{"title":"Injured bone-triggered osteokines secretion promotes diabetic wound healing.","authors":"Tong Shen,Kai Dai,Shuang Zhang,Jing Wang,Changsheng Liu","doi":"10.1038/s41413-025-00454-9","DOIUrl":"https://doi.org/10.1038/s41413-025-00454-9","url":null,"abstract":"The treatment of severe diabetic foot remains a clinical challenge. While it is established that bone can exert systemic effects through the secretion of osteokines on other organs, whether this endocrine function can be harnessed to promote diabetic wound healing remains unexplored. Here, we investigate the impact of a bone injury strategy on diabetic wound healing, leveraging the body's innate regenerative capacity to stimulate osteokine release and influence remote skin wound repair. This study demonstrates that the tibial defect significantly accelerates ipsilateral diabetic foot skin wound healing. Mechanistically, we identify osteokines, platelet-derived growth factor-BB (PDGF-BB), as the key to initiating this process. Bone defect triggers a substantial release of PDGF-BB, which reaches the skin wound site via peripheral circulation. At the skin wound site, PDGF-BB mediates the secretion of keratinocyte growth factor (KGF) from fibroblasts via the PDGFRβ signaling pathway, thereby promoting the rapid re-epithelialization of epidermal cells through a paracrine pathway. Additionally, elevated PDGF-BB levels enhance the regeneration of CD31hi Emcnhi blood vessels within the wound. Importantly, we demonstrate the therapeutic potential of osteokines by showing that a collagen hydrogel loaded with osteokines promotes wound healing in diabetic mice. Our findings reveal a clear link between bone and skin wound healing, providing a therapeutic inspiration for chronic wounds that are difficult to treat locally.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"114 1","pages":"83"},"PeriodicalIF":12.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Author Correction: Synovial fibroblast derived small extracellular vesicles miRNA15-29148 promotes articular chondrocyte apoptosis in rheumatoid arthritis. 作者纠正：类风湿性关节炎中滑膜成纤维细胞衍生的细胞外小泡miRNA15-29148促进关节软骨细胞凋亡。

IF 15 1区医学

Bone Research Pub Date : 2025-09-30 DOI: 10.1038/s41413-025-00468-3

Zhenyu Zhang, Lulu Liu, Huibo Ti, Minnan Chen, Yuechun Chen, Deyan Du, Wenjing Zhan, Tongtong Wang, Xian Wu, Junjie Wu, Dong Mao, Zhengdong Yuan, Jingjing Ruan, Genxiang Rong, Feng-Lai Yuan

引用次数: 0

Unraveling the mechanisms of bone diseases: targeting dendritic cells in osteoimmunology for internal homeostasis balance. 揭示骨病的机制：在骨免疫学中以树突状细胞为目标实现体内平衡。

IF 12.7 1区医学

Bone Research Pub Date : 2025-09-28 DOI: 10.1038/s41413-025-00456-7

Yanqi Chen,Siyuan Wang,Xiaoyu Chen,Zhifang Wu,Fuming He,Qianming Chen

{"title":"Unraveling the mechanisms of bone diseases: targeting dendritic cells in osteoimmunology for internal homeostasis balance.","authors":"Yanqi Chen,Siyuan Wang,Xiaoyu Chen,Zhifang Wu,Fuming He,Qianming Chen","doi":"10.1038/s41413-025-00456-7","DOIUrl":"https://doi.org/10.1038/s41413-025-00456-7","url":null,"abstract":"Bone repair and regeneration is a complex spatiotemporal process recruiting a variety of cell types, which need to precisely mediated for effective healing post-damage. The concept of osteoimmunology emphasizes the extensive and intricate crosstalk between the bone and the immune system. Despite the significant advancements in understanding osteoimmunology, the precise role of dendritic cells (DCs) in this field remains under investigation. As key antigen-presenting cells, DCs are critical in orchestrating adaptive immune responses and maintaining tissue homeostasis. Recent researches have further revealed the potential of DCs to influence the development or acceleration of inflammatory and autoimmune bone disease, as well as their interaction with skeletal cells in the context of bone repair and regeneration. Therefore, an in-depth understanding of DCs in the osteoimmunology would be valuable. Herein, we discuss the effects of DCs on bone homeostasis and bone-related diseases (i.e., rheumatoid arthritis (RA), periodontitis, bone regeneration, and other bone abnormalities diseases), and introduce the innovative DCs-targeting biomaterials, aimed at promoting bone repair and regeneration. Furthermore, we summarize the underlying crosstalk between DCs and other cells (i.e., osteoclasts, mesenchymal stromal stem cells (MSCs), hematopoietic stem and progenitor cells (HSPCs), T and B cells) in the bone homeostasis and bone-related diseases. In conclusion, we propose that osteoimmunology offers a promising perspective for unraveling the mechanisms of bone-related diseases; meanwhile, targeting DCs from the perspective of osteoimmunology may provide innovative ideas and resolutions to achieve the internal homeostasis balance.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"103 1","pages":"81"},"PeriodicalIF":12.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanism of Piezo1 regulating chondrocyte mitochondrial function and promoting fracture healing through β-catenin/LARS2 signaling pathway. Piezo1通过β-catenin/LARS2信号通路调节软骨细胞线粒体功能促进骨折愈合的机制。

IF 12.7 1区医学

Bone Research Pub Date : 2025-09-24 DOI: 10.1038/s41413-025-00459-4

Tao Zhang,Hongzhi Lv,Siming Jia,Lijun Wang,Weijian Liu,Kai Ding,Xiaofeng Du,Guangzhao Hou,Zhiyong Hou,Yingze Zhang,Weiguo Zou,Wei Chen,Yanbin Zhu

{"title":"Mechanism of Piezo1 regulating chondrocyte mitochondrial function and promoting fracture healing through β-catenin/LARS2 signaling pathway.","authors":"Tao Zhang,Hongzhi Lv,Siming Jia,Lijun Wang,Weijian Liu,Kai Ding,Xiaofeng Du,Guangzhao Hou,Zhiyong Hou,Yingze Zhang,Weiguo Zou,Wei Chen,Yanbin Zhu","doi":"10.1038/s41413-025-00459-4","DOIUrl":"https://doi.org/10.1038/s41413-025-00459-4","url":null,"abstract":"Piezo1, a key mechanosensor in bone homeostasis, plays a crucial role in fracture healing. However, the mechanisms through which Piezo1 regulates chondrocytes and affects endochondral ossification remain poorly understood. This study aimed to investigate the regulatory mechanisms of Piezo1 in chondrocytes during endochondral ossification. Using lineage tracing, we identified chondrocyte-to-osteoblast transdifferentiation during endochondral ossification, which was impaired by chondrocyte-specific Piezo1 knockout. Piezo1 deficiency disrupted mitochondrial bioenergetics, characterized by diminished membrane potential, reduced adenosine triphosphate (ATP) synthesis, suppressed oxygen consumption rates (basal and maximal respiration), and elevated mitochondrial superoxide generation, thereby impairing endochondral ossification during fracture healing. Single-cell RNA sequencing revealed upregulated Lars2 expression in hypertrophic chondrocytes following Piezo1 knockout. Inhibition of Lars2 in chondrocytes normalized mitochondrial dynamics-related markers (MFN1, MFN2, OPA1, DRP1) and restored mitochondrial functional homeostasis. This intervention concurrently reversed Piezo1 knockout-induced suppression of osteogenic markers (Col1, ALP, OCN, OPN, RUNX2), thereby enhancing fracture repair. Protein interaction analyses confirmed direct binding between β-catenin and Lars2. Mechanistically, Piezo1 governs Lars2 expression via β-catenin signaling. Our findings demonstrate that Piezo1 activation via Yoda1 enhances mitochondrial bioenergetics and accelerates fracture repair through the β-catenin/Lars2 axis, offering novel insights and therapeutic avenues for fracture treatment.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"94 1","pages":"79"},"PeriodicalIF":12.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nuclear FGF2 orchestrates phase separation-mediated rDNA chromatin architecture to control BMSCs cell fate. 核FGF2协调相分离介导的rDNA染色质结构来控制骨髓间充质干细胞的命运。

IF 12.7 1区医学

Bone Research Pub Date : 2025-09-24 DOI: 10.1038/s41413-025-00451-y

Hengguo Zhang,Zifei Wang,Zhenqing Liu,Xuan Li,Wansu Sun,Wenyu Zhen,Fei Xu,Rui Wang,Qi Yin,Shuqin Cao,Mingyue Wu,Jiacai He,Jianguang Xu,Yang Li,Quan Yuan

{"title":"Nuclear FGF2 orchestrates phase separation-mediated rDNA chromatin architecture to control BMSCs cell fate.","authors":"Hengguo Zhang,Zifei Wang,Zhenqing Liu,Xuan Li,Wansu Sun,Wenyu Zhen,Fei Xu,Rui Wang,Qi Yin,Shuqin Cao,Mingyue Wu,Jiacai He,Jianguang Xu,Yang Li,Quan Yuan","doi":"10.1038/s41413-025-00451-y","DOIUrl":"https://doi.org/10.1038/s41413-025-00451-y","url":null,"abstract":"Ribosomal RNA (rRNA) synthesis is intricately tied to cellular growth and proliferation. Basic fibroblast growth factor (FGF2), a pivotal factor for bone marrow mesenchymal stem cells (BMSCs), can stimulates rRNA transcription, though the underlying mechanism remains unknown. Here, we demonstrate that the cytoplasm-nucleus translocation of FGF2 is determined by the stable nuclear localization motif. Meanwhile, the nuclear FGF2 regulates rRNA expression and BMSCs proliferation via phase separation. Next, through FGF2 related epigenomics and 3D genomes analysis, we identified chromatin architectures during BMSCs differentiation and aging. In the process, topologically associating domains (TADs) and chromatin loops profiling revealed the attenuated genomic interaction among proximal chromosomes 13, 14, 15, 21, and 22, where phase-separated FGF2 facilitates rDNA transcription depend on specific super-enhancers (SEs). Furthermore, we validated that FGF2 orchestrates rDNA chromatin architecture in coordination with STAT5. Together, these findings underscore the pivotal role of FGF2 in rDNA chromatin architectures, which determines BMSCs cell fate.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"13 1","pages":"80"},"PeriodicalIF":12.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Research progress on sarcopenia in the musculoskeletal system. 肌肉骨骼系统中肌肉减少症的研究进展。

IF 12.7 1区医学

Bone Research Pub Date : 2025-09-23 DOI: 10.1038/s41413-025-00455-8

Xinning Mao,Ke Lv,Weihui Qi,Wenqiang Cheng,Tenghui Li,Yueli Sun,Hongting Jin,Hao Pan,Dong Wang

{"title":"Research progress on sarcopenia in the musculoskeletal system.","authors":"Xinning Mao,Ke Lv,Weihui Qi,Wenqiang Cheng,Tenghui Li,Yueli Sun,Hongting Jin,Hao Pan,Dong Wang","doi":"10.1038/s41413-025-00455-8","DOIUrl":"https://doi.org/10.1038/s41413-025-00455-8","url":null,"abstract":"Sarcopenia, a progressive and systemic skeletal muscle disorder marked by the accelerated deterioration of both muscle function and mass, is highly prevalent among the elderly population, significantly contributing to an elevated risk of adverse outcomes, including falls, fractures, and muscle weakness. Clinical investigations have identified a strong correlation between sarcopenia and several prevalent degenerative skeletal muscle disorders. This correlation is attributed to imbalances in joint mechanics resulting from localized muscle atrophy and the influence of musculoskeletal secretory factors. In this review, we discuss the broader implications of sarcopenia and critically evaluate the currently established assessment methods. Furthermore, the clinical significance of prevalent musculoskeletal disorders (including osteoporosis, osteoarthritis, and spinal pathologies) in relation to sarcopenia, alongside the underlying mechanisms influencing this relationship, is summarized. Additionally, the effects of sarcopenia on the therapeutic efficacy of medications and surgical interventions for musculoskeletal conditions are reviewed. Sarcopenia is intricately linked to the onset, progression, and prognosis of musculoskeletal disorders. Future research should prioritize elucidating the potential mechanisms that connect muscle loss with skeletal muscle diseases, and investigating whether mitigating sarcopenia symptoms could decelerate the progression of these disorders, thereby paving new pathways for therapeutic interventions.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"22 1","pages":"78"},"PeriodicalIF":12.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The impact of mitochondrial dysfunction on osteoarthritis cartilage: current insights and emerging mitochondria-targeted therapies 线粒体功能障碍对骨关节炎软骨的影响：当前的见解和新兴的线粒体靶向治疗

IF 12.7 1区医学

Bone Research Pub Date : 2025-09-01 DOI: 10.1038/s41413-025-00460-x

Siyuan Tan, Yujun Sun, Shixun Li, Haoyu Wu, Yue Ding

{"title":"The impact of mitochondrial dysfunction on osteoarthritis cartilage: current insights and emerging mitochondria-targeted therapies","authors":"Siyuan Tan, Yujun Sun, Shixun Li, Haoyu Wu, Yue Ding","doi":"10.1038/s41413-025-00460-x","DOIUrl":"https://doi.org/10.1038/s41413-025-00460-x","url":null,"abstract":"Osteoarthritis (OA) is a degenerative joint disease associated with age, prominently marked by articular cartilage degradation. In OA cartilage, the pathological manifestations show elevated chondrocyte hypertrophy and apoptosis. The mitochondrion serves as key energy supporter in eukaryotic cells and is tightly linked to a myriad of diseases including OA. As age advances, mitochondrial function declines progressively, which leads to an imbalance in chondrocyte energy homeostasis, partially initiating the process of cartilage degeneration. Elevated oxidative stress, impaired mitophagy and mitochondrial dynamics jointly contribute to chondrocyte pathology, with mitochondrial DNA haplogroups, particularly haplogroup J, influencing OA progression. Therapeutic approaches directed at mitochondria have demonstrated remarkable efficacy in treating various diseases, with triphenylphosphonium (TPP) emerging as the most widely utilized molecule. Other strategies encompass Dequalinium (DQA), the Szeto-Schiller (SS) tetrapeptide family, the KLA peptide, and mitochondrial-penetrating peptides (MPP), etc. These molecules share common properties of lipophilicity and positive charge. Through various technological modifications, they are conjugated to nanocarriers, enabling targeted drug delivery to mitochondria. Therapeutic interventions targeting mitochondria offer a hopeful direction for OA treatment. In the future, mitochondria-targeted therapy is anticipated to improve the well-being of life for the majority of OA patients. This review summarizes the link between chondrocyte mitochondrial dysfunction and OA, as well as discusses promising mitochondria-targeted therapies and potential therapeutic compounds.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"26 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of the unfolded protein response pathway in bone homeostasis and potential therapeutic target in cancer-associated bone disease 未折叠蛋白反应通路在骨稳态中的作用及癌症相关骨病的潜在治疗靶点

IF 12.7 1区医学

Bone Research Pub Date : 2025-08-28 DOI: 10.1038/s41413-025-00457-6

Molly E. Muehlebach, Sarah A. Holstein

{"title":"The role of the unfolded protein response pathway in bone homeostasis and potential therapeutic target in cancer-associated bone disease","authors":"Molly E. Muehlebach, Sarah A. Holstein","doi":"10.1038/s41413-025-00457-6","DOIUrl":"https://doi.org/10.1038/s41413-025-00457-6","url":null,"abstract":"The unfolded protein response pathway is an evolutionarily conserved cytoprotective signaling cascade, essential for cell function and survival. Unfolded protein response signaling is tightly integrated with bone cell differentiation and function, and chronic unfolded protein response activation has been identified in bone disease. The unfolded protein response has been found to promote oncogenesis and drug resistance, raising the possibility that unfolded protein response modulators may have activity as anti-cancer agents. Cancer-associated bone disease remains a major cause of morbidity for patients with multiple myeloma or bone-metastatic disease. Understanding the critical role of unfolded protein response signaling in cancer development and metastasis, as well as its role in bone homeostasis, may lead to novel mechanisms by which to target cancer-associated bone disease. In this review, we summarize the current research delineating the roles of the unfolded protein response in bone biology and pathophysiology, and furthermore, review unfolded protein response modulating agents in the contexts of cancer and cancer-associated bone disease.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"6 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association between osteoporosis and rotator cuff tears: evidence from causal inference and colocalization analyses 骨质疏松症和肩袖撕裂之间的关系：来自因果推理和共定位分析的证据

IF 12.7 1区医学

Bone Research Pub Date : 2025-08-28 DOI: 10.1038/s41413-025-00450-z

Yibin Liu, Rong Zhao, Zhiyu Huang, Feifei Li, Xing Li, Kaixin Zhou, Kathleen A. Derwin, Xiaofei Zheng, Hongmin Cai, Jinjin Ma

{"title":"Association between osteoporosis and rotator cuff tears: evidence from causal inference and colocalization analyses","authors":"Yibin Liu, Rong Zhao, Zhiyu Huang, Feifei Li, Xing Li, Kaixin Zhou, Kathleen A. Derwin, Xiaofei Zheng, Hongmin Cai, Jinjin Ma","doi":"10.1038/s41413-025-00450-z","DOIUrl":"https://doi.org/10.1038/s41413-025-00450-z","url":null,"abstract":"Osteoporosis is a known risk factor for rotator cuff tears (RCTs), but the causal correlation and underlying mechanisms remain unclear. This study aims to evaluate the impact of osteoporosis on RCT risk and investigate their genetic associations. Using data from the UK Biobank (n = 457 871), cross-sectional analyses demonstrated that osteoporosis was significantly associated with an increased risk of RCTs (adjusted OR [95% CI] = 1.38 [1.25–1.52]). A longitudinal analysis of a subset of patients (n = 268 117) over 11 years revealed that osteoporosis increased the risk of RCTs (adjusted HR [95% CI] = 1.56 [1.29–1.87]), which is notably varied between sexes in sex-stratified analysis. Causal inference methods, including propensity score matching, inverse probability weighting, causal random forest and survival random forest models further confirmed the causal effect, both from cross-sectional and longitudinal perspectives. A colocalization analysis across multiple datasets identified six candidate loci, including the successfully replicated PKDCC rs12996954 variant, which may help explain the shared genetic basis between osteoporosis and RCTs. In conclusion, osteoporosis significantly increases the risk of RCTs, emphasizing the importance of osteoporosis management in preventing RCTs. The identification of shared genetic loci provides new insights into their potential pathogenic mechanisms.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"24 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0