Bone & Joint Research最新文献

{"title":"Corrigendum.","authors":"Yayuan Guo, Xueliang Peng, Bin Cao, Qian Liu, Shen Li, Fulin Chen, Dalong Zhi, Shequn Zhang, Zhuoyue Chen","doi":"10.1302/2046-3758.143.BJR-2025-00002","DOIUrl":"https://doi.org/10.1302/2046-3758.143.BJR-2025-00002","url":null,"abstract":"","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 3","pages":"208"},"PeriodicalIF":4.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555427","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":"Aberrant anabolism hinders constructive metabolism of chondrocytes by pharmacotherapy in osteoarthritis.","authors":"Raquel Largo, Aranzazu Mediero, Cristina Villa-Gomez, Ismael Bermejo-Alvarez, Gabriel Herrero-Beaumont","doi":"10.1302/2046-3758.143.BJR-2024-0241.R1","DOIUrl":"https://doi.org/10.1302/2046-3758.143.BJR-2024-0241.R1","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a highly prevalent and disabling disease with an unmet therapeutic need. The characteristic cartilage loss and alteration of other joint structures result from a complex interaction of multiple risk factors, with mechanical overload consistently playing a central role. This overload generates an inflammatory response in the cartilage due to the activation of the innate immune response in chondrocytes, which occurs through various cellular mechanisms. Moreover, risk factors associated with obesity, being overweight, and metabolic syndrome enhance the inflammatory response both locally and systemically. OA chondrocytes, the only cells present in articular cartilage, are therefore inflamed and initiate an anabolic process in an attempt to repair the damaged tissue, which ultimately results in an aberrant and dysfunctional process. Under these circumstances, where the cartilage continues to be subjected to chronic mechanical stress, proposing a treatment that stimulates the chondrocytes' anabolic response to restore tissue structure does not appear to be a therapeutic target with a high likelihood of success. In fact, anabolic drugs proposed for the treatment of OA have yet to demonstrate efficacy. By contrast, multiple therapeutic strategies focused on pharmacologically managing the inflammatory component, both at the joint and systemic levels, have shown promise. Therefore, prioritizing the control of chronic innate pro-inflammatory pathways presents the most viable and promising therapeutic strategy for the effective management of OA. As research continues, this approach may offer the best opportunity to alleviate the burden of this incapacitating disease.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 3","pages":"199-207"},"PeriodicalIF":4.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555444","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":"The role of AGEs in muscle ageing and sarcopenia.","authors":"Zhaojing Guo, Hengzhen Li, Shide Jiang, Masoud Rahmati, Jingyue Su, Shengwu Yang, Yuxiang Wu, Yusheng Li, Zhenhan Deng","doi":"10.1302/2046-3758.143.BJR-2024-0252.R1","DOIUrl":"https://doi.org/10.1302/2046-3758.143.BJR-2024-0252.R1","url":null,"abstract":"<p><p>Sarcopenia is an ageing-related disease featured by the loss of skeletal muscle quality and function. Advanced glycation end-products (AGEs) are a complex set of modified proteins or lipids by non-enzymatic glycosylation and oxidation. The formation of AGEs is irreversible, and they accumulate in tissues with increasing age. Currently, AGEs, as a biomarker of ageing, are viewed as a risk factor for sarcopenia. AGE accumulation could cause harmful effects in the human body such as elevated inflammation levels, enhanced oxidative stress, and targeted glycosylation of proteins inside and outside the cells. Several studies have illustrated the pathogenic role of AGEs in sarcopenia, which includes promoting skeletal muscle atrophy, impairing muscle regeneration, disrupting the normal structure of skeletal muscle extracellular matrix, and contributing to neuromuscular junction lesion and vascular disorders. This article reviews studies focused on the pathogenic role of AGEs in sarcopenia and the potential mechanisms of the detrimental effects, aiming to provide new insights into the pathogenesis of sarcopenia and develop novel methods for the prevention and therapy of sarcopenia.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 3","pages":"185-198"},"PeriodicalIF":4.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555673","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":"Development of a novel rat long-bone nonunion model and efficacy evaluation of a prostaglandin EP4 selective agonist (AKDS001) combined with iliac bone grafting.","authors":"Daisuke Tateiwa, Masahiro Nishida, Joe Kodama, Hiromasa Hirai, Shinichi Nakagawa, Yuichiro Ukon, Kazuhiro Takeyama, Natsumi Yamamori, Kyoko Hirano, Masato Ikuta, Takayuki Kitahara, Takuya Furuichi, Masayuki Bun, Seiji Okada, Takashi Kaito","doi":"10.1302/2046-3758.143.BJR-2024-0220.R1","DOIUrl":"10.1302/2046-3758.143.BJR-2024-0220.R1","url":null,"abstract":"<p><strong>Aims: </strong>Nonunion occurs when a fracture fails to heal permanently, often necessitating surgical intervention to stimulate the bone healing response. Current animal models of long-bone nonunion do not adequately replicate human pathological conditions. This study was intended as a preliminary investigation of a novel rat nonunion model using a two-stage surgical intervention, and to evaluate the efficacy of a selective prostaglandin E2 receptor 4 agonist (AKDS001) as a novel nonunion therapeutic agent compared with existing treatments.</p><p><strong>Methods: </strong>Initially, Sprague-Dawley rats underwent intramedullary Kirschner wire (K-wire) fixation of a femoral fracture with the interposition of a 2 mm-thick silicon disc. After three weeks, the silicon disc was removed, and the intramedullary K-wire was replaced with plate fixation while maintaining the 2 mm defect. Contrary to the control group (1) that received no treatment, the following therapeutic interventions were performed at injury sites after freshening: (2) freshening group: no grafting; (3) iliac bone (IB) group: IB grafting; (4) AKDS group: AKDS001-loaded microspheres (MS) combined with IB (0.75 mg/ml); and (5) bone morphogenetic protein (BMP) group: grafting of a BMP-2-loaded collagen sponge (10 μg; 0.10 mg/ml). After six weeks, micro-CT (μCT) and histological analysis was performed.</p><p><strong>Results: </strong>In the control group, the radiological union rate was 0%, and histological findings showed that fracture sites comprised fibrous scar tissue, resembling the histology of human nonunion. The union rates in the freshening, IB, AKDS, and BMP groups were 16.7%, 0%, 62.5%, and 50.0%, respectively. The AKDS group demonstrated a significantly higher union rate than the IB group (p = 0.026). μCT and histological analysis indicated that the quality of newly formed bone was superior in the AKDS group than in the BMP group.</p><p><strong>Conclusion: </strong>We developed a novel long-bone nonunion model. The co-therapy of AKDS001-MS and IB grafting presents a promising new treatment for nonunion.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 3","pages":"166-175"},"PeriodicalIF":4.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540079","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":"Rapid multiplex micro-ELISA assay for simultaneous measurement of synovial biomarkers : a potential aid in diagnosing periprosthetic joint infection?","authors":"Martina Maritati, Michael Vogl, Max Sonnleitner, Andrej Trampuz","doi":"10.1302/2046-3758.143.BJR-2024-0100.R1","DOIUrl":"10.1302/2046-3758.143.BJR-2024-0100.R1","url":null,"abstract":"<p><strong>Aims: </strong>The diagnosis of periprosthetic joint infection (PJI) remains a challenge, as no single diagnostic test shows high diagnostic accuracy. Recently, the measurement of synovial biomarkers has shown promising results. The aim of this study was to present a novel multiplex micro-enzyme-linked immunosorbent assay (ELISA) method for the rapid and simultaneous measurement of alpha-defensin, interleukin (IL)-6, and calprotectin developed in a model buffer system and human spiked synovial fluid.</p><p><strong>Methods: </strong>A microfluidics- and chemiluminescence-based multiplex micro-ELISA point-of-care testing system was employed for the rapid and simultaneous measurement of alpha-defensin, calprotectin, and IL-6 developed in a model buffer system and spiked human synovial fluid. Cut-off values of 1.56 µg/ml for alpha-defensin, 50 µg/ml for calprotectin, and 0.031 µg/ml for IL-6 were extracted from the literature as optimal cut-off values for the diagnosis of PJI, and were used for comparison.</p><p><strong>Results: </strong>Limit of detection (LoD) was determined for each individual biomarker by means of calibration curves with serial dilutions in a model buffer system. LoDs of 0.008, 0.002, and 0.00014 µg/ml were determined for alpha-defensin, calprotectin, and IL-6, respectively. The spiked synovial fluid assay determined LoDs of 0.08, 0.31, and 0.004 µg/ml for alpha-defensin, calprotectin, and IL-6, respectively.</p><p><strong>Conclusion: </strong>These findings highlight the proposed platform's unique features, including simultaneous measurement of three key synovial biomarkers, minimal sample volume requirements (5 to 50 µl), lower LoDs compared to conventional tests, and a short processing turnaround time of 22 minutes. Further validation studies are necessary to confirm its clinical utility.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 3","pages":"176-184"},"PeriodicalIF":4.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540080","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":"A bilayer scaffold of collagen and nanohydroxyapatite promotes osteochondral defect in rabbit knee joints.","authors":"Yayuan Guo, Xueliang Peng, Bin Cao, Qian Liu, Shen Li, Fulin Chen, Dalong Zhi, Shequn Zhang, Zhuoyue Chen","doi":"10.1302/2046-3758.142.BJR-2024-0171.R1","DOIUrl":"10.1302/2046-3758.142.BJR-2024-0171.R1","url":null,"abstract":"<p><strong>Aims: </strong>A large number of surgical operations are available to treat osteochondral defects of the knee. However, the knee joint arthroplasty materials cannot completely mimic the articular cartilage and subchondral bone, which may bring some obvious side effects. Thus, this study proposed a biocompatible osteochondral repair material prepared from a double-layer scaffold of collagen and nanohydroxyapatite (CHA), consisting of collagen hydrogel as the upper layer of the scaffold, and the composite of CHA as the lower layer of the scaffold.</p><p><strong>Methods: </strong>The CHA scaffold was prepared, and properties including morphology, internal structure, and mechanical strength of the CHA scaffold were measured by scanning electron microscopy (SEM) and a MTS electronic universal testing machine. Then, biocompatibility and repair capability of the CHA scaffold were further evaluated using a rabbit knee cartilage defect model.</p><p><strong>Results: </strong>The CHA scaffold was well suited for the repair of articular cartilage and subchondral bone; the in vitro results showed that the CHA scaffold had good cytocompatibility. In vivo experiments demonstrated that the material had high biocompatibility and effectively induced cartilage and subchondral bone regeneration.</p><p><strong>Conclusion: </strong>The CHA scaffold has a high potential for commercialization and could be used as an effective knee repair material in clinical applications.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 2","pages":"155-165"},"PeriodicalIF":4.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11865975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514520","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":"Occurrence of cellular senescence in chronic human shoulder tendinopathies and its attenuation ex vivo by inhibition of Enhancer of Zeste 2.","authors":"Dominik Bühler, Morgane Hilpert, Andrea Barbero, Andreas M Müller, Sebastian A Müller, Ivan Martin, Karoliina Pelttari","doi":"10.1302/2046-3758.142.BJR-2023-0378.R2","DOIUrl":"10.1302/2046-3758.142.BJR-2023-0378.R2","url":null,"abstract":"<p><strong>Aims: </strong>Our aim was to investigate occurrence of senescent cells directly in tendon tissue biopsies from patients with chronic shoulder tendinopathies, and to correlate senescence with Enhancer of zeste 2 (EZH2) expression, the functional subunit of the epigenetic master regulator polycomb repressive complex.</p><p><strong>Methods: </strong>Human proximal long head of biceps tendons from patients with different chronic shoulder pathologies (n = 22), and controls from patients with humerus fracture (n = 6) and pathology (n = 4), were histologically scored for degeneration and analyzed for gene and protein expression of tendon specific factors, senescence markers, and EZH2. Tissues were further exposed to senotherapeutic compounds and the USA Food and Drugs Administration-approved selective EZH2 inhibitor EPZ-6438 and their senescence-associated secretory phenotype (SASP) assessed.</p><p><strong>Results: </strong>Expression of senescence markers (<i>CDKN2A</i>/p16, <i>CDKN2D</i>/p19) and <i>EZH2</i> was significantly higher in tendinopathies compared to fracture or healthy tissue controls and positively correlated with the degree of tissue degeneration. Immunofluorescent stainings demonstrated colocalization of p16 and p19 with EZH2 in tenocytes. Treatment of tendon biopsies with EPZ-6438 reduced secretion of a panel of SASP factors, including interleukin-6 (IL6), IL8, matrix metalloproteinase-3 (MMP3) or GRO1, similarly to the senotherapeutic compound AG490.</p><p><strong>Conclusion: </strong>We demonstrate that senescence traits accumulate in pathological tendon tissues and positively correlate with tissue degeneration. Increased expression of <i>CDKN2A</i>/p16 and <i>CDKN2D</i>/p19 coincides with EZH2 expression, while its inhibition decreased the secretion of SASP factors, indicating a possible regulatory role of EZH2 in tenocyte senescence in tendinopathies. Reduction of cellular senescence, e.g. with EPZ-6438, opens ways to new potential therapeutic approaches for enhancing regeneration in chronic tendinopathies.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 2","pages":"143-154"},"PeriodicalIF":4.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490708","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":"Mental health implications of fracture-related infections : a longitudinal quality of life study.","authors":"Nike Walter, Thomas Loew, Thilo Hinterberger, Melvin Mohokum, Volker Alt, Markus Rupp","doi":"10.1302/2046-3758.142.BJR-2024-0086.R2","DOIUrl":"10.1302/2046-3758.142.BJR-2024-0086.R2","url":null,"abstract":"<p><strong>Aims: </strong>Fracture-related infections (FRIs) are a major concern for patients and healthcare systems, yet their impact on mental health has been largely overlooked. This study aimed to assess the longitudinal impact of FRI on patients' quality of life.</p><p><strong>Methods: </strong>A prospective study was conducted at a level 1 trauma centre between January 2020 and December 2022. In total, 56 patients participated, with quality of life assessed at five timepoints: one week preoperatively, and one, three, six, and 12 months postoperatively. Statistical analysis was performed using repeated measures analysis of variance (ANOVA) with adjusted post-hoc analysis.</p><p><strong>Results: </strong>The preoperative Physical Component Summary score on the 36-Item Short-Form Health Survey questionnaire (SF-36) was 26.71, increasing to 30.40 at one month, remaining stable at three months. A modest increase was observed at six months (32.45, p = 0.003), but it decreased to 29.72 at 12 months. The preoperative Mental Component Summary score (SF-36) was 46.48, decreasing to 39.89 at one month (p = 0.027) and to 36.03 at three months (p ≤ 0.001). However, it improved at six (42.74) and 12 months (44.05). Positive changes were seen in EuroQol five-dimension questionnaire (EQ-5D) subdimensions, such as mobility, self-care, usual activities, and pain/discomfort, while anxiety/depression scores decreased over time. The EQ-5D visual analogue scale (VAS) score increased to 62.79 at six months (p ≤ 0.001) and decreased to 58.2 at 12 months (p = 0.011).</p><p><strong>Conclusion: </strong>FRIs substantially affect mental health and quality of life, particularly during the initial three months of treatment. This study emphasizes the importance of addressing psychological aspects early in FRI management, advocating for holistic care encompassing both physical and psychological aspects of treatment.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 2","pages":"136-142"},"PeriodicalIF":4.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456918","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":"eIF5A downregulated by mechanical overloading delays chondrocyte senescence and osteoarthritis by regulating the CREBBP-mediated Notch pathway.","authors":"Jialuo Huang, Jianrong Zheng, Jianbin Yin, Rengui Lin, Junfeng Wu, Hao-Ran Xu, Jinjian Zhu, Haiyan Zhang, Guiqing Wang, Daozhang Cai","doi":"10.1302/2046-3758.142.BJR-2024-0288.R1","DOIUrl":"10.1302/2046-3758.142.BJR-2024-0288.R1","url":null,"abstract":"<p><strong>Aims: </strong>To examine how eukaryotic translation initiation factor 5A (eIF5A) regulates osteoarthritis (OA) during mechanical overload and the specific mechanism.</p><p><strong>Methods: </strong>Histological experiments used human bone samples and C57BL/6J mice knee samples. All cell experiments were performed using mice primary chondrocytes. Messenger RNA (mRNA) sequencing was performed on chondrocytes treated with 20% cyclic tensile strain for 24 hours. Western blot (WB) and quantitative polymerase chain reaction were employed to detect relevant indicators of cartilage function in chondrocytes. We created the destabilization of the medial meniscus (DMM) model and the mechanical overload-induced OA model and injected with overexpressing eIF5A adenovirus (eIF5A-ADV). Cartilage degeneration was evaluated using Safranin O/Fast Green staining. Relative protein levels were ascertained by immunohistochemistry (IHC) and immunofluorescence (IF) staining.</p><p><strong>Results: </strong>After OA initiation, eIF5A caused an upregulation of type II collagen (COL2) and a downregulation of matrix metalloproteinase 13 (MMP13), P16, and P21, which postponed the aggravation of OA. Further sequencing and experimental findings revealed that eIF5A knockdown accelerated the progression of OA by boosting the expression of histone acetyltransferase cyclic-adenosine monophosphate response element binding protein (CREB)-binding protein (CREBBP) to mediate activation of the Notch pathway.</p><p><strong>Conclusion: </strong>Our findings identified a crucial functional mechanism for the onset of OA, and suggest that intra-articular eIF5A injections might be a useful therapeutic strategy for OA treatment.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 2","pages":"124-135"},"PeriodicalIF":4.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456898","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":"Development and validation of a novel prediction model for osteoporosis : from serotonin to fat-soluble vitamins.","authors":"Jinpeng Wang, Lianfeng Shan, Jing Hang, Hongyang Li, Yan Meng, Wenhai Cao, Chunjian Gu, Jinna Dai, Lin Tao","doi":"10.1302/2046-3758.142.BJR-2023-0409.R2","DOIUrl":"10.1302/2046-3758.142.BJR-2023-0409.R2","url":null,"abstract":"<p><strong>Aims: </strong>We aimed to develop and validate a novel prediction model for osteoporosis based on serotonin, fat-soluble vitamins, and bone turnover markers to improve prediction accuracy of osteoporosis.</p><p><strong>Methods: </strong>Postmenopausal women aged 55 to 65 years were recruited and divided into three groups based on DXA (normal, osteopenia, and osteoporosis). A total of 109 participants were included in this study and split into healthy (39/109, 35.8%), osteopenia (35/109, 32.1%), and osteoporosis groups (35/109, 32.1%). Serum concentrations of serotonin, fat-soluble vitamins, and bone turnover markers of participants were measured. Stepwise discriminant analysis was performed to identify efficient predictors for osteoporosis. The prediction model was developed based on Bayes and Fisher's discriminant functions, and validated via leave-one-out cross-validation. Normal and empirical volume under the receiver operating characteristic (ROC) surface (VUS) tests were used to evaluate predictive effects of variables in the prediction model.</p><p><strong>Results: </strong>Significant variables including oestrogen (E2), total procollagen type 1 amino-terminal propeptide (TP1NP), parathyroid hormone (PTH), BMI, vitamin K, serotonin, osteocalcin (OSTEOC), vitamin A, and vitamin D3 were used for the development of the prediction model. The training accuracy for normal, osteopenia, and osteoporosis is 74.4% (29/39), 80.0% (28/35), and 85.7% (30/35), respectively, while the total training accuracy is 79.8% (87/109). The internal validation showed excellent performance with 72.5% testing accuracy (72/109). Among these variables, serotonin and vitamin K exert important roles in the prediction of osteoporosis.</p><p><strong>Conclusion: </strong>We successfully developed and validated a novel prediction model for osteoporosis based on serum concentrations of serotonin, fat-soluble vitamins, and bone turnover markers. In addition, interactive communication between serotonin and fat-soluble vitamins was observed to be critical for bone health in this study.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 2","pages":"111-123"},"PeriodicalIF":4.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439535","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}