Calcified Tissue International最新文献

{"title":"Insights into Natural History, Phenotypic, and Molecular Spectrum in a Large Cohort of Osteosclerotic Disorders.","authors":"Dilek Uludağ Alkaya, Esra Usluer, Zeynep Alp Ünkar, Ali Şeker, İbrahim Adaletli, Nilay Güneş, Rıza Madazlı, Pınar Kadıoğlu, Murat Derbent, Beyhan Tüysüz","doi":"10.1007/s00223-025-01366-w","DOIUrl":"https://doi.org/10.1007/s00223-025-01366-w","url":null,"abstract":"<p><p>Osteosclerotic bone diseases include more than 30 rare diseases characterized by excessive bone formation. The aim of this study is to compare the molecular pathogenesis and prognostic features of 12 different osteosclerotic diseases. Thirty-four patients from 23 families were included, 25 of whom were followed for a period of one to 22 years. Exome sequencing was performed in 20 families. Primary hypertrophic osteoarthropathy (PHOAR1/2) was found in 12 patients, followed by juvenile Paget's disease (JPD)-5 in five, craniometaphyseal dysplasia (CMD) and Camurati-Engelmann disease (CED) in four, Ghosal hematodiaphyseal dysplasia (GHDD) in three patients, sclerosteosis-1 in two patients, and ultra-rare diseases including trichothiodystrophy-1, prenatal Caffey disease, melorheosteosis, and Lenz-Majewski hyperostotic dwarfism in one patient each. Patients with CMD and sclerosteosis-1 had severe cranial sclerosis leading to facial dysmorphism. CMD was characterized by metaphyseal widening, radiolucency, and diaphyseal sclerosis of the long bones in early childhood and later developed Erlenmeyer flask deformity sparing the vertebrae and pelvis, whereas sclerosteosis-1 manifested as generalized sclerosis. CED and GHDD share bone pain, difficulty in walking, and diaphyseal sclerosis, with some patients also having bone marrow involvement. Interestingly, patients with CED and JPD-5 showed osteopenia in early childhood, followed by the development of osteosclerosis in late childhood. Clinical and radiologic findings improved over time in PHOAR1 patients, whereas they progressed in JPD-5 and trichothiodystrophy-1 patients. Intra- and interfamilial clinical differences were observed in CMD, CED, JPD-5, and GHDD. The knowledge gained about the natural history of osteosclerotic diseases will make an important contribution to their diagnosis and management.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"59"},"PeriodicalIF":3.3,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of Skeletogenic Pathways by m6A RNA Modification: A Comprehensive Review.","authors":"Ehsan Pashay Ahi","doi":"10.1007/s00223-025-01367-9","DOIUrl":"10.1007/s00223-025-01367-9","url":null,"abstract":"<p><p>In the complex process of skeletal development, the significance of m6A RNA methylation-a predominant form of RNA modification-has not been fully explored. This review discuss how m6A RNA methylation plays an important, though not yet fully understood, role in regulating skeletal formation. It examines how m6A influences key signaling pathways essential for skeletal development and homeostasis, suggesting various possible interactions between m6A methylation and these critical pathways. While the exact mechanisms for many of these interactions remain to be elucidated, m6A RNA methylation is anticipated to be a key emerging regulator in skeletal structure development across vertebrates. Highlighting the need for further research, this overview provides an in-depth look at the potential regulatory interactions of m6A RNA methylation within skeletal system. Uniquely, this review is the most comprehensive compilation of evidence linking components of m6A RNA methylation to signaling pathways involved in skeletogenesis.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"58"},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TGF-β Enhances Phosphate-Driven Calcification of Human OA Articular Chondrocytes.","authors":"Roderick H M J Stassen, Guus G H van den Akker, Marjolein M J Caron, Don A M Surtel, Andy Cremers, Lodewijk W van Rhijn, Tim J M Welting","doi":"10.1007/s00223-025-01365-x","DOIUrl":"10.1007/s00223-025-01365-x","url":null,"abstract":"<p><p>The pathological relevance of articular cartilage calcification in osteoarthritis (OA) is becoming increasingly evident. We are only beginning to understand the pathobiological mechanisms that contribute to articular cartilage calcification in OA. How molecular environmental factors interact with calcification mechanisms is poorly explored. In this study, we developed an in vitro phosphate-driven calcification model for human OA articular chondrocytes, in which these cells are cultured in the presence of calcification medium containing adenosine triphosphate (ATP) and β-glycerophosphate (BGP). We employed this model to investigate the role of transforming growth factor β (TGF-β) in chondrocyte calcification. Chondrocyte culture in calcification medium resulted in mineral nodule formation over a time course of 7 days. The presence of calcium and phosphate deposition in these nodules was validated with von Kossa staining, scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDX), and colorimetric calcium and phosphate assays. Supplementation of calcification medium with TGF-β resulted in enhanced nodule formation with a different morphology and changed the expression of extracellular matrix-related genes such as collagen type I and III. In conclusion, we developed a new in vitro model for human OA articular chondrocyte calcification, in which we demonstrated a pro-calcifying role for TGF-β. This in vitro model may be used as a basis to aid the investigation of the influence of environmental factors on chondrocyte calcification and the development of new anti-calcification disease-modifying osteoarthritis drugs.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"57"},"PeriodicalIF":3.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Office Blood Pressure and Obesity in Children with X-Linked Hypophosphatemia.","authors":"Ineke Böckmann, Maren Leifheit-Nestler, Mirko Rehberg, Giuseppina Spartà, Katrina Evers, Karl Peter Schlingmann, Markus J Kemper, Annette Richter-Unruh, Olaf Hiort, Karina Grohmann-Held, Ute Derichs, Clemens Freiberg, Marcus Weitz, Desiree Dunstheimer, Elmar Schmid, Ulrike John-Kroegel, Oliver Metzing, Sabine Heger, Norbert Jorch, Hagen Staude, Ludwig Patzer, Elke Wühl, Miroslav Zivicnjak, Dirk Schnabel, Dieter Haffner","doi":"10.1007/s00223-025-01363-z","DOIUrl":"10.1007/s00223-025-01363-z","url":null,"abstract":"<p><p>X-linked hypophosphatemia (XLH) is the most common inherited form of hypophosphatemic rickets. Children with XLH have an increased risk of obesity, which may promote high blood pressure, but data on blood pressure in XLH are inconclusive. We aimed to assess blood pressure and its determinants in pediatric XLH patients. We conduct a prospective, multicenter observational study of children with XLH in Germany and Switzerland. Office blood pressure and body mass index (BMI) were annually measured in 128 pediatric XLH patients with a median follow-up of 2 years (range 1-6). Potential predictors of blood pressure were investigated by Spearman correlation. Seventeen percent of patients were treated with phosphate supplements and active vitamin D for a median of 8 years, 83% of patients received burosumab for 2.3 years with 3.1 years of prior treatment with phosphate supplements and active vitamin D. Median systolic (0.75 z-score) and diastolic (0.32 z-score) blood pressure and BMI (0.72 z-score) were increased compared to healthy children (each p < 0.01). The prevalence of obesity (9.8% vs. 3%), arterial hypertension (26.2% vs. 5%), and high-normal blood pressure (22.9% vs. 5%) was higher in the XLH cohort compared to the general pediatric population (each p < 0.001). Spearman rank correlation analysis revealed significant associations between both systolic (r = 0.24; p < 0.01) and diastolic (r = 0.20; p < 0.05) blood pressure with BMI, while the mode of treatment, i.e. burosumab versus phosphate supplements and active vitamin D, was no significant correlate. Children with XLH present with elevated office blood pressure values, associated with elevated BMI.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"56"},"PeriodicalIF":3.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Zoledronic Acid on Bone Mineral Density and Trabecular Score Following Denosumab Discontinuation in Older Adults in Long-Term Care.","authors":"Nami Safai Haeri, Subashan Perera, Susan L Greenspan","doi":"10.1007/s00223-025-01364-y","DOIUrl":"https://doi.org/10.1007/s00223-025-01364-y","url":null,"abstract":"<p><p>Discontinuation of denosumab can result in rebound bone loss and increased vertebral fracture risk. In residents of long-term care communities (LTCCs) with osteoporosis, there is limited data on managing the risks after discontinuation. We investigated the impact of a single dose of zoledronic acid on bone density and microarchitecture following two years of denosumab treatment. In an open-label, one-year extension study following a two-year double-blind, placebo-controlled, randomized clinical trial, 39 older adults aged 65 years and above, who were residents of LTCCs and participants in the PROUD (PReventing Osteoporosis Using Denosumab) trial, received a single 5 mg dose of zoledronic acid after completing four doses of denosumab 60 mg during the PROUD trial. We aim to evaluate the effects of a single 5 mg dose of zoledronic acid on bone mineral density (BMD) at the lumbar spine, total hip, femoral neck, and one-third radius, as well as on the spine trabecular bone score (TBS), over a one-year period. Additionally, we surveyed patients for fractures. Our study included 27 women and 12 men, with a mean age of 81.5 years. Twelve months after the administration of zoledronic acid, the mean percent changes from the end of the denosumab trial showed no significant decline in any of the BMD sites in both women and men. In women, the mean percent changes were as follows: spine 0.97 (95% CI: -0.7 to 2.7, p = 0.242) and total hip -0.10 (95% CI: -2.3 to 2.1, p = 0.927). In men, the changes were -0.32 (95% CI: -3.7 to 3.1, p = 0.832) for the spine and 1.79 (95% CI: -0.7 to 4.3, p = 0.139) for the total hip. These findings indicate no evidence of rebound bone loss. In women, TBS significantly increased by 3.9% (95% CI: 0.8 to 5.8, p = 0.007), suggesting improved bone microarchitecture. In men, there was a trend toward improvement in TBS, with an increase of 3.3% (95% CI: -4.0 to 13.0, p = 0.054). There were no reported fragility fractures among participants during the post-denosumab period. In residents of LTCCs with osteoporosis receiving a single 5 mg dose of zoledronic acid following two years of denosumab, we found no evidence of a loss in BMD or TBS. Further, participants experienced enhanced bone microarchitecture.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"55"},"PeriodicalIF":3.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone Effects of Anti-Cancer Treatments in 2024.","authors":"Marie Teissonnière, Mathieu Point, Emmanuel Biver, Peyman Hadji, Edith Bonnelye, Peter R Ebeling, David Kendler, Tobias de Villiers, Gerold Holzer, Jean-Jacques Body, Ghada El Hajj Fuleihan, Maria Luisa Brandi, René Rizzoli, Cyrille B Confavreux","doi":"10.1007/s00223-025-01362-0","DOIUrl":"10.1007/s00223-025-01362-0","url":null,"abstract":"<p><p>Considerable progress has been made in the management of cancer patients in the last decade with the arrival of anti-cancer immunotherapies (immune checkpoint inhibitors) and targeted therapies. As a result, a broad spectrum of cancers, not just hormone-sensitive ones, have seen several patients achieve profound and prolonged remissions, or even cures. The management of medium- and long-term side-effects of treatment and quality of life of patients are essential considerations. This is especially true for bone, as bone fragility can lead to increased fractures and loss of autonomy, ultimately reducing the possibility of resuming physical activity. Physical activity is essential for lasting oncological remission and prevention of fatigue. While the issue of hormone therapies and their association with breast cancer has been recognized for some time, the situation is relatively new with regards to targeted therapies and immunotherapies. This is particularly challenging given the wide range of available targeted therapies and their application to numerous cancer types. This article provides a comprehensive review of the bone effects of the main anti-cancer therapies currently in use. The review goes beyond glucocorticoids and hormone therapies and discusses for each drug category what is known regarding cellular effects, BMD effects, and fracture incidence.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"54"},"PeriodicalIF":3.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteomesopyknosis: A Bone-Sclerosing Disorder that May be Confused with Bone Metastases.","authors":"José A Riancho, Alvaro Del Real, Ana I Vega, Rosa Landeras, Anibal Ferrerira, Ana C Ferreira, Jose Sainz, Remedios Quirce, Eva Martínez de Castro","doi":"10.1007/s00223-025-01361-1","DOIUrl":"10.1007/s00223-025-01361-1","url":null,"abstract":"<p><p>Sclerosing bone disorders encompass a range of genetic and acquired diseases. The potential for bone metastases is often a significant concern, especially when multiple discrete lesions are present. Several non-malignant disorders can also produce similar patterns of bone abnormalities. Among these is osteomesopyknosis, a rare condition characterized by multiple sclerotic lesions in the axial skeleton. Only a few cases of this presumably genetic disease have been documented. In this report, we present a new case and review previously published cases to enhance understanding and facilitate recognition of this disorder within the broader category of sclerosing bone diseases.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"53"},"PeriodicalIF":3.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of the Ubiquitin-Associated Domain of sqstm1/p62 in Zebrafish Causes a Phenotype Resembling Paget's Disease of Bone.","authors":"Yentl Huybrechts, Raphaël De Ridder, Dylan Bergen, Björn De Samber, Eveline Boudin, Francesca Tonelli, Dries Knapen, Lucia Vergauwen, Dorien Schepers, Evelien Van Dijck, Qiao Tong, Anja Verhulst, Jan De Beenhouwer, Jan Sijbers, Chrissy Hammond, Antonella Forlino, Geert Mortier, Paul Coucke, P Eckhard Witten, Ronald Young Kwon, Andy Willaert, Gretl Hendrickx, Wim Van Hul","doi":"10.1007/s00223-025-01360-2","DOIUrl":"https://doi.org/10.1007/s00223-025-01360-2","url":null,"abstract":"<p><p>The ubiquitin-binding protein p62, encoded by Sequestosome 1 (SQSTM1), is an essential molecular adaptor for selective autophagy. Heterozygous mutations deleting or disrupting the ubiquitin-associated (UBA) domain of p62 have been reported as the major genetic cause for Paget's disease of bone (PDB), the second most common skeletal disease, characterized by hyperactive osteoclasts and focal increases of bone turnover. In this study, we aimed to determine the impact of a similar sqstm1/p62 mutation on the skeleton of zebrafish. We successfully established a sqstm1^tmΔUBA zebrafish line with premature truncation of the UBA domain and performed skeletal phenotyping of heterozygous and homozygous mutant zebrafish. Homozygous sqstm1^tmΔUBA zebrafish suffered from early lethality after 6 mpf, possibly related to a dysregulated autophagy process. Nevertheless, we detected skeletal abnormalities that were generally more severe in older animals and in homozygous versus heterozygous sqstm1^tmΔUBA zebrafish. MicroCT analysis and histologic staining showed alterations in the vertebral bodies and/or bone density in heterozygous sqstm1^tmΔUBA zebrafish. We also detected signs of osteocytic osteolysis in carriers of a mutant sqstm1^tmΔUBA allele, shown by a higher percentage of enlarged osteocyte lacunae at 12mpf (36% in heterozygote mutants, 20% in wild types). By performing scale histomorphometry, we also detected a higher degree of scale resorption in homozygous sqstm1^tmΔUBA zebrafish at 6 mpf. In conclusion, we have generated a Sqstm1 mutant zebrafish model with features of PDB, characterized by focal bone defects and increased osteoclast activity. This model may be useful to further define PDB disease mechanisms and other p62-related (patho)physiological processes.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"52"},"PeriodicalIF":3.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of Comorbid Hyperparathyroidism and Its Association with Renal Dysfunction in Asian Patients with X-Linked Hypophosphatemic Rickets/Osteomalacia.","authors":"Nobuaki Ito, Hee Gyung Kang, Toshimi Michigami, Noriyuki Namba, Takuo Kubota, Ayumi Shintani, Ryota Kawai, Daijiro Kabata, Haruka Ishii, Yayoi Nishida, Seiji Fukumoto, Keiichi Ozono","doi":"10.1007/s00223-025-01359-9","DOIUrl":"10.1007/s00223-025-01359-9","url":null,"abstract":"<p><p>In patients with X-linked hypophosphatemic rickets/osteomalacia (XLH) in Asia, the current prevalence of hyperparathyroidism and its association with renal dysfunction have not been determined. We used patient data retrospectively collected up to the time of informed consent in the SUNFLOWER study, a long-term observational study, to investigate the current treatment status and prevalence of comorbid hyperparathyroidism and its association with renal dysfunction in patients with XLH in Japan and South Korea. Of 69 patients who met the eligibility criteria, 32 (46.4%) did not have hyperparathyroidism (hereinafter referred to as non-hyperparathyroidism), 33 (47.8%) had secondary hyperparathyroidism, and four (5.8%) had tertiary hyperparathyroidism. Men were more prone to develop secondary and tertiary hyperparathyroidism, use oral phosphate at higher frequencies, and have a higher incidence of Stage ≥ 3 chronic kidney disease and Grade ≥ 3 renal calcification than women. Ongoing treatments for patients with XLH and non-hyperparathyroidism, secondary hyperparathyroidism, and tertiary hyperparathyroidism mainly consisted of active vitamin D (30 [93.8%], 25 [75.8%], and 3 [75.0%], respectively) and oral phosphate (21 [65.6%], 23 [69.7%], and 4 [100.0%], respectively). At informed consent, patients with tertiary hyperparathyroidism had the lowest estimated glomerular filtration rate values. Our study highlights the prevalence of comorbid hyperparathyroidism and its association with renal dysfunction in patients with XLH through a large-scale observational study in Asia.Trial registration: NCT03745521; UMIN000031605.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"50"},"PeriodicalIF":3.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atractylenolide I Attenuates Glucocorticoid-Induced Osteoporosis via Inhibiting NF-κB Signaling Pathway.","authors":"Yamei Liu, Xiaoqi Deng, Chen Chen, Binlan Fu, Min Wang, Jinglan Li, Liangliang Xu, Bin Wang","doi":"10.1007/s00223-025-01358-w","DOIUrl":"https://doi.org/10.1007/s00223-025-01358-w","url":null,"abstract":"<p><p>Long-term treatment with glucocorticoids significantly impacts bone health, with glucocorticoid-induced osteoporosis (GIOP) being the most prevalent consequence. Previous studies have established that Atractylenolide I (Atr I) possesses anti-inflammatory, antioxidant and anti-tumor properties, however, its specific effects on osteoclastogenesis and GIOP are still unclear. In this study, our in vitro results revealed that Atr I inhibited RANKL-stimulated osteoclast differentiation in a dose-dependent manner, disrupted the structure of the F-actin belt in mature osteoclasts, blocked RANKL-induced ROS production, and suppressed the expression of osteoclast-associated genes. Mechanistically, the findings indicated that Atr I inhibited the RANKL-induced activation of the NF-κB signaling pathway. In vivo, the micro-CT, bone histomorphometric analysis and histological data demonstrated that Dex administration led to significant bone loss, accompanied by a considerable increase in the number of osteoclasts on the bone surface. Conversely, treatment with Atr I effectively prevented these Dex-induced alterations. Taken together, this study suggests that Atr I may hold potential as a therapeutic agent for the treatment of GIOP.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"51"},"PeriodicalIF":3.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}