Calcified Tissue International最新文献

{"title":"Atypical Femoral Fractures in Adult Patients with Classical Osteogenesis Imperfecta.","authors":"Mikolaj Bartosik, Oskar Windels, Florian Barvencik, Michael Amling, Ralf Oheim","doi":"10.1007/s00223-026-01576-w","DOIUrl":"10.1007/s00223-026-01576-w","url":null,"abstract":"<p><p>Atypical femoral fractures (AFF) are rare fractures with characteristic radiographic features, most commonly associated with long-term bisphosphonate use. Their occurrence in patients with osteogenesis imperfecta (OI), a hereditary bone disease leading to bone fragility, is not well understood. In this study, 138 adults with genetically confirmed classical OI were screened for AFF. Five patients with AFF were identified and compared to an age- and treatment-matched adult OI cohort without AFF (n = 23). Demographical parameters, biochemical markers, bone mineral density (DXA), bone microarchitecture (HR-pQCT), and radiographs were analyzed. In addition, antiresorptive therapy and the duration of treatment were determined and compared. In the screened OI cohort, AFF prevalence was 3.6%. No significant differences were observed between groups regarding age, weight, height, BMI, fracture history, bone mineral density, or antiresorptive therapy exposure and duration. HR-pQCT showed no significant microarchitectural differences, although a trend toward higher cortical thickness was noted in AFF patients. AFF are a rare complication in adults with classical OI and appear to be multifactorial in origin. Our findings suggest that AFF are not exclusively related to antiresorptive therapy but may be influenced by disease-specific factors, particularly the underlying collagen defect, femoral deformities and altered biomechanics. Individualized management strategies are essential, and further studies are needed to clarify underlying mechanisms and best treatment options.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497164","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":"Integrated Genetic and Biochemical Approach to Patients with Bone Disorders Exhibiting Low Alkaline Phosphatase.","authors":"Naoko Hidaka, Soichiro Kimura, So Watanabe, Tomoyuki Akiyama, Kanako Tachikawa, Toshimi Michigami, Natsuho Adachi, Koki Irie, Yoshitomo Hoshino, Hajime Kato, Masaomi Nangaku, Sakae Tanaka, Noriko Makita, Taku Saito, Nobuaki Ito","doi":"10.1007/s00223-026-01574-y","DOIUrl":"10.1007/s00223-026-01574-y","url":null,"abstract":"<p><p>Hypophosphatasia (HPP) is a rare metabolic disorder caused by loss-of-function ALPL variants and characterized by heterogeneous skeletal and extra-skeletal manifestations. Although recent diagnostic criteria include ALPL variants, the diagnosis can be made based solely on clinical features. In adult-onset HPP, however, symptoms are often mild or nonspecific, including musculoskeletal symptoms and fatigue, making it difficult to differentiate from other conditions. This retrospective, cross-sectional study aimed to integrate genetic and biochemical data to enhance the clinical interpretation of low alkaline phosphatase (ALP) in patients with bone disorders. Among 865 consecutive adults visiting a bone-specialized outpatient department, patients with persistent hypophosphatasemia underwent ALPL sequencing. Clinical and biochemical characteristics were compared among three groups: biallelic or monoallelic variants with dominant-negative effect (DNE), monoallelic variants without DNE, and variant-negative individuals. Fifty-six patients (6.5%) showed persistent hypophosphatasemia. Two (0.2%) were compound heterozygotes, and 29 (3.4%) carried monoallelic variants without DNE. Clinical symptoms and secondary causes of hypophosphatasemia were similar between monoallelic without DNE and variant-negative patients, whereas serum ALP, urinary phosphoethanolamine (PEA), and plasma inorganic pyrophosphate (PPi) differed significantly. A model using thresholds of ALP < 35 IU/L, urinary PEA > 91 µmol/gCr, and plasma PPi > 1.96 µmol/L demonstrated high diagnostic performance for identifying patients with monoallelic variants without DNE. This study elucidated the complex clinical spectrum of patients with low ALP. Although clinical manifestations were comparable between monoallelic individuals without DNE and variant-negative individuals, distinct biochemical profiles were observed. Integrating genetic nosology into current diagnostic criteria may refine clinical decision-making.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13372997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454752","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":"Clinical Characteristics, Treatment Patterns, and Complications in Permanent Hypoparathyroidism: A Large Retrospective Cross-Sectional Study.","authors":"Ahmet Kürşat Soyer, Şefika Burçak Polat, Güler İnönü, Beril Turan Erdoğan, Feride Pınar Altay, Cevdet Aydın, Oya Topaloğlu, Reyhan Ersoy, Bekir Çakır, Ahmet Kürşat Soyer","doi":"10.1007/s00223-026-01573-z","DOIUrl":"https://doi.org/10.1007/s00223-026-01573-z","url":null,"abstract":"<p><p>We aimed to evaluate treatment patterns, complications, and associated risk factors in a large cohort of patients with permanent hypoparathyroidism (HypoPT). This retrospective cross-sectional study included 958 adults with permanent HypoPT. Clinical and laboratory features were compared by etiology: postsurgical (86.4%) and nonsurgical (13.6%). The surgical group was further stratified by benign versus malignant thyroid histopathology. Risk factors for HypoPT-related complications were assessed using regression analyses. Patients received calcium, calcitriol, thiazide diuretics, cholecalciferol, teriparatide, or palopegteriparatide. Nephrolithiasis/nephrocalcinosis, basal ganglia calcifications (BGC), cataract, and hypercalciuria were detected in 13.5, 15.2, 20.8, and 44.4%, respectively, intravenous (IV) calcium was required in 8.4% within two years. Compared with postsurgical group, nonsurgical patients had lower calcium and parathyroid hormone (PTH), higher phosphate levels, greater calcium and calcitriol requirements, higher rates of BGC and IV calcium requirement, and higher T-scores (p < 0.05); nephrolithiasis/nephrocalcinosis and cataract were also more frequent (p = 0.086 and 0.072). Compared with malignant histopathology, benign group was associated with a higher BGC prevalence and higher phosphate levels (p = 0.022 and < 0.001). Hypercalciuria was independently associated with nephrolithiasis/nephrocalcinosis; older age, nonsurgical etiology, longer disease duration, hyperphosphatemia, and undetectable PTH with BGC; nonsurgical etiology with cataract; younger age, treatment suboptimal-adherence, and absence of hypercalciuria with IV calcium requirement (p < 0.05). Additionally, in univariable analyses, high-dose calcitriol was associated with nephrolithiasis/nephrocalcinosis and high-dose calcium with BGC (p < 0.05). In conclusion, HypoPT-related complications were associated with hyperphosphatemia, hypercalciuria, undetectable PTH, and high-dose conventional treatment, underscoring the need for better treatments and future studies to determine whether PTH-replacement therapy reduces complication risks.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419069","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":"Insight into Natural History and Phenotype in Untreated Adults with X-Linked Hypophosphatemia.","authors":"Giampiero I Baroncelli, Filomena Cetani, Benedetta Toschi, Alessandra Bulleri, Alessandro Isola, Maria Rita Giuca, Elisabetta Carli, Maria Rita Sessa, Caterina Pelosini, Angela Michelucci, Pasquale Comberiati","doi":"10.1007/s00223-026-01555-1","DOIUrl":"10.1007/s00223-026-01555-1","url":null,"abstract":"<p><p>X-linked hypophosphatemia (XLH) is a rare genetic rachitic/osteomalacic and dental disorder caused by pathogenic variants in PHEX gene resulting in fibroblast growth factor 23 (FGF23) excess leading to hypophosphatemia by renal phosphate wasting and decreased 1,25-dihydroxyvitamin D production. The aim of the study was to provide insight into natural history and phenotype in untreated adults with XLH (no phosphate supplements and active vitamin D metabolites or burosumab). Clinical, biochemical, skeletal features, co-morbidities, and patient-reported outcomes (PROs) were examined in 52 patients (51.5 ± 12.2 years; 18 men and 34 women). Mean height Z-score and mean leg length Z-score were lower than normal (P < 0.0001) and were lower (P < 0.01) in men (-3.8 ± 1.2 and -4.2 ± 1.2, respectively) than in women (-2.9 ± 0.8 and -3.4 ± 0.9, respectively). BMI was in the range of overweight in 30 patients (57.7%) and in the range of obesity in 15 patients (28.8%). Most of patients had severe skeletal deformities and dental-periodontal abnormalities. Pseudofractures were documented in 17 patients (33%). Mean concentration of intact FGF23, osteocalcin, PINP, CTX, and BALP was higher in men compared to women (P < 0.05-P < 0.001). PROs ranged from moderate to severe scores, with no difference (P = NS) between sexes. The phenotype in adult individuals with XLH was characterized by severe and disproportionate short stature, overweight/obesity, severe skeletal deformities with difficulty walking, osteoarticular pain, poor dental health, and reduced quality of life. Stature and biochemical markers of bone turnover were more compromised in men than in women.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13354646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419045","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":"Cardiovascular Safety of Romosozumab Versus Other Anti-Osteoporosis Medications in Patients with Osteoporosis: A Nationwide Health Insurance Claims Database Study in Japan.","authors":"Yuki Fujita, Katsuyasu Kouda, Kenji Fujimori, Nobukazu Okimoto, Shinichi Nakatoh, Junko Tamaki, Shigeyuki Ishii, Sumito Ogawa, Masayuki Iki","doi":"10.1007/s00223-026-01572-0","DOIUrl":"https://doi.org/10.1007/s00223-026-01572-0","url":null,"abstract":"<p><p>Romosozumab (Rmab) is a potent anti-osteoporosis agent with dual effects on bone resorption and formation. Although superior to alendronate in fracture reduction, cardiovascular safety concerns have been raised. This study compared cardiovascular disease (CVD) incidence between Rmab and other anti-osteoporosis medications (AOMs) using Japan's National Database of Health Insurance Claims. Patients aged  ≥ 50 years initiating Rmab, parathyroid hormone analogues (PTH), denosumab (Dmab), or bisphosphonates (BP) between March 2019 and March 2023 were identified. Outcomes were acute myocardial infarction, ischemic heart disease, and cerebrovascular disease occurring within 570 days of initiation or within 180 days after discontinuation. Patients with prior myocardial infarction or cerebrovascular disease were excluded. Hazard ratios (HRs) were derived from Cox regression with inverse probability weighting using propensity scores. The study included 25,584 men and 236,467 women receiving Rmab; 50,688 and 289,132 on PTH; 50,319 and 460,182 on Dmab; and 232,484 and 1,144,757 on BP. Cumulative incidence of outcomes was highest with PTH, followed by Dmab, BP, and lowest with Rmab. Compared with PTH, adjusted HRs for Rmab in men were 0.49 for acute myocardial infarction, 0.59 for ischemic heart disease, and 0.70 for cerebrovascular disease. Compared with Dmab, HRs were 0.62, 0.62, and 0.59, respectively. Versus BP, HRs were 0.68, 0.74, and 0.72. All HRs were similarly below 1.0 in women. After adjustment for baseline characteristics, no excess incidence of cardiovascular events was observed among patients receiving Rmab compared with those receiving other AOMs.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410617","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":"Effects of Potassium Citrate Supplementation on Bone Turnover Markers in Postmenopausal Women: A GRADE-Assessed Systematic Review, Meta-analysis and Trial Sequential Analysis.","authors":"Najat AlSejari, Noura Saad Alkhulaifi, Rahaf Saad Alenezi, Abdullah M Alharran, Amal A Alsubaiei","doi":"10.1007/s00223-026-01569-9","DOIUrl":"10.1007/s00223-026-01569-9","url":null,"abstract":"<p><p>Osteoporosis and osteopenia are major health burdens among postmenopausal women. Potassium citrate, which is an alkaline salt that neutralizes the acid load in the diet is a preventive measure for bone loss. We conducted a systematic review and meta-analysis following PRISMA guidelines. We searched PubMed, Web of Science, Scopus, and Cochrane CENTRAL for randomized controlled trials examining potassium citrate supplementation effects on bone health outcomes in postmenopausal women. Random-effects models calculated mean differences with 95% confidence intervals. Trial sequential analysis assessed evidence sufficiency. Five RCTs involving 401 postmenopausal women were included. Potassium citrate significantly reduced urinary N-terminal telopeptide (NTX) at 1 month compared with placebo (MD = - 4.05 nmol BCE/mmol creatinine; 95% CI - 8.05 to - 0.05; p = 0.0474; I² = 0%). However, no significant effects were observed on serum C-terminal telopeptide (CTX) at 3 or 6 months, or on procollagen type 1 N-terminal propeptide (P1NP) at 3, 6, or 12 months. Potassium citrate significantly increased urinary potassium excretion at both 3 months and 6 months, while urinary calcium, serum calcium, parathyroid hormone, and urinary pH showed no statistically significant differences between groups. Trial sequential analysis indicated that the available evidence for P1NP at 3 and 6 months remains inconclusive, with the accrued sample size below the required information size. Potassium citrate supplementation showed a selective reduction in urinary NTX, suggesting a potential effect on bone resorption. However, no consistent significant effects were observed on other bone turnover markers, including CTX and P1NP, or on calcium-related biochemical outcomes. The clinical relevance of this finding remains uncertain, and further large, well-designed trials with longer follow-up are needed to clarify the role of potassium citrate in preventing postmenopausal bone loss.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410622","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":"A Rose by Any Other Name? Terminology and Ambiguity in Pregnancy- and Lactation-Associated Osteoporosis, Transient Osteoporosis of the Hip, and Bone Marrow Edema Syndrome.","authors":"Lars Grøvle, Eivind Hasvik, Anne Julsrud Haugen","doi":"10.1007/s00223-026-01570-2","DOIUrl":"https://doi.org/10.1007/s00223-026-01570-2","url":null,"abstract":"","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410607","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":"Capsanthin Attenuates Osteoporosis by Targeting the Urotensin II Receptor Pathway to Inhibit Oxidative Stress and NLRP3 Inflammasome Activation.","authors":"Ruonan Cai, Yuanyuan Liu, Qianqian Kong, Jin Sun","doi":"10.1007/s00223-026-01544-4","DOIUrl":"10.1007/s00223-026-01544-4","url":null,"abstract":"<p><p>Although multiple pharmacological options exist for postmenopausal osteoporosis (PMOP), the pursuit of better-tolerated and naturally derived alternatives remains active. This study evaluates the therapeutic potential of capsanthin (Cap), the principal carotenoid in red chili peppers, against estrogen deficiency-induced bone loss. Ovariectomized (OVX) mice were treated with Cap (5-20 mg/kg/day) for 12 weeks. Bone mass and microarchitecture were assessed by micro-computed tomography (µCT) and biomechanical testing. Serum markers of bone turnover and inflammation were measured by ELISA. Network pharmacology and molecular docking were employed to predict core targets, and the involvement of the urotensin II (UII) system and NLRP3 inflammasome was investigated using specific inhibitors in vitro. Cap treatment at 10-20 mg/kg significantly attenuated OVX-induced bone loss, increasing bone mineral density (BMD), improving trabecular microstructure (elevated BV/TV and Tb.Th, reduced Tb.Sp), and enhancing bone strength. Cap promoted osteogenic activity and suppressed osteoclastic resorption. Network analysis identified the UII signaling pathway as a key potential target, and molecular docking confirmed strong binding between Cap and UII. Mechanistically, Cap inhibited the UII/UT axis, leading to reduced oxidative stress (decreased ROS/H₂O₂, increased MnSOD) and suppression of NLRP3 inflammasome activation and pyroptosis, as evidenced by downregulation of NLRP3, caspase-1, IL-1β, and GSDMD. The osteoprotective effects of Cap were mimicked by UT receptor knockdown or NLRP3 inhibition in osteoblastic cells. Cap exerts protective effects against OVX-induced osteoporosis by promoting bone formation and inhibiting bone resorption. Its mechanism involves, at least in part, the inhibition of the UII/UT signaling pathway, which subsequently attenuates oxidative stress and NLRP3-mediated pyroptosis. These findings highlight cap as a promising natural candidate for further development in the management of osteoporosis.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396109","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":"ODAPH (p.Arg77*) Phenotype and Onset of Ameloblast Pathology During Postsecretory Transition Demonstrated by FIB-SEM Analyses of Odaph^C41*/C41* Mice.","authors":"Jan C-C Hu, Charles E Smith, Hong Zhang, Yuanyuan Hu, Tian Liang, Shih-Kai Wang, Kuan Yu Chu, Evans H Brown, James P Simmer","doi":"10.1007/s00223-026-01562-2","DOIUrl":"10.1007/s00223-026-01562-2","url":null,"abstract":"<p><p>Defects in Odontogenesis-Associated Phosphoprotein (ODAPH) cause autosomal recessive non-syndromic amelogenesis imperfecta (AI; OMIM #614832). We present a 14-year-old boy with delayed tooth eruption and generalized soft and yellow enamel. The proband's parents and two siblings were unaffected. Whole exome analyses identified the AI-causing homozygous ODAPH truncation mutation (p.Arg77*) in the proband. Both unaffected parents and one sibling were heterozygous for this change. The other sibling had the reference sequence. To better understand the role of ODAPH in normal amelogenesis and resolve conflicting reports of ODAPH expression and function during postsecretory transition (PST), we performed comprehensive Focused-Ion Beam Scanning Electron Microscopy analyses of continuously growing mandibular incisors from one wild-type and two Odaph^C41*/C41* mice. Montages of sagittal sections were constructed using 5000 × images covering the surface enamel, ameloblasts, stratum intermedium and papillary layer during late secretory, PST, and early maturation stages. Odaph^C41*/C41* ameloblasts completed the secretory stage showing no evidence of pathology. Dramatic histological differences between wild-type and Odaph^C41*/C41* ameloblasts were observed during postsecretory transition closely preceding the onset of cyst formation in Odaph^C41*/C41* ameloblasts. PST ameloblasts show marked abnormalities, including loss of polarity (nucleus moves distally), disrupted cellular organization, indistinct cell boundaries and rapid reduction in cell height. During PST and early maturation, a dark line indicative of a basal lamina is apparent in the superficial enamel, but it fails to maintain attachment with the ameloblast distal membrane, and a cyst forms between the enamel surface and the overlying flattened ameloblasts, which eliminates the entire maturation stage of amelogenesis. Immunohistochemistry of a Day 12 mandibular incisor detected ODAPH protein in PST and the maturation stage ameloloblasts, and concentrated along the basement membrane. We conclude that ODAPH is required for a successful transition into the maturation stage of amelogenesis. Loss of ODAPH function results in hypomineralized amelogenesis imperfecta.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13331816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374600","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":"Cytokine Networks Reprogramming the Osteo-Immune Microenvironment in Cancer Bone Metastasis.","authors":"Toru Hiraga","doi":"10.1007/s00223-026-01568-w","DOIUrl":"https://doi.org/10.1007/s00223-026-01568-w","url":null,"abstract":"<p><p>Bone metastasis is a major clinical challenge and is frequently associated with resistance to immunotherapy and progressive skeletal destruction. Although cytokines are recognized as key regulators of both immune responses and bone remodeling, their integrated roles in the bone metastatic niche remain incompletely understood. Here, we propose a conceptual framework in which cytokine-driven osteo-immune reprogramming shapes the bone microenvironment into a state that supports tumor persistence. Within this framework, cytokines can be categorized into three functional groups-immune-dominant mediators, osteo-immune regulators, and divergent factors-whose context-dependent activities collectively coordinate immune suppression and osteoclastic bone destruction. Rather than acting independently, these cytokines form interconnected networks that establish reinforcing interactions, thereby stabilizing an immunologically cold and therapy-resistant niche. This integrated perspective suggests that immune resistance in bone metastasis does not arise solely from tumor-intrinsic properties, but emerges from dynamic crosstalk in the osteo-immune axis. The spatiotemporal regulation of cytokine signaling likely defines stage-specific vulnerabilities, providing opportunities for therapeutic intervention. Targeting cytokine networks in combination with immune checkpoint inhibitors and bone-modifying agents may represent a rational strategy to disrupt pathogenic osteo-immune circuits. A deeper understanding of the reprogramming of the bone microenvironment by cytokines will be essential for enabling durable immunotherapeutic responses in patients with bone metastatic disease.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374463","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}