Calcified Tissue International最新文献

{"title":"Treatment with the Bifidobacterium longum Strain DSM 32947 Increases Bone Mineral Density in Female Mice.","authors":"Claes Ohlsson, Daniel Hägg, Karin Horkeby, Karin H Nilsson, Lina Lawenius, Jianyao Wu, Antti Koskela, Juha Tuukkanen, Louise Grahnemo, Ludwig Ermann Lundberg, Stefan Roos, Klara Sjögren","doi":"10.1007/s00223-025-01429-y","DOIUrl":"10.1007/s00223-025-01429-y","url":null,"abstract":"<p><p>Previous studies have shown that the gut microbiota regulates bone mass and that certain strains of Bifidobacterium longum prevent bone loss in ovariectomized (ovx) mice. A novel strain of Bifidobacterium longum (B. longum subsp. longum DSM 32947; BL) with a broad carbohydrate degradation capacity and the ability to stimulate certain lactobacilli was recently identified. In the present study, we tested if BL improves bone health in gonadal intact and ovx female mice.Ten-week-old C57BL/6 J female mice were subjected to ovx or sham surgery. One week after surgery, mice were treated with arabinoxylan oligosaccharides (AXOS; veh) or a combination of AXOS and BL for five weeks. BL treatment increased BL abundance in the cecal content.Dual-energy X-ray absorptiometry showed that BL increased total body bone mineral density in both sham and ovx mice compared with veh-treated mice (p < 0.01). Computed tomography analyses showed that BL increased trabecular bone volume fraction of the L4 vertebra, mainly due to increased trabecular thickness in both sham and ovx mice (p < 0.05). In addition, BL increased the mid-diaphyseal cortical bone area of the femur (p < 0.05) and improved its strength (p = 0.05).In conclusion, treatment with BL increases parameters for bone health in female mice.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"117"},"PeriodicalIF":3.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12405022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943915","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":"Bone Density, Microarchitecture, and Geometry Assessment in Patients with Pachydermoperiostosis Using Second-Generation High-Resolution Peripheral Quantitative Computed Tomography: A Case-Control Study.","authors":"Durairaj Arjunan, Jayaditya Ghosh, Sayka Barry, Md Sadam Hussain, Ashutosh Rai, Rimesh Pal, Sanjay K Bhadada, Márta Korbonits, Pinaki Dutta","doi":"10.1007/s00223-025-01427-0","DOIUrl":"https://doi.org/10.1007/s00223-025-01427-0","url":null,"abstract":"<p><p>Pachydermoperiostosis (PDP) is a rare genetic disorder manifesting with periostosis, clubbing, and thickened skin. The impact of PDP on bone density and microarchitecture is underexplored despite the potential derangement in bone health due to systemic inflammation. This cross-sectional case-control study was conducted in a tertiary care center in north India from July 2022 to July 2023. We compared treatment naïve PDP patients (n = 8) with age and BMI-matched apparently healthy controls. All participants underwent clinical examination and estimation of biochemical parameters including calcium, phosphorus, alkaline phosphatase, 25(OH)D, and iPTH. Bone turnover markers C-terminal telopeptide of type I collagen (CTX) and procollagen type I N-propeptide (P1NP) were also assessed. All patients underwent areal and volumetric bone density measurements using dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT). HR-pQCT analysis revealed diminished cortical volumetric bone mineral density and altered microarchitecture in PDP patients at the radius and tibia, characterized by increased cortical porosity. Bone geometry assessment demonstrated increased cross-sectional bone area both in the cortical and trabecular compartments. Finite element analysis (FEA) indicated a substantial reduction in failure load, cortical and trabecular von Mises stress (VMS) at the tibia and stiffness at the radius in PDP patients compared to controls. PDP patients had similar biochemical and bone turnover parameters to controls. Individuals with PDP show reduced cortical vBMD with disrupted bone microarchitecture. These changes may reflect PGE2-mediated inflammation and bone resorption, suggesting increased fracture risk and the need for ongoing monitoring.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"116"},"PeriodicalIF":3.2,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943917","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":"Early Postmenopausal Fragility Fractures and Elevated IgE: Two Cases Suggesting Hyper-IgE Syndrome and a Novel Adverse Reaction to Romosozumab.","authors":"Lucy Collins, Peter R Ebeling","doi":"10.1007/s00223-025-01428-z","DOIUrl":"https://doi.org/10.1007/s00223-025-01428-z","url":null,"abstract":"<p><p>Severe, treatment-refractory or early-onset osteoporosis should prompt evaluation for secondary causes. Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency disorder characterised by markedly elevated serum IgE, recurrent infections and skeletal anomalies, including osteoporosis and increased fracture burden. We present two cases of severe osteoporosis in early postmenopausal women. Both women exhibited markedly elevated IgE levels, raising the possibility of underlying HIES. Case 1, despite anabolic and anti-resorptive treatment, experienced multiple fragility fractures, with fracture burden out of keeping with bone mineral density. Case 2 did not respond to bisphosphonate therapy and developed a severe erythematous skin reaction following romosozumab therapy. Both cases highlight the importance of evaluating for secondary causes of osteoporosis. The novel reaction to romosozumab in Case 2 raises questions about its use in patients with immune dysregulation.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"115"},"PeriodicalIF":3.2,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943930","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":"Multiscale Analysis Reveals Altered Characteristics in Femur and Mandible of Mice on a High Phosphate Diet.","authors":"Kristin Nguyen, Minji Kim, Andrew J Cheline, Peter Tsatalis, Yasaman Samanian, Olivia Jackson, Daniel A Branch, Hannah F Sanders, Farah A Al-Omari, Young C Jang, Beth S Lee, Kedryn K Baskin, Do-Gyoon Kim","doi":"10.1007/s00223-025-01425-2","DOIUrl":"https://doi.org/10.1007/s00223-025-01425-2","url":null,"abstract":"<p><p>Excessive phosphate used as flavor enhancers and preservatives in processed foods can exacerbate cardiovascular and kidney diseases. In clinical and pre-clinical studies, chronic (over 52 weeks) high-phosphate diet (HPD) negatively affects bone health. We previously demonstrated that 12-week-HPD decreases exercise capacity and skeletal muscle metabolism in adult male mice; however, alteration of bone characteristics associated with HPD independent of disease complications is not well-characterized. Thus, we determined the effects of shorter-term-HPD on characteristics of mouse femurs and mandibles. Adult male mice were fed a normal phosphate diet (NPD) or HPD for 18 weeks, serum markers of mineral metabolism and bone formation and resorption were quantified in femurs, and histological analysis was performed on tibias. Volumetric, mineral density, and morphology parameters of femurs and mandibles were determined using micro-computed tomography, and dynamic mechanical analysis and fracture testing of the femur were conducted. Our studies revealed that 18-week-HPD significantly reduced bone quality (tissue mineral density (TMD) and cortical thickness) without changing bone quantity (total mineral content and volume) of both femurs and mandibles, and femur mechanical properties were aggravated increasing the risk of fracture. Serum markers of osteoclastic resorption and osteoblastic formation were increased with HPD, indicating active osteoclastic bone resorption and osteoblastic new bone formation. These findings provide detailed information on how excessive dietary phosphate substantially alters characteristics of bone, resulting in bone weakening.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"114"},"PeriodicalIF":3.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943979","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":"Moderate-to-High 5-Year Cumulative Disease Activity and Lower Bone Mineral Density at the Proximal Femur are Major Predictors of Fragility Fractures in Women with Longstanding Rheumatoid Arthritis: An Observational Cohort Study.","authors":"Fernanda P Ramos, Marcela M C Pinheiro, Luiza V A Silva, Eliana P C Viner, Vera L Szejnfeld, Charlles H M Castro","doi":"10.1007/s00223-025-01419-0","DOIUrl":"10.1007/s00223-025-01419-0","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) has a higher risk of fractures that is often neglected. We determined the prevalence and risk factors for fractures in women with longstanding RA. Consecutive women with RA from a tertiary hospital underwent bone densitometry (DXA) and spine radiography with morphometric analysis. Disease characteristics, activity, and medication use were assessed. Logistic and linear regression analyses identified risk factors for osteoporosis and fractures. The study included 179 women with RA aged 65.1 ± 9.7 years with a median disease duration of 21 (12.5) years (72% positive for rheumatoid factor). Glucocorticoid (GC), csDMARDs, b/tsDMARDs use, and current moderate-to-high disease activity were observed in 26.3%, 92.7%, 58.6%, and 45.3% of the patients, respectively. Densitometric osteoporosis and fractures were found in 43.6% and 28.5% of the patients, respectively. Fractures were observed in 51 patients (28.5%), primarily occurring at the spine (N = 43) and forearm (N = 10). Almost half of the patients with fractures (N = 24) had a BMD T-score greater than - 2.5. BMI (OR 0.916; 95%CI 0.854-0.983; P = 0.015) and smoking load (OR 1.023; 95%CI 1.002-1.044; P = 0.032) were predictors for osteoporosis, while cumulative 5-year disease activity (OR 3.474; 95%CI 1.557-7.751; P = 0.002) and total femur T-score (OR 0.646; 95%CI 0.436-0.956; P = 0.029) were predictors of fractures. Current GC dose and femoral neck T-score were predictors of spinal deformity index (R² = 0.108; P < 0.001). Almost half of the women with longstanding RA presenting with fractures had BMD values above the osteoporotic range. Moderate-to-high cumulative 5-year disease activity, GC use, and lower BMD at the proximal femur were risk factors for fractures.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"113"},"PeriodicalIF":3.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943907","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 Peripheral Magnetic Stimulation on Bone Healing After Fractures in Mice.","authors":"Bin Liu, Hanlin Jiang, Tingrui Zhao, Akira Ito, Hideki Moriyama","doi":"10.1007/s00223-025-01422-5","DOIUrl":"https://doi.org/10.1007/s00223-025-01422-5","url":null,"abstract":"<p><p>Bone fractures, especially in the elderly, are increasing, posing challenges to healthcare systems. Traditional treatment often focuses merely on bone repair and overlooks the overall healing environment. Peripheral magnetic stimulation (PMS), a non-invasive method, shows promise for bone regeneration. In our murine femoral fracture model study, male C57BL6/J mice were divided into a control group and three PMS treatment groups (10, 50, and 100 Hz). After a fracture, the mice received 30-min daily PMS sessions. The pain was monitored weekly using the von Frey test. Micro-computed tomography (μCT), biomechanics, and histology evaluated bone healing. Our results have shown that 10 and 100 Hz PMS significantly reduced pain and promoted early callus formation by speeding up early mineralized callus. After 4 weeks, the 10 Hz PMS improved mechanical strength, and the 10 and 100 Hz PMS increased bone mineral density. Histology revealed more cartilage, new bone formation, and enhanced osteoblast activity. PMS also decreased fibrous tissue, indicating better bone remodeling. The staining results confirmed that PMS promoted early cartilage formation, endochondral ossification, and increased vascular density. These findings suggest that PMS at 10 and 100 Hz accelerates endochondral ossification, enhances bone formation, and improves biomechanical strength, demonstrating its potential application value in fracture treatment.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"112"},"PeriodicalIF":3.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943904","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":"Evaluation of Low Alkaline Phosphatase Levels in Clinical Practice: Implications for Diagnosing Hypophosphatasia.","authors":"Gonul Buyukyilmaz, Serkan Bilge Koca, Refika Gören, Andac Uzdogan, Keziban Toksoy Adıguzel, Aylin Kılınç Uğurlu, Gonul Yardimci, Pınar Kocaay, Derya Tepe, Mehmet Boyraz, Esra Kilic, Fatih Gürbüz","doi":"10.1007/s00223-025-01424-3","DOIUrl":"10.1007/s00223-025-01424-3","url":null,"abstract":"<p><p>Persistent low serum alkaline phosphatase (ALP) levels are crucial in identifying genetic disorders such as hypophosphatasia (HPP). This study investigates the causes of low ALP levels in children, aiming to evaluate the demographic and clinical characteristics of those diagnosed with HPP.We evaluated 2243 children and adolescents, ranging from 0 to 19 years old between September 2019 and July 2024, who exhibited at least two ALP levels below the age- and gender-specific lower limit.In the patient group, 95.4% (2140 patients) exhibited transient low ALP levels, while 4.6% (103 patients) showed persistently low levels. In the persistent group, eleven additional medical conditions were identified, excluding HPP, with calorie depletion (anorexia, malnutrition) being the most common cause. The study identified 16 HPP patients (10 females, 6 males) with high phenotypic variability even within the same variants, comprising 0.71% of the whole group. Genetic testing identified 13 pathogenic/likely pathogenic ALPL gene variants (10 heterozygous, 3 homozygous), two of which were novel. Among HPP patients, 56.2% presented with HPP-related symptoms, most commonly short stature. We found a significant negative correlation between total ALP and serum pyridoxal phosphate (PLP) levels (Rho = - 0.55, p = 0.039), but no correlation with urine phosphoethanolamine.Persistently low ALP levels are a vital clinical indicator for a wide range of disorders, especially HPP. This study expands the phenotypic and genotypic profiles of HPP while improving our understanding of the disease in children. Increasing disease awareness, particularly for milder forms, is essential to avoid delayed diagnosis.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"111"},"PeriodicalIF":3.2,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871644","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":"Quantitative Computed Tomography-Based Analysis of Bone Structure in the Surgical Neck of the Humerus during Aging in Men.","authors":"Yeming Wang, Jian Li, Yutao Men, Wanfu Wei","doi":"10.1007/s00223-025-01403-8","DOIUrl":"10.1007/s00223-025-01403-8","url":null,"abstract":"<p><p>The changes in bone mineral density (BMD), bone structure, and bone size at the proximal humerus with aging, which can lead to fragile fractures in men, are not well understood. This study aimed to investigate age-related changes in the skeletal properties of the surgical neck of the humerus in men. We conducted a cross-sectional cohort study involving 193 Chinese men, divided into three age groups: Group I (20-50 years), Group II (51-64 years), and Group III (≥ 65 years). Bone mass, structure, and geometric properties were evaluated using quantitative computed tomography (QCT). Bone mineral density at the surgical neck showed the strongest negative correlation with age. However, cortical thickness did not significantly correlate with age. Medullary diameter, perimeter, and area increased by 2.68%, 2.72%, and 5.68% per decade, respectively. Periosteal expansion was evidenced by a 2.77%, 2.80%, and 5.57% per decade increase in periosteal diameter, perimeter, and total area. Significant differences in periosteal and medullary parameters were observed between age groups. Section modulus and second moments of area exhibited significant linear associations with age. Notably, these indices did not differ significantly between men aged 20-30 years and those over 80 years. Cortical thickness and periosteal diameter were most strongly associated with section modulus and second moments of area. The study demonstrated that periosteal expansion progresses with aging, paralleling the decline in BMD. Importantly, geometry-related bending and torsion resistance of the surgical neck were not significantly diminished in older men.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"110"},"PeriodicalIF":3.2,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871645","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":"The Impact of Sedentary Behavior and Physical Activity on Bone Health: A Narrative Review from the Rehabilitation Working Group of the International Osteoporosis Foundation.","authors":"Olivier Bruyère, David Scott, Alexandra Papaioannou, Bjoern Buehring, Bruno Muzzi Camargos, Roland Chapurlat, Thierry Chevalley, Elaine M Dennison, Jean-François Kaux, Nancy E Lane, Osvaldo Daniel Messina, Rene Rizzoli, Jorge Morales Torres, Julien Paccou, Jean-Yves Reginster, Sansin Tuzun, Robert D Blank, Stuart Silverman, Daniel Pinto","doi":"10.1007/s00223-025-01421-6","DOIUrl":"10.1007/s00223-025-01421-6","url":null,"abstract":"<p><p>Physical activity (PA) and sedentary behavior (SB) are two key lifestyle factors with profound implications for bone health across the lifespan. While PA is recognized for its positive effects on bone mineral density (BMD) and fracture prevention, emerging evidence highlights the detrimental consequences of prolonged sedentary time, independent of PA levels. This review synthesizes current knowledge on the impact of PA and SB on bone health outcomes, focusing on BMD and fracture risk in children, adolescents, adults, and older populations. A selection of epidemiological studies, systematic reviews, and meta-analyses was analyzed to explore the associations between movement behaviors and bone health indicators across different life stages. Particular attention was given to studies objectively measuring SB and PA and to the substitution effects of sedentary time with light or moderate-to-vigorous PA. In children and adolescents, higher levels of SB are associated with lower BMD, particularly at weight-bearing sites, while participation in weight-bearing and impact-loading PA positively influences bone mass accrual. In adults and older individuals, regular PA, including moderate-to-vigorous intensity weight-bearing PA and resistance training activities, is consistently linked to greater BMD and reduced fracture risk. Conversely, high sedentary time is associated with lower BMD and increased fracture incidence, particularly among frail or pre-frail individuals. Importantly, replacing sedentary time with even light-intensity PA yields measurable benefits for bone health, particularly among older adults and postmenopausal women, and may contribute to a reduced risk of fractures, although evidence remains limited. Promoting PA while minimizing SB should be central to clinical practice and public health policies aimed at maximizing and preserving skeletal health and preventing osteoporotic fractures, across the lifespan. Early intervention, continuous promotion across life stages, and adherence to WHO guidelines offer an effective, evidence-based framework for lifelong bone health maintenance.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"109"},"PeriodicalIF":3.2,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854705","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":"Clinical, Biochemical and Radiological Features of LRP5 Gene Variants in Children.","authors":"Graziamaria Ubertini, Danilo Fintini, Francesco d'Aniello, Flavia Urbano, Mariangela Chiarito, Alessia Angelelli, Natascia Di Iorgi, Maria Felicia Faienza","doi":"10.1007/s00223-025-01412-7","DOIUrl":"https://doi.org/10.1007/s00223-025-01412-7","url":null,"abstract":"<p><p>Alterations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene have been associated with primary osteoporosis, leading to recurrent low-trauma fractures. Heterozygous carriers typically show a milder phenotype, with reduced bone mass starting in early childhood. In this paper, we described the clinical features and therapeutic outcomes of a cohort of 7 children (5 males) harboring different variants in the LPR5 gene. Eight heterozygous variants of the LRP5 gene were identified (6 missense, 2 nonsense), two of which were likely pathogenic. One male patient was compound heterozygous, carrying two different variants, including p.(Arg570Gln), previously reported as pathogenic in homozygous form, and exhibited a more severe phenotype consistent with Osteoporosis-Pseudoglioma Syndrome, including vitreoretinal abnormalities. At initial presentation, most patients had a history of low-trauma long bone fractures, or spontaneous vertebral fractures, and bone/joint pain. Five of them received bisphosphonate therapy and one patient also received denosumab. No new fractures occurred during follow-up (9 months-4 years). Bone mineral density (BMD) increased in all patients (3-103%, mean: 55%), and partial vertebral reshaping was described. No adverse effects were reported. This pediatric case series highlights the phenotypic variability of LRP5 gene variants, and underscores the efficacy of bisphosphonate therapy in improving BMD and reducing fracture risk. However, while bisphosphonates remain the standard of care, further research is needed on precision therapies that target Wnt signaling and other pathways affected by LRP5 gene alterations.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"108"},"PeriodicalIF":3.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820670","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}