Bone最新文献

{"title":"Expanding the genetic spectrum of short rib polydactyly syndrome: Novel DYNC2H1 variants and functional insights","authors":"Bilgesu Ak ,&nbsp;Mete Akısü ,&nbsp;Asude Durmaz ,&nbsp;Mehmet Yalaz ,&nbsp;Demet Terek ,&nbsp;Ece Sönmezler ,&nbsp;Yavuz Oktay ,&nbsp;Haluk Akın ,&nbsp;Ayça Aykut","doi":"10.1016/j.bone.2025.117511","DOIUrl":"10.1016/j.bone.2025.117511","url":null,"abstract":"<div><h3>Introduction</h3><div>Short rib polydactyly syndrome (SRPS), with or without polydactyly, also known as Verma-Naumoff/Saldino-Noonan syndrome, is a type of skeletal ciliopathy. Initially, variants in the <em>IFT80</em> gene were implicated; however, approximately half of the SRPS cases are associated with variants in the <em>DYNC2H1</em> gene. Additionally, digenic variants involving <em>DYNC2H1</em> and <em>NEK1</em> can contribute to the syndrome.</div></div><div><h3>Materials and methods</h3><div>This case report describes a male patient presenting with characteristic SRPS features, including a constricted thorax and shortened limbs. Exome sequencing was performed to identify causative variants, followed by functional analyses to assess the pathogenicity of the identified variants, including a synonymous variant.</div></div><div><h3>Results</h3><div>Exome sequencing identified compound heterozygous variants in the <em>DYNC2H1</em> gene: a novel missense variant c.6439G&gt;T p.(Asp2147Tyr) and a synonymous variant c.6477G&gt;A p.(Gln2159=). Functional analyses confirmed that the synonymous variant triggers nonsense-mediated decay of the affected allele.</div></div><div><h3>Conclusion</h3><div>This study expands the spectrum of <em>DYNC2H1</em> variants associated with SRPS and emphasizes the importance of functional analyses in genetic diagnostics. Demonstrating pathogenicity for a synonymous variant highlights the necessity for comprehensive variant assessments to improve diagnostic accuracy and enable early intervention. These findings have significant implications for molecular diagnostics and personalized therapy strategies in skeletal ciliopathies.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"197 ","pages":"Article 117511"},"PeriodicalIF":3.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924839","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":"Metabolic, skeletal, and cartilage effects of a high-fat diet and the therapeutic impact of MGL3196 are age- and sex-dependent in mice","authors":"O. Perez ,&nbsp;G.A. Gomez ,&nbsp;C. Kesavan ,&nbsp;B. Edderkaoui ,&nbsp;A. Muralidharan ,&nbsp;S. Pourteymoor ,&nbsp;A. Quincey ,&nbsp;V.F. Sechriest ,&nbsp;S. Mohan","doi":"10.1016/j.bone.2025.117516","DOIUrl":"10.1016/j.bone.2025.117516","url":null,"abstract":"<div><div>Aged individuals with type 2 diabetes (T2D) may suffer from complications of common comorbid conditions like osteoporosis or osteoarthritis. MGL3196 (MGL) is a therapeutic thyroid hormone receptor beta (TRβ) agonist that has been shown to rescue non-alcoholic steatohepatitis by enhancing lipid metabolism. In a previous study, we demonstrated that MGL treatment protected against high-fat diet (HFD)-induced adiposity but increased HFD-induced trabecular bone loss in male mice. In this study, we explored the impact of MGL treatment on adiposity, bone, and cartilage in aged-21-month-old C57BL/6J mice after a 12-week HFD regimen. Our results show that MGL reduced body weight as well as adverse effects caused by HFD adiposity, in male mice only. Aged HFD-fed male mice experienced cortical bone loss, in contrast to the trabecular bone loss observed in adult male mice. Notably, MGL treatment further exacerbated the cortical bone loss. Mechanical testing of tibias from aged male mice by 3-point bending revealed a reduced maximum load and tibia stiffness with HFD and MGL treatment. Transcriptome analyses for cortical bone formation regulators unveiled a decreased expression of <em>Wnt16</em> and increased expression of the Wnt inhibitor, <em>Sost</em>, in the bones of HFD-fed male mice. Additionally, measurements of articular cartilage indicated that MGL treatment reduced articular cartilage degradation in both sexes, which was attributed to aging and a HFD. Our findings suggest tailored therapies are necessary to address the adverse effects of a HFD on fat, bone, and cartilage metabolism, specifically considering factors such as age and sex.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"198 ","pages":"Article 117516"},"PeriodicalIF":3.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060329","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":"How to identify children with cerebral palsy at risk of low bone mineral density","authors":"Marianne Lindblad Pedersen ,&nbsp;Johan Sebastian Ohlendorf ,&nbsp;Thomas Alexander Gerds ,&nbsp;Nanette Mol Debes ,&nbsp;Christina Engel Hoei-Hansen ,&nbsp;Bo Zerahn ,&nbsp;Jesper Johannesen","doi":"10.1016/j.bone.2025.117515","DOIUrl":"10.1016/j.bone.2025.117515","url":null,"abstract":"<div><h3>Aim</h3><div>Cerebral palsy is a common chronic motorically disabling condition in children. The aim of this study was to determine prevalence of low bone mineral density (BMD) in children with cerebral palsy and to examine the association between BMD with risk factors.</div></div><div><h3>Methods</h3><div>Cross sectional study of children with cerebral palsy analyzing Dual X-ray Absorptiometry, blood tests, full clinical medical examination including Tanner stage and nutritional status, measurement of anthropometrics and assessment of physical activity.</div></div><div><h3>Results</h3><div>The 81 participants were aged 2.1–17.4 years (median 9 years) and 64 out of 81 had a mild cerebral palsy (Gross Motor Function Classification System score of I-II). Mean BMD z-score was −0.2 (SD = 1.05, range −4.6 to 2.0). GMFCS score was negatively associated with BMD (p &lt; 0.01) as higher score led to 1.43 SD lower BMD [−1.97 to −0.89]. Weight bearing activity was negatively associated with lower BMD z-score (p = 0.01), as having &lt;30 min of weight bearing activity per day lead to 0.98 SD lower BMD [−1.75; −0.22]. Use of anti-seizure medication was negatively associated with BMD (BMD z-score 0.7 SD lower; p = 0.02, [−1.28; −0.12]). Serum vitamin D levels or fracture rates were not statistically significantly associated with BMD changes.</div></div><div><h3>Conclusion</h3><div>We found 17 % of children have low BMD regardless of motoric impairment level. GMFCS score, Sparse weight bearing activity and use of anti-seizure medicine were negatively associated to BMD. No significant associations were found with vitamin D, sex, BMI, puberty.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"197 ","pages":"Article 117515"},"PeriodicalIF":3.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924840","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":"Comparison of the bone remodeling in the midpalatal suture during maxillary expansion between young and middle-aged mice","authors":"Hyeran Helen Jeon ,&nbsp;Mary Cruz Contreras Salas ,&nbsp;Kyungjoon Park ,&nbsp;Lindsay Fisher ,&nbsp;Sara Ha ,&nbsp;Caroline Palmer ,&nbsp;Fionna Chan ,&nbsp;Dana T. Graves","doi":"10.1016/j.bone.2025.117512","DOIUrl":"10.1016/j.bone.2025.117512","url":null,"abstract":"<div><div>Maxillary expansion is a common orthodontic procedure for treating maxillary transverse deficiency. However, the cell responses to mechanical force may vary across different age groups, suggesting the need for age-specific treatment protocols. To compare the age-related responses to the mechanical force, we examined the 6-week- and 12-month-old mice undergoing maxillary expansion with 0.012-in. stainless steel orthodontic wire bonded to the maxillary first and second molars (25 g force). Mice were euthanized on days 0, 3, 7, and 14 for analysis. MicroCT analysis, tartrate-resistant acid phosphatase (TRAP) stain, and immunofluorescence/immunohistochemistry stain using antibodies to RUNX2, alkaline phosphatase (ALP), Gli1 and Ki67 along with the TUNEL assay, were conducted to evaluate suture width, osteoclast activity, new bone formation and mesenchymal stem cell (MSC) proliferation and apoptosis. Both 6-week- and 12-month-old mice exhibited successful midpalatal suture opening, but young mice demonstrated earlier and more intense osteoclast activity, along with higher expression of RUNX2 and ALP. Young mice also exhibited a higher percentage of Gli1+Ki67+ immunopositive cells, while middle-aged mice showed a higher percentage of Gli1+TUNEL+ positive cells on day 3 after maxillary expansion. Our findings suggest that aging negatively impacts mechanical force-induced bone remodeling by reducing osteoclastogenesis, osteogenesis, and MSC proliferation while increasing MSC apoptosis.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"197 ","pages":"Article 117512"},"PeriodicalIF":3.5,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907662","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":"Label-free rapid diagnosis of jaw osteonecrosis via the intersection of Raman spectroscopy and deep learning","authors":"Xiaobo Dai ,&nbsp;Bowen Yang ,&nbsp;Liangjun Zhou ,&nbsp;Ran You ,&nbsp;Shuai Chen ,&nbsp;ZhongXu Li ,&nbsp;Xingzhi Zeng ,&nbsp;Zhining Wen ,&nbsp;Chunjie Li ,&nbsp;Bing Yan","doi":"10.1016/j.bone.2025.117510","DOIUrl":"10.1016/j.bone.2025.117510","url":null,"abstract":"<div><h3>Objectives</h3><div>To establish a precise and efficient diagnostic framework for distinguishing medication-related osteonecrosis of the jaw, radiation-induced osteonecrosis of the jaw, and normal bone tissue, thus enhancing clinical decision-making and enabling targeted therapeutic interventions.</div></div><div><h3>Methods</h3><div>Raman spectroscopy was applied to investigate bone mineral composition, organic matrix content, and crystallinity in ninety bone tissue samples (30 MRONJ, 30 ORN, 30 control). Each mandible underwent 10 randomized spectral acquisitions, yielding 900 spectra across 200–2200 cm⁻¹. The raw spectral data were preprocessed using Labspec6 software (Horiba Scientific). Principal component analysis (PCA) and linear discriminant analysis (LDA) were employed for feature extraction and classification. Additionally, a ResNet18 deep learning architecture was employed to enhance diagnostic accuracy. The model's performance was evaluated using precision, recall, and the area under the receiver operating characteristic curve to ensure robustness.</div></div><div><h3>Results</h3><div>The PCA-LDA integration achieved 90.3 % accuracy in differentiating MRONJ, ORN, and healthy bone， with leave-one-out cross-validation confirming 89.1 % classification robustness. Furthermore, the ResNet18 deep learning model outperformed traditional classification methods, achieving 0.926 ± 0.024 accuracy, 0.924 ± 0.026 precision, 0.926 ± 0.024 recall, and 0.985 ± 0.007 AUROC on the validation set.</div></div><div><h3>Significance</h3><div>These findings underscore the significant potential of combining Raman spectroscopy with advanced deep learning techniques as a rapid, noninvasive, and highly reliable diagnostic tool. This approach not only enhances the ability to differentiate between MRONJ and ORN but also offers substantial implications for improving patient management and therapeutic outcomes in clinical practice.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"197 ","pages":"Article 117510"},"PeriodicalIF":3.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923273","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":"Automated micro-CT morphometry of femoral biopsies from hip arthroplasties: adaptive local thresholding, volume of interest wrapping and removal of debris","authors":"Deepti K. Sharma ,&nbsp;Agatha Labrinidis ,&nbsp;Xiangyu Dong ,&nbsp;Christopher Schultz ,&nbsp;Lucian B. Solomon ,&nbsp;Boopalan Ramasamy ,&nbsp;Stuart A. Callary ,&nbsp;Phil Salmon","doi":"10.1016/j.bone.2025.117502","DOIUrl":"10.1016/j.bone.2025.117502","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Bone biopsies are an important biological tool for investigating bone microarchitecture, which can be non-destructively imaged in 3D via micro-computed tomography (micro-CT). Image thresholding and delineation of a region of interest (ROI) are prerequisites for quantifying bone parameters. Validated automatic protocols enable quantification of biopsies that contain trabecular and cortical bone. However, irregularly shaped trabecular bone biopsies with peripheral and internal debris have required manual ROI delineation, which is time-intensive and subject to inter and intra-observer variance. We hypothesise that an automated workflow will be a suitable alternative to overcome these issues and objectively determine bone microarchitecture in surgical biopsies, at higher throughput suitable for clinical studies. Hence, the aim of this study was to develop an objective, reproducible and automated workflow to analyse microarchitecture of trabecular bone biopsies. To accomplish this aim, we tested six different methods of ROI delineation: a whole biopsy ROI, and both manual (slow) and automatically delineated (fast) reduced ROIs to remove peripheral debris, each with (adaptive thresholding and a set of morphological operations to remove debris) and without (global thresholding) processing in a subset (&lt;em&gt;n&lt;/em&gt; = 8) of intertrochanteric femoral biopsies obtained from patients undergoing hip arthroplasty. Number of objects, bone volume to tissue volume (BV/TV), trabecular separation (Tb.Sp), structure model index (SMI) and Euler number and trabecular pattern factor (Tb.Pf) were compared between the six workflows using Friedman's test and post-hoc pairwise comparisons with Bonferroni correction was performed. The two most reproducible techniques were tested for validation in a larger cohort of arthroplasty patients (&lt;em&gt;n&lt;/em&gt; = 60) and results were compared with appropriate &lt;em&gt;t&lt;/em&gt;-test. Subset analysis indicated that the manual and automated ROI with processing increased the ability to resolve real differences between these groups in parameters BV/TV, Tb.Sp and Euler number compared to with no processing and whole biopsy ROI approach. A validation cohort consisted of thirty osteoarthritis patients with a mean age 68.25 ± 8.64 and thirty neck of femur fracture with a mean age 82.4 ± 8.9. The manual technique failed to detect differences in BV/TV, SMI and Tb.Pf between the two patient groups (&lt;em&gt;p&lt;/em&gt; &gt; 0.05, for all) while the automated workflow demonstrated significant differences in these parameters between the OA and the NOF patients (&lt;em&gt;p&lt;/em&gt; &lt; 0.05). This is probably due to irregularity in the reference VOI volume introduced by manual ROI delineation reducing morphometric precision, compared to the automated method. In conclusion, our automated workflow performed better than customary practice; it represents a user-independent, high throughput technique to measure bone microarchitecture accurately in surgical biopsies.&lt;/div&gt;&lt;","PeriodicalId":9301,"journal":{"name":"Bone","volume":"197 ","pages":"Article 117502"},"PeriodicalIF":3.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886318","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":"Rebound hypercalcaemia timing is associated with cumulative weight-based denosumab dose for central giant cell granuloma treatment in children despite a dose weaning regimen","authors":"Alexander D. Chesover ,&nbsp;Jeremy Allgrove ,&nbsp;Alistair Calder ,&nbsp;Catherine Campbell ,&nbsp;Emmeline Heffernan ,&nbsp;Kshitij Mankad ,&nbsp;Rhiannon McBayDoherty ,&nbsp;Dearbhla McKenna ,&nbsp;Caroline Mills ,&nbsp;Madeline Rooney ,&nbsp;Nadeem Saeed","doi":"10.1016/j.bone.2025.117501","DOIUrl":"10.1016/j.bone.2025.117501","url":null,"abstract":"<div><div>Central giant cell granulomas (CGCG) are locally destructive, non-neoplastic lesions that express receptor activator of nuclear factor-κB (RANK) and RANK ligand. Denosumab, a monoclonal antibody against RANK ligand, is licensed in skeletally mature patients, with less experience in children who are at risk of rebound hypercalcaemia.</div><div>We describe the response to denosumab in five skeletally immature children with CGCG. Denosumab was started aged 2.1 to 11.6 years, for 8 to 22 months, with a cumulative dose of 9.6 to 58.8 mg/kg. Three patients followed a weaning protocol (using reducing dose frequency and zoledronic acid).</div><div>Denosumab ossified all lesions. Three patients had subsequent surgery, and one had recurrence. All had rebound hypercalcaemia, 8.9–47 weeks (median 23.3 weeks) after the last treatment dose. Four presented with symptomatic hypercalcaemia and acute kidney injury. Cumulative denosumab treatment dose/kg positively correlated with (1) time to rebound after the last treatment dose (r² = 0.94, <em>p</em> = 0.006); and (2) length of admission for hypercalcaemia treatment (r² = 0.87, <em>p</em> = 0.02). All patients had increased bone mineral density and metaphyseal sclerosis that improved after stopping denosumab. One had a clavicular fracture at the intersection of normal and high-density bone.</div><div>We propose that rebound hypercalcaemia should be an anticipated consequence of stopping denosumab in skeletally immature patients and exists on a spectrum. A higher cumulative denosumab dose/kg increases the time to rebound hypercalcaemia and its severity. Further work is needed to establish the lowest dose and the shortest treatment duration to balance effective treatment with minimising side effects.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"197 ","pages":"Article 117501"},"PeriodicalIF":3.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895698","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":"Value of inflammatory markers for monitoring disease severity and progression in granuloma induced by cosmetic oil injections","authors":"Ida Enggaard Kaae ,&nbsp;Sam Kafai Yahyavi ,&nbsp;Martin Blomberg Jensen ,&nbsp;Ebbe Eldrup","doi":"10.1016/j.bone.2025.117500","DOIUrl":"10.1016/j.bone.2025.117500","url":null,"abstract":"<div><h3>Objective</h3><div>Cosmetic oil injections can cause foreign body granulomas, leading to inflammation-driven extrarenal production of activated vitamin D (1,25(OH)₂D₃) and severe hypercalcemia. This study investigates longitudinal changes in inflammatory markers: interleukin 2 receptor (IL-2R), peptidyl dipeptidase (ACE), and ferritin in patients with oil-induced granuloma.</div></div><div><h3>Materials and methods</h3><div>109 male patients were stratified according to baseline calcium status. 28 % had hypercalcemia, and 72 % normocalcemia. Normocalcemic patients were subdivided based on serum parathyroid hormone (PTH) concentrations into suppressed (&lt; 2.0 pmol/L, <em>n</em> = 30) or normal (≥ 2.0 pmol/L, <em>n</em> = 49) concentrations. Blood samples were collected over 48 months and longitudinal changes in inflammatory markers and calcium homeostasis were examined using Pearson correlation and mixed model analyses.</div></div><div><h3>Results</h3><div>IL-2R, ACE, and ferritin were positively correlated with serum concentration of ionized calcium, while IL-2R was associated with serum 1,25(OH)₂D_3. In patients with hypercalcemia, IL-2R decreased at 6 (<em>p</em> = 0.041), 24 (<em>p</em> = 0.048), and 36 months (<em>p</em> = 0.035). ACE increased at 48 months (<em>p</em> = 0.008). In patients with normocalcemia and suppressed PTH, IL-2R increased at 24 months (<em>p</em> = 0.021), while serum ferritin increased in patients with normocalcemia and normal PTH at 6 (<em>p</em> = 0.040), 12 (<em>p</em> = 0.008), 24 (<em>p</em> = 0.028), and 48 months (<em>p</em> = 0.005).</div></div><div><h3>Conclusions</h3><div>Positive correlations were observed at baseline between ionized calcium concentrations and IL-2R, ionized calcium and ferritin, and 1,25(OH)₂D₃ and IL-2R. Hypercalcemia and suppressed PTH was associated with elevated IL-2R and ferritin concentrations at baseline. Over time, IL-2R and ferritin concentrations decreased in patients with hypercalcemia, some treated with immunomodulatory drugs. IL-2R and ferritin concentrations increased in untreated patients with normocalcemia.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"197 ","pages":"Article 117500"},"PeriodicalIF":3.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923271","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":"Association between estimated pulse wave velocity and hip fracture in middle-aged and older adults: A prospective cohort study in China","authors":"Wen-Kai Ke ,&nbsp;Jing-Ping Cheng ,&nbsp;Ling-Ling Xu","doi":"10.1016/j.bone.2025.117499","DOIUrl":"10.1016/j.bone.2025.117499","url":null,"abstract":"<div><h3>Background</h3><div>Hip fractures represent a significant public health challenge among middle-aged and older adults, with substantial implications for health and quality of life. This study aimed to investigate the association between estimated pulse wave velocity (ePWV) and hip fracture risk, with a comprehensive analysis of both overall and female population cohorts.</div></div><div><h3>Methods</h3><div>Utilizing data from the China Health and Retirement Longitudinal Study (CHARLS), this prospective cohort study included 11,024 participants aged 45 and older, with a 9-year follow-up period (2011-2020). The research employed Cox proportional hazards models to analyze the overall population and a specific female subgroup. The female subgroup analysis uniquely adjusted for menopausal status to provide a nuanced assessment of ePWV's relationship with hip fracture risk. Restricted cubic spline (RCS) analysis and threshold analysis were conducted to explore nonlinear associations between ePWV and hip fracture risk.</div></div><div><h3>Results</h3><div>During the follow-up period, 471 hip fractures were documented. In the overall population, each increment in ePWV quartile was associated with a significant 32 % increase in hip fracture risk (Hazard Ratio [HR]: 1.32, 95 % Confidence Interval [CI]: 1.18-1.49, <em>p</em> &lt; 0.001). The female subgroup analysis, after adjusting for menopausal status, revealed a 29 % increased hip fracture risk per ePWV quartile increment (HR: 1.29, 95 % CI: 1.09-1.53, <em>p</em> &lt; 0.05). Nonlinear analysis identified a critical threshold at 11.18 m/s, beyond which hip fracture risk significantly increased [HR (95%CI): 1.28 (1.12-1.47)].</div></div><div><h3>Conclusions</h3><div>The ePWV significantly correlates with hip fracture risk in middle-aged and older Chinese adults, offering novel insights into the relationship between arterial stiffness and fracture vulnerability. Future research should validate these findings and explore vascular health-based strategies for hip fracture prevention.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"197 ","pages":"Article 117499"},"PeriodicalIF":3.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882853","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":"Pulsed ultrasound and moderate exercise accelerate bone healing in an experimental tibial fracture model: biochemical, radiological and biomechanical evidence","authors":"Ligia Milanez Venturini ,&nbsp;Daniella Pacheco dos Santos Haupenthal ,&nbsp;João Afonso Spillere Dajori ,&nbsp;Laura de Roch Casagrande ,&nbsp;Rubya Pereira Zaccaron ,&nbsp;Camila da Costa ,&nbsp;Igor Ramos Lima ,&nbsp;Fernando Russo Costa do Bomfim ,&nbsp;Sabrina Zanchetta Lanza ,&nbsp;Yaodong Gu ,&nbsp;Anand Thirupathi ,&nbsp;Paulo Cesar Lock Silveira ,&nbsp;Alessandro Haupenthal","doi":"10.1016/j.bone.2025.117498","DOIUrl":"10.1016/j.bone.2025.117498","url":null,"abstract":"<div><div>Currently, therapeutic strategies involving mechanical stress play a key role in fracture consolidation. However, no literary evidence exists regarding the combined effects of low-intensity pulsed ultrasound (LIPUS) and moderate aerobic exercise. This study aimed to investigate the effects of LIPUS and moderate aerobic exercise on bone consolidation in 48 male Wistar rats. The animals were divided into four groups (<em>n</em> = 12 per group): Bone Fracture (BF); BF + LIPUS; BF + Exercise (Ex); BF + Ex + LIPUS. A transverse osteotomy with Kirschner wire fixation was performed, followed by therapeutic interventions for 19 days, three times a week. LIPUS was applied for 10 min (1.5 MHz, 0.4 W/cm², 3 cm² area), and aerobic exercise lasted 30 min/day with progressive speed. Radiographic analyses were conducted on days 1, 12, and 24 post-fracture, and euthanasia occurred 72 h after the final session. The combined group exhibited improved radiographic scores and increased birefringent collagen fibers. IL-4, IL-10, and TGF-β levels were significantly higher in treated groups, particularly the combined intervention. Additionally, oxidative stress markers showed reduced nitrite levels, controlled sulfhydryl oxidation, and enhanced SOD and GSH activity. Biomechanically, the combined group tolerated higher loads and demonstrated superior deformation capacity and tissue elasticity. The combination of aerobic exercise and LIPUS enhanced radiographic healing, modulated inflammation, reduced oxidative stress, and improved mechanical properties, supporting its potential for fracture rehabilitation.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"197 ","pages":"Article 117498"},"PeriodicalIF":3.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882851","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}