Bone最新文献

{"title":"Molecular mapping of articular cartilage CXCR4 expression after ACL injury via a novel small molecule-based probe","authors":"Michael D. Newton ,&nbsp;Mackenzie M. Fleischer ,&nbsp;Howard W.T. Matthew ,&nbsp;Tristan Maerz","doi":"10.1016/j.bone.2025.117463","DOIUrl":"10.1016/j.bone.2025.117463","url":null,"abstract":"<div><h3>Purpose</h3><div>Molecular imaging is a powerful modality to spatially resolve molecular changes across tissues, but application to articular cartilage remains limited. CXCR4 is an established marker of chondrocyte hypertrophy and potential therapeutic target for osteoarthritis. The purpose of this study was to develop and apply a CXCR4-targeted, near-infrared fluorescent (NIR) probe to a rat model of post-traumatic osteoarthritis (PTOA).</div></div><div><h3>Methods</h3><div>A CXCR4-targeted, small molecule-based NIR probe (“Cy7-AMD”) was synthesized. Sensitivity and specificity of Cy7-AMD to CXCR4 was validated in vitro (HUVECs), and ex vivo (rat osteochondral explants). To induce PTOA, female Lewis rats underwent noninvasive anterior cruciate ligament (ACL) rupture. At 7- and 28-days post-injury, injured/contralateral femora and tibiae were dissected, incubated in Cy7-AMD vs a non-targeting control, and imaged via NIR imaging, as well as conventional and contrast-enhanced micro-computed tomography. Imaging datasets were co-registered, cartilage tissue volumes were segmented, and paired cartilage thickness and NIR signal maps were generated and analyzed for PTOA-relevant changes.</div></div><div><h3>Results</h3><div>Compared to a non-targeting control probe, in vitro and ex vivo assays confirm sensitivity and specificity of Cy7-AMD to CXCR4. Flow cytometry confirmed high correspondence between Cy7-AMD- and antibody-based measurement of CXCR4 expression. Cy7-AMD rapidly equilibrated within cartilage, and fluorescent histology confirmed full-thickness penetration. Injured femoral cartilage exhibited heterogeneous CXCR4 expression, with increased signal deviation compared to contralateral femora. Spatial CXCR4 expression patterns correlated to cartilage thickness patterns; high CXCR4 expression at boundaries of low-thickness lesions suggests an association between CXCR4 expression and cartilage loss.</div></div><div><h3>Conclusions</h3><div>Small molecule-based probes are advantageous for mapping spatial patterns of molecular expression in rodent articular cartilage, deepening our understanding of PTOA progression.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"195 ","pages":"Article 117463"},"PeriodicalIF":3.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143637762","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":"DXA-based 3D finite element models predict hip fractures better than areal BMD in elderly women","authors":"Lorenzo Grassi ,&nbsp;Sami P. Väänänen ,&nbsp;Antti Voss ,&nbsp;Tomi Nissinen ,&nbsp;Reijo Sund ,&nbsp;Heikki Kröger ,&nbsp;Hanna Isaksson","doi":"10.1016/j.bone.2025.117457","DOIUrl":"10.1016/j.bone.2025.117457","url":null,"abstract":"<div><div>Bone strength is a major contributor to fracture risk. Areal bone mineral density (aBMD) obtained from dual-energy X-ray absorptiometry (DXA) is used as a surrogate for bone strength in fracture risk prediction. 3D finite element (FE) models predict bone strength better than aBMD but need 3D computed tomography and are not automated. We have earlier developed a method to automatically reconstruct the 3D hip anatomy from a 2D hip DXA image, followed by subject-specific FE-based prediction of proximal femoral strength. In this study, we evaluate the method's ability to predict incident hip fractures in a population-based cohort of women (OSTPRE). We used a sub-cohort including 46 cases with a hip fracture (&lt;10 years from DXA scan) and 2 healthy controls to each hip fracture case, matched by age, height, and body mass index. We automatically reconstructed the 3D hip anatomy and predicted proximal femoral strength using FE analysis for all the subjects of the sub-cohort. The FE-predicted proximal femoral strength was a significantly better predictor of incident hip fractures than aBMD (difference in area under the receiver operating characteristics curve, ΔAUROC = 0.10). This is the first time that 3D FE models obtained from a 2D hip DXA scan outperform aBMD in predicting incident hip fractures in a population-based prospectively followed cohort of women. Our approach provided an improved fracture risk prediction in a clinically feasible manner (only one single DXA image is needed) and without additional costs compared to the current clinical approach.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"195 ","pages":"Article 117457"},"PeriodicalIF":3.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Period prevalence and timing of contralateral hip fractures: An eighteen year retrospective cohort study, systematic review and meta-analysis of the literature","authors":"David Morris ,&nbsp;Tim Cheok ,&nbsp;Thomas Smith ,&nbsp;Jonghoo Sung ,&nbsp;Ruurd Jaarsma ,&nbsp;Luke Johnson","doi":"10.1016/j.bone.2025.117453","DOIUrl":"10.1016/j.bone.2025.117453","url":null,"abstract":"<div><h3>Purpose</h3><div>Second contralateral hip fractures (SCHF) are relatively uncommon. The overall prevalence of this is poorly reported in literature.</div></div><div><h3>Methods</h3><div>We performed a single centre retrospective cohort study in patients &gt;50 years old who sustained a SCHF between 1st of January 2005 and 30th of April 2023. A systematic search of the literature was then performed by searching PubMed, Embase, and Web of Science from the date of inception of each database through to the 22nd of February 2024. A meta-analysis was conducted to estimate the prevalence of SCHF and hip fracture pattern symmetry, incorporating both our results and that previously reported in literature.</div></div><div><h3>Results</h3><div>Our cohort study showed a period prevalence of 1.7 % within 1 year and 2.8 % within 2 years following a hip fracture. 65 studies were identified using our search strategy. The overall prevalence of SCHF was 7.3 % [95 % CI: 6.3–8.4]. Meta-regression suggested that studies conducted in Europe and North America showed higher prevalence than studies conducted in Asia. A similar fracture pattern was seen in 72.1 % [95 % CI: 69.7–74.4] of patients with SCHF.</div></div><div><h3>Conclusion</h3><div>SCHF are relatively uncommon. When they do occur, it is usually within 2 years of the index fracture. Asian populations had lower prevalence of SCHF when compared to their European and North American counterparts. Hip fracture pattern is symmetrical in most patients with a SCHF.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"195 ","pages":"Article 117453"},"PeriodicalIF":3.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601616","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":"Side-to-side differences in hip bone mineral density in patients with unilateral hip osteoarthritis","authors":"Keisuke Uemura ,&nbsp;Sotaro Kono ,&nbsp;Kazuma Takashima ,&nbsp;Kazunori Tamura ,&nbsp;Ryo Higuchi ,&nbsp;Hirokazu Mae ,&nbsp;Nobuo Nakamura ,&nbsp;Yoshito Otake ,&nbsp;Yoshinobu Sato ,&nbsp;Nobuhiko Sugano ,&nbsp;Seiji Okada ,&nbsp;Hidetoshi Hamada","doi":"10.1016/j.bone.2025.117456","DOIUrl":"10.1016/j.bone.2025.117456","url":null,"abstract":"<div><h3>Background</h3><div>Accurately evaluating bone mineral density (BMD) in patients with unilateral hip osteoarthritis (OA) is crucial for diagnosing osteoporosis and selecting implants for hip arthroplasty. Our goal was to measure the BMD differences between sides, examine contributing factors, and identify the optimal side for BMD assessment in these patients.</div></div><div><h3>Methods</h3><div>We analyzed 108 women with unilateral hip OA. Bilateral hip BMD was assessed automatically through quantitative CT (QCT) utilizing a validated, deep-learning-based approach. We evaluated BMD variations between the OA and healthy hips across total, neck, and distal regions. To determine their contributions, we analyzed factors, including patient demographics, Crowe classification, Bombelli classification, knee OA status, hip functional score, and gluteal muscle volume and density. Furthermore, we examined how side-to-side BMD differences influenced osteoporosis diagnosis using T-scores based on QCT.</div></div><div><h3>Results</h3><div>The average BMD on the OA side was 6.9 % lower in the total region, 14.5 % higher in the neck region, and 9.4 % lower in the distal region than on the healthy side. Contributing factors to the reduced BMD in the OA hip included younger age, Bombelli classification (atrophic type), and significant gluteal muscle atrophy. Diagnoses from the OA side revealed lower sensitivity (61 %) than those from the healthy side (88 %).</div></div><div><h3>Conclusions</h3><div>Analysis on one side alone yields a more precise osteoporosis diagnosis from the healthy side. Nonetheless, bilateral BMD assessment remains crucial, particularly in younger individuals and those with atrophic OA types. Although based on QCT, our findings support bilateral analysis by dual-energy X-ray absorptiometry for these patients.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"195 ","pages":"Article 117456"},"PeriodicalIF":3.5,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143593816","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":"Parental fracture history is associated with offspring early-life fracture risk: The Geelong Osteoporosis Study","authors":"Mia A. Percival ,&nbsp;Kara B. Anderson ,&nbsp;Julie A. Pasco ,&nbsp;Sarah M. Hosking ,&nbsp;Natalie K. Hyde","doi":"10.1016/j.bone.2025.117454","DOIUrl":"10.1016/j.bone.2025.117454","url":null,"abstract":"<div><h3>Aims</h3><div>Fractures during childhood and adolescence are common as peak bone mass has not yet been accrued. Previous studies have reported that offspring are at higher risk of a fragility fracture if one or both parents have experienced a fracture, however, it is not known if this association holds true for fractures experienced in early life, and if so, whether there are differential risk profiles across the sexes. Therefore, this study aimed to determine the associations between maternal and paternal fracture history and offspring fracture risk in early life.</div></div><div><h3>Methods</h3><div>At baseline, Geelong Osteoporosis Study participants self-reported fracture history for themselves and their parents. This analysis included personal fracture data relating to birth until 20 years of age and parental fracture for 1336 female and 1174 male participants who provided complete data, including age and site of fracture. Multivariable logistic regression models were used to assess the odds of participant fracture in childhood or adolescence in association with paternal and/or maternal fracture.</div></div><div><h3>Results</h3><div>In total, 141 (12.2 %) female and 323 (25.7 %) male participants reported at least one fracture by age 20 years. For females, there were 247 maternal and 211 paternal parents with fractures and in males, 233 maternal and 189 paternal fractures. A maternal fracture was associated with an increased odds of early life fracture in female participants (OR 1.86; 95 % CI 1.17–2.95) but not male participants (OR 1.16; 95 % CI 0.81–1.65), while a paternal fracture was associated with an increased odds of early life fracture in males (OR 1.47; 95 % CI 1.01–2.14) but not females (OR 1.61; 95 % CI 0.98–2.64).</div></div><div><h3>Conclusion</h3><div>Parental fracture history appears to have sex-specific associations with offspring early life fracture risk. Whereby maternal fracture history is associated with an increased risk of early life fracture in females, while paternal fracture history is associated with early life fracture risk in males.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"195 ","pages":"Article 117454"},"PeriodicalIF":3.5,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marrow adipogenic lineage precursors (MALPs) facilitate bone marrow recovery after chemotherapy","authors":"Huan Wang ,&nbsp;Lutian Yao ,&nbsp;Leilei Zhong ,&nbsp;Jiankang Fang ,&nbsp;Qi He ,&nbsp;Theresa M. Busch ,&nbsp;Keith Cengel ,&nbsp;Ling Qin","doi":"10.1016/j.bone.2025.117446","DOIUrl":"10.1016/j.bone.2025.117446","url":null,"abstract":"<div><div>Chemotherapy-induced hematopoietic toxicity is a multifactorial challenge in the treatment of oncology patients. The resultant bone marrow suppression is a major dose-limiting side effect. In this study, we utilized 5-fluorouracil (5-FU), a commonly used chemotherapeutic agent, to investigate the mechanisms underlying bone marrow recovery following chemotherapy. A single injection of 5-FU did not alter mouse bone structure but caused acute damage to bone marrow cellularity and vasculature. Single-cell RNA-sequencing of bone marrow mesenchymal lineage cells revealed a substantial reduction in early mesenchymal progenitors and a marked expansion of marrow adipogenic lineage precursors (MALPs) five days post-treatment. Furthermore, 5-FU upregulated the expression of myofibroblast markers in MALPs, indicating a myofibroblast transformation. Using <em>Adipoq-Cre</em> to label MALPs in vivo, we observed that 5-FU transiently increases the number of MALPs in the bone marrow by promoting their proliferation. Immunostaining confirmed the elevated expression of myofibroblast markers in MALPs. By day 14 after 5-FU injection, bone marrow cellularity and vasculature were largely restored; however, the ablation of MALPs significantly impaired this recovery. Taken together, our study uncovers the critical role of MALPs in facilitating bone marrow repair following chemotherapy-induced injury and identifies them as a potential cellular target for treating chemotherapy-induced myelosuppression.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"195 ","pages":"Article 117446"},"PeriodicalIF":3.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term impact of teriparatide on bone mineral density, trabecular bone score, and fracture risk relative to total hip T-score: A two-decade, registry-based cohort study","authors":"Laura Guyer ,&nbsp;Oliver Lehmann ,&nbsp;Mathias Wenger ,&nbsp;Sven Oser ,&nbsp;Ueli Studer ,&nbsp;Christian Steiner ,&nbsp;Hans-Rudolf Ziswiler ,&nbsp;Gernot Schmid ,&nbsp;HansJörg Häuselmann ,&nbsp;Stephan Reichenbach ,&nbsp;Thomas Lehmann ,&nbsp;Judith Everts-Graber","doi":"10.1016/j.bone.2025.117445","DOIUrl":"10.1016/j.bone.2025.117445","url":null,"abstract":"<div><h3>Background</h3><div>Teriparatide followed by antiresorptive therapy exhibits fracture reduction efficacy for up to 2 years, but it remains unclear if this leads to sustained increases in bone mineral density (BMD) and trabecular bone score (TBS), and if BMD correlates with fracture risk reduction.</div></div><div><h3>Methods</h3><div>In this multicenter cohort study, the effect of teriparatide administration for 18–24 months, followed by antiresorptive therapy, was assessed in patients partipicipating in a nationwide Swiss osteoporosis registry. BMD and TBS were measured up to 10 years before and after teriparatide initiation.</div></div><div><h3>Results</h3><div>A total of 624 patients (87 % female, age 67 ± 13 years) were enrolled from May 2004 to December 2023. Among them, 198 (32 %) received no treatment prior to teriparatide, while 426 had received previous antiresorptive therapies (median duration 5.9 years [2.2, 8.0]). All patients underwent subsequent antiresorptive therapy, mainly with bisphosphonates and denosumab. The incidences of vertebral, hip, and any fractures were 0.96, 0.11, and 1.37, respectively, within 2 years prior to teriparatide initiation. The total hip T-score did not correlate with fracture reduction under teriparatide. After transitioning from teriparatide to an antiresorptive regimen, fracture incidence remained low and BMD was significantly higher for up to 5 years after teriparatide compared to the pre-treatment period (T-score + 0.876 for lumbar spine, <em>p</em> &lt; 0.001; and + 0.112 for total hip, <em>p</em> &lt; 0.005), while TBS increased by 0.047 (p &lt; 0.001). Overall, significant improvement was observed in pretreated and treatment-naïve patients undergoing teriparatide treatment.</div></div><div><h3>Conclusion</h3><div>Teriparatide led to sustained lower incidences of vertebral, hip, and other fractures for up to 8 years after switching to antiresorptive agents in both pretreated and treatment-naïve patients. Additionally, BMD and TBS levels were significantly higher than those before teriparatide treatment. During teriparatide treatment, the total hip T-score did not correlate with fracture risk.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"195 ","pages":"Article 117445"},"PeriodicalIF":3.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143561372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding fracture healing: A scoping review of mechanistic pathways derived from transcriptional analysis in murine studies","authors":"Nazanin Nafisi ,&nbsp;Ahmad Hedayatzadeh Razavi ,&nbsp;Mohammad Javad Shariyate ,&nbsp;Maria V. Velasquez ,&nbsp;Mohammad Khak ,&nbsp;David Manoukian ,&nbsp;Arthur Klujian ,&nbsp;Hamid Mirzamohammadi ,&nbsp;Tom Cummiskey ,&nbsp;Mahboubeh R. Rostami ,&nbsp;Fatemeh Mirzamohammadi ,&nbsp;Ara Nazarian","doi":"10.1016/j.bone.2025.117444","DOIUrl":"10.1016/j.bone.2025.117444","url":null,"abstract":"<div><div>Fracture healing is a complex biological process involving orchestrated interactions among cells, growth factors, and transcriptional pathways. Despite significant advancements in understanding bone repair, non-union and delayed healing remain prevalent, especially in patients with comorbidities such as aging, diabetes, or substance use. Murine models serve as a cornerstone in fracture healing research, offering genetic manipulability, cost-effectiveness, and biological relevance to humans. This scoping review consolidates findings from studies conducted between 2010 and 2024, focusing on mechanistic pathways derived from transcriptional analysis in secondary bone healing as identified through bulk RNA sequencing of murine models.</div><div>Key mechanistic pathways were categorized and analyzed across the distinct phases of fracture healing—reactive, reparative, and remodeling—highlighting their unique roles in inflammation, ECM remodeling, cell proliferation, and tissue mineralization. The most recurrent mechanistic pathways included ECM-receptor interaction, focal adhesion, and signaling mechanisms such as MAPK and TGF-beta. Variability in methodologies and limited overlap among studies underscore the need for standardized protocols in RNA sequencing analysis. Additionally, comparisons across long bone fractures, hole defects, and craniofacial bone healing revealed shared molecular mechanisms alongside unique challenges, particularly in craniofacial models.</div><div>This scoping review underscores the promise of integrating systems biology approaches with transcriptomic data to elucidate the intricate regulatory networks governing fracture repair. Addressing the identified gaps in early-phase healing and harmonizing research methodologies will advance therapeutic strategies to reduce non-union rates and improve clinical outcomes.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"194 ","pages":"Article 117444"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544755","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":"Accuracy and precision of segmentation and quantification of wrist bone microarchitecture using photon-counting computed tomography ex vivo","authors":"Jilmen Quintiens ,&nbsp;Sarah L. Manske ,&nbsp;Steven K. Boyd ,&nbsp;Walter Coudyzer ,&nbsp;Melissa Bevers ,&nbsp;Evie Vereecke ,&nbsp;Joop van den Bergh ,&nbsp;G. Harry van Lenthe","doi":"10.1016/j.bone.2025.117443","DOIUrl":"10.1016/j.bone.2025.117443","url":null,"abstract":"&lt;div&gt;&lt;div&gt;The quantification of bone microarchitecture provides insight into bone health and the effects of disease or treatment, and is therefore highly relevant clinical information. Nonetheless, in vivo quantification of bone microarchitecture is mostly limited to high-resolution peripheral quantitative CT (HR-pQCT). This is a small field of view CT modality of which the gantry size only allows scanning of distal radius and tibia. Photon-counting CT (PCCT) is a novel clinical full-body CT with improved image resolution and quality compared to other clinical CT modalities, yet data on its capabilities in quantifying bone microarchitecture are limited. The aim of this study was to quantify the accuracy of two methods for trabecular bone segmentation on PCCT images as compared to the segmentations on micro-CT (μCT) and to use these segmentations to quantify the accuracy and agreement of trabecular bone morphometry measurements as compared to μCT, as well as the short-term precision.&lt;/div&gt;&lt;div&gt;This study analysed multimodal CT data, obtained from eight cadaveric forearms; the data includes two repeated PCCT scans, as well as a single HR-pQCT scan from the forearm, and μCT scans of all individual carpal bones. For each carpal bone, trabecular volumes of interest (VOI) were delineated on the μCT images, and the μCT reference segmentations and VOIs were resampled onto the PCCT and HR-pQCT images. HR-pQCT images were segmented with a global threshold of 320 mgHA/cm&lt;sup&gt;3&lt;/sup&gt;; PCCT images were segmented with either an identical global threshold or with an adaptive thresholding algorithm. Trabecular bone-volume fraction (Tb.BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular separation (Tb.Sp) were quantified for all segmented VOIs. Accuracy and agreement were calculated relative to μCT as the gold standard, short-term precision was calculated from the repeated PCCT scan.&lt;/div&gt;&lt;div&gt;For PCCT, adaptive threshold segmentation had significantly increased sensitivity compared to global threshold segmentation, along with a lower variance in its sensitivity and specificity. Concerning the microarchitecture quantification, for global threshold segmentation of PCCT images, correlations with μCT were significant, except for Tb.Sp. Correlation coefficients of Tb.BV/TV and Tb.N were not significantly different from those between HR-pQCT and μCT. Adaptive threshold segmentation led to higher correlation coefficients between PCCT and μCT of Tb.Th, Tb.N and Tb.Sp, although correlations of Tb.N remained poor for both PCCT and HR-pQCT. Moreover, adaptive thresholding led to a constant bias of Tb.BV/TV, Tb.Th and Tb.Sp, unlike the bias of HR-pQCT which was proportionally increasing with the size of the measurement. Finally, adaptive threshold segmentation led to a higher short-term precision than global threshold segmentation, with a root-mean-squared coefficient of variation below 0.65 % for all parameters.&lt;/div&gt;&lt;div&gt;We conclude that adaptive","PeriodicalId":9301,"journal":{"name":"Bone","volume":"194 ","pages":"Article 117443"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544751","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":"Novel estrogen receptor-α gene inactivating missense variant in a woman: Therapeutic challenge and long-term follow-up data","authors":"Eva Feigerlova","doi":"10.1016/j.bone.2025.117427","DOIUrl":"10.1016/j.bone.2025.117427","url":null,"abstract":"<div><h3>Background</h3><div>Rare mutations of the <em>ESR1</em> gene, encoding the estrogen receptor alpha (ERα), have been shown to cause estrogen resistance in humans. Phenotypic features include impaired maturation of epiphyseal cartilage, osteoporosis, and infertility. Clinical phenotype is not well described and the available data reflect inconsistency. To date, there are no effective therapeutic options.</div></div><div><h3>Method</h3><div>This retrospective study provides a detailed description of bone and metabolic phenotype and 8-year follow-up data of a female with a novel p.Met543Thr missense variant in the homozygous state, localized in the ligand-binding domain.</div></div><div><h3>Results</h3><div>The patient, first seen at the age of 21.3 years, presented with a tall stature (+2.2 SD), a delayed bone age (13 years). She had no breast development, normal axillary and pubic pilosity and bilateral axillary acanthosis nigricans. The metabolic phenotype included insulin resistance, decreased insulin sensitivity and increased leptinemia. The patient presented a continuous linear growth (height + 3SD at the age of 28.6 years). She had a severe osteoporosis of the lumbar spine (<em>Z</em>-score −3.9) and osteopenia of the femoral neck (Z-score −1.8). Osteoporosis worsened (Z-score −5.6 at the lumbar spine; Z-score −4.4 at the femoral neck) despite successive treatments with ethinyl-estradiol and tamoxifen (selective estrogen modulator). Markers of bone turnover were increased and unresponsive to treatment. Treatment with ethinyl-estradiol improved insulin sensitivity, lowered leptinemia, increased some estrogen-regulated liver proteins and the E2/T ratio.</div></div><div><h3>Conclusion</h3><div>This report brings new insights to the estrogen resistance syndrome and improves our understanding of the skeletal and tissue specific roles of ERα in humans.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"194 ","pages":"Article 117427"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528703","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}