Bone最新文献

{"title":"Automatic phantom-less calibration of routine CT scans for the evaluation of osteoporosis and hip fracture risk","authors":"Wen Li ,&nbsp;Yuanzhi Weng ,&nbsp;Renfei Zong ,&nbsp;Miao Wei ,&nbsp;Chen Zheng ,&nbsp;Minghao Wu ,&nbsp;Wenqin Zhou ,&nbsp;Jiayi Pu ,&nbsp;William Lu ,&nbsp;Fajin Lv","doi":"10.1016/j.bone.2025.117431","DOIUrl":"10.1016/j.bone.2025.117431","url":null,"abstract":"<div><div>Background/Purpose.</div><div>The diagnosis of osteoporosis remains a paramount concern for orthopedic surgeons worldwide. We aim to (1) evaluate the efficacy of automatic phantom-less quantitative computed tomography (PL-QCT) in diagnosing osteoporosis and (2) investigate its clinical value in predicting hip fracture risk.</div></div><div><h3>Methods</h3><div>A cohort of 705 patients was included in the study. Hip CT scans from 310 patients and spinal CT scans from 315 patients were analyzed using automatic PL-QCT. The consistency of bone mineral density (BMD) measurement obtained by dual-energy X-ray absorptiometry (DXA), phantom-based QCT (PB-QCT), and automatic PL-QCT was examined through linear regression analysis and Bland-Altman plots. The ability of automatic PL-QCT to predict osteoporosis and hip fracture risk was assessed using ROC analysis.</div></div><div><h3>Results</h3><div>Linear regression and Bland-Altman plots demonstrated a high level of agreement between BMD measurements from PL-QCT and those from hip DXA and lumbar PB-QCT. The AUC values for PL-QCT and PB-QCT in diagnosing osteoporosis were 0.903 (95 % CI 0.852–0.955) and 0.900 (95 % CI 0.847–0.953). The AUC values for predicting hip fracture risk, based on femoral neck BMD measured by PL-QCT and DXA, were 0.869 (95 % CI 0.823–0.915) and 0.831(95 % CI 0.778–0.885), respectively. When the femoral neck BMD was combined with the percentage of inter-muscular adipose tissue area, the AUC increased to 0.929 (95 % CI 0.897–0.961).</div></div><div><h3>Conclusion</h3><div>Automatic PL-QCT has shown superior performance in predicting hip fracture risk compared to DXA. Furthermore, the novel PL-QCT demonstrates comparable predictive efficacy to that of PB-QCT, suggesting its potential as a valuable tool in clinical practice.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"194 ","pages":"Article 117431"},"PeriodicalIF":3.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511712","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":"Use of double-echo ultrashort echo time magnetic resonance imaging to assess proximal femoral cortical bone changes in axial spondyloarthritis","authors":"Yitong Li,&nbsp;Bowen Hou,&nbsp;Yao Zhang,&nbsp;Yi Wang,&nbsp;Yongqiang Chu,&nbsp;Jing Zhang,&nbsp;Xiaoming Li","doi":"10.1016/j.bone.2025.117430","DOIUrl":"10.1016/j.bone.2025.117430","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;We quantitatively evaluated proximal femoral cortical bone changes associated with generalized bone loss in axial spondyloarthritis (axSpA) patients using double-echo ultrashort echo time (UTE) MRI. To achieve non-radiation, clinically available visualization of cortical microstructural deterioration in the proximal femur of axSpA and to determine the factors influencing it.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;div&gt;Patients with axSpA (&lt;em&gt;n&lt;/em&gt; = 83) and age- and sex-matched healthy controls (&lt;em&gt;n&lt;/em&gt; = 61) were recruited and underwent double-echo UTE MR scan of the nondominant proximal femur. Porosity index (PI) and cortical bone thickness (CbTh) were measured by two radiologists and their average measurements were used for subsequent analyses. Additionally, demographic characteristics of all subjects and disease-specific characteristics of axSpA patients were recorded. Proximal femoral cortical bone PI and CbTh values were compared between axSpA patients and healthy controls using independent samples &lt;em&gt;t&lt;/em&gt;-test. Correlation analyses (Pearson or Spearman or Point-biserial correlation coefficients) were conducted to investigate factors potentially associated with UTE measurements in axSpA patients, and Bonferroni correction was applied at the α = 0.002 level for more stringent correction. Multiple linear regression analyses were performed to further identify influencing factors of UTE measurements with multiple correlated variables.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 72 axSpA patients and 52 healthy control subjects were finally included. Patients and control subjects were comparable in sex, age, and body mass index (BMI). Proximal femoral cortical PI was higher (&lt;em&gt;p&lt;/em&gt; &lt; 0.001) and CbTh was lower (&lt;em&gt;p&lt;/em&gt; &lt; 0.001) in axSpA patients than in healthy controls. Sex (&lt;em&gt;p&lt;/em&gt; &lt; 0.001), BMI (&lt;em&gt;p&lt;/em&gt; = 0.003), disease duration (&lt;em&gt;p&lt;/em&gt; = 0.044), onset age (&lt;em&gt;p&lt;/em&gt; = 0.01), alkaline phosphatase (ALP) (&lt;em&gt;p&lt;/em&gt; &lt; 0.001), radiographic axSpA (r-axSpA) (&lt;em&gt;p&lt;/em&gt; = 0.02), Sacroiliac Joint Structural Score (&lt;em&gt;SSS&lt;/em&gt;)-backfill (&lt;em&gt;p&lt;/em&gt; = 0.03), SSS-ankylosis (&lt;em&gt;p&lt;/em&gt; = 0.01), and nonsteroidal anti-inflammatory drugs (NSAIDs) use (&lt;em&gt;p&lt;/em&gt; = 0.03) were potentially correlated to proximal femoral cortical PI, and among them, sex (&lt;em&gt;p&lt;/em&gt; &lt; 0.001) and BMI (&lt;em&gt;p&lt;/em&gt; = 0.01) were independently associated demographic characteristics, and ALP (&lt;em&gt;p&lt;/em&gt; = 0.02), SSS-backfill (&lt;em&gt;p&lt;/em&gt; = 0.044) and SSS-ankylosis (&lt;em&gt;p&lt;/em&gt; = 0.01) were independently associated disease-specific characteristics, and when all types of variables were considered, sex (&lt;em&gt;p&lt;/em&gt; &lt; 0.001), BMI (&lt;em&gt;p&lt;/em&gt; = 0.016), and SSS-ankylosis (&lt;em&gt;p&lt;/em&gt; = 0.042) were independently associated with PI. BMI (&lt;em&gt;p&lt;/em&gt; = 0.043) and NSAIDs use (&lt;em&gt;p&lt;/em&gt; = 0.041) were potentially negatively associated with CbTh.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Double-echo UTE measurements reve","PeriodicalId":9301,"journal":{"name":"Bone","volume":"194 ","pages":"Article 117430"},"PeriodicalIF":3.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488182","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":"Comment on “Characteristics of patients with very high fracture risk in a community-dwelling geriatric cohort”","authors":"Jian Tong","doi":"10.1016/j.bone.2025.117429","DOIUrl":"10.1016/j.bone.2025.117429","url":null,"abstract":"","PeriodicalId":9301,"journal":{"name":"Bone","volume":"194 ","pages":"Article 117429"},"PeriodicalIF":3.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511713","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":"Acute pain trajectories in elderly patients with fragility hip fractures","authors":"Paul Potnuru ,&nbsp;Christina Goehl ,&nbsp;Katherine S. Becker ,&nbsp;Alejandro Juul ,&nbsp;Madison Aycock ,&nbsp;Johanna Blair de Haan ,&nbsp;Sudipta Sen ,&nbsp;Michelle Ge ,&nbsp;Stephen J. Warner ,&nbsp;Nadia Hernandez","doi":"10.1016/j.bone.2025.117428","DOIUrl":"10.1016/j.bone.2025.117428","url":null,"abstract":"<div><h3>Background</h3><div>Pain management for hospitalized elderly patients with fragility hip fractures (FHF) remains challenging. This study aims to distinguish acute pain trajectories in FHF patients that can inform personalized analgesia management.</div></div><div><h3>Methods</h3><div>We conducted a prospective observational study of patients aged 65 and older with FHF at a Level I trauma center. The primary outcome was daily average pain assessed for five days post-injury using the Brief Pain Inventory (BPI). We used group-based trajectory modeling (GBTM) to distinguish acute pain trajectories. Then, factors and secondary outcomes (opioid use and hospital length of stay [LOS]) associated with more severe pain trajectories were identified.</div></div><div><h3>Results</h3><div>We enrolled 100 consecutive patients with FHF between June 2022 and June 2023. We identified three distinct acute pain trajectories: minimal pain, subsiding pain, and persistent pain. Factors associated with more severe pain trajectories included higher initial pain on admission (OR 1.17, 95 % CI 1.02–1.36, <em>P</em> = 0.047), higher BMI (OR 1.15, 95 % CI 1.02–1.29, <em>P</em> = 0.021), and intertrochanteric fracture type (OR = 6.46, 95 % CI 1.49–27.98, <em>P</em> = 0.013). The persistent pain trajectory was significantly associated with 40 % more opioid use (P = 0.01) and a longer LOS (LOS ratio = 1.45, 95 % CI 1.21–1.74, <em>P</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>Acute pain in FHF patients can be classified into distinct trajectories, providing a basis for personalized pain management. More severe pain trajectories are associated with higher opioid use and longer length of hospital stay.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"193 ","pages":"Article 117428"},"PeriodicalIF":3.5,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474888","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":"Notch signaling in osteoblast progenitor cells is required for BMP-induced bone formation","authors":"Heather M. Wilson ,&nbsp;Madison A. Buckles ,&nbsp;Parker K. Acevedo ,&nbsp;Christina Capobianco ,&nbsp;Danny M. Nguyen ,&nbsp;Karen Kessell ,&nbsp;Ingrid L. Bergin ,&nbsp;Yadav Wagley ,&nbsp;Ivo Kalajzic ,&nbsp;Kurt D. Hankenson","doi":"10.1016/j.bone.2025.117425","DOIUrl":"10.1016/j.bone.2025.117425","url":null,"abstract":"<div><div>Notch signaling is active during bone formation and prior studies have shown that it is required for both robust intramembranous and endochondral bone regeneration. Particularly, the systemic blockade of Notch signaling has been shown to inhibit BMP-induced bone formation in a murine calvarial defect model. In this study, we genetically disrupted the expression of both the dominant Notch receptor, Jagged-1, and the essential Notch signaling transcription factor Rbpj in osteoblast progenitors during calvarial bone healing. We found that Jagged-1 (and Jagged-2) expression by alpha Smooth Muscle Actin (αSMA) expressing progenitors is required for bone formation. Similarly, we found that Notch transcriptional activity within the αSMA lineage is required for BMP-induced bone regeneration. Inhibition of Notch signaling in the αSMA lineage resulted in decreased osteoblast progenitors, reduced vascularization, and sustained inflammation 10 days post-injury, with enhanced inflammation still present 42 days post-injury. We conclude that Jagged ligand induced Notch signaling within the osteoblast progenitor lineage is therefore required for bone morphogenetic proteins (BMP) induced bone regeneration. Modulation of Notch signaling may represent a new approach to promote bone repair.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"194 ","pages":"Article 117425"},"PeriodicalIF":3.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470231","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":"3D spatial distribution of Sost mRNA and sclerostin protein expression in response to in vivo tibia loading in female mice","authors":"Quentin A. Meslier ,&nbsp;Jacy Hoffmann ,&nbsp;Robert Oehrlein ,&nbsp;Daniel Kurczy ,&nbsp;James R. Monaghan ,&nbsp;Sandra J. Shefelbine","doi":"10.1016/j.bone.2025.117422","DOIUrl":"10.1016/j.bone.2025.117422","url":null,"abstract":"<div><div>Bones adapt to external mechanical loads through a process known as mechanoadaptation. Osteocytes are the bone cells that sense the mechanical environment and initiate a biological response. Investigating the changes in osteocyte molecular expression following mechanical loading has been instrumental in characterizing the regulatory pathways involved in bone adaptation. However, current methods for examining osteocyte molecular expression do not preserve the three-dimensional structure of the bone, which plays a critical role in the mechanical stimuli sensed by the osteocytes and their spatially controlled biological responses.</div><div>In this study, we used WISH-BONE (Whole-mount In Situ Histology of Bone) to investigate the spatial distribution of <em>Sost</em>-mRNA transcripts and its encoded protein, sclerostin, in 3D mouse tibia midshaft following in vivo tibia loading. Our findings showed a decrease in the percentage of <em>Sost</em>-positive osteocytes, after loading, along the posterior-lateral side of the tibia. The number of sclerostin-positive osteocytes were found to significantly decrease at a very specific 2D location of the tibia after loading. However, in 3D, the total number of sclerostin-positive osteocytes was similar between loaded and control legs.</div><div>This work is the first to provide a 3D analysis of <em>Sost</em> and sclerostin distribution in loaded versus contralateral mouse tibia midshafts. It also highlights the importance of the bone region analyzed and the method utilized when interpreting mechanoadaptation results. WISH-BONE represents a powerful tool for further characterization of mechanosensitive genes regulation in bone and holds the potential for advancing the development of new treatments targeting mechanosensitivity-related bone disorders.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"193 ","pages":"Article 117422"},"PeriodicalIF":3.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464892","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":"ERK inhibits osteoclast differentiation in RAW 264.7 cells through the osteoprotegerin-mediated autophagy","authors":"Soo-Young Shin ,&nbsp;In-Soon Kang ,&nbsp;Chaekyun Kim","doi":"10.1016/j.bone.2025.117424","DOIUrl":"10.1016/j.bone.2025.117424","url":null,"abstract":"<div><div>Osteoclasts (OCs) are bone-resorbing cells derived from the monocyte/macrophage lineage. The extracellular signal-regulated kinase (ERK) pathway controls cellular responses such as proliferation, differentiation, and survival, including those of OCs. In the present study, ERK inhibitors reduced the proliferation of bone marrow-derived macrophages (BMMs) and RAW 264.7 cells. However, ERK inhibitors decreased OC differentiation in BMMs but increased it in RAW 264.7 cells. ERK downregulation using small interfering RNA transfection also increased the OC differentiation and the expression of receptor activator of nuclear factor-κB, OC-specific markers, and OC-associated transcription factors in RAW 264.7 cells. These findings suggest ERK regulates OC differentiation in RAW 264.7 cells differently than in BMMs. Thus, we further investigated the mechanism by which ERK negatively regulates OC differentiation in RAW 264.7 cells. ERK inhibition decreased the expression of osteoprotegerin (OPG), a negative regulator of OC differentiation. OPG knockdown increased OC formation. ERK inhibitors activated the Akt/mammalian target of the rapamycin (mTOR) signaling pathway while inhibiting unc-51-like autophagy activating kinase 1 (ULK1). This resulted in decreased levels of microtubule-associated protein 1A/1B-light chain 3-II (LC3-II) and increased levels of p62, thereby reducing autophagy. In addition, OPG knockdown reduced autophagy by activating Akt/mTOR and inhibiting ULK1, resulting in decreased LC3-II and accumulated p62. Therefore, ERK inhibition promoted OC differentiation by downregulating OPG-mediated inhibition of osteoclastogenesis and autophagy in RAW 264.7 cells. These findings highlight ERK's complex role in OC differentiation and suggest that understanding ERK's dual impact on OC differentiation can provide insights into novel treatment strategies for bone-related disorders.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"193 ","pages":"Article 117424"},"PeriodicalIF":3.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416618","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":"Regulation of osteoclast-mediated bone resorption by lipids","authors":"Fang Luo,&nbsp;Tianyi Chen,&nbsp;Song Chen,&nbsp;Ding Bai,&nbsp;Xinyi Li","doi":"10.1016/j.bone.2025.117423","DOIUrl":"10.1016/j.bone.2025.117423","url":null,"abstract":"<div><div>Hyperactivation of osteoclasts has been identified as a significant etiological factor in several bone resorption-related disorders, including osteoporosis, periodontitis, arthritis, and bone metastasis of tumors. It has been demonstrated that the severity of these diseases is influenced by lipids that regulate osteoclast differentiation and activity through specific signaling pathways and cytokine levels. The regulatory mechanisms of different types of lipids on osteoclastogenesis vary across diverse disease contexts in bone resorption regulated by osteoclasts. This review presents an overview of the mechanisms underlying osteoclast formation and summarizes the pathways through which various lipids regulate osteoclastogenesis in different pathological contexts. We also discuss effective therapeutic strategies for osteolytic diseases based on modulation of lipid metabolism.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"193 ","pages":"Article 117423"},"PeriodicalIF":3.5,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377106","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":"Local antibiotic delivery: Recent basic and translational science insights in orthopedics","authors":"Amir Human Hoveidaei ,&nbsp;Seyedarad Mosalamiaghili ,&nbsp;Amirhosein Sabaghian ,&nbsp;Sina Hajiaghajani ,&nbsp;Ali Soltani Farsani ,&nbsp;Mahdi Sahebi ,&nbsp;Mohammad Poursalehian ,&nbsp;Basilia Onyinyechukwu Nwankwo ,&nbsp;Janet D. Conway","doi":"10.1016/j.bone.2025.117416","DOIUrl":"10.1016/j.bone.2025.117416","url":null,"abstract":"<div><h3>Background</h3><div>Infections remain a significant challenge in orthopedic settings despite advancements in preventive measures. Antibiotics are the primary defense against infections, but optimal delivery methods to the infection site are still being investigated. This review aims to examine existing approaches for local drug delivery from a basic science perspective.</div></div><div><h3>Recent findings</h3><div>Achieving adequate antibiotic concentration at the infection site is challenging due to compromised vasculature in ischemic conditions. Local administration methods, including antibiotic-loaded carriers such as impregnated bone grafts and various bone substitutes, are being explored as alternatives to systemic antibiotic use.</div></div><div><h3>Summary</h3><div>Various materials, including polymethyl methacrylate (PMMA), hydroxyapatite, calcium phosphate/sulfate, bone glass, and hydrogel, are being investigated for local antibiotic delivery. Some of these materials possess inherent antibacterial properties due to their chemical interactions. The selection of appropriate antibiotics, their dosage, release kinetics from the carrier material, physical behavior of the material/graft, and biocompatibility are key areas for further investigation in basic science research.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"193 ","pages":"Article 117416"},"PeriodicalIF":3.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367089","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":"Mineralised bone properties in a child with recessive osteogenesis imperfecta type XIV and in a conditional Tmem38b knockout murine model (Runx2-Cre; Tmem38bfl/fl)","authors":"Chloe E. Jones ,&nbsp;Stéphane Blouin ,&nbsp;Adalbert Raimann ,&nbsp;Gabriel Mindler ,&nbsp;Barbara M. Contento ,&nbsp;Roberta Besio ,&nbsp;Andreas Kranzl ,&nbsp;Benjamin Kraler ,&nbsp;Markus A. Hartmann ,&nbsp;Antonella Forlino ,&nbsp;Nadja Fratzl-Zelman","doi":"10.1016/j.bone.2025.117421","DOIUrl":"10.1016/j.bone.2025.117421","url":null,"abstract":"<div><h3>Introduction</h3><div>OI type XIV is caused by variants in the <em>TMEM38B</em> gene, encoding for the ubiquitously expressed endoplasmic reticulum trimeric intracellular cation channel type B (TRIC-B), causing disruptions in calcium homeostasis and collagen synthesis. Patients with OI type XIV present with a highly variable clinical phenotype, ranging from asymptomatic to severe. We present here data from a 6 year clinical follow-up of two affected siblings and bone tissue characterisation obtained during corrective surgery from one of the patients, as well as tibiae from a novel <em>Tmem38b</em> conditional knockout murine model (<em>Runx2-Cre; Tmem38b</em>^{<em>fl/fl</em>}).</div></div><div><h3>Methods</h3><div>Clinical examinations of the patients include bone mineral density (BMD) measurements using dual-energy x-ray absorptiometry (DXA) scanning and gait analyses. Quantitative backscattered electron imaging (qBEI) was used to investigate bone mineralisation density distribution (BMDD) and osteocyte lacunae properties, and confocal laser scanning microscopy was used to quantify the osteocyte lacuno-canalicular network (OLCN) in both human and murine specimens.</div></div><div><h3>Results</h3><div>Both patients (P1, P2) presented with muscular hypotension, fatigue, progression of lower limb deformities, and fractures. BMDD of the osteonal bone region of the tibia and fibula specimens obtained from P1 revealed no significant shift towards higher mineral content as seen in “classical” OI. Osteocyte lacunae porosity was elevated and analyses of the OLCN revealed a reduction in canalicular density and lacunar degree. <em>Runx2-Cre; Tmem38b</em>^{<em>fl/fl</em>} mice exhibited a very severe skeletal phenotype, with 10/12 of the tibiae showing evidence of fractures, bone deformations, or calluses. In contrast to the patient samples, both the cortex and metaphysis of mutant mice demonstrated a significant increase in the average mineral content (CaMean) and the peak of the distribution (CaPeak), as well as in osteocyte lacunae porosity (P &lt; 0.0001), whereas canalicular density (P &lt; 0.0001), and lacunar degree (P = 0.0004) were decreased.</div></div><div><h3>Conclusion</h3><div>While <em>Runx2-Cre; Tmem38b</em>^{<em>fl/fl</em>} mice exhibit hypermineralisation of the bone matrix, this is not apparent in bone specimens obtained from the OI type XIV patient. However, both human and murine bone tissue with absence of TRIC-B demonstrate the same abnormalities of the osteocyte lacunae porosity and osteocyte lacuno-canalicular network, indicating disruption to the OLCN which is likely a general hallmark of OI bone.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"193 ","pages":"Article 117421"},"PeriodicalIF":3.5,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191535","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}