Bone Reports最新文献

{"title":"A case of hypophosphatemia and elevated intact fibroblast growth factor 23 levels after short-term saccharated ferric oxide administration in a young woman and database analysis of adverse drug reactions in Japan","authors":"Teruhisa Kinoshita ,&nbsp;Yuki Kondo ,&nbsp;Yuka Sakazaki ,&nbsp;Hiroki Imaizumi ,&nbsp;Norio Takimoto ,&nbsp;Yoichi Ishitsuka","doi":"10.1016/j.bonr.2024.101754","DOIUrl":"https://doi.org/10.1016/j.bonr.2024.101754","url":null,"abstract":"<div><p>Intravenous iron replacement therapy is a common treatment for iron deficiency. Commonly used agents in this treatment include ferric carboxymaltose, ferric derisomaltose, and saccharated ferric oxide (SFO). These drugs are known to elevate fibroblast growth factor 23 levels, resulting in hypophosphatemia, but in past reports, hypophosphatemia attributable to SFO treatment has been associated mainly with prolonged administration over several weeks. The present study details our experience of a case of moderate hypophosphatemia (&lt;2 mg/dL) in a 22-year-old woman who had no specific history of hypophosphatemia during the first 5 days of SFO treatment, and showed an increase in intact fibroblast growth factor 23 levels within the first week of treatment. Cases of hypophosphatemia have been reported as occurring as early as 1 week after the start of SFO administration in the Japanese Adverse Drug Event Report database. These cases, along with our case, underline the need for awareness of the possibility of hypophosphatemia from the early stage of SFO administration, regardless of the patient's age or dosage, as well as the need to monitor patients to prevent complications.</p></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"21 ","pages":"Article 101754"},"PeriodicalIF":2.5,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352187224000214/pdfft?md5=83d372551d2afc8edc0d12705ddb6697&pid=1-s2.0-S2352187224000214-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140321054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Homogenized finite element analysis of distal tibia sections: Achievements and limitations","authors":"Mathieu Simon ,&nbsp;Michael Indermaur ,&nbsp;Denis Schenk ,&nbsp;Benjamin Voumard ,&nbsp;Ivan Zderic ,&nbsp;Dominic Mischler ,&nbsp;Michael Pretterklieber ,&nbsp;Philippe Zysset","doi":"10.1016/j.bonr.2024.101752","DOIUrl":"https://doi.org/10.1016/j.bonr.2024.101752","url":null,"abstract":"&lt;div&gt;&lt;p&gt;High-resolution peripheral quantitative computed tomography (HR-pQCT) based micro-finite element (μFE) analysis allows accurate prediction of stiffness and ultimate load of standardised (∼1 cm) distal radius and tibia sections. An alternative homogenized finite element method (hFE) was recently validated to compute the ultimate load of larger (∼2 cm) distal radius sections that include Colles' fracture sites. Since the mechanical integrity of the weight-bearing distal tibia is gaining clinical interest, it has been shown that the same properties can be used to predict the strength of both distal segments of the radius and the tibia. Despite the capacity of hFE to predict structural properties of distal segments of the radius and the tibia, the limitations of such homogenization scheme remain unclear. Therefore, the objective of this study is to build a complete mechanical data set of the compressive behavior of distal segments of the tibia and to compare quantitatively the structural properties with the hFE predictions. As a further aim, it is intended to verify whether hFE is also able to capture the post-yield strain localisation or fracture zones in such a bone section, despite the absence of strain softening in the constitutive model.&lt;/p&gt;&lt;p&gt;Twenty-five fresh-frozen distal parts of tibias of human donors were used in this study. Sections were cut corresponding to an in-house triple-stack protocol HR-pQCT scan, lapped, and scanned using micro computed tomography (μCT). The sections were tested in compression until failure, unloaded and scanned again in μCT. Volumetric bone mineral density (vBMD) and bone mineral content (BMC) were correlated to compression test results. hFE analysis was performed in order to compare computational predictions (stiffness, yield load and plastic deformation field pattern) with the compressive experiment. Namely, strain localization was assessed based on digital volume correlation (DVC) results and qualitatively compared to hFE predictions by comparing mid-slices patterns.&lt;/p&gt;&lt;p&gt;Bone mineral content (BMC) showed a good correlation with stiffness (R&lt;sup&gt;2&lt;/sup&gt; = 0.92) and yield (R&lt;sup&gt;2&lt;/sup&gt; = 0.88). Structural parameters also showed good agreement between the experiment and hFE for both stiffness (R&lt;sup&gt;2&lt;/sup&gt; = 0.96, slope = 1.05 with 95 % CI [0.97, 1.14]) and yield (R&lt;sup&gt;2&lt;/sup&gt; = 0.95, slope = 1.04 [0.94, 1.13]). The qualitative comparison between hFE and DVC strain localization patterns allowed the classification of the samples into 3 categories: bad (15 sections), semi (8), and good agreement (2).&lt;/p&gt;&lt;p&gt;The good correlations between BMC or hFE and experiment for structural parameters were similar to those obtained previously for the distal part of the radius. The failure zones determined by hFE corresponded to registration only in 8 % of the cases. We attribute these discrepancies to local elastic/plastic buckling effects that are not captured by the continuum-based FE approach exempt from strain s","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"21 ","pages":"Article 101752"},"PeriodicalIF":2.5,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352187224000196/pdfft?md5=1c996085a31ff4a54c97a986f15ee1c2&pid=1-s2.0-S2352187224000196-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140341724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fueling recovery: The importance of energy coupling between angiogenesis and osteogenesis during fracture healing","authors":"Fleur van Brakel,&nbsp;Yudong Zhao,&nbsp;Bram C.J. van der Eerden","doi":"10.1016/j.bonr.2024.101757","DOIUrl":"https://doi.org/10.1016/j.bonr.2024.101757","url":null,"abstract":"<div><p>Approximately half of bone fractures that do not heal properly (non-union) can be accounted to insufficient angiogenesis. The processes of angiogenesis and osteogenesis are spatiotemporally regulated in the complex process of fracture healing that requires a substantial amount of energy. It is thought that a metabolic coupling between angiogenesis and osteogenesis is essential for successful healing. However, how this coupling is achieved remains to be largely elucidated. Here, we will discuss the most recent evidence from literature pointing towards a metabolic coupling between angiogenesis and osteogenesis. We will describe the metabolic profiles of the cell types involved during fracture healing as well as secreted products in the bone microenvironment (such as lactate and nitric oxide) as possible key players in this metabolic crosstalk.</p></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"21 ","pages":"Article 101757"},"PeriodicalIF":2.5,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S235218722400024X/pdfft?md5=02b00ef1763596f83b16252cac304472&pid=1-s2.0-S235218722400024X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140309773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective role of exercise on breast cancer-related osteoporosis in women undergoing aromatase inhibitors: A narrative review","authors":"Claudia Cerulli ,&nbsp;Elisa Moretti ,&nbsp;Elisa Grazioli ,&nbsp;Gian Pietro Emerenziani ,&nbsp;Arianna Murri ,&nbsp;Eliana Tranchita ,&nbsp;Carlo Minganti ,&nbsp;Alessandra Di Cagno ,&nbsp;Attilio Parisi","doi":"10.1016/j.bonr.2024.101756","DOIUrl":"https://doi.org/10.1016/j.bonr.2024.101756","url":null,"abstract":"<div><p>Hormone therapy following surgery reduces the risk of breast cancer (BC) recurrence and progression of hormone-sensitive BC, especially in postmenopausal women. Despite the antitumor efficacy of hormone therapy, particularly of aromatase inhibitors, they cause long-term side effects, mainly bone density reduction. Exercise can slow the rate of bone loss, which reduces the risk of fractures from osteoporosis, and could be an integrative treatment able to mitigate the BC treatment side effects positively impacting bone health. This narrative review aims to discuss studies on the effect of exercise on bone health in BC women undergoing aromatase inhibitors, highlighting the possible role of exercise as complementary to conventional therapies. Additionally, according to the literature revision, exercise practical applications to improve bone health in these patients are summarized.</p></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"21 ","pages":"Article 101756"},"PeriodicalIF":2.5,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352187224000238/pdfft?md5=8ef94065503523d307f6d3e8db9bd091&pid=1-s2.0-S2352187224000238-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140309820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High rate of progression to symptomatic multiple myeloma in patients with smoldering myeloma and isolated osteoporotic vertebral fracture","authors":"Kevin Chevalier ,&nbsp;Sabrina Hamroun ,&nbsp;Samuel Bitoun ,&nbsp;Julien Henry ,&nbsp;Christian Roux ,&nbsp;Karine Briot ,&nbsp;Rakiba Belkhir ,&nbsp;Xavier Mariette ,&nbsp;Raphaèle Seror","doi":"10.1016/j.bonr.2024.101755","DOIUrl":"https://doi.org/10.1016/j.bonr.2024.101755","url":null,"abstract":"<div><p>Multiple myeloma (MM) frequently causes vertebral fractures (VF). Some are lytic lesions and others have the aspect of benign osteoporotic fractures not requiring anti-myeloma treatment. We explored outcome of these patients with smoldering myeloma (SM) and osteoporotic VF.</p><p>In this retrospective bi-centric study, patients were identified using a systematic keyword search on electronic medical records. Patients with SM and isolated VF of osteoporotic aspect without indications for myeloma-specific therapy were included.</p><p>Overall, 13 (7 %) of the 184 identified patients had SM and VF confirmed to be osteoporotic (median number of VF was 3). During follow-up, 12 (92 %) patients evolved to symptomatic MM, 7 (54 %) of them within 18 months (early progressors). Myeloma defining events were new lytic bone lesions in 7 patients (53.8 %). The serum calcium level was significantly higher in the early progressor group (median 2.35 IQR [2.31–2.38] and 2.28 IQR [2.21–2.29] respectively, <em>p</em> = 0.003). Early progressors had a higher number of VF at diagnosis (3.0 [2.0–5.5] vs 1.0 [1.0–2.5], <em>p</em> = 0.18) and more frequently evolved to symptomatic MM because of lytic bone lesions (5 [71 %] vs 2 [33 %], <em>p</em> = 0.13) compared to late progressors.</p><p>VF of osteoporotic appearance in the context of SM is a rare situation but at high risk of rapid progression to symptomatic MM, suggesting that they may represent bone fragility linked to MM infiltration rather than solely osteoporotic fractures. Further studies are needed to assess if earlier treatment might be beneficial in this population.</p></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"21 ","pages":"Article 101755"},"PeriodicalIF":2.5,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352187224000226/pdfft?md5=afe87f7f94161630eeb982607eb0b5b0&pid=1-s2.0-S2352187224000226-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140290845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lessons learned from the real-world diagnosis and management of hereditary hypophosphatemic rickets","authors":"Deepti Chaturvedi ,&nbsp;Taif EmadEldin Mehasi ,&nbsp;Assia Benbrahim ,&nbsp;Lubna ElDeeb ,&nbsp;Asma Deeb","doi":"10.1016/j.bonr.2024.101753","DOIUrl":"10.1016/j.bonr.2024.101753","url":null,"abstract":"<div><p>Hypophosphatemic rickets, which is often hereditary, is still under- or misdiagnosed in both children and adults, denying these individuals access to optimal management and genetic counseling. There have been recent calls to compile real-world data and share best practice on these rare conditions to guide clinical decision-making. Here we present eight clinical vignettes of patients with hypophosphatemic rickets encountered in our tertiary pediatric endocrinology practice. We describe the clinical features, genetics, and management of four cases of X-linked hypophosphatemia (<em>PHEX</em> mutations), one each of autosomal recessive hypophosphatemic rickets (<em>DMP1</em> mutation) and autosomal recessive vitamin D-dependent rickets type 1A (<em>CYP27B1</em> mutation), and two cases of distal renal tubular acidosis with <em>FOXI1</em> mutation-associated hypophosphatemic rickets. Our cases prompt consideration of the (i) frequent misdiagnosis of hypophosphatemic rickets in clinical practice and the importance of comprehensive genetic testing; (ii) variable expressivity of the causative mutations; and (iii) a lack of responsiveness and/or compliance to conventional therapy and the value of burosumab in modern management, provided access is equitable. These cases highlight common real-world themes and challenges to managing patients presenting with these diverse conditions, especially the burden of disease hidden by misdiagnosis. In sharing these cases, we hope to raise awareness of these conditions, promote best practice in genetic diagnosis and management, and further advocate for reimbursement equity for the best available therapies.</p></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"21 ","pages":"Article 101753"},"PeriodicalIF":2.5,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352187224000202/pdfft?md5=6dfd2cc5b734f76a4a725d477b1c9e6d&pid=1-s2.0-S2352187224000202-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140279518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microvascular disease not type 2 diabetes is associated with increased cortical porosity: A study of cortical bone microstructure and intracortical vessel characteristics","authors":"Maximilian T. Löffler ,&nbsp;Po-hung Wu ,&nbsp;Amir M. Pirmoazen ,&nbsp;Gabby B. Joseph ,&nbsp;Jay M. Stewart ,&nbsp;Isra Saeed ,&nbsp;Jing Liu ,&nbsp;Anne L. Schafer ,&nbsp;Ann V. Schwartz ,&nbsp;Thomas M. Link ,&nbsp;Galateia J. Kazakia","doi":"10.1016/j.bonr.2024.101745","DOIUrl":"https://doi.org/10.1016/j.bonr.2024.101745","url":null,"abstract":"<div><h3>Introduction</h3><p>Fracture risk is elevated in type 2 diabetes (T2D) despite normal or even high bone mineral density (BMD). Microvascular disease (MVD) is a diabetic complication, but also associated with other diseases, for example chronic kidney disease. We hypothesize that increased fracture risk in T2D could be due to increased cortical porosity (Ct.Po) driven by expansion of the vascular network in MVD. The purpose of this study was to investigate associations of T2D and MVD with cortical microstructure and intracortical vessel parameters.</p></div><div><h3>Methods</h3><p>The study group consisted of 75 participants (38 with T2D and 37 without T2D). High-resolution peripheral quantitative CT (HR-pQCT) and dynamic contrast-enhanced MRI (DCE-MRI) of the ultra-distal tibia were performed to assess cortical bone and intracortical vessels (outcomes). MVD was defined as ≥1 manifestation including neuropathy, nephropathy, or retinopathy based on clinical exams in all participants. Adjusted means of outcomes were compared between groups with/without T2D or between participants with/without MVD in both groups using linear regression models adjusting for age, sex, BMI, and T2D as applicable.</p></div><div><h3>Results</h3><p>MVD was found in 21 (55 %) participants with T2D and in 9 (24 %) participants without T2D. In T2D, cortical pore diameter (<span>Ct.Po.Dm</span><svg><path></path></svg>) and diameter distribution (<span>Ct.Po.Dm.SD</span><svg><path></path></svg>) were significantly higher by 14.6 μm (3.6 %, 95 % confidence interval [CI]: 2.70, 26.5 μm, <em>p</em> = 0.017) and by 8.73 μm (4.8 %, CI: 0.79, 16.7 μm, <em>p</em> = 0.032), respectively. In MVD, but not in T2D, cortical porosity was significantly higher by 2.25 % (relative increase = 12.9 %, CI: 0.53, 3.97 %, <em>p</em> = 0.011) and cortical BMD (Ct.BMD) was significantly lower by −43.6 mg/cm³ (2.6 %, CI: −77.4, −9.81 mg/cm³, <em>p</em> = 0.012). In T2D, vessel volume and vessel diameter were significantly higher by 0.02 mm³ (13.3 %, CI: 0.004, 0.04 mm³, <em>p</em> = 0.017) and 15.4 μm (2.9 %, CI: 0.42, 30.4 μm, <em>p</em> = 0.044), respectively. In MVD, vessel density was significantly higher by 0.11 mm⁻³ (17.8 %, CI: 0.01, 0.21 mm⁻³, <em>p</em> = 0.033) and vessel volume and diameter were significantly lower by −0.02 mm³ (13.7 %, CI: −0.04, −0.004 mm³, <em>p</em> = 0.015) and − 14.6 μm (2.8 %, CI: −29.1, −0.11 μm, <em>p</em> = 0.048), respectively.</p></div><div><h3>Conclusions</h3><p>The presence of MVD, rather than T2D, was associated with increased cortical porosity. Increased porosity in MVD was coupled with a larger number of smaller vessels, which could indicate upregulation of neovascularization triggered by ischemia. It is unclear why higher variability and average diameters of pores in T2D were accompanied by larger vessels.</p></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"20 ","pages":"Article 101745"},"PeriodicalIF":2.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352187224000123/pdfft?md5=3d14966779ac86845812bdf76c953c7e&pid=1-s2.0-S2352187224000123-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139992577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo imaging of bone collagen dynamics in zebrafish","authors":"Hiromu Hino,&nbsp;Shigeru Kondo,&nbsp;Junpei Kuroda","doi":"10.1016/j.bonr.2024.101748","DOIUrl":"https://doi.org/10.1016/j.bonr.2024.101748","url":null,"abstract":"<div><p>Type I collagen plays a pivotal role in shaping bone morphology and determining its physical properties by serving as a template for ossification. Nevertheless, the mechanisms underlying bone collagen formation, particularly the principles governing its orientation, remain unknown owing to the lack of a method that enables continuous in vivo observations. To address this challenge, we constructed a method to visualize bone collagen by tagging with green fluorescent protein (GFP) in zebrafish and observed the interactions between osteoblasts and collagen fibers during bone formation in vivo. When collagen type I alpha 2 chain (Col1a2)-GFP was expressed under the control of the osteoblast-specific promoters <em>osx</em> or <em>osc</em> in zebrafish, bone collagen was observed clearly enough to identify its localization, whereas collagen from other organs was not. Therefore, we determined that this method was of sufficient quality for the detailed in vivo observation of bone collagen. Next, bone collagen in the scales, fin rays, and opercular bones of zebrafish was observed in detail, when bone formation is more active. High-magnification imaging showed that Col1a2-GFP can visualize collagen sufficiently to analyze the collagen fiber orientation and microstructure of bones.</p><p>Furthermore, by simultaneously observation of bone collagen and osteoblasts, we successfully observed dynamic changes in the morphology and position of osteoblasts from the early stages of bone formation. It was also found that the localization pattern and orientation of bone collagen significantly differed depending on the choice of the expression promoter. Both promoters (<em>osx</em> and <em>osc</em>) used in this study are osteoblast-specific, but their Col1a2-GFP localizing regions within the bone were exclusive, with <em>osx</em> region localizing mainly to the outer edge of the bone and <em>osc</em> region localizing to the central area of the bone. This suggests the existence of distinct osteoblast subpopulations with different gene expression profiles, each of which may play a unique role in osteogenesis.</p><p>These findings would contribute to a better understanding of the mechanisms governing bone collagen formation by osteoblasts.</p></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"20 ","pages":"Article 101748"},"PeriodicalIF":2.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352187224000159/pdfft?md5=cb08f47d26cb5827c6314da29d639ff8&pid=1-s2.0-S2352187224000159-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140137962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disruption of FLNB leads to skeletal malformation by interfering with skeletal segmentation through the HOX gene","authors":"Qiming Xu ,&nbsp;Lijia Cui ,&nbsp;Yude Lin ,&nbsp;Leigh-Anne Cui ,&nbsp;Weibo Xia","doi":"10.1016/j.bonr.2024.101746","DOIUrl":"https://doi.org/10.1016/j.bonr.2024.101746","url":null,"abstract":"<div><p>Filamin B (FLNB) plays an important role in skeletal development. Mutations in <em>FLNB</em> can lead to skeletal malformation such as an abnormal number of ossification centers, indicating that the skeletal segmentation in the embryonic period may be interfered with. We established a mouse model with the pathogenic point mutation <em>FLNB</em> NM_001081427.1: c.4756G &gt; A (p.Gly1586Arg) using CRISPR-Cas9 technology. Micro-CT, HE staining and whole skeletal preparation were performed to examine the skeletal malformation. <em>In situ</em> hybridization of embryos was performed to examine the transcription of <em>HOX</em> genes during embryonic development. The expression of <em>FLNB</em> was downregulated in <em>FLNB</em>^{<em>G1586R/G1586R</em>} and <em>FLNB</em>^{<em>WT/G1586R</em>} mice, compared to <em>FLNB</em>^{<em>WT/WT</em>} mice. Fusions in tarsal bones were found in <em>FLNB</em>^{<em>G1586R/G1586R</em>} and <em>FLNB</em>^{<em>WT/G1586R</em>} mice, indicating that the skeletal segmentation was interfered with. In the embryo of <em>FLNB</em>^{<em>G1586R</em>/<em>G1586R</em>} mice (E12.5), the transcription levels of <em>HOXD10</em> and <em>HOXB2</em> were downregulated in the carpal region and cervical spine region, respectively. This study indicated that the loss-of-function mutation G1586R in <em>FLNB</em> may lead to abnormal skeletal segmentation, and the mechanism was possibly associated with the downregulation of <em>HOX</em> gene transcription during the embryonic period.</p></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"20 ","pages":"Article 101746"},"PeriodicalIF":2.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352187224000135/pdfft?md5=728bb9d200c17274480dd8ba735f03ab&pid=1-s2.0-S2352187224000135-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140030727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The multi-faceted nature of age-associated osteoporosis","authors":"A.E. Smit ,&nbsp;O.C. Meijer ,&nbsp;E.M. Winter","doi":"10.1016/j.bonr.2024.101750","DOIUrl":"https://doi.org/10.1016/j.bonr.2024.101750","url":null,"abstract":"<div><p>Age-associated osteoporosis (AAOP) poses a significant health burden, characterized by increased fracture risk due to declining bone mass and strength. Effective prevention and early treatment strategies are crucial to mitigate the disease burden and the associated healthcare costs. Current therapeutic approaches effectively target the individual contributing factors to AAOP. Nonetheless, the management of AAOP is complicated by the multitude of variables that affect its development. Main intrinsic and extrinsic factors contributing to AAOP risk are reviewed here, including mechanical unloading, nutrient deficiency, hormonal disbalance, disrupted metabolism, cognitive decline, inflammation and circadian disruption. Furthermore, it is discussed how these can be targeted for prevention and treatment. Although valuable as individual targets for intervention, the interconnectedness of these risk factors result in a unique etiology for every patient. Acknowledgement of the multifaceted nature of AAOP will enable the development of more effective and sustainable management strategies, based on a holistic, patient-centered approach.</p></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"20 ","pages":"Article 101750"},"PeriodicalIF":2.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352187224000172/pdfft?md5=39c67a98f90cb657a8bae1bf1149b52d&pid=1-s2.0-S2352187224000172-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140191265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}