{"title":"利用高分辨率显微 CT 对人体骨活检组织进行三维骨细胞裂隙形态测量:从单克隆抗体病到新诊断的多发性骨髓瘤。","authors":"Inés Moreno-Jiménez , Sharen Heinig , Unai Heras , Daniela Simone Maichl , Susanne Strifler , Ellen Leich , Stéphane Blouin , Peter Fratzl , Nadja Fratzl-Zelman , Franziska Jundt , Amaia Cipitria","doi":"10.1016/j.bone.2024.117236","DOIUrl":null,"url":null,"abstract":"<div><p>Osteocytes are mechanosensitive, bone-embedded cells which are connected via dendrites in a lacuno-canalicular network and regulate bone resorption and formation balance. Alterations in osteocyte lacunar volume, shape and density have been identified in conditions of aging, osteoporosis and osteolytic bone metastasis, indicating patterns of impaired bone remodeling, osteolysis and disease progression. Osteolytic bone disease is a hallmark of the hematologic malignancy multiple myeloma (MM), in which monoclonal plasma cells in the bone marrow disrupt the bone homeostasis and induce excessive resorption at local and distant sites. Qualitative and quantitative changes in the 3D osteocyte lacunar morphometry have not yet been evaluated in MM, nor in the precursor conditions monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). In this study, we characterized the osteocyte lacunar morphology in trabecular bone of the iliac crest at the ultrastructural level using high resolution microCT in human bone biopsy samples of three MGUS, two SMM and six newly diagnosed MM. In MGUS, SMM and MM we found a trend for lower lacunar density and a shift towards larger lacunae with disease progression (higher 50 % cutoff of the lacunar volume cumulative distribution) in the small osteocyte lacunae 20–900 μm<sup>3</sup> range compared to control samples. In the larger lacunae 900–3000 μm<sup>3</sup> range, we detected significantly higher lacunar density and microporosity in the MM group compared to the MGUS/SMM group. Regarding the shape distribution, the MGUS/SMM group showed a trend for flatter, more elongated and anisotropic osteocyte lacunae compared to the control group. Altogether, our findings suggest that osteocytes in human MM bone disease undergo changes in their lacunae density, volume and shape, which could be an indicator for osteolysis and disease progression. Future studies are needed to understand whether alterations of the lacunae architecture affect the mechanoresponsiveness of osteocytes, and ultimately bone adaptation and fracture resistance in MM and its precursors conditions.</p></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S8756328224002254/pdfft?md5=91e82e606b5aecf599b723475ea2e9c5&pid=1-s2.0-S8756328224002254-main.pdf","citationCount":"0","resultStr":"{\"title\":\"3D osteocyte lacunar morphometry of human bone biopsies with high resolution microCT: From monoclonal gammopathy to newly diagnosed multiple myeloma\",\"authors\":\"Inés Moreno-Jiménez , Sharen Heinig , Unai Heras , Daniela Simone Maichl , Susanne Strifler , Ellen Leich , Stéphane Blouin , Peter Fratzl , Nadja Fratzl-Zelman , Franziska Jundt , Amaia Cipitria\",\"doi\":\"10.1016/j.bone.2024.117236\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Osteocytes are mechanosensitive, bone-embedded cells which are connected via dendrites in a lacuno-canalicular network and regulate bone resorption and formation balance. Alterations in osteocyte lacunar volume, shape and density have been identified in conditions of aging, osteoporosis and osteolytic bone metastasis, indicating patterns of impaired bone remodeling, osteolysis and disease progression. Osteolytic bone disease is a hallmark of the hematologic malignancy multiple myeloma (MM), in which monoclonal plasma cells in the bone marrow disrupt the bone homeostasis and induce excessive resorption at local and distant sites. Qualitative and quantitative changes in the 3D osteocyte lacunar morphometry have not yet been evaluated in MM, nor in the precursor conditions monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). In this study, we characterized the osteocyte lacunar morphology in trabecular bone of the iliac crest at the ultrastructural level using high resolution microCT in human bone biopsy samples of three MGUS, two SMM and six newly diagnosed MM. In MGUS, SMM and MM we found a trend for lower lacunar density and a shift towards larger lacunae with disease progression (higher 50 % cutoff of the lacunar volume cumulative distribution) in the small osteocyte lacunae 20–900 μm<sup>3</sup> range compared to control samples. In the larger lacunae 900–3000 μm<sup>3</sup> range, we detected significantly higher lacunar density and microporosity in the MM group compared to the MGUS/SMM group. Regarding the shape distribution, the MGUS/SMM group showed a trend for flatter, more elongated and anisotropic osteocyte lacunae compared to the control group. Altogether, our findings suggest that osteocytes in human MM bone disease undergo changes in their lacunae density, volume and shape, which could be an indicator for osteolysis and disease progression. Future studies are needed to understand whether alterations of the lacunae architecture affect the mechanoresponsiveness of osteocytes, and ultimately bone adaptation and fracture resistance in MM and its precursors conditions.</p></div>\",\"PeriodicalId\":9301,\"journal\":{\"name\":\"Bone\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-08-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S8756328224002254/pdfft?md5=91e82e606b5aecf599b723475ea2e9c5&pid=1-s2.0-S8756328224002254-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Bone\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S8756328224002254\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bone","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S8756328224002254","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
摘要
骨细胞是对机械敏感的骨嵌入细胞,通过树突连接成裂隙-管状网络,调节骨吸收和形成的平衡。在衰老、骨质疏松症和溶骨性骨转移等情况下,已发现骨细胞裂隙体积、形状和密度发生变化,表明骨重塑、溶骨和疾病进展的模式受损。溶骨性骨病是血液系统恶性肿瘤多发性骨髓瘤(MM)的特征之一,骨髓中的单克隆浆细胞会破坏骨平衡,诱发局部和远处部位的过度吸收。目前尚未对多发性骨髓瘤三维骨细胞裂隙形态的定性和定量变化进行评估,也未对意义未定的单克隆性淋巴瘤(MGUS)和烟雾型多发性骨髓瘤(SMM)的前驱症状进行评估。在这项研究中,我们利用高分辨率显微 CT 技术,从超微结构层面描述了 3 例 MGUS、2 例 SMM 和 6 例新确诊 MM 的人体骨活检样本中髂嵴骨小梁中的骨细胞裂隙形态。在 MGUS、SMM 和 MM 中,与对照样本相比,我们发现随着疾病的发展(裂隙体积累积分布的 50% 临界值更高),在 20-900 μm3 范围内的小骨细胞裂隙中,裂隙密度呈降低趋势,并向更大的裂隙转变。在900-3000 μm3范围的较大腔隙中,我们发现MM组的腔隙密度和微孔率明显高于MGUS/SMM组。在形状分布方面,与对照组相比,MGUS/SMM 组的骨细胞腔呈扁平、拉长和各向异性趋势。总之,我们的研究结果表明,人类MM骨病患者的骨细胞腔密度、体积和形状会发生变化,这可能是溶骨和疾病进展的一个指标。未来的研究需要了解腔隙结构的改变是否会影响骨细胞的机械敏感性,并最终影响 MM 及其前体病变中骨的适应性和抗骨折性。
3D osteocyte lacunar morphometry of human bone biopsies with high resolution microCT: From monoclonal gammopathy to newly diagnosed multiple myeloma
Osteocytes are mechanosensitive, bone-embedded cells which are connected via dendrites in a lacuno-canalicular network and regulate bone resorption and formation balance. Alterations in osteocyte lacunar volume, shape and density have been identified in conditions of aging, osteoporosis and osteolytic bone metastasis, indicating patterns of impaired bone remodeling, osteolysis and disease progression. Osteolytic bone disease is a hallmark of the hematologic malignancy multiple myeloma (MM), in which monoclonal plasma cells in the bone marrow disrupt the bone homeostasis and induce excessive resorption at local and distant sites. Qualitative and quantitative changes in the 3D osteocyte lacunar morphometry have not yet been evaluated in MM, nor in the precursor conditions monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). In this study, we characterized the osteocyte lacunar morphology in trabecular bone of the iliac crest at the ultrastructural level using high resolution microCT in human bone biopsy samples of three MGUS, two SMM and six newly diagnosed MM. In MGUS, SMM and MM we found a trend for lower lacunar density and a shift towards larger lacunae with disease progression (higher 50 % cutoff of the lacunar volume cumulative distribution) in the small osteocyte lacunae 20–900 μm3 range compared to control samples. In the larger lacunae 900–3000 μm3 range, we detected significantly higher lacunar density and microporosity in the MM group compared to the MGUS/SMM group. Regarding the shape distribution, the MGUS/SMM group showed a trend for flatter, more elongated and anisotropic osteocyte lacunae compared to the control group. Altogether, our findings suggest that osteocytes in human MM bone disease undergo changes in their lacunae density, volume and shape, which could be an indicator for osteolysis and disease progression. Future studies are needed to understand whether alterations of the lacunae architecture affect the mechanoresponsiveness of osteocytes, and ultimately bone adaptation and fracture resistance in MM and its precursors conditions.
期刊介绍:
BONE is an interdisciplinary forum for the rapid publication of original articles and reviews on basic, translational, and clinical aspects of bone and mineral metabolism. The Journal also encourages submissions related to interactions of bone with other organ systems, including cartilage, endocrine, muscle, fat, neural, vascular, gastrointestinal, hematopoietic, and immune systems. Particular attention is placed on the application of experimental studies to clinical practice.