Pathology最新文献_第4页

Bone metabolism in pathology: current practice and future directions 骨代谢病理学：目前的实践和未来的方向。

IF 3 3区医学 Q1 PATHOLOGY

Pathology

Pub Date : 2026-03-01 Epub Date: 2025-12-18 DOI: 10.1016/j.pathol.2025.12.002

Cherie Chiang , Kay Weng Choy

引用次数: 0

Seeing beyond the surface: bone histomorphometry re-visited—implications for diagnostic pathology 透过表面看：骨组织形态计量学重新审视-诊断病理学的意义。

IF 3 3区医学 Q1 PATHOLOGY

Pathology

Pub Date : 2026-03-01 Epub Date: 2025-12-05 DOI: 10.1016/j.pathol.2025.10.006

Terrence Diamond , Cherie Chiang , Grahame J. Elder

First introduced in the 1950s following the development of the transiliac crest trephine and the advent of plastic embedding techniques, undecalcified bone biopsy revolutionised skeletal pathology by allowing in vivo assessment of mineralised bone. The addition of tetracycline double-labelling in 1969 enabled dynamic measurement of bone formation, and by the 1980s, histomorphometric nomenclature had been standardised, laying the foundation for quantitative diagnosis of metabolic bone disease. Despite these advances, the clinical use of undecalcified biopsy has waned, supplanted by surrogate tools such as dual-energy X-ray absorptiometry and serum markers of turnover. Yet bone biopsy remains the only method that simultaneously captures bone architecture, turnover dynamics, and mineralisation status. While decalcified specimens remain essential for evaluating marrow pathology, neoplasia, and infection, they obliterate the mineral phase, fluorochrome labels, and critical osteoid structures. In contrast, undecalcified, fluorochrome-labelled sections permit precise quantification of bone formation rates, mineralisation lag time, and micro-architectural integrity, offering a direct window into the physiological processes underlying skeletal disease. Histomorphometry has elucidated the pathogenesis of disorders, including osteomalacia, renal osteodystrophy, adynamic bone, and bisphosphonate-induced suppression. It also plays a central role in clarifying turnover status in atypical or treatment-resistant osteoporosis and in characterising the altered bone biology of myeloma and metastatic disease, where bone destruction often reflects not only tumour invasion but also uncoupled or arrested regeneration. Beyond standard histology and histomorphometry, microcomputed tomography of biopsy cores enables three-dimensional analysis of trabecular and cortical bone, while emerging techniques, such as Fourier-transform infrared spectroscopy, micro-indentation, and electron microscopy, offer new ways to evaluate bone composition, matrix maturity, and nanoscale organisation. This review re-introduces undecalcified bone biopsy as a vital diagnostic and investigative tool. We outline its methodology, clinical indications, and interpretive value across metabolic and cancer-related bone disorders and provide practical guidance for its implementation.

在20世纪50年代，随着经髂嵴环钻的发展和塑料埋入技术的出现，非钙化骨活检通过允许对矿化骨进行体内评估，彻底改变了骨骼病理学。1969年四环素双标记的加入使骨形成的动态测量成为可能，到20世纪80年代，组织形态计量学命名法已经标准化，为代谢性骨病的定量诊断奠定了基础。尽管取得了这些进展，但非钙化活检的临床应用已经减弱，取而代之的是双能x线吸收仪和血清代谢标志物等替代工具。然而，骨活检仍然是唯一一种同时捕获骨结构、转换动态和矿化状态的方法。虽然脱钙标本仍然是评估骨髓病理、肿瘤和感染的必要条件，但它们会消除矿物相、荧光标记和关键的类骨结构。相比之下，未钙化、荧光标记的切片可以精确量化骨形成率、矿化滞后时间和微结构完整性，为了解骨骼疾病的生理过程提供了直接的窗口。组织形态学已经阐明了疾病的发病机制，包括骨软化症、肾性骨营养不良、动力骨和双磷酸盐诱导的抑制。它还在澄清非典型或治疗抵抗性骨质疏松症的转换状态以及表征骨髓瘤和转移性疾病的骨生物学改变方面发挥核心作用，其中骨破坏通常不仅反映肿瘤侵袭，还反映不耦合或阻止再生。除了标准组织学和组织形态测量学之外，活检芯的显微计算机断层扫描可以对小梁和皮质骨进行三维分析，而傅里叶变换红外光谱、微压痕和电子显微镜等新兴技术为评估骨成分、基质成熟度和纳米级组织提供了新的方法。这篇综述再次介绍了未钙化骨活检作为一种重要的诊断和调查工具。我们概述了其方法，临床适应症，以及在代谢和癌症相关骨骼疾病中的解释价值，并为其实施提供实用指导。

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引用次数: 0

Functional reference limit: objectively defining the physiological relationship between serum vitamin D and parathyroid hormone 功能参考限度：客观界定血清维生素D与甲状旁腺激素的生理关系。

IF 3 3区医学 Q1 PATHOLOGY

Pathology

Pub Date : 2026-03-01 Epub Date: 2025-12-20 DOI: 10.1016/j.pathol.2025.11.006

Tze Ping Loh , Hui Qi Low , Perkin Ming Him Chan , Corey Markus , Chun Yee Lim

A functional reference limit is defined as the point of inflection (a ‘breakpoint’), representing a change in the statistical relationship, between two biologically related biomarkers. We describe a statistical framework to objectively define functional reference limits using the homoeostatic relationship between serum 25-hydroxy vitamin D (vitamin D) and parathyroid hormone as a proof of concept. Vitamin D (the independent variable) and parathyroid hormone (the dependent variable) measurements were extracted from the Melbourne Pathology laboratory information system database. A scatter plot of the biomarker pair was first generated to visually assess the presence of an inflection point (breakpoint). Following this, the measurements were grouped into fixed concentration intervals of 500, 800 and 1000 and normalised to ensure the range of values were identical for both biomarkers. The normalised data were split into two (left and right) frames, and two weighed linear regressions were fitted in a sliding manner along the concentration range to search for the optimal fit for both regressions, as determined by the smallest mean squared of residual. Using this approach, the optimal functional reference limit for vitamin D, where the breakpoint for parathyroid hormone was found at 28 nmol/L with 800 fixed concentration intervals and a mean squared of residual of 0.0022. This approach uses several statistical procedures to improve the fitting of the weighted linear regressions to objectively identify the functional reference limit. An Excel tool of this approach is available (Supplementary File 1).

功能参考极限被定义为拐点（“断点”），代表两个生物学相关生物标志物之间统计关系的变化。我们用血清25-羟基维生素D（维生素D）和甲状旁腺激素之间的稳态关系作为概念证明，描述了一个统计框架来客观地定义功能参考极限。维生素D（自变量）和甲状旁腺激素（因变量）的测量数据从墨尔本病理学实验室信息系统数据库中提取。首先生成生物标记对的散点图，以直观地评估拐点（断点）的存在。在此之后，测量结果被分组到500、800和1000的固定浓度区间，并进行归一化，以确保两种生物标志物的值范围相同。归一化的数据被分成两个（左和右）帧，两个加权线性回归沿着浓度范围以滑动方式拟合，以寻找两个回归的最佳拟合，由最小的残差均方确定。利用该方法确定了维生素D的最佳功能参考限度，其中甲状旁腺激素的断点为28 nmol/L， 800个固定浓度区间，残差的均方根为0.0022。该方法采用多种统计方法改进加权线性回归的拟合，客观地确定了功能参考极限。这种方法的Excel工具是可用的（补充文件1）。

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引用次数: 0

Spatial transcriptomics in bone research: navigating hype and hurdles 骨研究中的空间转录组学：导航炒作和障碍。

IF 3 3区医学 Q1 PATHOLOGY

Pathology

Pub Date : 2026-03-01 Epub Date: 2025-11-13 DOI: 10.1016/j.pathol.2025.10.003

Dimitri Sokolowskei , Achira Shah , Alexander J. Trostle , Conan Juan , Mimi C. Sammarco , Robert J. Tower

Spatial transcriptomics (ST) is a powerful technology that facilitates the measurement of gene expression levels within the native tissue architecture. Spatial-omics applications in musculoskeletal research have proven crucial in elucidating aspects of cellular heterogeneity, molecular mechanisms underlying injury, and gene expression patterning in tissue homeostasis and disease. However, the necessity for bone tissue decalcification and processing presents unique tissue-based challenges for the application of ST. Furthermore, ST intrinsic platform limitations, workflow bottlenecks, and analysis complications impose significant challenges to widespread utilisation. Here, we review current ST platforms and outline their respective advantages and limitations, discuss the current state of bone sample processing for use in omics-based approaches, and summarise basic bioinformatics considerations for downstream analysis. We describe how ST has been applied across different musculoskeletal tissues and animal models in the field so far and, finally, provide some potential future directions for the field in how ST approaches could be used to address lingering and future biological questions.

空间转录组学（ST）是一项功能强大的技术，有助于测量天然组织结构中的基因表达水平。空间组学在肌肉骨骼研究中的应用已被证明在阐明组织稳态和疾病中的细胞异质性、损伤的分子机制和基因表达模式方面至关重要。然而，骨组织脱钙和处理的必要性为ST的应用带来了独特的基于组织的挑战。此外，ST固有的平台限制、工作流程瓶颈和分析并发症给ST的广泛应用带来了重大挑战。在这里，我们回顾了当前的ST平台，概述了它们各自的优势和局限性，讨论了基于组学方法的骨样本处理的现状，并总结了下游分析的基本生物信息学考虑。我们描述了迄今为止ST在不同肌肉骨骼组织和动物模型中的应用情况，最后，为该领域提供了一些潜在的未来方向，即ST方法如何用于解决挥之不去的和未来的生物学问题。

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引用次数: 0

Interpreting alkaline phosphatase in clinical practice: integrating analytical advances and physiological context 在临床实践中解释碱性磷酸酶：整合分析进展和生理背景。

IF 3 3区医学 Q1 PATHOLOGY

Pathology

Pub Date : 2026-03-01 Epub Date: 2025-12-23 DOI: 10.1016/j.pathol.2025.11.005

Kenneth Andrew Sikaris , Karen Rankin

Accurate interpretation of serum alkaline phosphatase (ALP) levels is crucial in clinical practice, requiring a nuanced understanding of both analytical methods and physiological determinants. Recent advancements in ALP assay techniques, particularly the adoption of the IFCC reference method, have led to higher measured ALP values and necessitated a reassessment of reference intervals. This review integrates analytical developments with physiological context to guide clinicians in interpreting ALP results. Levels of ALP are influenced by age, gender, physiological states such as pregnancy and menopause, and anthropometric factors including body mass index and bone density. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) method, now widely implemented, yields results that are approximately 10% higher than those from previous assays, impacting reference interval accuracy and clinical flagging rates. Clinical causes of elevated ALP span hepatobiliary and bone disorders, malignancies, endocrine conditions and benign transient hyperphosphatasemia, while reduced ALP may signal rare genetic, hepatic or nutritional disorders. The use of gamma-glutamyl transferase as a diagnostic adjunct enhances specificity for hepatic sources of ALP elevation. Artefacts such as sample handling and reagent variability remain challenges in assay consistency. This article underscores the importance of correlating ALP results with clinical context, other laboratory findings and updated reference intervals. Ongoing education and harmonisation of reference intervals are essential for effective clinical decision-making and minimising unnecessary investigations, ensuring ALP remains a valuable tool in patient assessment.

准确解释血清碱性磷酸酶（ALP）水平在临床实践中至关重要，需要对分析方法和生理决定因素有细致入微的理解。ALP测定技术的最新进展，特别是IFCC参考方法的采用，导致更高的ALP测量值，需要重新评估参考区间。本综述将分析发展与生理背景结合起来，以指导临床医生解释ALP结果。ALP的水平受年龄、性别、怀孕和绝经等生理状态以及体重指数和骨密度等人体测量因素的影响。国际临床化学和实验室医学联合会（IFCC）方法目前已得到广泛应用，其结果比以前的检测方法高出约10%，影响了参考区间的准确性和临床标记率。ALP升高的临床原因包括肝胆和骨骼疾病、恶性肿瘤、内分泌疾病和良性的一过性高磷酸酶血症，而ALP降低可能是罕见的遗传、肝脏或营养紊乱的信号。使用γ -谷氨酰转移酶作为诊断辅助手段增强了肝源ALP升高的特异性。样品处理和试剂可变性等人为因素仍然是测定一致性的挑战。这篇文章强调了将ALP结果与临床背景、其他实验室结果和更新的参考区间联系起来的重要性。持续的教育和参考间隔的协调对于有效的临床决策和减少不必要的调查是必不可少的，确保ALP仍然是患者评估的宝贵工具。

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引用次数: 0

Vitamin D insufficiency and deficiency: in search of a bone disease 维生素D不足和缺乏：寻找骨病。

IF 3 3区医学 Q1 PATHOLOGY

Pathology

Pub Date : 2026-03-01 Epub Date: 2025-10-23 DOI: 10.1016/j.pathol.2025.08.009

Siobhan E.M. Brodrick , Ego Seeman

The definition of deficiency or insufficiency of vitamin D remains challenging because currently used thresholds of <30 nmol/L and between 30 and either 50 or 75 nmol/L are not consistently associated with clinical or biochemical abnormalities suggestive of secondary hyperparathyroidism, compromised bone volume, microarchitecture, or osteomalacia. Indeed, there is little convincing clinical, biochemical, bone densitometric, microarchitectural, or histomorphometric evidence that 25-hydroxyvitamin D [25(OH)D] levels between 30 and 75 nmol/L in community dwellers identify a vitamin D ‘insufficiency’ disease. There is evidence of modest elevations of serum parathyroid hormone in a minority of individuals with 25(OH)D level <30 nmol/L, alerting to the possibility of a ‘deficiency’ state. However, even at this level of ‘deficiency’, most individuals have no biochemical or bone structural abnormalities. Meta-analyses of studies grouped according to commonality in dosage of vitamin D, with or without calcium supplementation, are used to make inferences concerning the correct treatment regimens, but confounders make these inferences problematic. Few well-designed and well-executed placebo-controlled studies have tested the antifracture efficacy and safety of different doses of vitamin D or conducted factorial-designed placebo-controlled trials comparing vitamin D plus calcium supplements versus either drug alone. By contrast, it is likely that there is a vitamin D deficiency state compromising bone health in residents of nursing homes and patients with limited sunlight exposure, malnutrition, or malabsorption. These circumstances signal the possibility of emerging or established bone disease requiring investigation and supplementation if appropriate.

维生素D缺乏或不足的定义仍然具有挑战性，因为目前使用的阈值是

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引用次数: 0

Heritable metabolic bone disorders: a guide to current genetic testing and clinical management for adult endocrinologists 遗传性代谢性骨疾病：成人内分泌学家当前基因检测和临床管理指南。

IF 3 3区医学 Q1 PATHOLOGY

Pathology

Pub Date : 2026-03-01 Epub Date: 2025-12-18 DOI: 10.1016/j.pathol.2025.12.001

Shejil Kumar , Emma L. Duncan , Lisa Hayes , Yemima Berman , Roderick J. Clifton-Bligh , Sunita M.C. De Sousa

Heritable metabolic bone disorders [including X-linked hypophosphataemia (XLH), hypophosphatasia and osteogenesis imperfecta (OI)] are rare skeletal conditions often presenting in childhood and requiring lifelong multidisciplinary care. Adult endocrinologists frequently find themselves as part of the caring team in an area of medicine experiencing dramatic changes over the past two decades; both diagnostically and therapeutically. Optimal management of skeletal dysplasia requires in-depth understanding of molecular aetiology, genetic testing strategies, and result interpretation; and state-of-the-art management approaches including newer targeted therapies that address fundamental molecular mechanisms. Together, these factors are expanding the reach of genetic testing into mainstream clinical practice. This review will discuss the aetiopathogenesis and clinical burden across the lifespan of three of the more common heritable metabolic bone disorders, outline a modern approach to genetic testing, and discuss current and future therapeutic landscapes informed by recent genomic progress—with the explicit aim of providing practising physicians with a workable and up-to-date approach to the care of individuals with XLH, hypophosphatasia, and OI.

遗传性代谢性骨疾病[包括x连锁低磷血症（XLH）、低磷血症和成骨不全症（OI）]是罕见的骨骼疾病，通常出现在儿童时期，需要终身多学科治疗。在过去的二十年里，成人内分泌学家经常发现自己是医学领域经历巨大变化的护理团队的一部分；无论是诊断上还是治疗上。骨骼发育不良的最佳管理需要深入了解分子病因学、基因检测策略和结果解释；最先进的管理方法，包括解决基本分子机制的新靶向疗法。总之，这些因素正在扩大基因检测进入主流临床实践的范围。这篇综述将讨论三种更常见的遗传性代谢性骨疾病的发病机制和临床负担，概述一种现代的基因检测方法，并讨论当前和未来的治疗前景，根据最近的基因组进展，明确的目的是为执业医生提供一个可行的和最新的方法来治疗XLH、低磷酸酶和成骨不全患者。

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引用次数: 0

Anaemia and bone disease 贫血和骨病。

IF 3 3区医学 Q1 PATHOLOGY

Pathology

Pub Date : 2026-03-01 Epub Date: 2025-11-20 DOI: 10.1016/j.pathol.2025.10.005

Karen Van , Jasna Aleksova , Phillip Wong , John Kanellis , Peter R. Ebeling , Frances Milat

Anaemia and bone disease commonly co-exist, particularly in chronic conditions such as haemoglobinopathies and chronic kidney disease. The effects on bone are mediated by multiple factors, including marrow expansion, iron overload, endocrine dysfunction, and disruptions in mineral metabolism. These changes compromise bone strength, increasing the risk of osteoporosis and fractures. Although therapeutic advances such as iron infusion and chelation therapy have significantly improved the management of anaemia and patient outcomes, their effects on bone health are often under-recognised with osteoporosis detection occurring after a fracture. Furthermore, with denosumab being a popular anti-resorptive choice amongst clinicians, an emerging and under-appreciated complication is the increasing number of case reports describing hypophosphataemia associated with concurrent anti-resorptive and parenteral iron. This review discusses the bi-directional relationship between anaemia and bone metabolism. By focusing on the central role of fibroblast growth factor-23 (FGF-23), as a link between anaemia, phosphate regulation, and bone metabolism, this review draws attention to under-recognised skeletal risks. Importantly, it offers practical recommendations for monitoring, bridging mechanistic insights with clinical practice where current guidelines remain limited.

贫血和骨病通常并存，特别是在血红蛋白病和慢性肾病等慢性疾病中。对骨骼的影响是由多种因素介导的，包括骨髓扩张、铁超载、内分泌功能障碍和矿物质代谢中断。这些变化损害了骨骼强度，增加了骨质疏松和骨折的风险。尽管铁输注和螯合治疗等治疗进步显著改善了贫血的管理和患者的预后，但它们对骨骼健康的影响往往被低估，因为骨折后会发现骨质疏松症。此外，随着denosumab在临床医生中成为一种流行的抗再吸收选择，一个新兴的、未被重视的并发症是越来越多的病例报告描述了与同时抗再吸收和肠外铁相关的低磷血症。本文就贫血与骨代谢的双向关系作一综述。通过关注成纤维细胞生长因子-23 （FGF-23）的中心作用，作为贫血、磷酸盐调节和骨代谢之间的联系，本综述提请注意未被认识的骨骼风险。重要的是，它为监测提供了实用的建议，将机制见解与当前指南仍然有限的临床实践联系起来。

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引用次数: 0

Screening for multiple myeloma has low yield as part of a secondary osteoporosis screen 作为继发性骨质疏松筛查的一部分，多发性骨髓瘤的筛查率很低。

IF 3 3区医学 Q1 PATHOLOGY

Pathology

Pub Date : 2026-03-01 Epub Date: 2025-12-19 DOI: 10.1016/j.pathol.2025.11.004

Joanna Y. Gong , Sandra Iuliano , Aye N. Tint , Jas-mine Seah , MaiAnh Nguyen , Cherie Chiang

Multiple myeloma (MM) is a secondary cause of osteoporosis, and universal screening is recommended post fragility fracture. However, the longitudinal yield of this approach has not been evaluated. We aimed to assess the yield of the secondary osteoporosis screen in the Austin Health Fracture Liaison Service (FLS) database between 1 June 2009 and 1 June 2014. Patient demographics, fragility fracture type, bone density, and pathology results, including serum protein electrophoresis (SPE), urine Bence Jones protein (BJP), and serum free light chains, were extracted. SPE results were classified as normal, inflammatory, or monoclonal [including monoclonal gammopathy of undetermined significance (MGUS) or MM]. Over 5 years, 1026 initial SPE results were available for 1592 confirmed fragility fractures in 1589 patients who accepted the FLS invitation. The median age was 72 years (IQR 62–81), 26% were men, and 24% sustained a hip or pelvic fracture. Screening for MM was performed a median of 7 days (IQR 3–35) post fracture and revealed 796 (78%) normal, 179 (17%) inflammatory, and 51 (5%) monoclonal results. Repeat SPE for 121 patients with initial inflammatory SPE results yielded an additional six monoclonal results. The monoclonal cohort was followed for a median of 4.4 years (IQR 2.4–7.5); this yielded 4.2% MGUS and 0.3% MM diagnoses. The total cost of universal MM screening was AUD $88,638. The yield of myeloma screening was low and associated with a significant cost. All new MM cases were already flagged by other routine pathology tests.

多发性骨髓瘤（MM）是骨质疏松症的继发原因，建议在脆性骨折后进行普遍筛查。然而，这种方法的纵向产量尚未得到评估。我们的目的是评估2009年6月1日至2014年6月1日期间奥斯汀健康骨折联络服务（FLS）数据库中继发性骨质疏松症筛查的成分率。提取患者人口统计资料、脆性骨折类型、骨密度和病理结果，包括血清蛋白电泳（SPE）、尿Bence Jones蛋白（BJP）和血清游离轻链。SPE结果分为正常、炎症或单克隆[包括意义不明的单克隆γ病（MGUS）或MM]。在5年多的时间里，1589名接受FLS邀请的1592名确诊易碎性骨折患者获得了1026个SPE初步结果。中位年龄为72岁（IQR 62-81）， 26%为男性，24%为髋部或骨盆骨折。骨折后平均7天（IQR 3-35）进行MM筛查，结果显示796例（78%）正常，179例（17%）炎症，51例（5%）单克隆。对121例初始炎性SPE结果的患者进行重复SPE分析，获得另外6个单克隆结果。该单克隆队列的中位随访时间为4.4年（IQR为2.4-7.5）；这导致4.2%的MGUS和0.3%的MM诊断。通用MM筛查的总费用为88,638澳元。骨髓瘤筛查的成功率很低，而且成本很高。所有新的MM病例已被其他常规病理检查标记。

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引用次数: 0

Reflex hepatitis C RNA testing in a private pathology setting. 反射丙型肝炎RNA测试在私人病理设置。

IF 3 3区医学 Q1 PATHOLOGY

Pathology

Pub Date : 2026-02-07 DOI: 10.1016/j.pathol.2025.11.012

Michael C Wehrhahn, Ana Domazetovska, Miriam Paul, Benjamin H Armstrong, Darcy Gray, Megan Yu, Elena Martinez, Jim P Newcombe

引用次数: 0