Osteoarthritis and cartilage open最新文献

Investigating predictors of pain events during trials of knee osteoarthritis: A post-hoc analysis of two phase III trials 调查膝关节骨关节炎试验中疼痛事件的预测因素：两个III期试验的事后分析

IF 2.8

Osteoarthritis and cartilage open

Pub Date : 2026-01-22 DOI: 10.1016/j.ocarto.2026.100746

Andrea Bak Kaaber , Jakob Mejdahl Bentin , Ida Sofie Adrian , Morten Asser Karsdal , Asger Reinstrup Bihlet

Objective

This study aims to explore the associations between clinical characteristics, including medical history, and the frequency, severity, and type of pain events (PEs) over a two-year period in patients with knee osteoarthritis (OA).

Design

A post-hoc analysis was conducted on data from two double-blinded, randomized, placebo-controlled, multicenter phase-III trials assessing the efficacy and safety of salmon calcitonin in patients with painful and radiographic knee OA. 2206 patients aged 51–80 years were included. Adverse events (AEs) were recorded and categorized into PEs and non-PEs. Logistic regression models were used to assess associations, adjusting for confounders such as age, sex, and body mass index (BMI).

Results

Of the 8183 AEs recorded, 27.6 % were classified as PEs. Higher BMI was associated with lower odds of reporting PEs (OR: 0.94, p = 0.02), while male patients reported fewer PEs than females (OR: 0.83, p = 0.04). Insomnia and depression were linked to increased odds of PEs. In the PE population, higher BMI was associated with increased odds of moderate and severe PEs. KL grade 3 was linked to lower odds of moderate and severe PEs.

Conclusions

The study identifies female sex and certain medical histories as significant predictors of PEs in knee OA patients. A higher BMI was associated with lower odds of reporting PEs but for those who reported PEs, higher BMI was associated with more severe PEs. These results should be interpreted with caution due to methodological limitations, however the findings indicate risk factors for pain events and suggest further research into these associations.

目的本研究旨在探讨两年内膝关节骨关节炎（OA）患者的临床特征（包括病史）与疼痛事件（PEs）的频率、严重程度和类型之间的关系。DesignA对两项双盲、随机、安慰剂对照、多中心iii期试验的数据进行了事后分析，以评估鲑鱼降钙素对疼痛性膝关节骨性关节炎患者的疗效和安全性。2206例患者，年龄51-80岁。记录不良事件（ae）并将其分为pe和非pe。使用逻辑回归模型评估相关性，调整混杂因素，如年龄、性别和体重指数（BMI）。结果8183例ae中，pe占27.6%。BMI越高，报告pe的几率越低（OR: 0.94, p = 0.02），而男性患者报告pe的几率低于女性患者（OR: 0.83, p = 0.04）。失眠和抑郁与pe的几率增加有关。在PE人群中，较高的BMI与中度和重度PE的几率增加有关。KL 3级与中度和重度pe发生率较低有关。结论：该研究确定女性性别和某些病史是膝关节OA患者pe的重要预测因素。较高的BMI与报告pe的几率较低相关，但对于报告pe的人来说，较高的BMI与更严重的pe相关。由于方法学的限制，这些结果应该谨慎解释，然而，这些发现表明了疼痛事件的危险因素，并建议对这些关联进行进一步的研究。

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引用次数: 0

The infrapatellar fat pad mediates environmental exposure for clinical outcomes in knee osteoarthritis 髌下脂肪垫介导膝骨关节炎临床结果的环境暴露

IF 2.8

Osteoarthritis and cartilage open

Pub Date : 2026-01-22 DOI: 10.1016/j.ocarto.2026.100749

Anping Shen , Ruoyu Zhuang , Yan Xue , Jin Wang , Laijun Yan , Muyun Yang , Qinguang Xu , Yuelong Cao

Objective

This cross-sectional study aimed to investigate whether the infrapatellar fat pad (IPFP) mediates the relationship between environmental exposures and clinical symptoms in patients with knee osteoarthritis (KOA).

Methods

A total of 108 participants with KOA were included in this study, and environmental exposure data, including temperature, wind speed, and relative humidity, were obtained from local meteorological records. IPFP characteristics were quantitatively assessed using 3.0T magnetic resonance imaging (MRI), including morphometric and signal intensity (SI) parameters. Clinical symptoms were evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Principal component analysis (PCA) was used to reduce dimensionality of IPFP MRI features. Mediation analysis was performed to examine whether IPFP parameters mediated the effect of environmental exposures on WOMAC scores.

Results

PCA revealed that SI parameters accounted for 56.87 % of the total variance in IPFP features, while morphometric parameters explained 16.65 %. Correlation analysis showed that most SI parameters (e.g., mean SI, SD SI) were significantly associated with WOMAC scores (ranging from r = 0.20 to 0.49, p < 0.05), in contrast to morphometric measures. Environmental exposures, particularly lower temperatures, higher wind speed, and daily weather changes, were significantly correlated with increased SI. Mediation analysis demonstrated that IPFP MRI parameters, particularly SI parameters, significantly mediated the effects of environmental exposures on pain and total WOMAC scores.

Conclusions

The IPFP, particularly its SI characteristics, mediates the relationship between environmental exposures and clinical symptoms in KOA.

目的探讨髌下脂肪垫（IPFP）是否在环境暴露与膝骨关节炎（KOA）患者临床症状之间起中介作用。方法本研究共纳入108例KOA患者，环境暴露资料包括气温、风速、相对湿度等，均来源于当地气象记录。使用3.0T磁共振成像（MRI）定量评估IPFP特征，包括形态学和信号强度（SI）参数。临床症状评估使用西安大略和麦克马斯特大学骨关节炎指数（WOMAC）。采用主成分分析（PCA）对IPFP MRI特征进行降维处理。通过中介分析检验IPFP参数是否介导了环境暴露对WOMAC评分的影响。结果spca分析显示，SI参数占IPFP特征总方差的56.87%，形态学参数占16.65%。相关分析显示，与形态计量学相比，大多数SI参数（例如，平均SI， SD SI）与WOMAC评分显著相关（r = 0.20至0.49,p < 0.05）。环境暴露，特别是较低的温度、较高的风速和每日天气变化，与SI的增加显著相关。中介分析表明，IPFP MRI参数，特别是SI参数，显著调节了环境暴露对疼痛和WOMAC总分的影响。结论IPFP，特别是其SI特征，介导了环境暴露与KOA临床症状之间的关系。

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引用次数: 0

The severity of fatigue and its interplay with biological and psychological factors in people with hand osteoarthritis – Results from the Nor-Hand study 手部骨关节炎患者的疲劳程度及其与生理和心理因素的相互作用——来自无手研究的结果

IF 2.8

Osteoarthritis and cartilage open

Pub Date : 2026-01-17 DOI: 10.1016/j.ocarto.2026.100747

Daniel H. Bordvik , Marthe Gløersen , Elisabeth Mulrooney , Pernille Steen Pettersen , Lene Maria Sundbakk , Tuhina Neogi , Ingvild Kjeken , Ida K. Haugen

Background

Fatigue represents a concurrent yet uncommonly addressed symptom among people with hand osteoarthritis (OA). We aimed to explore fatigue severity and its interplay with other variables among hand OA patients.

Methods

We used baseline data collected in the Nor-Hand study, a cohort comprising participants with hand OA recruited at Diakonhjemmet Hospital. We measured fatigue severity by using a numeric rating scale (NRS, range: 0–10). Drawing on correlations from our dataset, existing literature, and input from a patient research partner, we estimated regularized networks to explore the interplay of fatigue. Network nodes represented variables (i.e., measures of fatigue, all bodily pain, anxiety/depression, self-efficacy, age, comorbidities, body mass index and sleep), and edges represented weighted conditional non-directional relationships between nodes. In sensitivity models, radiographic OA severity, high-sensitivity C-reactive protein, grip strength and indices of central pain sensitization were added. Network accuracy and stability were tested by bootstrapping (n = 1000).

Results

Our sample included 300 participants (mean (standard deviation) age; 60.8 (6.2) years, 88 % women). The mean (SD) severity of fatigue was 4.1 (2.9) NRS points. Network analyses identified comorbidities, all bodily pain, symptoms of anxiety/depression, and sleep problems as central and strongly related to fatigue, independent of additional variables included in sensitivity analyses. Edge weights and node centrality estimates were considered accurate and stable based on bootstrapped confidence intervals.

Conclusion

Fatigue is likely significant and strongly related to comorbidities, pain, symptoms of anxiety/depression, and sleep problems among hand OA patients. Longitudinal studies using more diverse samples and comprehensive variable selections are warranted.

背景：疲劳是手骨关节炎（OA）患者并发但不常见的症状。我们的目的是探讨手部OA患者的疲劳严重程度及其与其他变量的相互作用。方法：我们使用在无手研究中收集的基线数据，这是一个由Diakonhjemmet医院招募的手部OA患者组成的队列。我们使用数字评定量表（NRS，范围：0-10）来测量疲劳程度。根据我们的数据集、现有文献和患者研究伙伴的输入，我们估计了正则化网络来探索疲劳的相互作用。网络节点代表变量（即疲劳、所有身体疼痛、焦虑/抑郁、自我效能、年龄、合并症、体重指数和睡眠），边缘代表节点之间加权的条件非定向关系。在敏感性模型中，增加影像学OA严重程度、高敏感性c反应蛋白、握力和中枢性疼痛致敏指标。通过bootstrapping （n = 1000）检验网络的准确性和稳定性。结果我们的样本包括300名参与者(平均（标准差）年龄；60.8（6.2）岁，88%为女性)。疲劳严重程度的平均（SD）为4.1 (2.9)NRS点。网络分析确定了合并症，所有身体疼痛、焦虑/抑郁症状和睡眠问题为中心，与疲劳密切相关，独立于敏感性分析中包含的其他变量。基于自适应置信区间的边缘权值和节点中心性估计被认为是准确和稳定的。结论疲劳可能与手部OA患者的合并症、疼痛、焦虑/抑郁症状和睡眠问题密切相关。纵向研究使用更多样化的样本和全面的变量选择是必要的。

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引用次数: 0

High glucose upregulates BMAL1 in chondrocytes from macroscopically normal and osteoarthritic human cartilage but this only results in increased collagen synthesis in chondrocytes from macroscopically normal cartilage regions 高葡萄糖上调宏观正常和骨关节炎软骨软骨细胞中的BMAL1，但这只导致宏观正常软骨区域软骨细胞中胶原合成增加

IF 2.8

Osteoarthritis and cartilage open

Pub Date : 2026-01-14 DOI: 10.1016/j.ocarto.2026.100744

Lekha Jain , Jacob T. Munro , Jade Tamatea , Nicola Dalbeth , Raewyn C. Poulsen

Objective

Osteoarthritic (OA) chondrocytes exhibit limited capacity for new collagen synthesis. High glucose promotes collagen I and III production by fibroblasts. The purpose of this study was to determine if it also promotes collagen II (COL2) synthesis by chondrocytes.

Design

Chondrocytes isolated from osteoarthritic (OA) and macroscopically normal (MN) cartilage from patients with knee OA were maintained in 1 % oxygen in 4 mM or 10 mM glucose for up to 24 h.

Results

Secreted COL2 levels were higher in MN but not OA chondrocytes maintained in 10 mM versus 4 mM glucose with increased COL2 production specifically evident in the first 6 h of high glucose exposure. COL2A1 and proly-4-hydroxylase α2 (P4HA2) RNA and protein were upregulated by high glucose in MN and OA chondrocytes at this timepoint. While P4HA2 levels were similar in MN and OA chondrocytes, COL2A1 RNA and SOX9 protein levels were lower in OA chondrocytes. BMAL1 protein levels were elevated by high glucose in both MN and OA chondrocytes at 6 h and BMAL1 knockdown reduced P4HA2 and COL2A1 in both MN and OA chondrocytes at this timepoint.

Conclusions

These data demonstrate a novel mechanism by which high glucose-mediated upregulation of BMAL1 promotes collagen synthesis in chondrocytes. Although high glucose leads to similar upregulation of BMAL1 and P4HA2 in both MN and OA chondrocytes, overall lower COL2A1 RNAin OA chondrocytes likely limits their ability to upregulate secreted procollagen II levels. Hence, MN but not OA chondrocytes show increased collagen II production in high glucose.

目的骨关节炎（OA）软骨细胞合成新胶原的能力有限。高葡萄糖促进成纤维细胞生成I和III型胶原。本研究的目的是确定它是否也能促进软骨细胞合成胶原II （COL2）。从膝关节OA患者的骨关节炎（OA）和宏观正常（MN）软骨中分离的软骨细胞在4毫米或10毫米葡萄糖中1%的氧气中维持24小时。结果MN中分泌的COL2水平较高，而OA软骨细胞在10毫米葡萄糖中维持的水平与4毫米葡萄糖相比，在高葡萄糖暴露的前6小时COL2产生明显增加。在这个时间点，MN和OA软骨细胞的COL2A1和P4HA2 (proly-4-hydroxylase α2, P4HA2) RNA和蛋白被高糖上调。虽然MN和OA软骨细胞中P4HA2水平相似，但OA软骨细胞中COL2A1 RNA和SOX9蛋白水平较低。在6小时时，MN和OA软骨细胞中的BMAL1蛋白水平因高糖而升高，BMAL1敲低降低了MN和OA软骨细胞中的P4HA2和COL2A1。这些数据证明了高糖介导的BMAL1上调促进软骨细胞胶原合成的新机制。虽然高糖会导致MN和OA软骨细胞中BMAL1和P4HA2类似的上调，但总体上较低的COL2A1 RNAin可能限制了OA软骨细胞上调分泌的前胶原II水平的能力。因此，MN软骨细胞而不是OA软骨细胞在高葡萄糖状态下显示胶原II生成增加。

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引用次数: 0

The stability of pain phenotypes in people with hand osteoarthritis – results from the NOR-HAND study 手部骨关节炎患者疼痛表型的稳定性-来自NOR-HAND研究的结果

IF 2.8

Osteoarthritis and cartilage open

Pub Date : 2026-01-14 DOI: 10.1016/j.ocarto.2026.100745

Daniel H. Bordvik , Elisabeth Mulrooney , Pernille Steen Pettersen , Marthe Gløersen , Lene Maria Sundbakk , Tuhina Neogi , Ingvild Kjeken , Ida K. Haugen

Objective

In a hand osteoarthritis (OA) cohort, we aimed to explore pain phenotypes and characterize their stabilities using the multidimensional framework developed by The Initiative on Methods, Measurement and Pain Assessment in Clinical Trials (IMMPACT).

Methods

We included participants attending the visits at baseline (2016–17) and follow-up (2019–21) in the Nor-Hand study. To identify pain phenotypes (i.e., classes), we conducted latent transition analyses modelling self-reported pain severity, neuropathic-like pain, fatigue, sleep, anxiodepressive symptoms, pain catastrophizing, and quantitative sensory testing (QST). We compared a model including QST with a model without. Longitudinal stability of classes was assessed. Changes in indicator variables across participants with vs. without between-class transitioning were compared.

Results

We analysed 213 participants (86.9 % women) with a baseline mean age (standard deviation) of 60.9 (6.0) years. Both models identified four classes exhibiting similar results on differences in pain severity and psychosocial burden (kappa 0.91). Although phenotype stability varied (probability range: 0.48–0.95), most participants (_∼80 %) remained in the same class at both visits. Most participants transitioning between classes shifted to a less severe pain class (32/44 (72.7 %) in the QST model; 36/45 (80.0 %) in the clinical model), showing larger improvements in pain and psychosocial burden than non-transitioners.

Conclusion

Four distinct pain phenotypes were identified among persons with hand OA. Excluding QST from our model did not influence phenotype composition or characteristics. Various longitudinal phenotype stability was observed. Between-class transitions were often characterized by less pain and psychosocial burden, potentially due to regression to the mean or improved disease coping.

在一项手骨关节炎（OA）队列研究中，我们旨在利用临床试验方法、测量和疼痛评估倡议（impact）开发的多维框架来探索疼痛表型并表征其稳定性。方法：我们纳入了基线（2016 - 2017年）和随访（2019 - 2021年）的无手研究参与者。为了确定疼痛表型（即类别），我们进行了潜在转换分析，模拟自我报告的疼痛严重程度、神经性疼痛、疲劳、睡眠、焦虑抑郁症状、疼痛灾难性和定量感觉测试（QST）。我们将包含QST的模型与不包含QST的模型进行了比较。评估了班级的纵向稳定性。比较了有和没有班级间转换的参与者之间指标变量的变化。结果我们分析了213名参与者（86.9%为女性），基线平均年龄（标准差）为60.9（6.0）岁。两种模型都确定了四个类别，在疼痛严重程度和心理社会负担方面表现出相似的结果（kappa 0.91）。虽然表型稳定性有所不同（概率范围：0.48-0.95），但大多数参与者（约80%）在两次访问时都保持在同一类别。在QST模型中，大多数在类别之间转换的参与者转移到疼痛程度较轻的类别（32/44 (72.7%)）；临床模型中有36/45(80.0%)，在疼痛和心理社会负担方面比未变性者有更大的改善。结论手部OA患者存在四种不同的疼痛表型。从我们的模型中排除QST并不影响表型组成或特征。观察到各种纵向表型稳定性。班级之间的过渡往往以较少的痛苦和心理社会负担为特征，这可能是由于回归到平均水平或改善了疾病应对。

{"title":"The stability of pain phenotypes in people with hand osteoarthritis – results from the NOR-HAND study","authors":"Daniel H. Bordvik , Elisabeth Mulrooney , Pernille Steen Pettersen , Marthe Gløersen , Lene Maria Sundbakk , Tuhina Neogi , Ingvild Kjeken , Ida K. Haugen","doi":"10.1016/j.ocarto.2026.100745","DOIUrl":"10.1016/j.ocarto.2026.100745","url":null,"abstract":"<div><h3>Objective</h3><div>In a hand osteoarthritis (OA) cohort, we aimed to explore pain phenotypes and characterize their stabilities using the multidimensional framework developed by The Initiative on Methods, Measurement and Pain Assessment in Clinical Trials (IMMPACT).</div></div><div><h3>Methods</h3><div>We included participants attending the visits at baseline (2016–17) and follow-up (2019–21) in the Nor-Hand study. To identify pain phenotypes (i.e., classes), we conducted latent transition analyses modelling self-reported pain severity, neuropathic-like pain, fatigue, sleep, anxiodepressive symptoms, pain catastrophizing, and quantitative sensory testing (QST). We compared a model including QST with a model without. Longitudinal stability of classes was assessed. Changes in indicator variables across participants with vs. without between-class transitioning were compared.</div></div><div><h3>Results</h3><div>We analysed 213 participants (86.9 % women) with a baseline mean age (standard deviation) of 60.9 (6.0) years. Both models identified four classes exhibiting similar results on differences in pain severity and psychosocial burden (kappa 0.91). Although phenotype stability varied (probability range: 0.48–0.95), most participants (<sub>∼</sub>80 %) remained in the same class at both visits. Most participants transitioning between classes shifted to a less severe pain class (32/44 (72.7 %) in the QST model; 36/45 (80.0 %) in the clinical model), showing larger improvements in pain and psychosocial burden than non-transitioners.</div></div><div><h3>Conclusion</h3><div>Four distinct pain phenotypes were identified among persons with hand OA. Excluding QST from our model did not influence phenotype composition or characteristics. Various longitudinal phenotype stability was observed. Between-class transitions were often characterized by less pain and psychosocial burden, potentially due to regression to the mean or improved disease coping.</div></div>","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"8 1","pages":"Article 100745"},"PeriodicalIF":2.8,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Studying the formation of the zone of calcified cartilage in bovine cartilage explants ex vivo 牛软骨离体外植体中软骨钙化区形成的研究

IF 2.8

Osteoarthritis and cartilage open

Pub Date : 2026-01-12 DOI: 10.1016/j.ocarto.2026.100743

Jietao Xu , Andrea Schwab , Elias Salzer , Nicole Kops , Pieter A.J. Brama , Eric Farrell , Gerjo J.V.M. van Osch

Objective

The zone of calcified cartilage (ZCC) connects non-calcified articular cartilage to the subchondral bone, acting as transitional layer. Regeneration of this layer is key for cartilage repair but remains a challenge. Knowledge on the formation of this layer during development is limited. This study describes the use of an ex vivo explant culture model to investigate the formation of the ZCC.

Design

Explants were harvested from immature bovine metacarpophalangeal joints and cultured in the presence of β-glycerophosphate for 3 weeks as osteochondral explants, full-thickness cartilage or divided in top and bottom cartilage layers. To investigate cell-driven vs matrix-dependent calcification, explants were devitalized. Calcification was analysed using calcium uptake, micro-computed tomography, gene expression analysis, and histological stainings.

Results

A distinct area of calcified cartilage formed in the explants ex vivo. This layer showed similar characteristics to the ZCC in mature bovine tissue. Viable chondrocytes in bottom layers actively contributed to cartilage calcification, while calcification in top layers was only present in devitalized top layer explants. Top layers inhibited cartilage calcification in bottom layers and expressed higher levels of FGF18, PTHLH and MGP, while the bottom layers expressed more ALPL, COL10A1 and IHH.

Conclusion

We present the first ex vivo model allowing to study and modulate cartilage calcification and the formation of the ZCC. We demonstrated an inherent zone-specific calcification pattern within the cartilage explants. This model allows future studies investigating mechanisms of ZCC formation in cartilage repair procedures, and the role of the top layer in pathological cartilage calcifications and potential interventions.

目的钙化软骨带（ZCC）是连接非钙化关节软骨与软骨下骨的过渡层。这一层的再生是软骨修复的关键，但仍然是一个挑战。关于这一层在开发过程中形成的知识是有限的。本研究采用离体外植体培养模型研究ZCC的形成。设计从未成熟的牛掌指关节中收获植物，在β-甘油磷酸酯的存在下培养3周，作为骨软骨外植体，全层软骨或分为上下软骨层。为了研究细胞驱动与基质依赖的钙化，我们对外植体进行了失活处理。通过钙摄取、显微计算机断层扫描、基因表达分析和组织学染色分析钙化情况。结果体外移植体形成明显的软骨钙化区。这一层表现出与牛成熟组织中ZCC相似的特征。底层活软骨细胞积极促进软骨钙化，顶层钙化仅存在于失活的顶层外植体中。顶层抑制底层软骨钙化，表达较高水平的FGF18、PTHLH和MGP，底层表达较高水平的ALPL、COL10A1和IHH。结论我们建立了第一个研究和调节软骨钙化和ZCC形成的离体模型。我们证明了软骨移植体内固有的区域特异性钙化模式。该模型允许未来研究软骨修复过程中ZCC形成的机制，以及顶层在病理性软骨钙化中的作用和潜在的干预措施。

{"title":"Studying the formation of the zone of calcified cartilage in bovine cartilage explants ex vivo","authors":"Jietao Xu , Andrea Schwab , Elias Salzer , Nicole Kops , Pieter A.J. Brama , Eric Farrell , Gerjo J.V.M. van Osch","doi":"10.1016/j.ocarto.2026.100743","DOIUrl":"10.1016/j.ocarto.2026.100743","url":null,"abstract":"<div><h3>Objective</h3><div>The zone of calcified cartilage (ZCC) connects non-calcified articular cartilage to the subchondral bone, acting as transitional layer. Regeneration of this layer is key for cartilage repair but remains a challenge. Knowledge on the formation of this layer during development is limited. This study describes the use of an <em>ex vivo</em> explant culture model to investigate the formation of the ZCC.</div></div><div><h3>Design</h3><div>Explants were harvested from immature bovine metacarpophalangeal joints and cultured in the presence of β-glycerophosphate for 3 weeks as osteochondral explants, full-thickness cartilage or divided in top and bottom cartilage layers. To investigate cell-driven vs matrix-dependent calcification, explants were devitalized. Calcification was analysed using calcium uptake, micro-computed tomography, gene expression analysis, and histological stainings.</div></div><div><h3>Results</h3><div>A distinct area of calcified cartilage formed in the explants <em>ex vivo</em><em>.</em> This layer showed similar characteristics to the ZCC in mature bovine tissue. Viable chondrocytes in bottom layers actively contributed to cartilage calcification, while calcification in top layers was only present in devitalized top layer explants. Top layers inhibited cartilage calcification in bottom layers and expressed higher levels of <em>FGF18</em>, <em>PTHLH</em> and <em>MGP</em>, while the bottom layers expressed more <em>ALPL</em>, <em>COL10A1</em> and <em>IHH</em>.</div></div><div><h3>Conclusion</h3><div>We present the first <em>ex vivo</em> model allowing to study and modulate cartilage calcification and the formation of the ZCC. We demonstrated an inherent zone-specific calcification pattern within the cartilage explants. This model allows future studies investigating mechanisms of ZCC formation in cartilage repair procedures, and the role of the top layer in pathological cartilage calcifications and potential interventions.</div></div>","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"8 1","pages":"Article 100743"},"PeriodicalIF":2.8,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tolerability of high intensity interval training (HIIT) in individuals living with knee OA and at risk for cardiovascular disease: A prospective cohort study (THIPO) 一项前瞻性队列研究（THIPO）：高强度间歇训练（HIIT）对有心血管疾病风险的膝关节OA患者的耐受性

IF 2.8

Osteoarthritis and cartilage open

Pub Date : 2026-01-12 DOI: 10.1016/j.ocarto.2025.100712

Mathilde Espe Pedersen , Thomas Bandholm , Mathias Ried-larsen , Cecilie Bartholdy , Tanja Schjødt Jørgensen , Asbjørn Seenithamby Poulsen , Kasper Stagberg Madsen , Marius Henriksen

Objective

To explore the tolerability of a 12-week High Intensity Interval Training (HIIT) program in individuals with knee osteoarthritis (OA) at elevated risk for cardiovascular disease (CVD).

Methods

Forty-one individuals with knee OA and elevated CVD risk participated in a 12-week HIIT program with three weekly supervised sessions (36 in total) on treadmills, cross-trainers, row- and cycle ergometers. The program comprised a 10-min warm-up, followed by eight 2-min intervals of high intensity (>80 % of HRmax) followed by 2 min of moderate training intensity (60 % of HRmax), and 5 min of cool down. Tolerability was assessed by investigator consensus using a decision guiding framework based on attendance, incidence of knee pain flares resulting in non-compliance with the HIIT program during the 12-week period and change in knee pain (0–10 scale) at session start from the first to the last week of the program.

Results

The average Borg Rating of Perceived Exertion (RPE) score during intervals was 16.2 (SD 1.2) over the 12 weeks. Average attendance to sessions was 88 %. The prevalence of knee flares increased from 3 to 5 from the first to the last 6 weeks, and the number of participants with ≥1 point knee pain reduction from week 1 to week 12 was 19 (46 %). According to KOOS thresholds, participants had mild difficulty in Pain, ADL, and Symptoms; moderate difficulty in Knee-related Quality of Life; and moderate-to-severe difficulty in Function in Sports and Recreation.

Conclusion

In conclusion, the HIIT program appeared tolerable for most individuals with knee OA and elevated CVD risk including those with mild-to-moderate difficulties in pain, function, and quality of life, supporting its potential feasibility in this clinical population.

目的探讨心血管疾病（CVD）高危膝骨关节炎（OA）患者对12周高强度间歇训练（HIIT）的耐受性。方法41例膝关节OA和心血管疾病风险升高的患者参加了一项为期12周的HIIT计划，每周进行3次有监督的训练（总共36次），分别在跑步机、交叉训练器、划船和循环计力器上进行。该计划包括10分钟的热身，然后是8次2分钟的高强度间歇训练（HRmax的80%），然后是2分钟的中等强度训练（HRmax的60%），最后是5分钟的冷却。耐受性通过研究者共识评估，采用决策指导框架，该框架基于出席率、12周期间不遵守HIIT计划导致的膝关节疼痛发作发生率以及从计划的第一周到最后一周开始的膝关节疼痛变化（0-10级）。结果12周内，两组间期RPE评分平均为16.2 （SD 1.2）。会议的平均出勤率为88%。从第1周到最后6周，膝关节耀斑的发生率从3个增加到5个，从第1周到第12周，膝关节疼痛减轻≥1点的参与者人数为19人（46%）。根据oos阈值，受试者在疼痛、ADL和症状方面存在轻度困难；膝关节相关生活质量中度困难；在运动和娱乐功能方面有中重度困难。总之，HIIT方案对于大多数患有膝关节OA和CVD风险升高的患者，包括那些在疼痛、功能和生活质量方面存在轻至中度困难的患者，似乎是可耐受的，支持其在该临床人群中的潜在可行性。

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引用次数: 0

Clinical characteristics and physical activity levels of patients with knee osteoarthritis with and without a previous knee injury: A cross-sectional study 有或无既往膝关节损伤的膝骨关节炎患者的临床特征和身体活动水平：一项横断面研究

IF 2.8

Osteoarthritis and cartilage open

Pub Date : 2026-01-05 DOI: 10.1016/j.ocarto.2025.100741

Richard E. Magony, Jeffrey S. Brooks, Jenna M. Schulz, Derek N. Pamukoff, Jane S. Thornton

Objective

To compare clinical characteristics and physical activity levels of patients with mild-to-moderate knee osteoarthritis (OA).

Methods

A total of 262 individuals with mild-to-moderate knee OA recruited from the Technology, Exercise Programming, and Activity Prescription for Enhanced Mobility (TEAM) Study (NCT04544904) were categorized into two groups: 1) no previous knee injury (NTOA group), or 2) previous knee injury (PTOA group). We collected participants’ demographics, Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales, Arthritis Self-Efficacy questionnaire, Intermittent and Constant Osteoarthritis Pain (ICOAP) questionnaire, previous sport participation, radiographic OA features, and medical history. A smartphone application measured daily steps and self-reported physical activity levels were measured using the Global Physical Activity Questionnaire. A 30-s chair-stand and 40-m walk test assessed physical function.

Results

The NTOA group was older (62.3 ± 9.0 vs. 58.2 ± 7.4 years, p < 0.05) and had lower daily steps (4372 ± 263 vs. 5776 ± 445 steps, p_adj < 0.05) and previous sport participation (62.6 % vs. 81.7 %, p < 0.05) than the PTOA group. Anthropometric measurements, sex, radiographic OA scores, comorbidities, smoking, and alcohol consumption were not different. The NTOA group had lower KOOS Pain (58.0 ± 1.2 vs. 64.3 ± 2.1, p_adj < 0.05) and Activities of Daily Living (65.6 ± 1.3 vs. 73.9 ± 2.3, p_adj < 0.05), higher ICOAP (44.2 ± 1.6 vs. 34.7 ± 2.8, p_adj < 0.05), longer 40-m walk times (27.1 ± 0.4 vs. 24.1 ± 0.7 s, p_adj < 0.05) and lower 30-s chair-stand repetitions (12.1 ± 0.4 vs. 14.3 ± 0.7, p_adj < 0.05).

Conclusion

The PTOA group had higher daily steps and better physical and psychological health status than the NTOA group, independent of age and sex. Physical activity interventions may benefit those with NTOA more given their lower activity and greater symptomatology.

目的比较轻中度膝骨性关节炎（OA）患者的临床特点和运动水平。方法从TEAM （TEAM）研究（NCT04544904）中招募的262例轻中度膝关节OA患者分为两组：1)既往无膝关节损伤（NTOA组）和2)既往膝关节损伤（PTOA组）。我们收集了参与者的人口统计资料、膝关节损伤和骨关节炎结局评分（oos）亚量表、关节炎自我效能问卷、间歇性和持续性骨关节炎疼痛（ICOAP）问卷、既往运动参与情况、骨关节炎影像学特征和病史。智能手机应用程序测量每日步数，并使用全球身体活动问卷测量自我报告的身体活动水平。30秒的椅架和40米的步行测试评估了身体功能。结果NTOA组患者年龄（62.3±9.0岁比58.2±7.4岁，p < 0.05），日步数（4372±263步比5776±445步，p < 0.05）和既往运动参与（62.6%比81.7%,p < 0.05）低于PTOA组。人体测量、性别、放射学OA评分、合并症、吸烟和饮酒并无差异。NTOA组kos疼痛（58.0±1.2比64.3±2.1,padj < 0.05）和日常生活活动（65.6±1.3比73.9±2.3,padj < 0.05）较低，ICOAP（44.2±1.6比34.7±2.8,padj < 0.05）较高，40米步行时间较长（27.1±0.4比24.1±0.7 s, padj < 0.05）， 30秒椅立重复次数较低（12.1±0.4比14.3±0.7,padj < 0.05）。结论与年龄、性别无关，PTOA组患者的日步数高于NTOA组，身心健康状况优于NTOA组。体育活动干预可能对NTOA患者更有利，因为他们的活动较少，症状更严重。

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引用次数: 0

Association between symptomatic knee osteoarthritis and health-related quality of life in individuals with type 2 diabetes: A cross-sectional study 2型糖尿病患者症状性膝骨关节炎与健康相关生活质量的相关性：一项横断面研究

IF 2.8

Osteoarthritis and cartilage open

Pub Date : 2026-01-05 DOI: 10.1016/j.ocarto.2025.100742

Abdalmohsen Almodahka , Alanna Weisman , Baiju R. Shah , Tristan Watson , Ian Stanaitis , Amish Parikh , Robert Goldberg , Lorraine Lipscombe , Gillian A. Hawker , Lauren K. King

Objective

Knee osteoarthritis (OA) and type 2 diabetes (T2D) commonly coexist, but their combined impact on health-related quality of life (HRQoL) remains understudied. We assessed the association between symptomatic knee OA and HRQoL in individuals with T2D and explored potential explanations.

Design

We conducted a secondary analysis of a cross-sectional study of individuals with T2D. Symptomatic knee OA was defined using NICE criteria (age ≥45 years, activity-related knee pain, morning stiffness ≤30 min; no inflammatory arthritis). HRQoL (EQ-VAS, 0–100), sleep disturbance (PROMIS Sleep Disturbance 4a), depressed symptoms (PROMIS Depression 8b), fatigue (PROMIS Fatigue 4a), and walking limitation (Health Assessment Questionnaire) were assessed via questionnaire. Linear regression modeled associations between knee OA and HRQoL, adjusting for age, gender, BMI, education, and comorbidities. The explanatory effects of sleep, mood, and mobility were assessed via further sequential adjustment.

Results

We included 341 participants: mean age 66.4 years, 51.9 % female, 29.0 % had knee OA. Participants with T2D and knee OA reported lower HRQoL, greater sleep disturbance, fatigue, depressive symptoms, and walking limitations than those without knee OA. Knee OA was associated with lower HRQoL (β = −11.96; 95 % CI: −16.59 to −7.32) in the unadjusted analysis. Adjustment for confounders partially attenuated this effect (β = −8.33; 95 % CI: −12.72 to −3.94). Further adjustment for sleep, mood, and walking limitations fully attenuated the association.

Conclusion

Symptomatic knee OA is strongly associated with impaired HRQoL in T2D, explained by sleep disturbance, low mood, and mobility limitation. Integrated care addressing OA may improve quality of life in this population.

目的膝关节骨性关节炎（OA）和2型糖尿病（T2D）通常共存，但它们对健康相关生活质量（HRQoL）的综合影响仍未得到充分研究。我们评估了t2dm患者症状性膝关节炎与HRQoL之间的关系，并探讨了可能的解释。我们对T2D患者的横断面研究进行了二次分析。症状性膝关节炎的定义采用NICE标准（年龄≥45岁，活动相关性膝关节疼痛，晨僵≤30分钟，无炎症性关节炎）。采用问卷法评估HRQoL （EQ-VAS, 0-100）、睡眠障碍（PROMIS sleep disorders 4a）、抑郁症状（PROMIS Depression 8b）、疲劳（PROMIS fatigue 4a）和行走限制（健康评估问卷）。线性回归模拟了膝关节OA和HRQoL之间的关系，调整了年龄、性别、BMI、教育程度和合并症。通过进一步的顺序调整来评估睡眠、情绪和活动的解释效应。结果我们纳入341名参与者：平均年龄66.4岁，51.9%为女性，29.0%为膝关节OA。与没有膝关节OA的参与者相比，患有T2D和膝关节OA的参与者报告HRQoL较低，睡眠障碍、疲劳、抑郁症状和行走受限更严重。在未调整分析中，膝关节OA与较低的HRQoL相关（β = - 11.96; 95% CI: - 16.59至- 7.32）。对混杂因素的调整部分减弱了这种效应（β = - 8.33; 95% CI: - 12.72至- 3.94）。对睡眠、情绪和行走限制的进一步调整完全减弱了这种关联。结论症状性膝关节炎与T2D患者HRQoL受损密切相关，可能与睡眠障碍、情绪低落和活动受限有关。针对OA的综合护理可以改善这一人群的生活质量。

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引用次数: 0

Association between knee osteoarthritis and volumetric bone mineral density 膝关节骨性关节炎与体积骨密度的关系

IF 2.8

Osteoarthritis and cartilage open

Pub Date : 2026-01-02 DOI: 10.1016/j.ocarto.2025.100740

Duy K. Hoang , An T. Truong , Linh N. Luu , Tan D. Nguyen , Nhan M. Le , Huy G. Nguyen , Lan T. Ho-Pham , David J. Hunter , Tuan V. Nguyen

Objective

Although patients with radiographic knee osteoarthritis (OA) have a higher areal bone mineral density (BMD) than non-OA individuals, their fracture risk was not significantly different. This study sought to define the association between radiographic knee OA and volumetric BMD.

Methods

We enrolled 944 men and 1506 women aged 40 years or older, selected randomly from Ho Chi Minh City, Vietnam. Knee radiographs were assessed using the Kellgren and Lawrence scale, with grades two or higher indicating knee osteoarthritis (OA). Areal bone mineral density (aBMD) at the femoral neck and lumbar spine was measured using DXA (Hologic Corp, USA). Trabecular and cortical volumetric bone density (vBMD) at the tibia bone were also measured using pQCT XCT2000 (Stratec, Germany). The difference in aBMD and vBMD between individuals with and without OA was quantified using effect size (ES) and 95 % confidence interval (CI).

Results

The prevalence of radiographic knee OA in this cohort was approximately 31 % (n = 755), which increased with age. Compared to non-OA individuals, those with knee OA had higher femoral neck aBMD (ES = 0.04, 95 % CI: 0.02–0.05; P = 0.0002). However, knee OA patients had lower vBMD at the cortical tibia bone (ES = − 8.15, 95 % CI: −14.52 to −1.8; P = 0.01).

Conclusion

These data suggest that approximately a third of Vietnamese people aged 40 and over might have radiographic knee OA. The tibial cortical vBMD was significantly lower in persons with knee OA.

目的膝关节骨性关节炎（OA）患者的面骨矿物质密度（BMD）高于非OA患者，但其骨折风险无显著性差异。本研究试图确定膝关节骨密度与骨密度的相关性。方法从越南胡志明市随机抽取40岁及以上男性944例，女性1506例。膝关节x线片采用Kellgren和Lawrence评分法进行评估，分级为2级或更高表示膝关节骨关节炎（OA）。使用DXA （Hologic Corp， USA）测量股骨颈和腰椎的面骨矿物质密度（aBMD）。使用pQCT XCT2000 （strategy, Germany）测量胫骨小梁和皮质体积骨密度（vBMD）。采用效应量（ES）和95%置信区间（CI）对OA患者和非OA患者的aBMD和vBMD差异进行量化。结果该队列中膝关节骨性关节炎的发生率约为31% (n = 755)，随年龄增长而增加。与非OA患者相比，膝关节OA患者股骨颈aBMD较高（ES = 0.04, 95% CI: 0.02-0.05; P = 0.0002）。然而，膝关节OA患者的胫骨皮质骨vBMD较低（ES = - 8.15, 95% CI: - 14.52至- 1.8;P = 0.01）。结论：这些数据表明，大约三分之一的40岁及以上的越南人可能患有膝关节骨性关节炎。膝关节OA患者的胫骨皮质vBMD明显较低。

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引用次数: 0