@article{MTMT:34609829,
	title = {Rapid decline of kidney function increases fracture risk in the general population: Insights from TLGS},
	url = {https://m2.mtmt.hu/api/publication/34609829},
	author = {Masrouri, Soroush and Esmaeili, Farzad and Tohidi, Maryam and Azizi, Fereidoun and Hadaegh, Farzad},
	doi = {10.1016/j.bone.2023.116974},
	journal-iso = {BONE},
	journal = {BONE},
	volume = {179},
	unique-id = {34609829},
	issn = {8756-3282},
	abstract = {<bold>Background: </bold>Although the association between Chronic Kidney Disease (CKD) and all-cause fractures was addressed in previous studies, the association between estimated glomerular filtration rate (eGFR) decline and fractures was poorly addressed. For the first time we examined the association between rapid kidney function decline (RKFD) and fracture incidence among Iranian general population.<bold>Methods: </bold>In a Tehranian community-based cohort, RKFD was defined as a 30 % decline in eGFR over 2-3 years. Cox proportional hazards models, adjusted for age, sex, current eGFR, diabetes mellitus, hypertension, dyslipidemia, current smoking, obesity status, waist circumference, prevalent cardiovascular diseases, aspirin, steroid use, education level, and marital status, were used to examine the association of RKFD with different fracture outcomes.<bold>Results: </bold>Among 5305 (3031 women) individuals aged >= 30 years, during the median follow-up of 9.62 years, 226 fracture events were observed. The multivariable hazard ratio of RKFD for any-fracture events, lower-extremity, and major osteoporotic fractures were 2.18 (95 % CI, 1.24-3.85), 2.32 (1.15-4.71), and 2.91 (1.29-6.58), respectively. These associations remained significant after accounting for the competing risk of death. The impact of RKFD on the development of incident all-cause fractures was not modified by gender [men: 2.64 (1.11-6.25) vs. women: 2.11 (1.00-4.47)] and according to current CKD status [without CKD: 2.34 (1.00-5.52) vs. with CKD: 2.59 (1.04-6.44)] (all P for interaction >0.5).<bold>Conclusions: </bold>RKFD can increase the incidence of fractures among general population, the issue that was equally important among non-CKD individuals, emphasizing the need for early identification and management in those with rapidly declining eGFR.},
	keywords = {FRACTURE; osteoporosis; rapid kidney function decline; Osteoporotic fracture; eGFR decline},
	year = {2024},
	eissn = {1873-2763}
}

@article{MTMT:34600523,
	title = {Risk of fracture in women with glucocorticoid requiring diseases is independent from glucocorticoid use: An analysis on a nation-wide database},
	url = {https://m2.mtmt.hu/api/publication/34600523},
	author = {Adami, Giovanni and Gatti, Davide and Rossini, Maurizio and Giollo, Alessandro and Gatti, Matteo and Bertoldo, Francesco and Bertoldo, Eugenia and Mudano, Amy S. and Saag, Kenneth G. and Viapiana, Ombretta and Fassio, Angelo},
	doi = {10.1016/j.bone.2023.116958},
	journal-iso = {BONE},
	journal = {BONE},
	volume = {179},
	unique-id = {34600523},
	issn = {8756-3282},
	abstract = {Objective: Glucocorticoid-induced osteoporosis (GIOP) is a common cause of secondary osteoporosis. However, glucocorticoid requiring diseases pose a risk themselves for fracture. The aim of the present study was to determine the risk of fracture associated with variety of glucocorticoid requiring diseases independently from glucocorticoid use and other risk factors for osteoporosis.Methods: We conducted a retrospective cross-sectional analysis of a nation-wide cohort (DeFRACalc79 database). We used multivariable regression analysis adjusting for several risk factors for fracture and glucocorticoid intake to estimate the independent role of glucocorticoid requiring illnesses on fracture risk.Results: We found that patients with rheumatoid arthritis, connective tissue diseases, chronic obstructive pulmonary disease (COPD) and neurological diseases were at greater risk of vertebral or hip fracture (crude ORs 1.31, 1.20, 1.92 and 2.97 respectively). After adjusting for potential confounders COPD and neurological diseases remained significantly associated with an increased risk of vertebral or hip fractures (aORs 1.33, 95 % CI 1.18-1.49 and 2.43, 95 % CI 2.17-2.74). Rheumatoid arthritis, COPD, IBD and neurological diseases also significantly increased the risk of non-vertebral, non-hip fractures (aORs 1.23, 1.42, 1.52 and 1.94 respectively).Conclusion: Some glucocorticoid requiring diseases were independently associated with an increased risk of fractures. COPD and neurological diseases with both vertebral and non-vertebral fracture risk while RA and IBD were independently associated only with non-vertebral, non-hip fractures.},
	keywords = {Inflammation; GLUCOCORTICOIDS; osteoporosis; FRACTURES; Bone mineral density (BMD)},
	year = {2024},
	eissn = {1873-2763},
	orcid-numbers = {Adami, Giovanni/0000-0002-8915-0755}
}

@article{MTMT:34568563,
	title = {Nano-hydroxyapatite structures for bone regenerative medicine: Cell-material interaction},
	url = {https://m2.mtmt.hu/api/publication/34568563},
	author = {Hoveidaei, A.H. and Sadat-Shojai, M. and Mosalamiaghili, S. and Salarikia, S.R. and Roghani-shahraki, H. and Ghaderpanah, R. and Ersi, M.H. and Conway, J.D.},
	doi = {10.1016/j.bone.2023.116956},
	journal-iso = {BONE},
	journal = {BONE},
	volume = {179},
	unique-id = {34568563},
	issn = {8756-3282},
	year = {2024},
	eissn = {1873-2763}
}

@article{MTMT:34532354,
	title = {Bone ineral density, vitamin D and osseous metabolism indices in neurofibromatosis type 1: A systematic review and meta-analysis},
	url = {https://m2.mtmt.hu/api/publication/34532354},
	author = {Kaspiris, A. and Vasiliadis, E. and Iliopoulos, I.D. and Panagopoulos, F. and Melissaridou, D. and Lianou, I. and Ntourantonis, D. and Savvidou, O.D. and Papadimitriou, E. and Pneumaticos, S.G.},
	doi = {10.1016/j.bone.2023.116992},
	journal-iso = {BONE},
	journal = {BONE},
	volume = {180},
	unique-id = {34532354},
	issn = {8756-3282},
	year = {2024},
	eissn = {1873-2763}
}

@article{MTMT:34504441,
	title = {Influence of psychostimulants on bone mineral density and content among children with attention deficit hyperactivity disorder. A systematic review},
	url = {https://m2.mtmt.hu/api/publication/34504441},
	author = {Burns, C. and Michelogiannakis, D. and Ahmed, Z.U. and Rossouw, P.E. and Javed, F.},
	doi = {10.1016/j.bone.2023.116982},
	journal-iso = {BONE},
	journal = {BONE},
	volume = {179},
	unique-id = {34504441},
	issn = {8756-3282},
	abstract = {There is a controversy over the influence of psychostimulant medications on bone mineral density (BMD) and bone mineral content (BMC) among children with attention-deficit-hyperactivity-disorder (ADHD). The aim of the present systematic review was to assess the influence of psychostimulant medications on BMD and BMC among children with ADHD. A comprehensive search of electronic databases, including PubMed, Scopus, Embase, and Cochrane Library, was conducted to identify relevant studies published up until July 2023. Clinical studies that addressed the focused question “Do psychostimulant medications affect bone mineral density and content in children with ADHD?” were included. Letters to the Editor, studies on animal-models, ex-vivo and in-vitro studies, commentaries and reviews were excluded. The primary outcome measures were changes in BMD and BMC. Study quality was assessed using the risk of bias for non-randomized studies-exposure tool. Five non-randomized clinical studies were included. The number of participants ranged from 18 to 6489 with mean ages ranging from 7.3 to 13.75 years. The study durations ranged between five and seven years. In all studies osseous evaluation was done using dual-energy X-ray absorptiometry. The bone locations examined included total body, lumbar-spine, femur, femoral-neck, femoral body, and pelvis. Two studies reported that psychostimulant medications reduce BMC and BMD. In one study, bone turnover, serum leptin and fat levels were reduced in children using psychostimulant medications but no unusual reduction recorded among controls. In general, 80 % of the studies concluded that psychostimulant medications compromise BMC and BMD. Power analysis was done in one study. One study had a low RoB and the remaining demonstrated some concerns. Given the methodological concerns observed in the included studies, arriving at a definitive conclusion regarding the effects of psychostimulant medications on BMC, BMD, and bone turnover in children with ADHD is challenging. However, it is important to acknowledge that an association between psychostimulant medications and these bone-related parameters cannot be disregarded. © 2023 Elsevier Inc.},
	keywords = {Animals; Adolescent; Adolescent; Humans; review; human; animal; Child; Child; disease duration; risk assessment; Bone Density; Bone Density; leptin; outcome assessment; Femur; Lumbar Vertebrae; lumbar vertebra; lumbar spine; systematic review; Absorptiometry, Photon; Attention Deficit Disorder with Hyperactivity; bone turnover; bone turnover; bone tissue; bone mineral; attention deficit hyperactivity disorder; attention deficit hyperactivity disorder; bone mineral density; bone mineral content; Femur Neck; dual energy X ray absorptiometry; pelvis; power analysis; psychostimulant agent; psychostimulants; femoral neck; photon absorptiometry; femoral shaft},
	year = {2024},
	eissn = {1873-2763}
}

@article{MTMT:34499025,
	title = {The effect of deep learning-based lesion segmentation on failure load calculations of metastatic femurs using finite element analysis},
	url = {https://m2.mtmt.hu/api/publication/34499025},
	author = {Ataei, A. and Eggermont, F. and Verdonschot, N. and Lessmann, N. and Tanck, E.},
	doi = {10.1016/j.bone.2023.116987},
	journal-iso = {BONE},
	journal = {BONE},
	volume = {179},
	unique-id = {34499025},
	issn = {8756-3282},
	abstract = {Bone ranks as the third most frequent tissue affected by cancer metastases, following the lung and liver. Bone metastases are often painful and may result in pathological fracture, which is a major cause of morbidity and mortality in cancer patients. To quantify fracture risk, finite element (FE) analysis has shown to be a promising tool, but metastatic lesions are typically not specifically segmented and therefore their mechanical properties may not be represented adequately. Deep learning methods potentially provide the opportunity to automatically segment these lesions and change the mechanical properties more adequately. In this study, our primary focus was to gain insight into the performance of an automatic segmentation algorithm for femoral metastatic lesions using deep learning methods and the subsequent effects on FE outcomes. The aims were to determine the similarity between manual segmentation and automatic segmentation; the differences in predicted failure load between FE models with automatically segmented osteolytic and mixed lesions and the models with CT-based lesion values (the gold standard); and the effect on the BOne Strength (BOS) score (failure load adjusted for body weight) and subsequent fracture risk assessments. From two patient cohorts, a total number of 50 femurs with osteolytic and mixed metastatic lesions were included in this study. The femurs were segmented from CT images and transferred into FE meshes. The material behavior was implemented as non-linear isotropic. These FE models were considered as gold standard (Finite Element no Segmented Lesion: FE-no-SL), whereby the local calcium equivalent density of both femur and metastatic lesion was extracted from CT-values. Lesions in the femur were manually segmented by two biomechanical experts after which final lesion segmentation for each femur was obtained based on consensus of opinions between two observers. Subsequently, a self-configuring variant of the popular deep learning model U-Net known as nnU-Net was used to automatically segment metastatic lesions within the femur. For these models with segmented lesions (Finite Element with Segmented Lesion: FE-with-SL), the calcium equivalent density within the metastatic lesions was set to zero after being segmented by the neural network, simulating absence of load-bearing capacity of these lesions. The models (either with or without automatically segmented lesions) were loaded incrementally in axial direction until failure was simulated. Dice coefficient was used to evaluate the similarity of the manual and automatic segmentation. Mean calcium equivalent density values within the automatically segmented lesions were calculated. Failure loads and patterns were determined. Furthermore, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for both groups by comparing the predictions to the occurrence or absence of actual fracture within the patient cohorts. The automatic segmentation algorithm performed in a none-robust manner. Dice coefficients describing the similarity between consented manual and automatic segmentations were relatively low (mean 0.45 ± standard deviation 0.33, median 0.54). Failure load difference between the FE-no-SL and FE-with-SL groups varied from 0 % to 48 % (mean 6.6 %). Correlation analysis of failure loads between the two groups showed a strong relationship (R2 > 0.9). From the 50 cases, four cases showed clear deviations for which models with automatic lesion segmentation (FE-with-SL) showed considerably lower failure loads. In the whole database including osteolytic and mixed lesions, sensitivity and NPV remained the same, but specificity and PPV decreased from 94 % to 83 %, and from 78 % to 54 % respectively from FE-no-SL to FE-with-SL. This study indicates that the nnU-Net yielded none-robust outcomes in femoral lesion segmentation and that other segmentation algorithms should be considered. However, the difference in failure pattern and failure load between FE models with automatically segmented osteolytic and mixed lesions were relatively small in most cases with a few exceptions. On the other hand, the accuracy of fracture risk assessment using the BOS score was lower compared to the FE-no-SL. In conclusion, this study showed that automatic lesion segmentation is a none-solved issue and therefore, quantifying lesion characteristics and the subsequent effect on the fracture risk using deep learning will remain challenging. © 2023 The Authors},
	keywords = {Femur; Finite Element; Deep learning; Lesion segmentation; bone fracture risk},
	year = {2024},
	eissn = {1873-2763}
}

@article{MTMT:34467449,
	title = {Systematic review of computed tomography parameters used for the assessment of subchondral bone in osteoarthritis},
	url = {https://m2.mtmt.hu/api/publication/34467449},
	author = {Schadow, Jemima E. and Maxey, David and Smith, Toby O. and Finnila, Mikko A. J. and Manske, Sarah L. and Segal, Neil A. and Wong, Andy Kin On and Davey, Rachel A. and Turmezei, Tom and Stok, Kathryn S.},
	doi = {10.1016/j.bone.2023.116948},
	journal-iso = {BONE},
	journal = {BONE},
	volume = {178},
	unique-id = {34467449},
	issn = {8756-3282},
	abstract = {Objective: To systematically review the published parameters for the assessment of subchondral bone in human osteoarthritis (OA) using computed tomography (CT) and gain an overview of current practices and standards. Design: A literature search of Medline, Embase and Cochrane Library databases was performed with search strategies tailored to each database (search from 2010 to January 2023). The search results were screened independently by two reviewers against pre-determined inclusion and exclusion criteria. Studies were deemed eligible if conducted in vivo/ex vivo in human adults (>18 years) using any type of CT to assess subchondral bone in OA. Extracted data from eligible studies were compiled in a qualitative summary and formal narrative synthesis. Results: This analysis included 202 studies. Four groups of CT modalities were identified to have been used for subchondral bone assessment in OA across nine anatomical locations. Subchondral bone parameters measuring similar features of OA were combined in six categories: (i) microstructure, (ii) bone adaptation, (iii) gross morphology (iv) mineralisation, (v) joint space, and (vi) mechanical properties. Conclusions: Clinically meaningful parameter categories were identified as well as categories with the potential to become relevant in the clinical field. Furthermore, we stress the importance of quantification of parameters to improve their sensitivity and reliability for the evaluation of OA disease progression and the need for standardised measurement methods to improve their clinical value.},
	keywords = {computed tomography; systematic review; osteoarthritis; subchondral bone},
	year = {2024},
	eissn = {1873-2763}
}

@article{MTMT:34406193,
	title = {Osteoblast-derived exosomes promote osteogenic differentiation of osteosarcoma cells via URG4/Wnt signaling pathway},
	url = {https://m2.mtmt.hu/api/publication/34406193},
	author = {Leng, Y. and Li, J. and Long, Z. and Li, C. and Zhang, L. and Huang, Z. and Xi, J. and Liu, Y.},
	doi = {10.1016/j.bone.2023.116933},
	journal-iso = {BONE},
	journal = {BONE},
	volume = {178},
	unique-id = {34406193},
	issn = {8756-3282},
	abstract = {Osteosarcoma is a primary malignant bone tumor. Although surgery and chemotherapy are the main treatment methods, the overall curative effect remains unsatisfactory. Therefore, there is an urgent need to develop new therapeutic options for osteosarcoma. In this study, the effect and molecular mechanism of osteoblast-derived exosomes on the treatment of osteosarcoma were evaluated. Human primary osteoblasts were cultured to observe the effects of osteoblast-derived exosomes on the osteogenic differentiation of osteosarcoma cells both in vitro and in vivo. Alizarin red staining and alkaline phosphatase detection were used to evaluate the degree of osteogenic differentiation, and immunofluorescence and Western blotting were used to detect protein expression. The results showed that osteoblast-derived exosomes effectively inhibited the proliferation of osteosarcoma cells and promoted their mineralization in vitro. The exosomes also significantly inhibited tumor growth and promoted tumor tissue mineralization in vivo. Osteoblast-derived exosomes upregulated the expression of bone sialoprotein, osteonectin, osteopontin, runt-related transcription factor 2, and Wnt inhibitory factor 1, downregulated the expression of cyclin D1, and suppressed the nuclear accumulation of β-catenin and promoted its phosphorylation in vitro and in vivo. However, these effects were significantly reversed by upregulated gene (URG) 4 overexpression. These findings suggest that osteoblast-derived exosomes could activate the osteogenic differentiation process in osteosarcoma cells and promote their differentiation by targeting the URG4/Wnt signaling pathway. © 2023},
	keywords = {Adult; Female; ARTICLE; MOUSE; human; Child; Cell Differentiation; school child; controlled study; nonhuman; animal tissue; animal experiment; cell proliferation; clinical article; in vitro study; protein phosphorylation; Western blotting; Gene Expression; Young Adult; MINERALIZATION; human cell; protein expression; human tissue; in vivo study; immunofluorescence; alkaline phosphatase; Bone Transplantation; upregulation; down regulation; staining; Bagg albino mouse; beta Catenin; Osteopontin; transcription factor RUNX2; cyclin D1; Osteoblasts; osteoblast; exosome; cancer inhibition; Osteosarcoma; Wnt protein; osteonectin; Exosomes; sialoprotein; Wnt signaling; osteosarcoma cell; differentiation therapy; URG4},
	year = {2024},
	eissn = {1873-2763}
}

@article{MTMT:34599703,
	title = {Denosumab treatment lapses, discontinuation, and off-treatment fracture risk: A retrospective study of patients with osteoporosis in a real-world clinical setting},
	url = {https://m2.mtmt.hu/api/publication/34599703},
	author = {Cruchelow, Katie R. and Peter, Megan E. and Chakrabarti, Anwesa and Gipson, Hannah M. and Gregory, W. Taylor and DeClercq, Josh and Choi, Leena and Tanner, S. Bobo},
	doi = {10.1016/j.bone.2023.116925},
	journal-iso = {BONE},
	journal = {BONE},
	volume = {177},
	unique-id = {34599703},
	issn = {8756-3282},
	abstract = {Introduction: The purpose of this study was to retrospectively examine predictors of fracture risk when adult patients experienced a denosumab treatment lapse or discontinuation in a real-world clinic setting.Materials and methods: Eligible patients were adults who had received >= 2 doses of denosumab at an academic health center in the United States. Demographics, treatment doses, reasons for missed doses, and fractures, were collected retrospectively from electronic health records, from an 8-year period (2010-2018). The number of times each patient incurred a treatment lapse, defined as >= 240 days between two doses (excluding lapse due to discontinuation, death, or transfer of care) was computed. The occurrence of denosumab discontinuation (excluding discontinuation due to death or transfer of care), whether the patient initiated alternative therapy, and the reason for each lapse and discontinuation were collected. Cox proportional hazards models assessed characteristics associated with risk of fracture and treatment discontinuation. A logistic regression model was used to determine if cumulative amount of time off medication (i.e., cumulative lapse time) was associated with a higher likelihood of incurring a fracture.Results: We included 534 patients: 95 % White, 86 % women, 33 % tobacco users, 13 % diagnosed with diabetes, median age 69 years (Interquartile Range (IQR): 62-77), and median Body Mass Index (BMI) 25 kg/m2 (IQR: 22-28). Thirty-six percent of patients incurred 250 lapses; 10 % discontinued therapy. Dental problems/pro-cedures and logistical barriers were the most common reasons for lapses and discontinuations. Nineteen percent (n = 103) incurred a total of 190 fractures; of these, 121 were osteoporotic, 50 were vertebral. Risk of any, osteoporotic, and vertebral fractures were associated with off-treatment status (hazard ratio [HR] = 1.7, p = 0.043; HR = 2.0, p = 0.026; and HR = 4.2, p = 0.001, respectively) and older age (HR = 1.3, p = 0.015; HR = 1.5, p = 0.001; and HR = 1.8, p = 0.005, respectively). Older age was associated with higher risk of discontinuation (HR = 1.4, p = 0.022). There was a non-significant trend of a nonlinear association between incurring a fracture and cumulative lapse time (p = 0.087).Conclusion: Denosumab treatment lapses are common, and off-treatment status may be associated with a higher risk of fractures. Clinical teams should proactively identify and address adverse effects and potential logistical barriers to reduce the risk of treatment lapses.},
	keywords = {osteoporosis; denosumab; discontinuation; real -world data},
	year = {2023},
	eissn = {1873-2763}
}

@article{MTMT:34371951,
	title = {Composition and micromechanical properties of the femoral neck compact bone in relation to patient age, sex and hip fracture occurrence},
	url = {https://m2.mtmt.hu/api/publication/34371951},
	author = {Kochetkova, Tatiana and Hanke, Markus S. and Indermaur, Michael and Groetsch, Alexander and Remund, Stefan and Neuenschwander, Beat and Michler, Johann and Siebenrock, Klaus A. and Zysset, Philippe and Schwiedrzik, Jakob},
	doi = {10.1016/j.bone.2023.116920},
	journal-iso = {BONE},
	journal = {BONE},
	volume = {177},
	unique-id = {34371951},
	issn = {8756-3282},
	abstract = {Current clinical methods of bone health assessment depend to a great extent on bone mineral density (BMD) measurements. However, these methods only act as a proxy for bone strength and are often only carried out after the fracture occurs. Besides BMD, composition and tissue-level mechanical properties are expected to affect the whole bone's strength and toughness. While the elastic properties of the bone extracellular matrix (ECM) have been extensively investigated over the past two decades, there is still limited knowledge of the yield properties and their relationship to composition and architecture. In the present study, morphological, compositional and micropillar compression bone data was collected from patients who underwent hip arthroplasty. Femoral neck samples from 42 patients were collected together with anonymous clinical information about age, sex and primary diagnosis (coxarthrosis or hip fracture). The femoral neck cortex from the inferomedial region was analyzed in a site-matched manner using a combination of micromechanical testing (nanoindentation, micropillar compression) together with micro-CT and quantitative polarized Raman spectroscopy for both morphological and compositional characterization. Mechanical properties, as well as the sample-level mineral density, were constant over age. Only compositional properties demonstrate weak dependence on patient age: decreasing mineral to matrix ratio (p = 0.02, R-2 = 0.13, 2.6 % per decade) and increasing amide I sub-peak ratio I-similar to(1660)/I-similar to(1683) (p = 0.04, R-2 = 0.11, 1.5 % per decade). The patient's sex and diagnosis did not seem to influence investigated bone properties. A clear zonal dependence between interstitial and osteonal cortical zones was observed for compositional and elastic bone properties (p < 0.0001). Site-matched microscale analysis confirmed that all investigated mechanical properties except yield strain demonstrate a positive correlation with the mineral fraction of bone. The output database is the first to integrate the experimentally assessed microscale yield properties, local tissue composition and morphology with the available patient clinical information. The final dataset was used for bone fracture risk prediction in-silico through the principal component analysis and the Na & iuml;ve Bayes classification algorithm. The analysis showed that the mineral to matrix ratio, indentation hardness and micropillar yield stress are the most relevant parameters for bone fracture risk prediction at 70 % model accuracy (0.71 AUC). Due to the low number of samples, further studies to build a universal fracture prediction algorithm are anticipated with the higher number of patients (N > 200). The proposed classification algorithm together with the output dataset of bone tissue properties can be used for the future comparison of existing methods to evaluate bone quality as well as to form a better understanding of the mechanisms through which bone tissue is affected by aging or disease.},
	keywords = {Aging; NANOINDENTATION; hip fracture; PCA; micro-CT; Micropillar compression; Naive Bayes; Femtosecond laser ablation; coxarthrosis; Quantitative Polarized Raman spectroscopy},
	year = {2023},
	eissn = {1873-2763}
}