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Article: TX2019slab: A New P and S Tomography Model Incorporating Subducting Slabs

Lu, Chang / Grand, Stephen P. / Lai, Hongyu / Garnero, Edward J.

Journal of geophysical research. 2019 Nov., v. 124, no. 11

2019

Abstract: ... in tomography models. In order to better account for known subducting slabs, we performed a new P and S wave ... in the starting model. In addition, velocity and source locations were inverted for simultaneously. Our new P and ... The S to P heterogeneity ratio based on the new tomography model indicates that thermal elastic effects ...

Abstract	Large numbers of earthquakes occur in subduction zones that are marked by dipping, narrow high seismic velocity slabs. The existence of these fast velocity slabs can cause serious earthquake mislocation problems that can bias estimates of seismic travel time residuals. This can affect the recovery of subducting slabs in tomography as well as introduce significant artifacts into lower mantle structure in tomography models. In order to better account for known subducting slabs, we performed a new P and S wave joint tomography inversion incorporating a three‐dimensional thermal model of subducting slabs in the starting model. In addition, velocity and source locations were inverted for simultaneously. Our new P and S models feature higher‐amplitude subducting slabs compared with previous global tomography results. The S to P heterogeneity ratio based on the new tomography model indicates that thermal elastic effects alone cannot explain all the heterogeneities in the lower mantle. Much of the observed abnormal S to P heterogeneity ratio can be explained by anelastic effects, the spin transition, and phase transitions of bridgmanite to post‐perovskite in the lower mantle.
Keywords	earthquakes ; geophysics ; models ; research ; subduction ; tomography
Language	English
Dates of publication	2019-11
Size	p. 11549-11567.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ISSN	2169-9313
DOI	10.1029/2019JB017448
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The Utility of Biomarkers in Osteoporosis Management.

Garnero, Patrick

Molecular diagnosis & therapy

2017 Volume 21, Issue 4, Page(s) 401–418

Abstract: The measurement of bone turnover markers is useful for the clinical investigation of patients with osteoporosis. Among the available biochemical markers, the measurements of serum procollagen type I N-terminal propeptide (PINP) and the crosslinked C- ... ...

Abstract	The measurement of bone turnover markers is useful for the clinical investigation of patients with osteoporosis. Among the available biochemical markers, the measurements of serum procollagen type I N-terminal propeptide (PINP) and the crosslinked C-terminal telopeptide (serum CTX) have been recommended as reference markers of bone formation and bone resorption, respectively. The important sources of preanalytical and analytical variability have been identified for both markers, and precise measurement can now be obtained. Reference interval data for PINP and CTX have been generated across different geographical locations, which allows optimum clinical interpretation. However, conventional protein-based markers have some limitations, including a lack of specificity for bone tissue, and their inability to reflect osteocyte activity or periosteal metabolism. Thus, novel markers such as periostin, sclerostin and, sphingosine 1-phosphate have been developed to address some of these shortcomings. Recent studies suggest that the measurements of circulating microRNAs, a new class of marker, may represent early biological markers in osteoporosis. Bone markers have been shown to be a useful adjunct to bone mineral density for identifying postmenopausal women at high risk for fracture. Because levels of bone markers respond rapidly to both anabolic and anticatabolic drugs, they are very useful for investigating the mechanism of action of new therapies and, potentially, for predicting their efficacy to reduce fracture risk.
MeSH term(s)	Biomarkers/blood ; Bone Density/drug effects ; Bone Density Conservation Agents/therapeutic use ; Bone Morphogenetic Proteins/blood ; Bone Resorption/blood ; Bone Resorption/diagnosis ; Bone Resorption/drug therapy ; Bone Resorption/pathology ; Cell Adhesion Molecules/blood ; Collagen Type I/blood ; Disease Management ; Female ; Genetic Markers ; Humans ; Lysophospholipids/blood ; MicroRNAs/blood ; Osteoporosis/blood ; Osteoporosis/diagnosis ; Osteoporosis/drug therapy ; Osteoporosis/pathology ; Peptide Fragments/blood ; Peptides/blood ; Postmenopause/blood ; Procollagen/blood ; Prognosis ; Sphingosine/analogs & derivatives ; Sphingosine/blood
Chemical Substances	Biomarkers ; Bone Density Conservation Agents ; Bone Morphogenetic Proteins ; Cell Adhesion Molecules ; Collagen Type I ; Genetic Markers ; Lysophospholipids ; MicroRNAs ; POSTN protein, human ; Peptide Fragments ; Peptides ; Procollagen ; SOST protein, human ; collagen type I trimeric cross-linked peptide ; procollagen Type I N-terminal peptide ; sphingosine 1-phosphate (26993-30-6) ; Sphingosine (NGZ37HRE42)
Language	English
Publishing date	2017-03-08
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	2232796-4
ISSN	1179-2000 ; 1177-1062
ISSN (online)	1179-2000
ISSN	1177-1062
DOI	10.1007/s40291-017-0272-1
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Article ; Online: Plasma Cartilage Acidic Protein 1 Measured by ELISA Is Associated With the Progression to Total Joint Replacement in Postmenopausal Women.

Garnero, Patrick / Gineyts, Evelyne / Rousseau, Jean-Charles / Sornay-Rendu, Elisabeth / Chapurlat, Roland D

The Journal of rheumatology

2024 Volume 51, Issue 2, Page(s) 176–180

Abstract: Objective: To investigate the association of plasma cartilage acidic protein 1 (CRTAC1), a novel biochemical marker of osteoarthritis (OA), and total joint replacement (TJR) in postmenopausal women.: Methods: The association of plasma CRTAC1 with the ...

Abstract	Objective: To investigate the association of plasma cartilage acidic protein 1 (CRTAC1), a novel biochemical marker of osteoarthritis (OA), and total joint replacement (TJR) in postmenopausal women. Methods: The association of plasma CRTAC1 with the incidence of TJR was investigated in a prospective cohort including 478 postmenopausal women. A total of 38 women underwent a TJR for OA during a median follow-up of 18 years. Every one of the TJR cases were age- and BMI (kg/m Results: Increased CRTAC1 was associated with a higher risk of TJR with an odds ratio (OR) of 1.80 (95% CI 1.11-2.92) for 1 SD increase, which remained significant after adjusting for Western Ontario and McMaster Universities Osteoarthritis Index, knee OA baseline severity (Kellgren-Lawrence grade), hip OA, and hip bone mineral density. Urinary crosslinked C-telopeptide of type II collagen (CTX-II) was also associated with a higher risk of TJR with an adjusted OR of 1.83 (95% CI 1.11-3.00). When CRTAC1 and CTX-II were included in the same model, both markers were significantly associated with TJR with similar ORs. Conclusion: CRTAC1 is a new risk indicator of TJR for OA in postmenopausal women. Combined with knee and hip OA and CTX-II, it may help to identify subjects at risk for TJR.
MeSH term(s)	Humans ; Female ; Osteoarthritis, Hip/surgery ; Prospective Studies ; Postmenopause ; Osteoarthritis, Knee/surgery ; Osteoarthritis, Knee/epidemiology ; Knee Joint ; Biomarkers ; Arthroplasty, Replacement, Hip ; Enzyme-Linked Immunosorbent Assay ; Cartilage ; Calcium-Binding Proteins/metabolism
Chemical Substances	Biomarkers ; CRTAC1 protein, human ; Calcium-Binding Proteins
Language	English
Publishing date	2024-02-01
Publishing country	Canada
Document type	Journal Article
ZDB-ID	194928-7
ISSN	1499-2752 ; 0315-162X
ISSN (online)	1499-2752
ISSN	0315-162X
DOI	10.3899/jrheum.2023-0684
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Article ; Online: The Role of Collagen Organization on the Properties of Bone.

Garnero, Patrick

Calcified tissue international

2015 Volume 97, Issue 3, Page(s) 229–240

Abstract: Bone is a complex tissue constituted by a collagen matrix filled in with crystal of hydroxyapatite (HAP). Bone mechanical properties are influenced by the collagen matrix which is organized into hierarchical structures from the individual type I collagen ...

Abstract	Bone is a complex tissue constituted by a collagen matrix filled in with crystal of hydroxyapatite (HAP). Bone mechanical properties are influenced by the collagen matrix which is organized into hierarchical structures from the individual type I collagen heterotrimer flanked by linear telopeptides at each end to the collagen fibrils that are interconnected by enzymatic and non-enzymatic cross-links. Although most studies focused on the role of collagen cross-links in bone strength, other organizational features may also play a role. At the molecular level it has been shown that homotrimer of type I collagen found in bone tissue of some patients with osteogenesis imperfecta (OI) is characterized by decreased mechanical competence compared to the regular heterotrimer. The state of C-telopeptide isomerization-which can be estimated by the measurement in body fluids of the native and isomerized isoforms-has also been shown to be associated with bone strength, particularly the post-yield properties independent of bone size and bone mineral density. Other higher hierarchical features of collagen organization have shown to be associated with changes in bone mechanical behavior in ex vivo models and may also be relevant to explain bone fragility in diseases characterized by collagen abnormalities e.g., OI and Paget's disease. These include the orientation of collagen fibrils in a regular longitudinal direction, the D-spacing period between collagen fibrils and the collagen-HAP interfacial bonding. Preliminary data indicate that some of these organizational features can change during treatment with bisphosphonate, raloxifene, and PTH suggesting that they may contribute to their anti-fracture efficacy. It remains however to be determined which of these parameters play a specific and independent role in bone matrix properties, what is the magnitude of mechanical strength explained by collagen organization, whether they are relevant to explain osteoporosis-induced bone fragility, and how they could be monitored non-invasively to develop efficient bone quality biomarkers.
MeSH term(s)	Animals ; Bone Density/physiology ; Bone and Bones/metabolism ; Collagen/metabolism ; Fractures, Bone/metabolism ; Humans ; Osteoporosis/metabolism
Chemical Substances	Collagen (9007-34-5)
Language	English
Publishing date	2015-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	304266-2
ISSN	1432-0827 ; 0944-0747 ; 0008-0594 ; 0171-967X
ISSN (online)	1432-0827
ISSN	0944-0747 ; 0008-0594 ; 0171-967X
DOI	10.1007/s00223-015-9996-2
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Article ; Online: Erratum to: The Role of Collagen Organization on the Properties of Bone.

Garnero, Patrick

Calcified tissue international

2015 Volume 97, Issue 3, Page(s) 241

Language	English
Publishing date	2015-09
Publishing country	United States
Document type	Published Erratum
ZDB-ID	304266-2
ISSN	1432-0827 ; 0944-0747 ; 0008-0594 ; 0171-967X
ISSN (online)	1432-0827
ISSN	0944-0747 ; 0008-0594 ; 0171-967X
DOI	10.1007/s00223-015-0011-8
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Article ; Online: New developments in biological markers of bone metabolism in osteoporosis.

Garnero, Patrick

Bone

2014 Volume 66, Page(s) 46–55

Abstract: Over the last 15 years several biological markers of bone turnover have been developed with increased specificity and sensitivity. In osteoporosis clinical studies, the IOF and IFCC organizations have recently recommended the measurements of serum type I ...

Abstract	Over the last 15 years several biological markers of bone turnover have been developed with increased specificity and sensitivity. In osteoporosis clinical studies, the IOF and IFCC organizations have recently recommended the measurements of serum type I collagen N-propeptide (PINP) and the crosslinked C-terminal telopeptide (serum CTX) as markers of bone formation and bone resorption, respectively. However these markers have some limitations including a lack of specificity for bone tissue, their inability to reflect osteocyte activity or periosteal apposition. In addition they do not allow the investigation of bone tissue quality an important determinant of skeletal fragility. To address these limitations, new developments in markers of bone metabolism have been recently achieved. These include assays for periostin, a matricellular protein preferentially localized in the periosteal tissue, sphingosine 1-phosphate, a lipid mediator which acts mainly on osteoclastogenesis and the osteocyte factors such as sclerostin and FGF-23. Recent studies have shown an association between the circulating levels of these biological markers and fracture risk in postmenopausal women or elderly men, although data require confirmation in additional prospective studies. Finally, recent studies suggest that the measurements of circulating microRNAs may represent a novel class of early biological markers in osteoporosis. It is foreseen that with the use of genomics and proteomics, new markers will be developed to ultimately improve the management of patients with osteoporosis.
MeSH term(s)	Biomarkers/blood ; Biomarkers/metabolism ; Bone and Bones/metabolism ; Humans ; Models, Biological ; Osteoporosis/blood ; Osteoporosis/metabolism
Chemical Substances	Biomarkers
Language	English
Publishing date	2014-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	632515-4
ISSN	1873-2763 ; 8756-3282
ISSN (online)	1873-2763
ISSN	8756-3282
DOI	10.1016/j.bone.2014.05.016
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Article ; Online: A new serum biochemical marker of synovium turnover predicts radiographic progression in patients with early arthritis.

Garnero, Patrick / Gineyts, Evelyne / Rousseau, Jean-Charles / Richette, Pascal / Sellam, Jérémie / Chapurlat, Roland

Rheumatology (Oxford, England)

2023 Volume 63, Issue 3, Page(s) 874–881

Abstract: Objective: To investigate whether serum Col 3-4, a new biochemical marker of synovial tissue turnover, was associated with progression of joint damage in patients with early arthritis.: Methods: A total of 788 early arthritis patients (<6 months of ... ...

Abstract	Objective: To investigate whether serum Col 3-4, a new biochemical marker of synovial tissue turnover, was associated with progression of joint damage in patients with early arthritis. Methods: A total of 788 early arthritis patients (<6 months of symptoms, 82% diagnosis of RA, 18% undifferentiated arthritis) from the prospective ESPOIR study were investigated. Progression was defined as an increase of 1 or 5 unit(s) in radiographic van der Heijde modified Sharp score between baseline and 1 or 5 years, respectively. Associations between baseline Col 3-4 and progression were assessed by logistic regression. Results: Each standard deviation increase of baseline Col 3-4 levels was associated with an increased 5-yr total damage progression with an odds ratio (OR, 95% CI) of 1.51 (1.21, 1.88), which remained significant when DAS28, C-reactive protein and anti-citrullinated protein antibodies positivity were included in the model [OR (95% CI): 1.34 (1.01, 1.76)]. Further adjustment for bone erosion did not modify the association. Patients with both Col 3-4 in the highest quintile and bone erosion had a >2-fold higher risk of progression [OR (95% CI): 7.16 (2.31, 22)] than patients with either high Col 3-4 [2.91 (1.79, 4.73)] or bone erosion [2.36 (2.38, 3.70)] alone. Similar associations were observed for prediction of 12 months progression. Conclusions: Increased serum Col 3-4 is associated with a higher risk of structural progression, independently of major risk factors. Col 3-4 may be useful in association with bone erosion to identify patients with early arthritis at higher risk.
MeSH term(s)	Humans ; Arthritis, Rheumatoid/complications ; Prospective Studies ; Disease Progression ; Synovial Membrane/diagnostic imaging ; Biomarkers
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-07-20
Publishing country	England
Document type	Journal Article
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/kead375
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Article: Soluble biological markers in osteoarthritis.

Rousseau, Jean-Charles / Chapurlat, Roland / Garnero, Patrick

Therapeutic advances in musculoskeletal disease

2021 Volume 13, Page(s) 1759720X211040300

Abstract: In recent years, markers research has focused on the structural components of cartilage matrix. Specifically, a second generation of degradation markers has been developed against type II collagen neoepitopes generated by specific enzymes. A particular ... ...

Abstract	In recent years, markers research has focused on the structural components of cartilage matrix. Specifically, a second generation of degradation markers has been developed against type II collagen neoepitopes generated by specific enzymes. A particular effort has been made to measure the degradation of minor collagens III and X of the cartilage matrix. However, because clinical data, including longitudinal controlled studies, are very scarce, it remains unclear whether they will be useful as an alternative to or in combination with current more established collagen biological markers to assess patients with osteoarthritis (OA). In addition, new approaches using high-throughput technologies allowed to detect new types of markers and improve the knowledge about the metabolic changes linked to OA. The relative advances coming from phenotype research are a first attempt to classify the heterogeneity of OA, and several markers could improve the phenotype characterization. These phenotypes could improve the selection of patients in clinical trials limiting the size of the studies by selecting patients with OA characteristics corresponding to the metabolic pathway targeted by the molecules evaluated. In addition, the inclusion of rapid progressors only in clinical trials would facilitate the demonstration of efficacy of the investigative drug to reduce joint degradation. The combination of selective biochemical markers appears as a promising and cost-effective approach to fulfill this unmet clinical need. Among the various potential roles of biomarkers in OA, their ability to monitor drug efficacy is probably one of the most important, in association with clinical and imaging parameters. Biochemical markers have the unique property to detect changes in joint tissue metabolism within a few weeks.
Language	English
Publishing date	2021-09-29
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2516075-8
ISSN	1759-7218 ; 1759-720X
ISSN (online)	1759-7218
ISSN	1759-720X
DOI	10.1177/1759720X211040300
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Article ; Online: The cartilage degradation marker, urinary CTX-II, is associated with the risk of incident total joint replacement in postmenopausal women. A 18 year evaluation of the OFELY prospective cohort.

Garnero, P / Sornay-Rendu, E / Chapurlat, R

Osteoarthritis and cartilage

2020 Volume 28, Issue 4, Page(s) 468–474

Abstract: ... higher in patients with TJR (+34%, P = 0.001 vs women with no TJR). Increased baseline CTX-II levels were ... 95 CI): 1.31 (1.01-1.71), P = 0,04]. When women were categorized as low and high CTX-II (lower and ... P = 0.01].: Conclusion: CTX-II is an independent risk indicator of TJR in postmenopausal women ...

Abstract	Objective: Identifying objective risk-indicators for total joint replacement (TJR) is useful to enrich population at high risk in OA clinical trials. We investigate the association of urinary CTX-II, a biochemical marker of cartilage breakdown, with the risk of TJR. Method: 478 postmenopausal women (mean age 65.5 ± 7.5 yr) from the OFELY cohort were studied. CTX-II, serum CTX-I (bone resorption) and PINP (bone formation), were measured at baseline. Association between CTX-II and incidence of TJR was assessed by Cox Hazard Regression. Results: During a median (95%CI) 17.8 (15.0-18.1) years follow-up, 38 women sustained a TJR, including hip (n = 29) or knee (n = 9) replacement. CTX-II -but not CTX-I or PINP- was higher in patients with TJR (+34%, P = 0.001 vs women with no TJR). Increased baseline CTX-II levels were associated with a higher risk of TJR with a Hazard Ratio (HR) (95 CI) of 1.45 (1.13-1.85) per 1 SD increase after adjustment for age, BMI and total hip BMD. CTX-II remained significantly associated with the risk of TJR after further adjustment for total WOMAC, prevalent knee OA (KL ≥ 2) and self-reported hip OA [HR (95 CI): 1.31 (1.01-1.71), P = 0,04]. When women were categorized as low and high CTX-II (lower and above the 95 percentile of healthy premenopausal women, respectively), subjects with high levels had an age-BMI-hip BMD adjusted HR (95 CI) of 3.00 (1.54-5.85) compared to women with low levels which remained significant after further adjustment for WOMAC, knee and/or hip OA [HR (95 CI): 2.45 (1.25-4.89), P = 0.01]. Conclusion: CTX-II is an independent risk indicator of TJR in postmenopausal women suggesting that it may be useful to identify subjects at high risk of TJR.
MeSH term(s)	Aged ; Arthroplasty, Replacement/statistics & numerical data ; Arthroplasty, Replacement, Hip/statistics & numerical data ; Arthroplasty, Replacement, Knee/statistics & numerical data ; Biomarkers ; Bone Density ; Cohort Studies ; Collagen Type I/blood ; Collagen Type II/urine ; Female ; France/epidemiology ; Humans ; Longitudinal Studies ; Middle Aged ; Osteoarthritis, Hip/epidemiology ; Osteoarthritis, Hip/metabolism ; Osteoarthritis, Hip/surgery ; Osteoarthritis, Knee/epidemiology ; Osteoarthritis, Knee/metabolism ; Osteoarthritis, Knee/surgery ; Peptide Fragments/blood ; Peptide Fragments/urine ; Peptides/blood ; Postmenopause ; Procollagen/blood ; Proportional Hazards Models ; Prospective Studies
Chemical Substances	Biomarkers ; C-terminal cross-linking telopeptide of type II collagen, human ; Collagen Type I ; Collagen Type II ; Peptide Fragments ; Peptides ; Procollagen ; collagen type I trimeric cross-linked peptide ; procollagen Type I N-terminal peptide
Language	English
Publishing date	2020-01-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1167809-4
ISSN	1522-9653 ; 1063-4584
ISSN (online)	1522-9653
ISSN	1063-4584
DOI	10.1016/j.joca.2019.12.012
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Article: The contribution of collagen crosslinks to bone strength.

Garnero, Patrick

BoneKEy reports

2012 Volume 1, Page(s) 182

Abstract: Collagen crosslinking is a major post-translational modification of collagen which has important roles in determining the biomechanical competence of bone. Crosslinks can be divided into enzymatic lysil oxidase-mediated and non-enzymatic glycation- ... ...

Abstract	Collagen crosslinking is a major post-translational modification of collagen which has important roles in determining the biomechanical competence of bone. Crosslinks can be divided into enzymatic lysil oxidase-mediated and non-enzymatic glycation-induced (advanced glycation end products, AGE) molecules. In addition, collagen in bone can also undergo spontaneous isomerization and racemization of the aspartic acid residues with the C-telopeptide (CTX), leading to the formation of two isomers namely α (newly formed collagen) and β (matured isomerized collagen) CTX. Several in vitro and ex vivo studies, relating the bone content of these crosslinks with bone strength, have shown that they contributed to the mechanical competence of trabecular and cortical bone-mainly on the post-yield properties-in part independent of the bone mineral content. In addition, AGEs such as pentosidine have been reported to alter the formation and propagation of microdamage by making the bone more brittle. The bone content of AGEs and isomerization can also be modified by antiresorptive and anabolic therapies. They may thus explain part of the antifracture efficacy of these treatments. The main challenge consists in the transposition of these in vitro/ex vivo studies to clinical applications for the development of a non-invasive biomarker, as none of currently identified collagen crosslinks (both enzymatic and nonenzymatic) is bone specific. Nevertheless, serum or urine levels of pentosidine and the ratio of α/β CTX have been reported to predict fracture risk in postmenopausal women, in men and in patients with type 2 diabetes.
Language	English
Publishing date	2012-09-19
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2816308-4
ISSN	2047-6396
ISSN	2047-6396
DOI	10.1038/bonekey.2012.182
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