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Riera H.,University of Los Andes, Venezuela | Vera M.,University of Los Andes, Venezuela | Torres A.R.,University of Los Andes, Venezuela | Esquivel J.A.,Autonomous University of Nuevo León | And 23 more authors.
Journal of Clinical Rheumatology | Year: 2015

Background: Latin America is a heterogeneous region made up of different populations, cultures, latitudes, altitudes, and immigrants from different areas and ethnic groups. Objective: The purpose of this study is to describe the clinical and demographic profile of patients with osteoarthritis (OA) evaluated by a selected group of rheumatologists in 13 Latin American countries. Methods: Adescriptive, observational, cross-sectional studywas conducted in 13 Latin American countries of patients with symptomatic OA. Data were collected over a 3-month period using an ad hoc questionnaire to evaluate the clinical and demographic features of OA seen by rheumatologists. Results: Among the 3040 patients, their average age was 62.5 years, and female-to-male ratio was 4.8:1. Patients with body mass index of greater than 30 kg/m2 or obesity was found in 38.2%. Approximately 88% had primary OA. Joints with OA were as follows: knee 31.2%, hand 9.5%, hand and knee 22.9%, proximal and distal interphalangeal joints (erosive OA) 6.5%, axial 6.6%, and hip 1.3%. Approximately 88.5% had radiographic severity of grade 2 or 3 on Kellgren-Lawrence scale (0-4). Nonsteroidal anti-inflammatory drugs were the predominant OA treatment included in combinations with glucosamine sulfate/chondroitin and viscosupplementation. Associated comorbidities included hypertension (39%), obesity (36.3%), diabetes mellitus (12%), and without comorbidity (12.7%). Conclusions: This is 1 of the largest population studies that evaluated the characteristics of OA in 3040 patients evaluated by rheumatologists in 13 Latin American countries. This study provides important data for each Latin American country to develop new health care planning in management of OA. © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Arden N.,University of Oxford | Richette P.,University Paris Diderot | Cooper C.,University of Oxford | Cooper C.,University of Southampton | And 26 more authors.
Drugs and Aging | Year: 2015

Osteoarthritis (OA), a disease affecting different patient phenotypes, appears as an optimal candidate for personalized healthcare. The aim of the discussions of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group was to explore the value of markers of different sources in defining different phenotypes of patients with OA. The ESCEO organized a series of meetings to explore the possibility of identifying patients who would most benefit from treatment for OA, on the basis of recent data and expert opinion. In the first meeting, patient phenotypes were identified according to the number of affected joints, biomechanical factors, and the presence of lesions in the subchondral bone. In the second meeting, summarized in the present article, the working group explored other markers involved in OA. Profiles of patients may be defined according to their level of pain, functional limitation, and presence of coexistent chronic conditions including frailty status. A considerable amount of data suggests that magnetic resonance imaging may also assist in delineating different phenotypes of patients with OA. Among multiple biochemical biomarkers identified, none is sufficiently validated and recognized to identify patients who should be treated. Considerable efforts are also being made to identify genetic and epigenetic factors involved in OA, but results are still limited. The many potential biomarkers that could be used as potential stratifiers are promising, but more research is needed to characterize and qualify the existing biomarkers and to identify new candidates. © 2015, The Author(s).


Bruyere O.,University of Liège | Cooper C.,University of Southampton | Cooper C.,University of Oxford | Arden N.,University of Southampton | And 15 more authors.
Drugs and Aging | Year: 2015

Osteoarthritis is a syndrome affecting a variety of patient profiles. A European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and the European Union Geriatric Medicine Society working meeting explored the possibility of identifying different patient profiles in osteoarthritis. The risk factors for the development of osteoarthritis include systemic factors (e.g., age, sex, obesity, genetics, race, and bone density) and local biomechanical factors (e.g., obesity, sport, joint injury, and muscle weakness); most also predict disease progression, particularly joint injury, malalignment, and synovitis/effusion. The characterization of patient profiles should help to better orientate research, facilitate trial design, and define which patients are the most likely to benefit from treatment. There are a number of profile candidates. Generalized, polyarticular osteoarthritis and local, monoarticular osteoarthritis appear to be two different profiles; the former is a feature of osteoarthritis co-morbid with inflammation or the metabolic syndrome, while the latter is more typical of post-trauma osteoarthritis, especially in cases with severe malalignment. Other biomechanical factors may also define profiles, such as joint malalignment, loss of meniscal function, and ligament injury. Early- and late-stage osteoarthritis appear as separate profiles, notably in terms of treatment response. Finally, there is evidence that there are two separate profiles related to lesions in the subchondral bone, which may determine benefit from bone-active treatments. Decisions on appropriate therapy should be made considering clinical presentation, underlying pathophysiology, and stage of disease. Identification of patient profiles may lead to more personalized healthcare, with more targeted treatment for osteoarthritis. © 2015, The Author(s).


Reginster J.-Y.,University of Liège | Reiter-Niesert S.,Federal Institute for Drugs and Medical Devices BfArM | Bruyere O.,University of Liège | Berenbaum F.,University Pierre and Marie Curie | And 13 more authors.
Osteoarthritis and Cartilage | Year: 2015

Objective: The European Society on Clinical and Economic aspects of Osteoporosis and Osteoarthritis (ESCEO) organised a working group to evaluate the need for updating the current European guideline on clinical investigation of drugs used in the treatment of osteoarthritis (OA). Design: Areas of potential attention were identified and the need for modifications, update or clarification was examined. Proposals were then developed based on literature reviews and through a consensus process. Results: It was agreed that the current guideline overall still reflects the current knowledge in OA, although two possible modifications were identified. The first relates to the number and timing of measurements required as primary endpoints during clinical trials of symptom-relieving drugs, either drugs with rapid onset of action or slow acting drugs. The suggested modifications are intended to take into consideration the time related clinical need and expected time response to these drugs - i.e., a more early effect for the first category in addition to the maintenance of effect, a more continuous benefit over the long-term for the latter - in the timing of assessments.Secondly, values above which a benefit over placebo should be considered clinically relevant were considered. Based on literature reviews, the most consensual values were determined for primary endpoints of both symptom-relieving drugs (i.e., pain intensity on a visual analogue scale (VAS)) and disease-modifying drugs (i.e., radiographic joint-space narrowing). Conclusions: This working document might be considered by the European regulatory authorities in a future update of the guideline for the registration of drugs in OA. © 2015 The Authors.


Villalvilla A.,Bone and Joint Research Unit | Villalvilla A.,Newcastle University | Gomez R.,Bone and Joint Research Unit | Gomez R.,Institute IDIS | And 4 more authors.
Maturitas | Year: 2016

Objectives Despite the high prevalence of osteoarthritis (OA) in postmenopausal women, a relationship between circulating estrogen levels and the development of OA has not been found. Therefore, the purpose of this study was to evaluate the expression and activity of aromatase, a key enzyme in local production of estrogens, in human OA cultured articular chondrocytes, and to determine the physiological relevance of this enzyme in cartilage. Methods Human OA articular chondrocytes were isolated and cultured. Local production of estradiol was measured after incubation with 100ng/ml testosterone for 8 and 24 h. Furthermore, chondrocytes were culture for 2 h, 48 h, 7 days or 15 days, or in alginate beads for 10 days. Aromatase, type II and X collagen, aggrecan, alkaline phosphatase, and Runx2 expression were evaluated in cartilage, freshly isolated chondrocytes and cultured chondrocytes. Results Aromatase was expressed and active in cultured human chondrocytes. Human cartilage, freshly isolated chondrocytes, and chondrocytes cultured for 2 h expressed an insignificant amount of aromatase; however, expression arose after 48 h of culture and remained increased thereafter. Aromatase expression was not related to estrogen deprivation and was inversely correlated with differentiation. Re-differentiation did not reduce its expression. Conclusions Aromatase presents an almost undetectable expression in human cartilage but is induced in cultured chondrocytes. Therefore, human cartilage might act as a mere target for estrogens rather than a producer, and researchers using cell expansion in culture for latter therapies should consider these changes in estrogen metabolism which may not be reverted after re-differentiation. © 2015 Elsevier Ireland Ltd. All rights reserved.


Reginster J.-Y.,University of Liège | Reiter-Niesert S.,Federal Institute for Drugs and Medical Devices BfArM | Bruyere O.,University of Liège | Berenbaum F.,University Pierre and Marie Curie | And 12 more authors.
Osteoarthritis and Cartilage | Year: 2015

Objective: The European Society on Clinical and Economic aspects of Osteoporosis and Osteoarthritis (ESCEO) organised a working group to evaluate the need for updating the current European guideline on clinical investigation of drugs used in the treatment of osteoarthritis (OA). Design: Areas of potential attention were identified and the need for modifications, update or clarification was examined. Proposals were then developed based on literature reviews and through a consensus process. Results: It was agreed that the current guideline overall still reflects the current knowledge in OA, although two possible modifications were identified. The first relates to the number and timing of measurements required as primary endpoints during clinical trials of symptom-relieving drugs, either drugs with rapid onset of action or slow acting drugs. The suggested modifications are intended to take into consideration the time related clinical need and expected time response to these drugs - i.e., a more early effect for the first category in addition to the maintenance of effect, a more continuous benefit over the long-term for the latter - in the timing of assessments.Secondly, values above which a benefit over placebo should be considered clinically relevant were considered. Based on literature reviews, the most consensual values were determined for primary endpoints of both symptom-relieving drugs (i.e., pain intensity on a visual analogue scale (VAS)) and disease-modifying drugs (i.e., radiographic joint-space narrowing). Conclusions: This working document might be considered by the European regulatory authorities in a future update of the guideline for the registration of drugs in OA. © 2015 The Authors.


Reginster J.-Y.,University of Liège | Cooper C.,University of Southampton | Cooper C.,University of Oxford | Hochberg M.,University of Maryland Baltimore County | And 12 more authors.
Current Medical Research and Opinion | Year: 2015

Despite the near concurrent publication by influential scientific organizations, there are important differences in interpretation of the evidence base and the conclusions derived from the recent Osteoarthritis Research Society International (OARSI) guidelines for the management of knee osteoarthritis, the American College of Rheumatology (ACR) guidelines (concerning also hip and hand osteoarthritis) and the algorithm recommendations by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). This is particularly evident for the drug class of symptomatic slow-acting drugs in osteoarthritis. In this paper, we highlight these differences and try to understand where they derive from, proposing an evidence-based interpretation. © 2015 All rights reserved: reproduction in whole or part not permitted.


Villalvilla A.,Bone and Joint Research Unit | Gomez R.,Northumbria University | Roman-Blas J.A.,Bone and Joint Research Unit | Largo R.,Bone and Joint Research Unit | Herrero-Beaumont G.,Bone and Joint Research Unit
Expert Opinion on Therapeutic Targets | Year: 2014

Introduction: Stromal cell-derived factor 1 (SDF-1) is a potent chemoattractant cytokine with various biological functions such as stem cell mobilization, inflammatory cell infiltration and angiogenesis. Therefore, it has also been implicated in several pathological processes, from ischemic conditions to cancer. Remarkably, SDF-1 and its receptors, CXCR4 and CXCR7, are also present in joint tissues, where they play a role in the pathogenesis of rheumatoid arthritis (RA) and osteoarthritis (OA). Areas covered: This review summarizes the physiological and pathological role of SDF-1 signaling and its involvement in RA and OA. That includes synovial inflammation, bone erosion, cartilage degradation and increased bone turnover. Although this cytokine could play different roles in these rheumatic diseases, specific and differentiated therapeutic targets in each process can be identified. Current therapeutic strategies to block SDF-1 signaling in several diseases and their possible use in rheumatic diseases are also discussed. Expert opinion: Emerging drugs that block CXCR4 or CXCR7 in different disorders may represent promising therapies for rheumatic disease via inhibition of key pathological events involved in the progression of RA and OA. © 2014 Informa UK, Ltd.


PubMed | Bone and Joint Research Unit
Type: Journal Article | Journal: Expert opinion on therapeutic targets | Year: 2014

Stromal cell-derived factor 1 (SDF-1) is a potent chemoattractant cytokine with various biological functions such as stem cell mobilization, inflammatory cell infiltration and angiogenesis. Therefore, it has also been implicated in several pathological processes, from ischemic conditions to cancer. Remarkably, SDF-1 and its receptors, CXCR4 and CXCR7, are also present in joint tissues, where they play a role in the pathogenesis of rheumatoid arthritis (RA) and osteoarthritis (OA).This review summarizes the physiological and pathological role of SDF-1 signaling and its involvement in RA and OA. That includes synovial inflammation, bone erosion, cartilage degradation and increased bone turnover. Although this cytokine could play different roles in these rheumatic diseases, specific and differentiated therapeutic targets in each process can be identified. Current therapeutic strategies to block SDF-1 signaling in several diseases and their possible use in rheumatic diseases are also discussed.Emerging drugs that block CXCR4 or CXCR7 in different disorders may represent promising therapies for rheumatic disease via inhibition of key pathological events involved in the progression of RA and OA.


PubMed | Institute IDIS, IIS Fundacion Jimenez Diaz and Bone and Joint Research Unit
Type: | Journal: Maturitas | Year: 2016

Despite the high prevalence of osteoarthritis (OA) in postmenopausal women, a relationship between circulating estrogen levels and the development of OA has not been found. Therefore, the purpose of this study was to evaluate the expression and activity of aromatase, a key enzyme in local production of estrogens, in human OA cultured articular chondrocytes, and to determine the physiological relevance of this enzyme in cartilage.Human OA articular chondrocytes were isolated and cultured. Local production of estradiol was measured after incubation with 100 ng/ml testosterone for 8 and 24h. Furthermore, chondrocytes were culture for 2h, 48 h, 7 days or 15 days, or in alginate beads for 10 days. Aromatase, type II and X collagen, aggrecan, alkaline phosphatase, and Runx2 expression were evaluated in cartilage, freshly isolated chondrocytes and cultured chondrocytes.Aromatase was expressed and active in cultured human chondrocytes. Human cartilage, freshly isolated chondrocytes, and chondrocytes cultured for 2h expressed an insignificant amount of aromatase; however, expression arose after 48 h of culture and remained increased thereafter. Aromatase expression was not related to estrogen deprivation and was inversely correlated with differentiation. Re-differentiation did not reduce its expression.Aromatase presents an almost undetectable expression in human cartilage but is induced in cultured chondrocytes. Therefore, human cartilage might act as a mere target for estrogens rather than a producer, and researchers using cell expansion in culture for latter therapies should consider these changes in estrogen metabolism which may not be reverted after re-differentiation.

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