[Show abstract][Hide abstract] ABSTRACT: Rheumatoid arthritis (RA) patients are at an increased risk of developing comorbid conditions. A close monitoring of the disease targeting a status of low disease activity is associated with a better outcome. The aim of this trial was to evaluate the impact of a nurse-led programme on comorbidities and the impact of patient self-assessment of disease activity on the management of RA.
[Show abstract][Hide abstract] ABSTRACT: Introduction: Oxytocin (OT), a neurohypophysial hormone regulated by estrogen and leptin, may play a role in bone metabolism in humans as suggested by animal studies. This study assess the relationship between OT and bone status in a large population of post menopausal women. Subjects and methods: Subjects were included in the Osteoporosis and Ultrasound study (OPUS), a 6-yr prospective study in a population-based cohort. Final visit data were used for this cross-sectional study. OT, leptin and estradiol serum levels were measured in 1097 post-menopausal women and compared with bone mineral density (BMD), fractures and the bone turnover markers (BTM) procollagen type 1 N-terminal propeptide (PINP), bone alkaline phosphatase (bone ALP) and C-telopeptide of type 1 collagen (CTX). Results: Median age was 70.8 years, 16% were osteoporotic, 48% osteopenic, and 29% had at least one fracture. OT serum level was related to spine (r=+0.12, p=0.0002) and total hip BMD (r=+0.21, p<0.0001) and with BTM (PINP: r=-0.13, p<0.0001, bone ALP: r=-0.07, p=0.02, CTX: r=-0.18, p<0.0001). The relationship of OT with BMD was independent of BTM. After adjustment for confounding factors, the correlation between OT serum level and BMD remains significant at the hip in women with unmeasureable oestradiol or leptin above the median value. There was no significant relationship between OT serum levels and fractures. Conclusion: High OT levels are associated with high BMD especially at the hip in women with low estradiol or high leptin serum levels. The mechanism may be explained by the effect of OT on bone turnover.
The Journal of clinical endocrinology and metabolism 01/2014; · 6.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chondrogenesis has been widely investigated in vitro using bone marrow-derived mesenchymal stromal cells (BM-MSCs) or primary chondrocytes. However, their use raises some issues partially circumvented by the availability of Adipose tissue-derived MSCs. Herein; we characterized the chondrogenic potential of human Multipotent Adipose-Derived Stem (hMADS) cells, and their potential use as pharmacological tool. hMADS cells are able to synthesize matrix proteins including COMP, Aggrecan and type II Collagen. Furthermore, hMADS cells express BMP receptors in a similar manner to BM-MSC, and BMP6 treatment of differentiated cells prevents expression of the hypertrophic marker type X Collagen. We tested whether IL-1β and nicotine could impact chondrocyte differentiation. As expected, IL-1β induced ADAMTS-4 gene expression and modulated negatively chondrogenesis while these effects were reverted in the presence of the IL-1 receptor antagonist. Nicotine, at concentrations similar to those observed in blood of smokers, exhibited a dose dependent increase of Aggrecan expression, suggesting an unexpected protective effect of the drug under these conditions. Therefore, hMADS cells represent a valuable tool for the analysis of in vitro chondrocyte differentiation and to screen for potentially interesting pharmacological drugs.
Biochemical and Biophysical Research Communications 10/2013; · 2.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several markers of comorbidities and cardiovascular (CV) risk are disturbed in moderate to severe psoriasis (PsO). The effect of systemic treatments of psoriasis on these markers remains poorly understood.
To study the frequency of disturbance of inflammatory parameters and markers of comorbidities and CV risk associated with moderate to severe PsO and psoriatic arthritis (PsA), and to assess their evolution under systemic treatments.
Monocentric prospective study on patients with PsO and PsA starting a systemic treatment for their psoriasis. The following markers were evaluated at baseline (M0), 3 months (M3) and 6 months (M6); weight, fasting blood glucose, blood pressure, uric acid, hepatic steatosis, smoking, lipid, metabolic and inflammatory parameters.
Forty-three patients, 31 PsO and 12 PsA, were included. Forty completed the study. Response to treatment was good, with 71% of the population obtaining a Psoriasis Area and Severity Index (PASI) of 75. All patients had at least one comorbidity, and 45% had two or more. A statistically significant decrease was observed only for inflammatory parameters (C-reactive protein [CRP], P = 0.004) and erythrocyte sedimentation rate (ESR, P = 0.002). We did not observe any correlation between the PASI and CRP (correlation coefficient 0.128, P = 0.438) or ESR (correlation coefficient 0.294, P = 0.069) for responding patients.
We observed a high frequency of disturbance of inflammatory parameters and markers of comorbidities and CV risk in a population with moderate to severe PsO and PsA, most of which were not detected before. A significant decrease in inflammatory parameters was noted after the introduction of systemic therapy, while other parameters remained unaffected by the treatment, except the weight that increased under biologics therapies.
Journal of the European Academy of Dermatology and Venereology 08/2013; · 2.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Osteoporosis is particularly frequent in subjects suffering from chronic obstructive pulmonary disease (COPD) and asthma, because they share numerous common risk factors: aging (for COPD), smoking, vitamin D deficiency, inactivity, muscular weakness, systemic inflammation, are an integral part of the physiopathology of COPD and asthma. Oral corticosteroid used in the severe forms of COPD and asthma contribute to the risk of osteoporosis in these frail patients and the application of the guidelines for steroid-induced osteoporosis is crucial. Inhaled corticosteroid, basis of asthma treatment and also used in some forms of COPD, has a less clear impact on bone status; however recent publications are in favour of a moderate effect, but long-term studies are necessary at these patients with long term treatments. Finally, severe kyphosis related to multiple vertebral ribs and sternal fractures can contribute to an alteration of respiratory function. The management of these patients is based on a global evaluation of fracture risk including the risk factors of osteoporosis and the measure bone mineral density, the non pharmacological measures of the osteoporosis treatment, vitamin D supplementation often required and, if needed, specific drugs of osteoporosis. This review emphasizes the need to increase vigilance of practitioners about the risk of osteoporosis in COPD and asthma.
Revue du Rhumatisme Monographies 04/2013; 80(2):136–140.
[Show abstract][Hide abstract] ABSTRACT: Objectifs
Cette étude visait à décrire la prévalence de l’arthrose du genou ou de la hanche, l’histoire naturelle de la maladie, ainsi que les facteurs pronostiques de son développement et les éléments déterminant le coût et l’accès aux soins pour une cohorte de patients en France.
Les sujets âgés de 40 à 75 ans, souffrant d’arthrose symptomatique du genou et/ou de la hanche uni- ou bilatérales (confirmées par les critères de l’ACR), au stade 2 ou supérieur dans la classification de Kellgren & Lawrence (KL), ont été recrutés à partir d’une enquête de prévalence en population générale pour constituer la cohorte multicentrique KHOALA. Les données de base collectées incluaient les données sociodémographiques et cliniques ; les scores WOMAC, IKS et Harris pour la douleur et la fonction ; le score MAQ pour l’activité physique ; l’index de comorbidité fonctionnelle ; le score GHQ28 pour le statut psychologique ; et les scores SF-36 (générique) et OAKHQOL (spécifique) pour l’évaluation de la qualité de vie. Des échantillons de sang et d’urine ont été collectés.
Huit-cent-soixante-dix-huit personnes ont été incluses, 222 atteintes d’arthrose de la hanche (âge moyen 61,2 ± 8,8 ans), 607 atteintes d’arthrose du genou (âge moyen 62,0 ± 8,5 ans) et 49 atteintes d’arthrose de la hanche et du genou (âge moyen 64,9 ± 7,9 ans). L’indice de masse corporelle (IMC) moyen était de 26,9 ± 4,5 pour les arthroses de la hanche et de 30,3 ± 6,3 pour les arthroses du genou. Les patients souffrant d’arthrose de la hanche et du genou avaient respectivement des index de comorbidité moyens de 1,99 et 2,06. La sévérité radiographique de la maladie pour des stades 2, 3 et 4 dans la classification de KL étaient, respectivement, de 69,8 %, 26,1 % et 4,1 % pour les arthroses de la hanche, et de 44,5 %, 30,3 %, et 25,2 % pour les arthroses du genou. En comparaison avec la population générale, les scores SF-36 standardisés selon l’âge et le sexe étaient fortement diminués pour les arthroses du genou et de la hanche dans toutes ses dimensions, particulièrement dans les dimensions physiques et émotionnelles.
Les patients vont être suivis annuellement, tour à tour par courrier et par une visite clinique. Cette cohorte, représentative de patients souffrant d’arthrose du genou et de la hanche, va être une opportunité pour de futures recherches collaboratives.
[Show abstract][Hide abstract] ABSTRACT: Phosphated diabetes are rare diseases, characterized by renal phosphate wasting, which results in hypophosphatemia, bone demineralization and osteomalacia. We review the pathophysiology of phosphate metabolism, revolutionized by the discovery of phosphatonines, particularly the FGF23, which sheds a new light on the various etiologies which are detailed: tumor-induced osteomalacia, genetic phosphate diabetes (X-linked hypophosphatemia, autosomal-dominant hypophosphatemic rickets, autosomal-recessive hypophosphatemic rickets, hypophosphatemic rickets with hypercalciuria, hypophosphatemia with nephrolithiasis by mutation of NPT2A and NHERF1), hyperparathyroidism, Fanconi syndrome and drug-induced phosphated diabetes. Diagnostic tools, improved by FGF23 dosage and treatment are also discussed.
Revue du Rhumatisme Monographies 09/2012; 79(4):253–257.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: This study aimed to describe the prevalence of symptomatic knee and hip osteoarthritis (OA) and its course over time, as well as identify prognostic factors of OA course and determinants of costs and access to care in France in a patient cohort. METHODS: Subjects aged 40 to 75 years, with uni- or bilateral symptomatic hip and/or knee OA (ACR criteria), Kellgren and Lawrence (KL) stage 2 or greater, were recruited from a French national prevalence survey for the multicenter KHOALA cohort study. Data collected at baseline included sociodemographic and clinical data; WOMAC, IKS and Harris scores for pain and function; MAQ score for physical activity; functional comorbidity index; GHQ28 score for psychological status; and SF-36 (generic) and OAKHQOL (specific) scores for quality of life. Blood and urine samples were collected. RESULTS: Eight hundred and seventy-eight subjects were included, 222 with OA of the hip (mean age 61.2±8.8 years), 607 knee (mean age 62.0±8.5 years) and 49 both hip and knee (mean age 64.9±7.9 years). Mean body mass index was 26.9±4.5 for hip OA and 30.3±6.3 for knee OA. Hip and knee OA patients had 1.99 and 2.06 comorbidities, on average, respectively. Disease severity on X-rays for KL stages 2, 3 and 4 for hip OA was 69.8, 26.1 and 4.1%, respectively, and for knee OA, 44.5, 30.3, and 25.2%. As compared with population norms, age- and sex-standardized SF-36 scores were greatly decreased for both knee and hip OA in all dimensions, particularly physical and emotional dimensions. PERSPECTIVES: Patients will be followed up annually, alternately by mail and clinical visit. This cohort of representative patients with knee and hip OA will be an opportunity for future collaborative research.
[Show abstract][Hide abstract] ABSTRACT: To assess the efficacy and safety of rituximab (RTX) in patients with refractory idiopathic inflammatory myopathies (IIMs).
RTX efficacy was based on improvement in three criteria: creatine phosphokinase (CPK) level, daily CS dose and physicians' opinion. A decrease in CPK level or CS dose was significant if it was >25%.
Thirty patients were studied (21 women; age 52.5 years, disease duration 6.1 years). All had previously received immunosuppressors (ISs). Twenty-five patients received 1 g of RTX twice 2 weeks apart and five received 4 weekly RTX infusions (375 mg/m(2)). RTX was given in association with IS in 21 patients. Twenty-eight patients received CS (mean dose 21.2 mg/day). Mean follow-up was 17.2 months. Thirteen adverse events were reported, including seven infections and one serious infection (pyelonephritis). RTX was effective in 16 patients. Duration of efficacy was 15.5 months. Of the 20 patients with baseline CPK level ≥2 × upper limit of normal (ULN), 11 (55%) improved. The main level fell from 20.7 to 11 × ULN. CS decreased in 15 patients, stopped in 4, remained stable in 8 and increased in the remaining 3. The CS dose decreased from 21.2 to 9.9 mg/day. The physicians' opinion was favourable in 21 patients. Manual muscle testing was performed in only five patients: it increased from 87 to 91/100 at 6 months.
RTX was well tolerated and had some beneficial effects on patients with IIM, the main limitation of this study resulted in a lack of manual muscle testing.
[Show abstract][Hide abstract] ABSTRACT: Osteoarthritis (OA) epidemiologic data are scarce in Europe. To estimate the prevalence of symptomatic knee and hip OA in a multiregional sample in France.
A two-phase population-based survey was conducted in six regions in 2007-2009. On initial phone contact using random-digit dialing, subjects 40-75 years old were screened with a validated questionnaire. Subjects screened positive were invited for ascertainment: physical examination and hip and/or knee radiography (Kellgren-Lawrence grade≥2). Multiple imputation for data missing not-at-random was used to account for refusals.
Of 63,232 homes contacted, 27,632 were eligible, 9621 subjects screened positive, 3707 participated fully in the ascertainment phase, and 1010 had symptomatic OA: 317 hip, 756 knee. Hip OA prevalence according to age class ranged from 0.9% to 3.9% for men and 0.7-5.1% for women. Knee OA ranged from 2.1% to 10.1% for men and 1.6-14.9% for women. Both differed by geographical region. The hip and knee standardized prevalence was 1.9% and 4.7% for men and 2.5% and 6.6% for women, respectively.
This confirmed the feasibility of using a screening questionnaire for eliciting population-based estimates of OA. In France, it increases with age and is greater among women above the age of 50. The geographical disparity of hip and knee OA parallels the distribution of obesity. Study registration ID number 906297 at http://www.clinicaltrials.gov/.
Osteoarthritis and Cartilage 08/2011; 19(11):1314-22. · 4.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is growing evidence that oxytocin, which regulates appetite, plays a role in bone remodelling and improves osteoporosis. We previously showed a significant decrease in circulating oxytocin levels in postmenopausal osteoporotic women compared to healthy controls. However, factors involved in the pathophysiology of osteoporosis, such as estrogens and leptin, are known to regulate oxytocin secretion. Herein, we evaluated the relationships between oxytocin and other hormonal factors known to regulate bone remodeling and body composition in postmenopausal osteoporotic women, compared to healthy controls.
In 20 postmenopausal women with severe osteoporosis compared to 16 healthy controls, we measured serum levels of oxytocin, high sensitive estradiol, testosterone, FSH, LH, SHBG, TSH, osteocalcin, serum type I collagen carboxy-terminal telopeptide, leptin. Bone mineral density and body composition were also measured with DXA.
Osteoporotic women had significantly lower oxytocin, leptin and LH serum levels and higher CTX and SHBG; all other biological parameters were similar in both groups. Fat mass and lean mass were significantly decreased in osteoporotic women. Oxytocin serum levels were significantly correlated to bone mineral density but not to any other measured parameter, including leptin, estradiol and age. In a logistic regression analysis, osteoporosis remained significantly correlated to oxytocin, regardless of age.
Low oxytocin serum levels appeared to be associated with severe osteoporosis, independently of other factors associated with osteoporosis or known to regulate oxytocin serum levels, such as estradiol or leptin, reinforcing the concept that oxytocin may be involved in the pathophysiology of postmenopausal osteoporosis.
[Show abstract][Hide abstract] ABSTRACT: Antidepressants but also neuroleptic drugs (NL) are widely used in the population. Their impact on bone health is not trivial. It varies according to the mechanism of action of each molecule. Firstly, depression by itself is associated with a decrease of bone mineral density (BMD) and an increased risk of fractures related to the pathophysiology of the disease and to lifestyle. Whereas only selective serotonin reuptake inhibitors (SSRI) lead to a decrease of BMD, all antidepressants (tricyclic antidepressants and SSRI) are associated with an increased risk of fall and fractures, mostly at peripheral sites. This risk is marked with the SSRI and rapidly decreases after treatment discontinuation. Typical NL block dopamine receptors, leading to hyperprolactinemia, which in turn could induce hypogonadism. Atypical NL act both on the dopamine and the serotonin pathways. They can induce hyperprolactinemia with various severities according to their affinity for dopamine receptors. Under NL, the decrease of BMD is directly related to the importance of hyperprolactinemia, underlining the interest of detecting signs of hypogonadism. Current treatment by NL comes along with an increased risk of fall and fractures as observed with antidepressants. This risk is more important for classical NL and disappears when the treatment is discontinued. An evaluation of the risk of fracture, including bone densitometry and the risk of fall, is a relevant question for patients with long-term treatment with these drugs.
Revue du Rhumatisme Monographies 01/2011; 78(2):76-80.
[Show abstract][Hide abstract] ABSTRACT: Objectif
Il est de plus en plus évident que l’ocytocine, qui régule l’appétit, joue un rôle dans le remodelage osseux et améliore l’ostéoporose. Nous avons déjà montré une diminution significative des taux d’ocytocine circulante au cours de l’ostéoporose post-ménopausique de la femme en comparaison à des sujets sains. Cependant, des facteurs impliqués dans la physiopathologie de l’ostéoporose, comme les œstrogènes et la leptine, sont connus pour réguler la sécrétion d’ocytocine. Ci-après, nous avons étudié les relations entre l’ocytocine et d’autres facteurs hormonaux connus pour réguler le remodelage osseux et la composition corporelle dans l’ostéoporose post-ménopausique de la femme, en comparaison à des sujets sains.
Chez 20 femmes post-ménopausées avec ostéoporose sévère comparées à 16 sujets sains contrôles, nous avons mesuré les taux sériques d’ocytocine, d’œstradiol par dosage hautement sensible, de testostérone, Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), Sex Hormone Binding Globulin (SHBG), Thyroid Stimulating Hormone (TSH), ostéocalcine, télopeptide N terminal du collagène de type I, leptine. La densité minérale osseuse et la composition corporelle étaient également déterminées par absorptiométrie biphotonique à rayons X (DXA).
Les femmes ostéoporotiques ont des taux sériques significativement plus faibles d’ocytocine, de leptine et de LH et des taux plus élevés de CTX et de SHBG ; tous les autres paramètres biologiques étaient similaires dans les deux groupes. La masse graisseuse et la masse maigre étaient significativement diminuées chez les femmes ostéoporotiques. Les taux sériques d’ocytocine étaient significativement corrélés à la densité minérale osseuse mais avec aucun autre paramètre mesuré, y compris la leptine, l’œstradiol et l’âge. Dans une analyse de régression logistique, l’ostéoporose demeurait significativement corrélée à l’ocytocine, indépendamment de l’âge.
De faibles taux sériques d’ocytocine semblent être associés à une ostéoporose sévère, indépendamment d’autres facteurs associés à l’ostéoporose ou connus pour réguler les taux sériques d’ocytocine, comme l’œstradiol ou la leptine, renforçant le concept selon lequel l’ocytocine peut être impliquée dans la physiopathologie de l’ostéoporose post-ménopausique.
Revue Du Rhumatisme - REV RHUM. 01/2011; 78(5):453-458.