Pathologies du genou : de la clinique aux traitements locaux et à la prothèse du genou

National audienceNe rêvons pas : on ne sait pas très bien expliquer l’étymologie du mot genou. Mécaniquement, la racine indo-européenne *gen conduit à « articulation » ou « angle » ; le terme goniomètre en est issu. Plus poétiquement, dans les langues indo-européennes, le mot genou pourrait être issu de la racine *gne-, *gen(e) qui donne à la fois : naître (latin gignere, grec γίγνɛσθαι) selon l’usage ancien de faire reconnaître le nouveau-né en le mettant sur les genoux de son père [1] ; connaître (γιγνωσκω), la connaissance étant une deuxième naissance

Miscellaneous non-inflammatory musculoskeletal conditions. Rare thesaurismosis and xanthomatosis.

International audienceThe focus will be on xanthomatosis, a tissue danger signal which needs to be recognized by the clinician, and its relationship with monogenetic lipoprotein disorders (cholesterol, triglycerides), bile acid and sterol metabolism, particularly on metabolic pathways and genetics as well as on musculoskeletal and cardiovascular involvement, and their implications for clinical management. The critical question is to assess coronary heart disease risk, requiring correct identification of the pattern of lipoprotein disorders and of the causes (primary or secondary). Familial hypercholesterolemia must be suspected in adults and children with raised total cholesterol, especially when there is a personal or a family history of premature coronary heart disease, usually requiring potent statins to achieve adequate LDL-cholesterol lowering, even if we do not know safety of long-term therapy and whether treatments of dyslipidemia early in life prevent cardiovascular diseases in adulthood. Cerebrotendinous xanthomatosis is a treatable disease and must be suspected if there is a history of infantile chronic diarrhea and/or juvenile cataracts, even in the absence of tendon xanthomas. Current evidence for the prevention and screening, diagnosis, and treatment of dyslipidemia are available for the clinicians

Douleurs latérales mécaniques du genou

National audienceLateral knee pain is a common presenting complaint with many possible causes. History and physical examination can decrease imaging indication and narrow the possible causes explained by an articular (lateral knee osteoarthritis, patellofemoral syndrome, proximal tibiofibular joint, lateral meniscus tear, discoid lateral meniscus), a musculotendinous (iliotibial band syndrome, biceps femoris, popliteus syndrome) or an osseous origin (osteonecrosis, complex regional pain syndrome, stress fracture…). Referred pain resulting from hip joint pathology, L4 or L5 radiculopathy also may cause lateral knee pain.Les douleurs latérales du genou constituent un motif de consultation fréquent avec de nombreuses causes. L’interrogatoire et l’examen clinique peuvent limiter les indications de l’imagerie et réduire le nombre de causes possibles expliquées par une origine articulaire (arthrose fémoro-tibiale latérale, syndrome fémoro-patellaire, articulation tibiofibulaire supérieure, ménisque latéral, discoïde), abarticulaire (syndrome de la bandelette iliotibiale, tendinopathie bicipitale, poplitée) ou osseuse (ostéonécrose, syndrome régional douloureux complexe, fractures de fatigue). Les douleurs référées résultant d’une coxopathie, d’une radiculopathie L4 ou L5 peuvent aussi être responsables de douleurs latérales du genou

Trabecular bone microarchitecture is related to the number of risk factors and etiology in osteoporotic men.

International audienceMicroarchitecture of trabecular bone is a very important component of bone quality in osteoporosis and a determinant of vertebral fracture in men with low bone mineral density (BMD). In contrast to women, male osteoporosis is, in most cases, secondary. The relationships between microarchitecture and different risk factors have never been evaluated in men. About 152 men with low BMD at the lumbar spine or hip (BMD, T-score < -2.5) were included in this study. Risk factors were: age, BMI, alcohol intake, corticosteroid therapy, hypogonadism, and chronic diseases. Transiliac bone biopsies were obtained and histomorphometry was done on an image analyzer; the following parameters were measured: cortical thickness (Ct.Th), trabecular bone volume (BV/TV), trabecular thickness (Tb.Th), separation (Tb.Sp) and number (Tb.N), interconnectivity Index (ICI), star volume of the bone marrow, and strut analysis with node and free-end count. The 50 men with two risk factors had a lower BMD, lower Ct.Th and a significant higher star volume than those with one factor or idiopathic osteoporosis. The 26 men with at least three risk factors, had a lower BMD, a reduction of BV/TV and Ct.Th and a marked disorganization of the trabecular network (increased Tb.Sp, ICI, star volume, and free-end to free-end struts). The prevalence of vertebral fractures was higher in these patients. When the main risk factor was considered, a marked decrease in trabecular bone connectivity was observed in hypogonadic men. In osteoporotic men, higher the number of risk factors, lower the connectivity of trabecular network and higher the vertebral fracture risk

Bone status in a mouse model of genetic hemochromatosis.

International audienceUNLABELLED: Genetic hemochromatosis is a cause of osteoporosis; mechanisms leading to iron-related bone loss are not fully characterized. We assessed the bone phenotype of HFE (-/-) male mice, a mouse model of hemochromatosis. They had a phenotype of osteoporosis with low bone mass and alteration of the bone microarchitecture. INTRODUCTION: Genetic hemochromatosis is a cause of osteoporosis. However, the mechanisms leading to iron-related bone loss are not fully characterized. Recent human data have not supported the hypothesis of hypogonadism involvement. The direct role of iron on bone metabolism has been suggested. METHODS: Our aim was to assess the bone phenotype of HFE (-/-) male mice, a mouse model of human hemochromatosis, by using microcomputed tomography and histomorphometry. HFE (-/-) animals were sacrificed at 6 and 12 months and compared to controls. RESULTS: There was a significant increase in hepatic iron concentration and bone iron content in HFE (-/-) mice. No detectable Perls' staining was found in the controls' trabeculae. Trabecular bone volume (BV/TV) was significantly lower in HFE (-/-) mice at 6 and 12 months compared to the corresponding wild-type mice: 9.88 ± 0.82% vs 12.82 ± 0.61% (p = 0.009) and 7.18 ± 0.68% vs 10.4 ± 0.86% (p = 0.015), respectively. In addition, there was an impairment of the bone microarchitecture in HFE (-/-) mice. Finally, we found a significant increase in the osteoclast number in HFE (-/-) mice: 382.5 ± 36.75 vs 273.4 ± 20.95 ¢/mm(2) (p = 0.004) at 6 months and 363.6 ± 22.35 vs 230.8 ± 18.7 ¢/mm(2) (p = 0.001) at 12 months in HFE (-/-) mice vs controls. CONCLUSION: Our data show that HFE (-/-) male mice develop a phenotype of osteoporosis with low bone mass and alteration of the microarchitecture. They suggest that there is a relationship between bone iron overload and the increase of the osteoclast number in these mice. These findings are in accordance with clinical observations in humans exhibiting genetic hemochromatosis and support a role of excess iron in relation to genetic hemochromatosis in the development of osteoporosis in humans

Hyperferritinemia increases the risk of hyperuricemia in HFE-hereditary hemochromatosis

International audienceObjectives: Hyperuricemia is becoming increasingly frequent in the population, and is known to besometimes the cause of gout. The impact of uric acid is still not clearly understood, however. The ironmetabolism may interact with the uric acid metabolism. The aim of this study was to examine the relationship between the serum uric acid and serum ferritin levels in a cohort of hemochromatosis patientswho were homozygous for the HFE p. Cys282Tyr mutation. Methods: 738 patients with the HFE gene mutation Cys282Tyr in the homozygous state were includedin the study. The variables measured during the initial evaluation were compared in univariate analysisby Student's t test. In multivariate analysis, linear stepwise regression was used. Results: In the group of hyperuricemic patients, ferritinemia was significantly higher than in the group ofnonhyperuricemic patients (1576.7 +/- 1387.4 mu g/l vs. 1095.63 +/- 1319.24 mu g/l, P < 0.005). With multivariate analysis, only ferritin and BMI independently explained the uricemia (R-2= 0.258) after adjustmentfor age, glycemia and CRP. The correlation between uricemia and log(ferritin) with partial regressioncorrelation coefficients was 0.307 (P < 0.01). Conclusions: The increase in uricemia is associated with the increase in ferritin in a population of patientswho were homozygous for the HFE gene mutation p. Cys282Tyr and this independently of factors commonly associated with hyperuricemia. The increase in uric acid associated with hyperferritinemia, couldbe a response to the visceral toxicity of excess non-transferrin bound iron linked to oxidative stress viathe antioxidant properties of uric acid. (C) 2016 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved

Iron excess limits HHIPL-2 gene expression and decreases osteoblastic activity in human MG-63 cells.

International audienceIn order to understand mechanisms involved in osteoporosis observed during iron overload diseases, we analyzed the impact of iron on a human osteoblast-like cell line. Iron exposure decreases osteoblast phenotype. HHIPL-2 is an iron-modulated gene which could contribute to these alterations. Our results suggest osteoblast impairment in iron-related osteoporosis. INTRODUCTION: Iron overload may cause osteoporosis. An iron-related decrease in osteoblast activity has been suggested. METHODS: We investigated the effect of iron exposure on human osteoblast cells (MG-63) by analyzing the impact of ferric ammonium citrate (FAC) and iron citrate (FeCi) on the expression of genes involved in iron metabolism or associated with osteoblast phenotype. A transcriptomic analysis was performed to identify iron-modulated genes. RESULTS: FAC and FeCi exposure modulated cellular iron status with a decrease in TFRC mRNA level and an increase in intracellular ferritin level. FAC increased ROS level and caspase 3 activity. Ferroportin, HFE and TFR2 mRNAs were expressed in MG-63 cells under basal conditions. The level of ferroportin mRNA was increased by iron, whereas HFE mRNA level was decreased. The level of mRNA alpha 1 collagen type I chain, osteocalcin and the transcriptional factor RUNX2 were decreased by iron. Transcriptomic analysis revealed that the mRNA level of HedgeHog Interacting Protein Like-2 (HHIPL-2) gene, encoding an inhibitor of the hedgehog signaling pathway, was decreased in the presence of FAC. Specific inhibition of HHIPL-2 expression decreased osteoblast marker mRNA levels. Purmorphamine, hedgehog pathway activator, increased the mRNA level of GLI1, a target gene for the hedgehog pathway, and decreased osteoblast marker levels. GLI1 mRNA level was increased under iron exposure. CONCLUSION: We showed that in human MG-63 cells, iron exposure impacts iron metabolism and osteoblast gene expression. HHIPL-2 gene expression modulation may contribute to these alterations. Our results support a role of osteoblast impairment in iron-related osteoporosis

Predictive value of tender joints compared to synovitis for structural damage in rheumatoid arthritis

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Comparison of ACR 1987 and ACR/EULAR 2010 criteria for predicting a 10-year diagnosis of rheumatoid arthritis.

International audienceOBJECTIVE: To compare the diagnostic accuracy of the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) and 1987 ACR criteria for rheumatoid arthritis (RA) in a cohort of patients with recent-onset arthritis followed-up for 10 years. METHODS: One hundred and sixty-four patients with recent-onset arthritis of less than 1 year's duration were included prospectively between 1995 and 1997. The diagnosis of RA was defined as having a diagnosis of RA made by the office-based rheumatologist 10 years after enrolment. We compared the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the criteria sets at baseline. RESULTS: At baseline, 60 of the 164 patients had alternative diagnoses better explaining the arthritis and 13 had erosions typical for RA; of the 91 remaining patients, 33 had at least 6 ACR/EULAR points (indicating definite RA), and 58 had fewer than 6 points. The ACR/EULAR criteria had a quite similar sensitivity than the 1987 ACR criteria (33/57 [57.9%] for ACR/EULAR criteria vs 34/57 [59.6%] for the 1987 ACR criteria), but higher specificity, PPV, and NPV (95/107 [88.8%], 34/46 [73.9%], and 95/118 [80.5%], respectively) than the 1987 ACR criteria (80/107 [74.8%], 33/63 [52.4%], and 80/104 [76.9%], respectively). CONCLUSION: ACR/EULAR criteria performed substantially better than ACR 1987 criteria for predicting a diagnosis of RA after 10 years. Much of the improvement was ascribable to the use of exclusion criteria. BULLET POINTS: (1) The ACR/EULAR criteria had the same sensitivity, but higher specificity, PPV, and NPV than the 1987 ACR criteria; (2) Much of the improvement was ascribable to the use of exclusion criteria