Jordi Carbonell

Effect of alendronate on cultured normal human osteoblasts

Alendronate is an aminobisphosphonate with a potent anti-reabsorptive action that does not appear to interfere with bone mineralization, and is even able to increase bone mineral density in osteoporotic postmenopausal women through a still not fully understood mechanism. This study was conducted to assess the direct effect of alendronate on diverse aspects of normal human osteoblast physiology. For that purpose, the in vitro effect of a wide range of concentrations [from 10(-1) to 10(-12) mol/L] of alendronate on cell viability, proliferation, collagen synthesis, and the mineral-depositing capacity of normal human osteoblasts was tested. Alendronate effects were examined at 48 and 96 h of culture in the presence or absence of fetal calf serum. In vitro alendronate affected osteoblast viability at concentrations equal to or higher than 10(-4) mol/L. At concentrations equal to or higher than 10(-3) mol/L, no viable cells were observed in cultures. In vitro alendronate at concentrations between 10(-5) and 10(-12) mol/L did not have any effect on the proliferative capacity of normal human osteoblasts determined by two different techniques: (1) tritiated thymidine incorporation to DNA and (2) cell counting. Collagen synthesis by normal human osteoblasts showed a tendency to decrease following incubation with alendronate supplemented with fetal calf serum. This decrease was only statistically significant after 96 h of culture; however, a dose-response effect could not be documented. Finally, no effect of alendronate was observed on calcium deposition in vitro by normal human osteoblasts at concentrations equal to or lower than 10(-5) mol/L. In conclusion, the present study shows that alendronate in vitro does not affect viability, proliferation, and mineral deposit capacity of normal human osteoblasts at the concentration at which it inhibits by 50% the resorptive capacity of osteoclasts that for this drug has been reported as 2 x 10(-9) mol/L.

Cannabis use in patients with fibromyalgia: effect on symptoms relief and health-related quality of life.

Background The aim of this study was to describe the patterns of cannabis use and the associated benefits reported by patients with fibromyalgia (FM) who were consumers of this drug. In addition, the quality of life of FM patients who consumed cannabis was compared with FM subjects who were not cannabis users. Methods Information on medicinal cannabis use was recorded on a specific questionnaire as well as perceived benefits of cannabis on a range of symptoms using standard 100-mm visual analogue scales (VAS). Cannabis users and non-users completed the Fibromyalgia Impact Questionnaire (FIQ), the Pittsburgh Sleep Quality Index (PSQI) and the Short Form 36 Health Survey (SF-36). Results Twenty-eight FM patients who were cannabis users and 28 non-users were included in the study. Demographics and clinical variables were similar in both groups. Cannabis users referred different duration of drug consumption; the route of administration was smoking (54%), oral (46%) and combined (43%). The amount and frequency of cannabis use were also different among patients. After 2 hours of cannabis use, VAS scores showed a statistically significant (p<0.001) reduction of pain and stiffness, enhancement of relaxation, and an increase in somnolence and feeling of well being. The mental health component summary score of the SF-36 was significantly higher (p<0.05) in cannabis users than in non-users. No significant differences were found in the other SF-36 domains, in the FIQ and the PSQI. Conclusions The use of cannabis was associated with beneficial effects on some FM symptoms. Further studies on the usefulness of cannabinoids in FM patients as well as cannabinoid system involvement in the pathophysiology of this condition are warranted.

Cluster analysis of clinical data identifies fibromyalgia subgroups.

Introduction Fibromyalgia (FM) is mainly characterized by widespread pain and multiple accompanying symptoms, which hinder FM assessment and management. In order to reduce FM heterogeneity we classified clinical data into simplified dimensions that were used to define FM subgroups. Material and Methods 48 variables were evaluated in 1,446 Spanish FM cases fulfilling 1990 ACR FM criteria. A partitioning analysis was performed to find groups of variables similar to each other. Similarities between variables were identified and the variables were grouped into dimensions. This was performed in a subset of 559 patients, and cross-validated in the remaining 887 patients. For each sample and dimension, a composite index was obtained based on the weights of the variables included in the dimension. Finally, a clustering procedure was applied to the indexes, resulting in FM subgroups. Results Variables clustered into three independent dimensions: “symptomatology”, “comorbidities” and “clinical scales”. Only the two first dimensions were considered for the construction of FM subgroups. Resulting scores classified FM samples into three subgroups: low symptomatology and comorbidities (Cluster 1), high symptomatology and comorbidities (Cluster 2), and high symptomatology but low comorbidities (Cluster 3), showing differences in measures of disease severity. Conclusions We have identified three subgroups of FM samples in a large cohort of FM by clustering clinical data. Our analysis stresses the importance of family and personal history of FM comorbidities. Also, the resulting patient clusters could indicate different forms of the disease, relevant to future research, and might have an impact on clinical assessment.

Rapid reduction in tenosynovitis of the wrist and fingers evaluated by MRI in patients with rheumatoid arthritis after treatment with etanercept

Objective To assess the efficacy of etanercept in reducing tenosynovitis evaluated by MRI of the hand (h-MRI) in patients with active rheumatoid arthritis (RA) refractory to disease-modifying antirheumatic drug (DMARD) after 6 weeks of treatment. Methods 31 patients with active RA defined by a disease activity score (DAS28) >3.2 and synovitis in the hands were randomised into two groups: 19 patients received 50 mg weekly subcutaneous etanercept added to previous DMARD treatment and 12 patients continued with previous DMARD therapy. Clinical evaluation, blood tests, functional capacity evaluation and h-MRI were performed at the start of the investigation and at week 6. Tenosynovitis was evaluated on T1-weighted sequences with fat suppression after gadolinium as the presence of a peritendinous signal enhancement on axial images using a new method including wrist and finger tendons. The reliability, sensitivity to change and responsiveness of this method were also evaluated. Results Scores for tenosynovitis showed a significant reduction in the etanercept group compared with placebo (p=0.01) after 6 weeks of treatment. Adding MRI joint synovitis to tenosynovitis scores gave an even higher significant reduction in the etanercept group (p=0.007). A positive and statistically significant correlation between tenosynovitis and DAS28, erythrocyte sedimentation rate and C-reactive protein was found, but not with functional capacity. Responsiveness for tenosynovitis was small but was higher when joint synovitis scores were added. Conclusion Addition of etanercept significantly reduced MRI tenosynovitis of the wrist and fingers in patients with active RA refractory to DMARD treatment. The method of scoring tenosynovitis showed good reliability and moderate responsiveness.

Bone metabolism and histomorphometric changes in rheumatoid arthritis

Objective : We studied bone metabolism and histomorphometry in 66 patients with rheumatoid arthritis. Methods : Cross-sectional study. Results : BMD at the forearm but not at the lumbar spine was decreased. Age, body mass index and fibrinogen correlated significantly with decreased BMD, whereas age and disease duration were predictors of vertebral fractures. Biochemical parameters were normal but 25 vitamin D levels were markedly reduced. There were significant decreases in bone volume, mean wall thickness, mineral apposition rate (with highly prolonged mineralisation lag time), number of osteoclasts, and osteoclast surface, and increases in resorption surfaces. Mean plate trabecular separation and density were also deeply affected. Conclusions : Patients with rheumatoid arthritis showed a reduced bone volume and decreased bone turnover, which is further aggravated by microarchitectural deterioration stressing the severe osteoporosis associated with the disease. These findings are consistent with the effect of hypovitaminosis D and low values of vitamin D in serum.

La atención de los médicos hacia el cuidado de su propia salud. Resultados de una encuesta postal

Objetivo Examinar las actitudes de los medicos en relacion al cuidado de su salud, tanto en el campo de las medidas preventivas como en caso de enfermedad. Participantes y metodo Se envio un cuestionario postal estructurado a una muestra representativa de los medicos colegiados en la provincia de Barcelona seleccionada aleatoriamente por grupos de edad, genero, residencia y forma de ejercicio (n = 795). Resultados Contesto la encuesta el 34% de los medicos seleccionados. La mitad de los encuestados (49%) reconoce no tener medico de cabecera y solo el 33% utiliza el que le corresponde en la Seguridad Social. El 48% carece de historia clinica. Es frecuente (52%) consultar a distintos companeros ante cualquier problema de salud. Solo el 48% sigue las indicaciones del medico que ha consultado y el 82% se automedica de modo habitual. En relacion con las actitudes preventivas, el 47% no efectua los examenes de salud que ofrece el centro de trabajo y el 19,5% de los que si se someten a ellos no sigue las recomendaciones propuestas. Conclusiones Una elevada proporcion de medicos adopta actitudes inadecuadas en relacion con el cuidado de su salud, lo que hace recomendable una reflexion en la propia profesion sobre la necesidad de cambiar estos comportamientos.

Enfermedad ósea de Paget: estudio de 314 pacientes

Fundamento Describir las caracteristicas clinicas y analiticas de los pacientes con enfermedadosea de Paget en el momento del diagnostico. Pacientes y metodo Estudio multicentrico y retrospectivo que ha incluido a 314 pacientes. Eldiagnostico se realizo mediante gammagrafia con polifosfato de 99Tc y radiografia simple. Seanalizaron los datos epidemiologicos, motivo del diagnostico, huesos afectados, grado de extensionmediante el indice de Coutris, complicaciones durante la evolucion y actividad de la enfermedadcon el indice de Renier. Los resultados se han analizado con el paquete estadisticoSPSS. Resultados Ciento cincuenta y nueve (50,5%) eran varones y la media (DE) de edad de 64,9(12,6) anos; en 288 (72,6%) el diagnostico fue casual y 201 (63,9%) presentaron una enfermedadpoliostotica; las localizaciones mas frecuentes fueron el hueso coxal, craneo y columnalumbar. La afectacion del sacro fue mas frecuente en el varon que en la mujer (p Conclusiones Aunque con frecuencia la enfermedad de Paget es asintomatica, en el momentodel diagnostico se presenta en muchas ocasiones de forma poliostotica y activa. El conocimientode la extension y la actividad de la enfermedad mediante una simple formula matematicason utiles para tomar una decision terapeutica.

Genome-wide analysis of single nucleotide polymorphisms and copy number variants in fibromyalgia suggest a role for the central nervous system.

Summary Variants in NRXN3 and MYT1L are associated with fibromyalgia. Our results point to a role for the central nervous system in susceptibility to fibromyalgia. ABSTRACT Fibromyalgia (FM) is a highly disabling syndrome defined by a low pain threshold and a permanent state of pain. The mechanisms explaining this complex disorder remain unclear, and its genetic factors have not yet been identified. With the aim of elucidating FM genetic susceptibility factors, we selected 313 FM cases having low comorbidities, and we genotyped them on the Illumina 1 million duo array. Genotypic data from 220 control women (Illumina 610k array) was obtained for genome‐wide association scan (GWAS) analysis. Copy number variants in FM susceptibility were analyzed by array comparative genomic hybridization (aCGH) experiments on pooled samples using the Agilent 2 × 400K platform. No single nucleotide polymorphism (SNP) reached GWAS association threshold, but 21 of the most associated SNPs were chosen for replication in 952 cases and 644 controls. Four of the SNPs selected for replication showed a nominal association in the joint analysis, and rs11127292 (MYT1L) was found to be associated to FM with low comorbidities (P = 4.28 × 10−5, odds ratio [95% confidence interval] = 0.58 [0.44–0.75]). aCGH detected 5 differentially hybridized regions. They were followed up, and an intronic deletion in NRXN3 was demonstrated to be associated to female cases of FM with low levels of comorbidities (P = .021, odds ratio [95% confidence interval] = 1.46 [1.05–2.04]). Both GWAS and aCGH results point to a role for the central nervous system in FM genetic susceptibility. If the proposed FM candidate genes were further validated in replication studies, this would highlight a neurocognitive involvement in agreement with latest reports.

Screening for the presence of FMR1 premutation alleles in women with fibromyalgia

Fibromyalgia is a chronic condition characterized by widespread pain, fatigue, non-restorative sleep and cognitive difficulties that affects 2-4% of the general population. Recently a possible relationship between the FMR1 premutation and fibromyalgia has been pointed out. In attempt to gather more data we screened for the FMR1 CGG expansion 700 DNA samples from unrelated fibromyalgia patients. This data might be useful for evaluating the incorporation of this test in rheumatologic procedures for women with fibromyalgia. The observed frequency of FMR1 premutation carriers (3 of 700, 0.4%) is not significantly different from the estimated rate in the general female population (1/250-1/400) (P=0.539, P=0.716). Clinical examination of the FMR1 premutation carriers identified revealed that all of them had important neurological symptoms with regard to muscular symptoms, neurocognitive alterations and neurovegetative impairments. With regard to other clinical aspects of the disease the cases apparently did not differ from the average fibromyalgia patients. On the basis of our results an FMR1 screening among fibromyalgia female patients would not be recommended. However it would be worthwhile to further evaluate the different clinical presentations that fibromyalgia patients might present based on their FMR1 premutation carrier status.

Self-reported screening questionnaire for the assessment of Joint Hypermobility Syndrome (SQ-CH), a collagen condition, in Spanish population

Background and Objectives: To develop a self-assessment screening ques- tionnaire (SQ-CH), with image illustrated criteria to easily identify collagen anomalies and to assist Hypermobility�s evaluation in a Spanish sample. Methods: One hundred ninety one participants were recruited form an anxiety outpa- tient unit of a general university hospital and from a primary care setting, underwent a complete and rigorous evaluation of hypermobility. First, all participants completed the self-reported measures for the screening of Hypermobility Syndrome, the 7 self-reported items in y/n format aiming to validate (SQ-CH) and the 5 item self-reporting questionnaire of Hakim and Grahame (2003). Secondly, each of the participants was individual assessed by a trained clinician on the Beighton and Hospital del Mar evaluation for the diagnosis of Joint Hypermobility Syndrome. Results : Significant correlations were found between the SQ-CH and the Beighton and Hospital del Mar scales as well as with the 5-item self-reporting questionnaire. Results on temporal stability, specificity and sensitivity of the SQ-CH were satisfactory, and the best cut-off point was set at 3 positive items (i.e. answered affirmatively). Conclusions: The developed screening questionnaire for hypermobility (SQ-CH) is, to our knowledge, the first self-assessment questionnaire to evaluate the symptoms of the joint hypermobility syndrome in a Spanish population. It has shown good validity and good reliability and is therefore ready for its use as a screening tool to assess this collagen condition in all sort of potential suffers, particularly, patients suffering from anxiety.