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Background: Paget's disease of bone (PDB) is a disorder focussed on the bone with an increase in the number, size and activity of the osteoclasts. Some epidemiological data support the theory of its relationship with toxic or infectious environmental agents, whose interaction with some predisposing genetic alterations may lead to PDB. The glutathione S-transferases (GST) are involved in the metabolism of toxins, by catalysing the nucleophilic attack of the physiological substrate, reduced glutathione or GSH (g-Glu-Cys-Gly) on the electrophilic centre of a great number of toxic structures. We studied whether the variability of the GSTM1, GSTP1 and GSTT1 genes is related to the risk of developing PDB. Patients and methods: We analysed 148 patients diagnosed with PDB, and 207 control individuals matched in sex and age with no history of bone alterations. Using genomic DNA obtained from peripheral blood the presence-absence of the GSTM1 and GSTT1 genes was studied by means of multiplex PCR. The study of the Ile105Val GSTP1 gene was carried out using PCR and subsequent digestion with the restriction enzyme BsmAI. The distribution of genotypes was analysed by means of the Pearson chi-square test. When statistically significant differences were found we carried out a multivariate logistical regression to determine the risk which the presence of a particular genotype could generate. We used the CSPSS 21.0 program. Differences were considered to be statistically significant when the value of p<0.05. Results: We found differences in the distribution of the presence-absence of the deletion in the GSTM1 gene; not being a carrier for the deletion or being a heterozygous carrier in the GSTM1 gene confers a lower risk of developing PDB (OR=0.56, 95% CI: 0.36-0.87; p=0.011). In the study of the GSTT1 and GSTP1 genes there were no significant differences. Conclusion: The detoxifying activity diminishes when two copies of the GSTM1 gene with deletions are inherited by reducing in enzyme activity, which has been associated with a greater susceptibility to some cancers, alcoholic hepatopathy and other inflammatory problems. We are not aware of any description of its association with PDB. PDB is observed more frequently in carriers of the homozygous deletion in the GSTM1 gene. This fact could explain the epidemiological findings which link PDB to exposure to certain environmental agents.

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Background Ankylosing spondylitis (AS) is a chronic inflammatory disease that primarily affects the axial skeleton. It associated loss of vertebral and hips bone mineral density (BMD) due to inflammation. Both changes in biomechanical properties of the spine as decreased BMD condition increased bone fragility. The prevalence of vertebral fractures in clinical literature varies between 10-17%. Nonsteroidal antiinflammatory drugs (NSAIDs) are drugs with analgesic and anti-inflammatory effect considered the mainstay of treatment in AS. In Spain, data from the Registry of Spondyloarthopaties of the Spanish Society of Rheumatology (REGISPONSER) 2006 showed that 95% were taking NSAIDs and 61% consumed them daily. The administration of NSAIDs could be prevented continuously radiographic progression in AS as well as the risk of fractures according to the literature. Objectives We analyzed longitudinally the impact of taking NSAIDs in BMD and the presence of fractures in a sample of 69 patients with AS. Methods Patients with AS were included according to modified New York criteria. In such patients epidemiological characteristics (age, gender), year of diagnosis, treatment with NSAIDs (daily vs only if pain is present), toxic habits, body mass index (BMI), ESR, CRP, disease activity (BASDAI), physical measurements, function (BASFI), bone density and the presence of fractures (according to Genant semiquantitative method) were collected. We exclude patients treated with biological therapies and those treated with modifying BMD drugs or with some associated metabolic bone disease. Results 69 patients (47 men and 22 women) were analyzed. The mean age was 49 years (23-87), with a time of disease duration of 13.4 years. The use of NSAIDs was only if the patient had pain in 66.7% of cases. Regarding BMD, 45% of patients had a decrease in BMD at the spine and 40.6% at the hip, but we didn't found statistically significant differences in the way of taking NSAIDs (p=0.61 and p=0.42 respectively). They had vertebral fractures 11 to 69 patients, with no statistically significant differences among those taking NSAIDs continuously or on demand (p=0.998). These differences were still not significant after adjustment for confounders. Conclusions In our patients, the use of NSAIDs is mainly only if there's pain, which contrasts with the revised literature. We observed a decrease in BMD of our patients, considering that it is young population, although no differences were found in patients as the dose of NSAIDs. The incidence of fractures in our patients is 16%, with no difference between groups as taking NSAIDs. Thus we can conclude that in our AS patients taking NSAIDs daily or only if they've pain does not affect BMD or the presence of fractures. References Per Aspenberg. Drugs and fracture repair. Acta Orthopaedica 2005; 76(6): 741-748. Mayor González M y Batlle Gualda E. ¿Cόmo hay que administrar los AINE en la espondilitis anquilosante? Semin Fund Esp Reumatol 2008;9:137-43. Vosse D, Landewé R, van der Heijde D et al. A...