The aim of the study was to investigate the distribution of 163 A/G osteoprotegerin gene promoter and 1181 G/C osteoprotegerin exon 1 polymorphisms in a group of women with different hormonal status and to analyze their relationship with BMD. Osteoprotegerin polymorphisms and BMD were analyzed in 332 women (69 premenopausal and 263 postmenopausal). BMD was quantified at the lumbar spine (L 2-4), femoral neck, and total hip. Genotyping for the presence of different polymorphisms was performed using the Custom Taqman ((R)) SNP Genotyping assays. There were not significant differences in BMD according to 163 A/G genotype. However, significant differences in lumbar spine BMD were found according to 1181 G/C alleles. Thus, women with CC genotype had significant higher BMD at the lumbar spine than those with GC or GG genotype. No differences were found in femoral neck and total hip BMD. In age-adjusted models, the 1181 G/C OPG polymorphism explained 2.2% of BMD variance at the spine, 0.3% at the femoral neck, and 0.9% at the total hip in the whole group. In the subgroup of premenopausal women, the polymorphism was strongly related to spine BMD, and explained 11.5% of the variance, whereas body weight explained 7.9%. The 1181 G/C polymorphism was associated with lumbar spine BMD in Spanish women. Premenopausal women with the CC genotype had a higher BMD.
Weight gain has become one of the most common and concerning side effects of antipsychotic treatment. The mechanisms whereby antipsychotics induce weight gain are not known. It has been suggested that peptides related to food intake and energy balance could play a role in weight gain secondary to antipsychotic therapy. To better understand the pathophysiology of antipsychotic-induced weight gain, we studied the effects of 3 antipsychotic drugs (haloperidol, olanzapine, and risperidone) on peptides involved in energy balance (insulin, ghrelin, leptin, adiponectin, visfatin, and resistin) in a population of drug-naive patients with first episode of psychosis.A significant increase in weight (10.16 kg [SD, 8.30 kg]; P < 0.001), body mass index (3.56 kg/m [SD, 2.89 kg/m]; P < 0.001), and fasting insulin (3.93 muU/mL [SD, 3.93 muU/mL]; P = 0.028), leptin (6.76 ng/mL [SD, 7.21 ng/mL]; P < 0.001), and ghrelin (15.47 fmol/mL [SD, 47.90 fmol/mL]; P = 0.009) plasma levels were observed. The increments in insulin and leptin concentrations were highly correlated with the increment in weight and body mass index and seem to be a consequence of the higher fat stores. The unexpected increase in ghrelin levels might be related with the causal mechanism of weight gain induced by antipsychotics. Finally, the 3 antipsychotics had similar effects in all parameters evaluated.
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