Study Of Association Between Glucocorticoid Receptor Gene And Glucocorticoid-Induced Osteopenia And Osteoporosis

Objective To investigate the association among the bone mineral density (BMD), the glucocorticoid receptor gene expression and the clinical indexes of patients with nephrotic syndrome receiving glucocorticoid therapy. To explore the risk factors and predictors of glucocorticoid-induced osteoporosis.Methods 83 patients with nephrotic syndrome receiving glucocorticoid therapy in the First affiliated Hospital of Guangxi medical university during March to December,2009 were observed. BMD in the lumbar spine and the femoral neck was measured. And the clinical datas were collected including age, sex, body mass index (BMI), histological type, the time and accumulative dose of glucocorticoid treatment,the state of osteoporosis prevention. The expression of glucocorticoid receptorα(GRα) and glucocorticoid receptorβ(GRβ) messenger RNA (mRNA) was detected by reverse transcription-polymerase chain reaction, and the value of GRβ/GRαwas calculated. The association between the above factors and BMD was analyzed by the regression analysis.Results A Total of 83 patients were divided into two groups:the normal bone mass group (43 patients), the osteopenia and osteoporosis group (40 patients). There were no significant differences of age, BMI and the average daily dose of glucocorticoid treatment between the two groups (P>0.05). The time and accumulative dose of glucocorticoid treatment in the osteopenia and osteoporosis group were significantly higher than in the normal bone mass group (P＜0.05).There were no significant differences of the expression of GRamRNA between the two groups in male and all patients (P>0.05), while in female patients the expression of GRamRNA in the osteopenia and osteoporosis group were significantly lower than in the normal bone mass group (P<0.05). The expression of GRPmRNA and the value of GRβ/GRa in the osteopenia and osteoporosis group were significantly higher than in the normal bone mass group in all patients whether male or female (P＜0.05).The accumulative dose of glucocorticoid treatment were higher in the group taking Vitamin D and calcium than in the untreated group (P＜0.05), while there were no significant differences of age, BMI, the time of glucocorticoid treatment and the incidence of osteopenia and osteoporosis between the two groups (P>0.05).The relationship of various factors and BMD was analyzed by linear regression analysis. The analysis showed that BMI was positively correlated with BMD in the lumbar spine,and the time of glucocorticoid treatment and the GRPmRNA expression were negatively correlated with it. Age was negatively correlated with BMD in the femoral neck and Wards district, and the expression of GRamRNA was positively correlated with it. The accumulative dose of glucocorticoid and the value of GRβ/GRa were negatively correlated with BMD in the lumbar spine and the proximal femur. The association between all factors and glucocorticoid-induced osteoporosis was analyzed by logistic regression analysis. The analysis showed that age was a risk factor of osteopenia and osteoporosis in the femoral Wards district.The accumulative dose of glucocorticoid was a risk factor of osteopenia and osteoporosis in the lumbar spine. The increased GRPmRNA expression probably was a risk factor of osteopenia and osteoporosis in the lumbar spine and the femoral Wards district.The increased value of GRβ/GRa was a risk factor of osteopenia and osteoporosis in the lumbar spine and the proximal femur.Conclusion Age was a risk factor of osteopenia and osteoporosis in the femoral Wards district. The accumulative dose of glucocorticoid was a risk factor of osteopenia and osteoporosis in the lumbar spine. The increased GRPmRNA expression in peripheral blood mononuclear cell probably was a risk factor of osteopenia and osteoporosis in the lumbar spine and the femoral Wards district. The increased value of GRβ/GRa was a risk factor of osteopenia and osteoporosis in the lumbar spine and the proximal femur. And it probably was an early predictor of glucocorticoid-induced osteopenia and osteoporosis.