OBJECTIVE: To observe bone loss and analyze its risk factors in renal transplantation recipients, to investigate the prevalence of polymophism of the the vitamin D receptor(VDR) gene and study the relationship between bone mineral density (BMD) and VDR gene polymorphism in the the renal transplantation patients in Shanghai. To explore the effects of calcitriol monotherapy or in combination with alendronate on bone loss in kidney transplantation patients.METHODS: A cross-sectional study was conducted to investigate bone metabolism in 140 kidney transplantation patients with stable renal function(serum creatinine≤2mg/dl) and follow-up regularly in our hospital. The main risk factors on bone mineral density at the lumbar vertebral and hip was analysised. The VDR genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism . BMD was measured by dual-energy X-ray absorptionmetry. 30 kidney recipients (7 men and 23 women, aged 48.26 +/- 7.53 years) diagnosed as osteopenia or osteoporosis by densitometry were enrolled and randomized into two groups: (1) group A(14 patients): 0.50 microg/day of calcitriol; (2) group B(16 patients): 10 mg/day of alendronate and 0.50 microg/day of calcitriol. Serum creatinine, calcium, phosphorus, magnesium, urine calcium excretion, serum parathyroid hormone, osteocalcin, serum 1,25 dihydroxy vitamin D[1,25(OH)2 vitamin D] and urine pyridinoline were measured at baseline and 6 months later. Densitometric reevaluation at lumbar vertebral and proximal femur was performed after the 6-month treatment period.RESULTS: The BMD of lumbar spine and femoral was decreased in some patients from 36% to 88% according to different sites. Mean levels of serum 1,25(OH)2D3, PTH, BGP, calcium, phosphorus and magnesium were normal. It was demonstrated that cyclosporin(CsA) doses and BMI were predictors for BMD at lumbar spine; BMI and male patients were predictors for changes of density in neck of femoral BMD; age and time posttransplantation were the negative predictors for ward's region of femoral, serum level of calcium and BMI were predictors for femoral trochanter. Correlation and linear regression analysis did not show impact of prednisone doses, serum levelsof PTH and BGP on BMD, but there were significant correlation between serum level of PTH and serum phosphorus, duration of dialysis, prednisone doses. Serum BGP was also positively correlated to time posttransplantation. The frequencies distribution of Fok I, Aap I, Bsm I and Taq I alleles in 80 renal transplantation patients in Shanghai all in accordance with the Hardy-Weinberg equilibrium. No significant difference was found between Fok I, Bsm I ,Taq I genotypes and BMD when these polymorphisms were considered independently, except for Apa I genotype. When a pooled analysis of VDR gene (Fok I, Aap I, Bsm I and Taq I) was carried out, cross-genotyping Fok I and Bsm I polymorphisms was significantly associated with BMD at the lumbar vertebral (BMD values were adjusted for cumulative prednisone, gender and blood cyclosporine concertration ), and cross-genotyping Apa I and Bsm I polymorphisms was also significantly associated with BMD at the lumbar vertebral (BMD values were adjusted for duration of dialysis before transplantation, cumulative prednisone and gender). At the randomization time, group A and group B patients did not differ as to the main demographic, clinical variables, metabolic variables and bone mineral density. After treatment, bone density of femoral neck and ward's triangle increased significantly both in the group A and group B patients. The improvement in BMD is better in patients of group B than those in group A.CONCLUSION: The prevalence of osteopenia and osteoporosis is high in renal transplant recipients. Except for age, gender and BMI, use of prednisone contributes importantly to them. Cyclosporine is possibly a protective factor on bone metabolism. Apa I polymorphism of VDR gene is associated with BMD. VDR gene Bsm I and Fok I, Apa I had a combined effect on the BMD in...
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