Vitamin D Receptor Gene Polymorphism and Bone Mineral Density in Hypercalciuric Calcium-Stone-Forming Patients

Abstract

Reduced bone mineral density (BMD) and an increased risk of vertebral fracture have been reported in calcium-stone-forming (CSF) patients presenting with idiopathic hypercalciuria. We investigated the association between BsmI vitamin D receptor (VDR) polymorphism and BMD in 68 hypercalciuric CSF patients (35 males and 33 premenopausal females, mean age ± SD = 39 ± 10 years). BMD was measured at lumbar spine (L₂–L₄) and femur neck sites using dual energy X-ray absorptiometry. A 72-hour dietary record and a 24-hour urine sample were obtained from each patient to determine calcium intake and excretion. The allelic frequency found for the sample as a whole was 16% BB, 44% Bb and 40% bb. Mean BMD values did not significantly differ among BB, Bb and bb patients at L₂–L₄ (1.162 ± 0.10, 1.133 ± 0.11 and 1.194 ± 0.19 g/cm², mean ± SD, respectively) or at neck sites (0.920 ± 0.11, 0.931 ± 0.15 and 0.982 ± 0.15 g/cm², respectively). Calcium intake and excretion were also not significantly different among the three genotypes. Patients were then divided into two groups, normal BMD, T-score ≧–1 (n = 34) and low BMD, T-score <–1 (n = 34), to further evaluate the allele influence on previous bone loss. Despite a trend for a higher mean BMD at spine or neck sites for patients with one or two b alleles when compared to BB patients, the difference did not reach statistical significance. The distribution of BB, Bb and bb genotypes in the low-bone-mass group (15, 47 and 38%, respectively) was similar to that in the normal-bone-mass group (18, 41 and 14%, respectively). These data suggest that BsmI VDR polymorphism does not play an important role in the bone loss seen in hypercalciuric CSF patients.

Vitamin D Receptor and Calcium-Sensing Receptor Gene Polymorphisms in Hypercalciuric Stone-Forming Patients

“…In the present series, VDR allele distribution did not differ between osteopenic or normal BMD patients. In a previous evaluation by our group [16], conducted exclusively in hypercalciuric calcium-stone-forming patients, we also found that VDR polymorphism was not associated with loss of BMD. Nor did Vezzoli et al [22] find an association of FokI polymorphism with BMD in hypercalciuric patients.…”

“…In some reports in which hypercalciuria had been ascribed to intestinal calcium hyperabsorption or renal leak, no association between BsmI polymorphism with absorptive hypercalciuria was found [20,25] while overrepresentation of bb was observed among those exhibiting renal leak [24]. Since we found no differences of VDR alleles between absorptive or fasting hypercalciuric patients in a prior study encompassing a smaller number of patients [16], data regarding urinary calcium were pooled in the present analysis for comparison between normo- and hypercalciuric patients.…”

“…Several studies about common allelic variations in VDR in disorders of calcium metabolism, using Bsm I, Apa I, Taq I and Fok I restriction enzymes have been performed, but the results were controversial [12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32]. While some studies disclosed an association between VDR polymorphism and bone mineral density (BMD) [12,13,14,15], others did not [16,17,18,19].…”

“…While some studies disclosed an association between VDR polymorphism and bone mineral density (BMD) [12,13,14,15], others did not [16,17,18,19]. Although the link between stone formation and VDR has not yet been clarified, and these polymorphisms do not alter the amino acid sequence of the VDR protein, allelic differences in the 3′ untranslated region may alter the regulation of messenger RNA stability and/or translation and thus affect vitamin D activity, or even mediate calcitriol action in the regulation of expression of other target genes involved in renal tubular calcium reabsorption [12,27,33].…”

“…In addition, even if a specific VDR genotype does not provide evidence for a VDR defect per se, it could be a marker for the disease that could aid in the identification of a possible disease locus [12]. Evaluation of VDR polymorphisms among kidney stone formers, hypercalciuric or not, have shown distinct findings [16,20,21,22,23,24,25,26,27,28,29,30,31,32]. Some investigators found a positive association between polymorphic variations in VDR gene with risk or recurrence of stone formation [27,28,29] but other studies were negative [30,31].…”