The goal of the study was to investigate the possibility of an association between polymorphisms and single alleles of BsmI, ApaI, TaqI of the vitamin D receptor (VDR) gene with bone mineral density (BMD) and prevalence of vertebral/non-vertebral fractures in a group of postmenopausal Polish women with osteoporosis. The study group comprised of 501 postmenopausal females with osteoporosis (mean age 66.4 ± 8.9), who were diagnosed on the basis of either the WHO criteria or self-reported history of low-energy fractures. The three polymorphisms were determined by PCR (polymerase chain reaction) and RFLP (restriction fragment length polymorphism). BMD at the lumbar spine and femoral neck was assessed by dual energy X-ray absorptiometry (DXA). 285 fractures were reported in the whole group (168 vertebral and 117 non-vertebral). Incidence of non-vertebral fractures was significantly higher in the carriers of single alleles a of ApaI, b of BsmI and T of TaqI VDR gene polymorphisms (p = 0.021, 0.032, 0.020, respectively). No significant associations between allelic variants of the studied polymorphisms and BMD or fracture incidence were found. (1).The presence of single alleles a,b and T of ApaI, BsmI, TaqI VDR gene polymorphisms respectively, might serve as an indicator of non-vertebral fractures. (2). Lack of association between the VDR gene polymorphisms and BMD suggests that VDR contributes to low-energy fractures also through other ways.

IntroductionThe aim of the study was to assess the role of patient counselling, nurse assistance and effects of biochemical examinations in adherence of women with postmenopausal osteoporosis to alendronate 70 administration over 12 months of therapy.Material and methodsCompliance and persistence to alendronate 70 therapy were assessed in a prospective study of 123 postmenopausal women, followed up for one year. The patients were divided into 4 groups (controls, counselled group, biochemical group and nurse assisted group) with monitoring every 6 months; in the nurse assisted group, additional phone contacts were made after 3 and 9 months of treatment. After 12 months, compliance and persistence were analysed. The medication possession ratio (MPR) was regarded as optimal when its value exceeded 80%.ResultsThe compliance to alendronate 70 therapy was 54.03% in the control group and the mean persistence with medication was 197 days. The MPR above 80% was observed in 37.5%, and, after 1 year, 43.75% of patients were found persistent with the therapy. In the remaining groups, both compliance and persistence were higher but not statistically significantly, compared to the control group. Neither patient's age, education, diet, nor physical activity influenced the compliance with prescribed therapy. The most common reason to discontinue therapy was either its side effects or smoking.ConclusionsThe obtained results suggest that better adherence with medical recommendations is observed in patients who receive additional attention, e.g. counselling, biochemical tests or nursing care. The critical elements for therapy discontinuation were side effects and smoking.

Associations of the FokI, BsmI, ApaI, and TaqI polymorphisms of the vitamin D receptor (VDR) gene with the bone mineral density (BMD) of the lumbar part of the spinal column (BMD LS) and the neck of the femur (BMD FN), and with the occurrence of fractures, were studied using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis on DNA isolated from peripheral blood of 239 women and 40 men from the region of western Poland. Three polymorphisms of the 3' end of the VDR gene (BsmI, ApaI, TaqI) indicated a strong linkage disequilibrium. Association analysis of the VDR gene FokI polymorphism with BMD LS showed a dose effect of allele f. The association of the bAT haplotype of the BsmI, ApaI, and TaqI polymorphisms of the VDR gene with BMD FN was statistically significant. The association of the ApaI polymorphism with the occurrence of fractures was observed. Associations were also observed between the occurrence of fractures and the baT haplotypes of the VDR gene.

Osteoporosis is more frequent in inflammatory bowel disease (IBD) patients. A reduction in bone mineral mass in these individuals is caused not only by inflammatory processes in the bowel, because osteoporosis occurs already in very young IBD patients and in newly diagnosed individuals who have not yet undergone any pharmacological treatment. One of individual determinants of the bone turnover parameters is osteoprotegerin (OPG) encoded by the TNFRSF11B gene. The c.-223C > T polymorphism in this gene has been extensively studied in post-menopausal osteoporosis patients. However, no such studies exist for osteoporosis related to IBD. The aim of our study was to determine whether the c.-223C > T (rs2073617) polymorphism in the 5′UTR region of the gene encoding osteoprotegerin is a functional polymorphism which may change the gene expression and resulting OPG levels, and so be associated with osteopenia and osteoporosis, and impaired bone metabolism in Crohn’s disease and ulcerative colitis patients. Our study included 198 IBD patients and 41 healthy controls. Lumbar spine and femoral neck bone mineral density, T-score, Z-score as well as OPG, RANKL, vitamin D, calcium and interleukin 4 and 10 concentrations were determined for all study subjects. Genotyping of the TNFRSF11B polymorphic site was performed by restriction fragment length polymorphism technique. Statistical analyses were conducted using Statistica software. Odds ratios, 95 % confidence intervals, and P values were calculated using the HWE calculator. Our results did not allow determining an unequivocal association between the polymorphic variants of the TNFRSF11B 5′UTR region and a susceptibility to osteoporosis in IBD patients. We have shown, however, that the c.-223T allele was twice as more frequent in Crohn’s disease (CD) patients than among controls (OR = 1.99, P value = 0.009). Interestingly, average osteoprotegerin levels in CD patients did not significantly differ from those in controls, whereas in ulcerative colitis patients, OPG levels were significantly lower. We have concluded that low OPG levels may be associated with osteoporosis in ulcerative colitis, but it is not correlated with the c.-223C > T polymorphism in the TNFRSF11B gene. In CD patients, in turn, we observed increased RANKL levels. Our observations confirm different pathogeneses of Crohn’s disease and ulcerative colitis as well as different molecular backgrounds of osteoporosis associated with these two diseases.

Graves' (GD) hyperthyroidism induces accelerated bone turnover that leads to decreased bone mineral density (BMD). The role of the VDR gene in predisposition to primary osteoporosis has been recognized. Recent studies show associations between the VDR gene polymorphisms and susceptibility to autoimmune diseases. Here we analyzed if VDR gene polymorphisms: BsmI, ApaI, TaqI, and FokI may predispose women with Graves' hyperthyroidism to BMD reduction or to disease development. The subjects were 75 premenopausal female Polish patients with GD and 163 healthy women. The genotyping was performed by the use of the restriction fragment length polymorphism analysis (RFLP). We studied the association of the VDR polymorphisms and their haplotypes with patients' BMD and also SNPs and haplotypes association with Graves' disease. We found a strong linkage disequilibrium for the BsmI, ApaI, and TaqI polymorphims that formed three most frequent haplotypes in Graves' women: baT (47.9%), BAt (34.9%), and bAT (16.4%). We did not show statistically significant association of analyzed VDR polymorphisms or haplotypes with decreased bone mineral density in Graves' patients. However, the presence of F allele had a weak tendency to be associated with Graves' disease (with OR=1.93; 95% CI: 0.97-3.84; p=0.058). VDR gene polymorphisms do not predict the risk of decreased BMD in Polish women with Graves'. It may be speculated that the F allele carriers of the VDR-FokI polymorphism are predisposed to Graves' disease development.