广西壮、汉族绝经后妇女维生素D受体基因型与骨密度的关系

目的 探讨维生素D受体基因(VDR)型在广西壮、汉族绝经后妇女中的分布及其与骨密度(BMD)的关系。方法 在广西居住20年以上、无血缘关系的健康绝经后妇女198名,其中三代均为壮族的116名,均为壮族的82名。记录他们的年龄、绝经年龄,测量他们的身高、体重。用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法测定受试者的VDR基因型;用双能X线吸收法测定髋部、腰椎和前臂的骨密度。结果 壮、汉两组妇女VDR基因型和VDR等位基因频率分布均无显著性差异(P>0.05);198名妇女BB、Bb、bb基因型检出率分别为6.57％、66.16％和27.27％;B、b等位基因分别为39.65％和60.35％。BB基因型组第二腰椎(L2)BMD较bb基因型组低10.03％(P=0.047),第四腰椎(L4)BMD分别较bb、Bb基因型组低9.63％(P=0.043)和12.44％(P=0.005)。BB基因型组骨质疏松发生率最高(46.15％),Bb基因型组次之(19.86％),bb基因型组最低(14.81％),差异有显著性(P=0.04)。结论 VDR基因型与广西壮、汉族绝经后妇女BMD有关联,BB基因型可能可作为预测广西壮、汉族绝经后妇女骨质疏松危险性的遗传学标志之一。     

The Contribution of Vitamin D Receptor Gene Polymorphisms in Osteoporosis and Familial Osteoporosis

It is well established that genetic factors play a major role in the pathogenesis of osteoporosis. Previous reports have suggested that vitamin D receptor (VDR) gene polymorphisms, particularly the BB, tt and AA genotypes, are associated with low bone mineral density (BMD). If these VDR genotypes are indeed an important determinant of BMD, then a population of related osteoporotic individuals (mother–daughter or sister–sister relationship) should have a high prevalence of the BB, tt or AA VDR genotypes. To test this hypothesis we determined the VDR genotypes in 26 osteoporotic persons (age 44.3 ± 12.7 years, mean ± SD) belonging to 12 families. Furthermore, for comparison with existing studies, we applied the VDR genotype analysis in a population of 53 unrelated healthy subjects (age 45.2 ± 9.8 years, mean ± SD) and 59 unrelated osteoporotic subjects (age 52.1 ± 9.0 years, mean ± SD). The menopausal status of the healthy and osteoporotic populations was pre-, peri- and mostly early postmenopausal. The proportions of the three genotypes, BB, tt and AA, within the 12 osteoporotic families were 15%, 12% and 27%, respectively, whereas the proportions of the other three homozygous genotypes (bb, TT, aa) were 50%, 50% and 23%. The distribution of the BB, tt and AA genotypes in the normal population was 21%, 21% and 36%, respectively (vs bb, TT, aa: 36%, 38%, 21%), whereas in the osteoporotic population it was 24%, 20% and 34% (vs bb, TT, aa: 27%, 34%, 14%). Our data indicate that there is not a statistically significant (p>0.05) difference in the VDR genotype frequencies within osteoporotic families as compared with the same genotypes in the population of unrelated normal or osteoporotic subjects. VDR genotype analysis showed no significant relation between VDR polymorphisms and BMD or Z-score values at the lumbar spine. This study demonstrates the lack of a heritability pattern between the BB, tt and AA genotypes and low BMD. Received: 29 October 1998 / Accepted: 19 April 1999     

Vitamin D Receptor Gene Polymorphisms, Bone Mass, Bone Loss and Prevalence of Vertebral Fracture: Differences in Postmenopausal Women and Men

Bone mineral density (BMD), the major determinant of fracture risk, is under strong genetic control. Although polymorphisms of the vitamin D receptor (VDR) gene have been suggested to account for some of the genetic variation in bone mass, the influence of VDR genotypes on osteoporosis remains controversial. Previous published studies have focused mainly on women, but the pattern of response in men has not been determined. Using the BsmI restriction enzyme, we studied the influence of the different VDR genotypes on bone mass, bone loss and the prevalence of vertebral fractures in a population-based sample of both sexes (n = 326). BMD was measured at the lumbar spine and femoral neck, with a 4-year interval, using dual-energy X-ray absorptiometry. Vertebral fractures were assessed by two lateral radiographs at the beginning and end of the study. The prevalence of the three possible VDR genotypes was similar to those in other Caucasian populations and no differences were found between men and women. Women with the favorable bb genotype showed significantly higher BMD values at the lumbar spine and femoral neck, and a positive rate of BMD change at the femoral neck compared with women with the BB and Bb genotypes. Moreover, women with the bb genotype showed a trend toward a lower prevalence and incidence of vertebral fractures (p= 0.07). We have not found any differences between VDR genotypes in men. In conclusion, VDR gene polymorphisms are related to bone mass and bone loss in women; also a trend in the prevalence of vertebral fractures was observed in postmenopausal women but not in men. Received: 8 June 1998 / Accepted: 7 December 1998     

The BsmI vitamin D receptor gene polymorphism in Israeli populations and in perimenopausal and osteoporotic Ashkenazi women.

BACKGROUND: The association between vitamin D receptor (VDR) gene polymorphisms and bone mineral density (BMD) is controversial, and may be effected by ethnic ancestry and age. AIMS: To determine the distribution of the BsmI VDR gene polymorphism in healthy Israeli populations, and to study its association with BMD in perimenopausal and osteoporotic Ashkenazi women. METHODS: Allele and genotype frequencies of the VDR gene defined by BsmI restriction site were determined in 634 healthy Israelis of seven ethnic groups, 90 Ashkenazi perimenopausal women and in 75 Ashkenazi osteoporotic women. Genotype-related differences in spinal and femoral neck BMD were determined in Ashkenazi perimenopausal women. Allele and genotype frequencies in Ashkenazi osteoporotic women were compared with Ashkenazi controls. RESULTS: The frequency of the BB genotype was higher in Yemenites compared with Ashkenazi and Libyan Jews (23, 11 and 8%, respectively, p < 0.05), and lower in Ashkenazi compared with Iraqi and Persian Jews (11, 20 and 21%, respectively, p = 0.05). BMD did not vary by genotype in perimenopausal women, nor were there differences in the frequencies of the B allele or the BB genotype in osteoporotic women compared with controls. CONCLUSIONS: There is ethnic variability in the frequency of the BsmI VDR gene polymorphism. In Ashkenazi perimenopausal and osteoporotic women this polymorphism is not associated with BMD.     

Lack of association between estrogen receptor genotypes and bone mineral density, fracture history, or muscle strength in elderly women.

The PvuII polymorphism of the estrogen receptor (ESR) gene and its relation to bone mineral density (BMD), fracture history, and muscle strength was studied in 313 postmenopausal (76 +/- 5 years) women of Caucasian origin, of whom 142 had suffered from a fragility fracture after the age of 50 years (14 with fracture of the hip, 38 of the spine, 45 of the wrist, and 85 of other bones). The ESR genotype distribution was similar in women with and without a history of fragility fracture (PP 21%, Pp 43%, pp 36% compared with PP 18%, Pp 47%, pp 35%). We did not find a correlation between the ESR genotypes and BMD at the lumbar spine, the femoral neck, or the proximal forearm. No association was found with grip or quadriceps strength. We further evaluated the relationship between the vitamin D receptor (VDR) and ESR haplotypes and BMD in a random subgroup of 270 elderly women. No differences were found in women with the BBpp versus the bbPP haplotype in the femoral neck (mean difference +/- SD, in Bbpp compared with bbPP groups: -0.05 +/- 0.15 g/cm2), the spine (0.01 +/- 0.13 g/cm2), or the forearm (0.04 +/- 0.08 g/cm2). The significant association of quadriceps strength with VDR genotypes (25% lower in BB compared with bb genotype, p < 0.05) was not influenced by ESR haplotypes. We conclude that in elderly Caucasian women the PvuII ESR polymorphism is not associated with osteoporosis, fracture history, nor muscle strength and does not influence the association of bone density and muscle strength with polymorphism of the VDR.     

Does the vitamin D receptor genotype predict bone mineral loss in haemodialysed patients?

Background. It has been suggested that the vitamin D receptor (VDR) gene BsmI-polymorphism is a genetic determinant of bone metabolism. Design. To test this hypothesis, the relationship between VDR genotypes, bone mineral density (baseline and after 18 months) and parameters of calcium metabolism and bone turnover were investigated prospectively in 88 haemodialysed patients not receiving active vitamin D metabolites. Methods. Whole body, lumbar spine and femoral neck bone mineral density (BMD) were assessed by dual energy X-ray absorptiometry (DEXA). In addition calcium, phosphorus, 25(OH)D3, 1,25(OH)2D3, osteocalcin serum concentrations, alkaline phosphatase activity and intact, 1,84 PTH levels were measured. Results. VDR genotype BB, Bb and bb were found in 27, 49 and 24% of patients. Initial BMD (g/cm²) of whole body, lumbar spine and femoral neck did not differ between genotypes (whole body: BB 1.055 ± 0.120, Bb 1.082 ± 0.102, bb 1.128 ± 0.120; lumbar spine: BB 1.075 ± 0.199, Bb 1.079 ± 0.185, bb 1.099 ± 0.170; femoral neck: BB 0.808 ± 0.160, Bb 0.862 ± 0.127, bb 0.842 ± 0.125; mean ± SD), but the decrease of whole body and femoral neck BMD during 18 months was significantly (P < 0.02) different between the genotype groups (whole body: BB -0.048 ± 0.028, Bb -0.031 ± 0.029, bb -0.024 ± 0.023; femoral neck BB -0.044 ± 0.069, Bb -0.032 ± 0.081, bb -0.012 ± 0.029 g/cm²). Conclusions. This preliminary study suggests faster mineral loss in BB genotype of VDR in haemodialysed patients.     

老年男性维生素D受体基因多态性与骨密度关系的研究

目的研究维生素D受体(vitamin D receptor,VDR)基因多态性在老年男性中的分布, 并进一步研究其与骨密度的关系。方法采用聚合酶链反应-限制性片段长度多态性(PCR- RFLP)方法,分析145例老年男性的VDR基因型,同时用双能X线吸收法测定腰椎及髋部骨密度。结果 VDR基因型分别为BB,0．014;Bb,0．117;bb,0．869。骨质疏松组与非骨质疏松组之间VDR基因型分布频率的差异无显著性(P>0．05)。比较各基因型组的骨密度,bb组及 Bb组只有在股骨颈处显示出BMD均低于BB组,差异有显著性(P<0．05),其它部位,三个基因型组的BMD均差异无显著性(P>0．05)。结论老年男性VDR基因型分布频率与某些西方国家人群分布不同,其VDR基因型与骨密度无明显相关性。VDR基因可能不是我们所研究群体 BMD的主要遗传基因。     

VDR基因型分布及其与骨矿含量的关系

近年来，在骨质疏松研究领域，维生素Ｄ受体基因（ＶＤＲ）与骨量及骨代谢的研究受到许多国外学者的重视。我们利用国际合作的机会，对９６名沈阳妇女ＶＤＲ基因进行了分析。研究对象来自于一项正在进行的骨代谢影响因素研究课题。采用标准方法（Ｎｕｃｌｅｏｎｋｉｔ，ｓｃｏｔｌａｂ，ＵＫ）从白细胞中提取ＤＮＡ，以聚合酶链反应（ＰＣＲ）来扩增特定基因段。用ＢｓａＭＩ限制性内切酶消化ＰＣＲ产物，以２％琼脂糖电泳分离判定ＶＤＲ基因型。使用ＤＰＸ－Ｌ（ＬｕｎａｒＵＳＡ）骨矿测定仪测定研究对象的腰椎（Ｌ２～４）及髋部骨矿含量（ＢＭＣ）。结果：与其他国家人群相比，该人群ＶＤＲ基因的分布状态不同。ＶＤＲ基因的ｂｂ型占总数的９１．７％；Ｂｂ型仅占８．３％，而且ＢＢ基因型完全不存在。在青年妇女中发现ｂｂ基因型组股骨颈ＢＭＣ高于Ｂｂ型组股骨颈ＢＭＣ（Ｐ＝０．０２７）。老年妇女ｂｂ基因型组股骨颈ＢＭＣ也高于Ｂｂ型组，但差异无统计学意义，没有发现其他部位ＢＭＣ与ＶＤＲ基因型有关。     

FokI polymorphism at translation initiation site of the vitamin D receptor gene predicts bone mineral density and vertebral fractures in postmenopausal Italian women.

A novel T/C polymorphism (ATG to ACG) at the translation initiation site of the vitamin D receptor (VDR) gene, defined by FokI restriction endonuclease, has been recently associated with variation in bone mineral density (BMD) and rates of bone loss in a group of postmenopausal Mexican-American women. The presence of the restriction site, designated as f, allows protein translation to initiate from the first ATG, while the allele lacking the site, indicated as F, initiates translation at a second ATG. In this study, we investigated the role of FokI polymorphism in a group of 400 postmenopausal women of Italian descent stratified for BMD into osteoporotic (n = 164), osteopenic (n = 117), and normal (n = 119) groups. There were 159 (41%) FF homozygotes, 55 (14%) ff homozygotes, and 186 (45%) Ff heterozygotes. In the whole population, we observed a weak association between FokI polymorphism and lumbar BMD (p = 0.06, analysis of covariance [ANCOVA]) but not with femoral neck BMD (p = 0.5, ANCOVA). Interestingly, the effect of FokI genotypes on lumbar BMD was influenced by the years since menopause such that differences in BMD related to different VDR allelic variants were greater among women in the first 5 years of menopause (p = 0.04, ANCOVA), progressively declining afterward. In addition, a significantly higher prevalence of ff genotype in osteoporotic than in osteopenic and normal women was observed (p = 0.04, Chi-square test). Finally, ff genotype resulted significantly over-represented in the group of women with a vertebral fracture as compared with controls (p = 0.003, Chi-square test), equivalent to a relative risk of 2.58 (95% confidence intervals 1.36-4.91). We conclude that in this population, FokI polymorphism at the VDR gene locus accounts for a part of the heritable component of BMD at the lumbar spine.     

Risk factors for osteoporosis after renal transplantation and effect of vitamin D receptor Bsm I polymorphism

Objective

Rapid loss of vertebral or hip mineral density after renal transplantation is a major complication which occurs within 6-12 months. The aim of this study was to evaluate risk factors contributing to bone disease in the early stage after renal transplantation and the effect of vitamin D receptor (VDR) gene polymorphisms.

Methods

We prospectively followed for up to 12 months 44 patients (29 men and 15 women) with end-stage renal disease who underwent kidney transplantation. All patients received prednisone with either cyclosporine (CsA)/mycophenolate mofetil (MMF) or tacrolimus (Tac)/MMF therapy. Spine, hip, and whole body bone mineral density (BMD) was measured at 12 months after transplantation. According to World Health Organization recommendations, our patients were categorized as normal, osteopenic, or osteoporotic BMD levels. VDR alleles were genotyped as BB, Bb, or bb by polymerase chain reactions based on polymorphism at the Bsm I restriction site.

Results

Forty-six percent of patients were normal, 43% osteopenic, and 11% osteoporotic. Significant risk factors for osteoporosis among renal transplant recipients were younger age and pretransplant high intact parathyroid hormone (iPTH) levels. (P values .045 and .027, respectively). According to polymorphic group categorization, posttransplant serum Ca was significantly higher in patients with BB or Bb genotype than in those with bb genotype (P = .012). Although there was no statistical significance regarding iPTH levels, it was higher among Bb+BB than the bb genotype group. Also, first-year BMD analysis after transplantation according to Bsm I polymorphism showed significant differences in femur BMD levels according to the dual classification of polymorphism (P < .05). The BMD levels in the bb group was higher than in the Bb+BB group.

Conclusions

Although high pretransplant iPTH levels and younger age enhanced posttransplant bone loss, functionally different alleles of the VDR gene may modulate bone turnover during the first year after renal transplantation.     

绝经后女性血清硒水平与骨质疏松骨密度和骨代谢指标相关性研究

目的探索血清硒水平与绝经后妇女骨代谢指标以及腰椎和髋部骨密度之间相关性。方法检测156例正常骨密度和162例骨质疏松症的血清硒、25-羟基维生素D、PTH、骨钙素、PINP、CTX和NTX/Cr等指标水平。腰椎和股骨颈的BMD通过双能X线吸收法测量。探索了血清硒水平与骨密度的关系。结果骨质疏松症女性的血清硒水平低于正常骨密度的女性(P0.05)。在骨质疏松症妇女中,血清硒水平与年龄、绝经年限、BMI、PTH、骨钙素、PINP、CTX和NTX/Cr水平呈负相关,与25-羟基维生素D水平呈正相关。在正常骨密度组,血清硒水平与这些参数均未发现明显的相关性。调整年龄和BMI后,腰椎和股骨颈骨密度与血清硒及25-羟基维生素D水平呈显著正相关,与绝经年限、PTH、骨钙素、PINP、CTX和NTX/Cr呈负相关。对年龄和BMI进行调整后,进行多元回归分析以确定BMD的预测因子,血清硒和PINP、CTX是腰椎和股骨颈骨密度的显著预测因子。结论绝经后女性患者血清硒水平降低与腰椎和股骨颈骨密度降低密切有关。     

甲状旁腺素和维生素D受体基因多态对糖尿病患者骨密度的影响

目的探讨甲状旁腺素(PTH)基因多态性与中国北方汉族人糖尿病患者骨密度的关系,联合分析维生素D受体(VDR)基因和PTH基因多态性与骨密度的相关性。方法选自青岛市内分泌糖尿病医院1998年1月~2002年1月住院的糖尿病患者,运用聚合酶链反应限制性片段长度多态性(PCR-RFLP)技术检测了1型糖尿病(T1DM)组54例,2型糖尿病(T2DM)组104例,健康对照(CON)组102例,260例中国北方汉族人PTH基因多态性;采用双能X线吸收法骨密度仪(DEXA)测量骨密度。结果校正年龄和BMI后,1型糖尿病组腰椎、股骨颈骨密度低于对照组(P0.05);2型糖尿病组与对照组相比,骨密度差异无显著性(P0.05);甲状旁腺素(BSTB1位点)基因型和等位基因分布频率在1型糖尿病组、2型糖尿病组与对照组间差异无显著性(P0.05);在对照组及2型糖尿病组,BB基因型者腰椎(L2-4)和股骨颈部位骨密度显著高于Bb/bb基因型(P0.05);在1型糖尿病组,BB基因型仅腰椎L2-4部位骨密度高于Bb/bb基因型(P0.05);联合VDR基因多态(Apa I酶切位点)分析结果表明,Bbaa基因型在腰椎和股骨颈骨密度低于其他基因型(P0.05)。结论糖尿病患者PTH基因多态性(BSTB1位点)可能是预测骨量减少、骨质疏松易感性的遗传标志。联合VDR基因多态(Apa I酶切位点)有助于识别糖尿病患者发生骨质疏松的高危人群。     

Pretreatment levels of bone turnover and the antifracture efficacy of alendronate: the fracture intervention trial.

The influence of pretreatment bone turnover on alendronate efficacy is not known. In the FIT, we examined the effect of pretreatment bone turnover on the antifracture efficacy of daily alendronate given to postmenopausal women. The nonspine fracture efficacy of alendronate was significantly greater among both osteoporotic and nonosteoporotic women with higher baseline levels of the bone formation marker PINP. INTRODUCTION: Previous trials have shown that high bone turnover is associated with greater increases in BMD among bisphosphonate-treated women. The influence of pretreatment bone turnover levels on antifracture efficacy has not been well studied. MATERIALS AND METHODS: We randomized women 55-80 years of age with femoral neck BMD T scores < or = -1.6 to alendronate (ALN), 5-10 mg/day (n = 3105), or placebo (PBO; n = 3081). At baseline, 3495 women were osteoporotic (femoral neck BMD T score < or = -2.5 or prevalent vertebral fracture), and 2689 were not osteoporotic (BMD T score > -2.5 and no prevalent vertebral fracture). Pretreatment levels of bone-specific alkaline phosphatase (BSALP), N-terminal propeptide of type 1 collagen (PINP), and C-terminal cross-linked telopeptide of type 1 collagen (sCTx) were measured in all participants using archived serum (20% fasting). The risk of incident spine and nonspine fracture was compared in ALN- and PBO-treated subjects stratified into tertiles of baseline bone marker level. RESULTS AND CONCLUSIONS: During a mean follow-up of 3.2 years, 492 nonspine and 294 morphometric vertebral fractures were documented. Compared with placebo, the reduction in nonspine fractures with ALN treatment differed significantly among those with low, intermediate, and high pretreatment levels of PINP levels (p = 0.03 for trend). For example, among osteoporotic women in the lowest tertile of pretreatment PINP (<41.6 ng/ml), the ALN versus PBO relative hazard for nonspine fracture was 0.88 (95% CI: 0.65, 1.21) compared with a relative hazard of 0.54 (95% CI: 0.39, 0.74) among those in the highest tertile of PINP (>56.8 ng/ml). Results were similar among women without osteoporosis at baseline. Although they did not reach statistical significance, similar trends were observed with baseline levels of BSALP. Conversely, spine fracture treatment efficacy among osteoporotic women did not differ significantly according to pretreatment marker levels. Spine fracture treatment efficacy among nonosteoporotic women was related to baseline BSALP (p = 0.05 for trend). In summary, alendronate nonspine fracture efficacy is greater among both osteoporotic and nonosteoporotic women with high pretreatment PINP. If confirmed in other studies, these findings suggest that bisphosphonate treatment may be most effective in women with elevated bone turnover.     

维生素D受体基因TaqⅠ多态性与绝经后妇女骨密度的关系

目的 了解福州地区绝经后妇女维生素D受体基因TaqⅠ多态性的分布,探讨维生素D受体基因TaqⅠ多态性与绝经后妇女骨密度的关系.方法 用双能X线骨密度仪检测592例绝经后妇女的腰椎、股骨颈、大转子和Wards三角骨密度,应用PCR-RFLP技术检测维生素D受体基因TaqⅠ多态性.结果 ①维生素D受体基因型分布频率为TT型90.37%,tt型0.17%,Tt型9.46%.等位基因频率为T 95.1%,t 4.9%,基因型分布符合Hardy-Weinberg定律.②分析其基因型与骨密度的关系:TT、tt、Tt 3种基因型在腰椎、股骨颈、大转子、Ward's区4个部位骨密度差异均无显著性.结论 维生素D受体基因TaqⅠ多态性与骨密度间无关联,不能作为预测福州地区绝经后妇女发生骨质疏松危险性的遗传标志.     

Estrogen receptor (ER) gene polymorphism may predict the bone mineral density response to raloxifene in postmenopausal women on chronic hemodialysis

The estrogen receptor (ER) gene has been considered as a candidate genetic marker for osteoporosis, and PvuII and XbaI polymorphisms of the ERalpha gene have been associated with low bone mineral density (BMD). We investigated whether ER polymorphism could predict the response of BMD in 28 postmenopausal women on hemodialysis with marked osteopenia or osteoporosis, randomized to receive raloxifene, a selective estrogen receptor modulator (SERM), or placebo for 1 year. BMD was assessed by dual X-ray absorptiometry and PvuII and XbaI restriction fragment-length polymorphism of the ER gene was determined using polymerase chain reaction. Baseline lumbar spine or femoral neck BMD parameters were not different between patients presenting either homozygous PP or xx when compared with heterozygous Pp or Xx genotypes. After 1 year, patients on raloxifene, presenting with PP or xx genotypes (but not those with Pp or Xx), showed a significantly higher mean lumbar spine BMD (0.942 +/- 0.18 vs. 0.925 +/- 0.17 g/cm2, p < .01) and lower serum pyridinoline (19.7 +/- 9.7 vs. 30.6 +/- 16.5 nmol/L, p < .02) when compared with baseline values. No changes were detected in the placebo-treated patients or in the femur neck sites. In conclusion, after 1 year on raloxifene, postmenopausal osteoporotic women on chronic hemodialysis, homozygous for the P or x (PP or xx) alleles of the ER, exhibited a better lumbar spine BMD response and decreased serum pyridinoline values when compared with heterozygous women (Pp or Xx), suggesting that ERalpha allelic variants may explain, at least in part, the different outcomes after treatment of osteoporosis with SERM.     

Vitamin D Receptor Genotypes and Intestinal Calcium Absorption in Postmenopausal Women

Several studies have shown that bone mass and bone turnover are genetically determined. This genetic component is thought to be mediated in part by polymorphisms at the vitamin D receptor (VDR) locus, even though the underlying molecular mechanisms are still unknown. To evaluate a possible site of differential action of the VDR gene alleles we examined their correlation with intestinal calcium absorption in 120 Caucasian postmenopausal women (aged 61 ± 0.6 years). VDR gene polymorphisms for Apa I, Bsm I, and Taq I restriction endonucleases were assessed by Southern blotting analysis. The most common genotypes observed in our population were AaBbTt (37%), AABBtt (20%), aabbTT (15%), AabbTT (15%), and AABbTt (9%). Although there was some evidence of 13% higher lumbar BMD values in aabbTT genotype with respect to AABBtt genotype, this difference of approximately 0.1 g/cm² did not reach statistical significance, possibly because of the limited number of observations. On the contrary, no relationship was found between genotypes and femoral neck BMD values. Intestinal calcium absorption was significantly lower in BB and tt genotypes than, in bb and TT genotypes, respectively, and in AABBtt genotype than in either aabbTT or AaBbTt genotypes (P= 0.0015 ANOVA). No significant differences in intact PTH, alkaline phosphatase, 25OHD₃, and 1,25(OH)₂D₃ were found among subjects with different VDR genotypes. These results are consistent with a possible role of VDR alleles on intestinal calcium absorption.     

血清催产素浓度与绝经后女性骨密度相关性研究

目的探讨催产素与绝经后妇女骨代谢指标以及腰椎和髋部骨密度之间相关性。方法检测185例骨密度正常和132例患骨质疏松症女性的血清催产素、瘦素、雌激素和骨代谢指标浓度。腰椎和股骨颈的BMD通过双能X线吸收法测量。结果患骨质疏松症女性的血清催产素浓度低于骨密度正常的女性(P0.05)。骨质疏松症组中血清催产素浓度与年龄、绝经年限、体质量指数(body mass index,BMI)和血清PINP、BLAP和CTX浓度呈负相关;与瘦素和雌激素具有明显正相关性;在正常骨密度组中,血清催产素浓度和各种指标未发现明显的相关性。调整年龄和BMI后,腰椎和股骨颈骨密度仍然与绝经年限以及血清PINP、BLAP和CTX浓度呈负相关,与雌激素、瘦素和催产素浓度呈正相关。对年龄和BMI进行调整后,进行多元回归分析显示绝经年限、血清催产素、PINP和CTX是腰椎和股骨颈骨密度的显著预测因子。结论绝经后女性患者较高的血清催产素水平与较高的腰椎和股骨颈骨密度有关。     

Association between a family history of fractures and bone mineral density in early postmenopausal women.

The aim of this analysis was to measure the strength of the association between a family history of fractures and bone mineral density (BMD), and to determine what definition of family fracture history best predicts BMD. Five hundred and eighty postmenopausal women aged 45-59 at recruitment completed a risk factor questionnaire. Women were asked to recall details of fractures sustained by any female relative. BMD measurements taken at five sites were used. The data were analysed using linear regression, adjusting for age. Two hundred and ninety-seven (52.8%) women reported a family history of fractures, and they had a significantly lower BMD at two of the sites measured (p < 0.05). The associations with BMD were most significant when only counting fractures that occurred in the subject's mother or a sister as a result of low trauma, with no restrictions made on age at the time of fracture and site of fracture (p < 0.01 at three sites; 0.01 < p < 0.05 at two sites). Women with a family history according to this definition had a 4.6% reduction in BMD at the femoral neck. When T scores were used to categorize women as either osteopenic/osteoporotic (T < -1) or normal at the femoral neck, the sensitivity of using this definition was 39% and the specificity was 74%. The small group of women that reported a low-trauma hip fracture in a mother or sister (n = 23) had a mean femoral neck BMD which was 8.9% lower than that of the remainder of the sample, although this difference was less statistically significant than when low trauma fractures at any site were counted. Of these 23 women, 70% were osteopenic or osteoporotic, compared with 57% of those reporting a low-trauma fracture at any site and 47% of the sample as a whole. The sensitivity of this definition, however, was low (6%). From these analyses it can be concluded that the definition of family fracture history that best predicts BMD in postmenopausal women is a fracture at any age in a mother or sister resulting from low trauma, although the sensitivity and specificity of using a family history of fractures by itself to screen for low BMD were poor.     

Association of the vitamin D receptor genotype BB with low bone density in hyperthyroidism.

Bone mineral density (BMD) is modulated by genetic and environmental factors or certain diseases. In several conditions such as low calcium intake, an influence of vitamin D receptor (VDR) polymorphisms on BMD has been suggested. In the present study, we investigated the relationship of Bsm I and Fok I polymorphisms of the VDR gene and BMD in patients with hyperthyroidism, a disease that often results in low BMD. Bsm I and Fok I genotypes were determined in 76 postmenopausal hyperthyroid patients and 62 healthy postmenopausal women as controls. Patients and controls were matched for age, time since menopause, and lifestyle factors and were free of estrogen medication. BMD evaluation included axial dual X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (PQCT). Low BMD was defined as -2.5 STD below the young adult mean value. Biochemical parameters investigated were thyroid hormones, osteocalcin, and 25-(OH)-vitamin D3 as well as routine laboratory data. Low BMD was found in 61% of hyperthyroid patients and in only 23% of euthyroid controls. In the group of hyperthyroid patients with low bone density, the BB genotype (VDR Bsm I polymorphisms) was significantly more frequent (39%) than in controls (13%; p = 0.003) and hyperthyroid patients with normal BMD (6%; p = 0.013). The odds ratio (OR) for low BMD in patients with BB genotype was 5.7 (95% CI, 1.7-19.1; p < 0.005) as compared with the Bb and bb genotypes and 5.5 (95% CI, 2.3-13.2; p < 0.0001) for hyperthyroidism alone. The cumulative risk for low BMD in patients with hyperthyroidism and BB genotype was 31.4 (95% CI, 3.9-256; p < 0.0003). VDR Fok I genotypes showed no significant relationship with BMD or other general or bone-specific parameters. Thus, hyperthyroidism and the genetic background of a BB genotype may promote synergistically the development of low BMD in hyperthyroid patients. Screening for the BB genotype in these patients therefore could help to identify those with particularly high risk for the development of low BMD and allow early treatment.     

Bone mineral density and serum levels of aminoterminal propeptides and cross-linked N-telopeptides of type I collagen in elderly men

Serum levels of aminoterminal extension propeptides (PINP), the carboxyterminal telopeptide (ICTP), and the cross-linked N-telopeptides (NTx) of type I collagen were determined in 78 healthy, elderly men aged 76 +/- 5 years in 1993 and 1996 and compared with bone mineral density (BMD) measurements of their lumbar spine, femoral neck, and total body regions made using dual X-ray absorptiometry. Compared with 11 men who had normal lumbar spine (SBMD) and femoral neck BMD (NBMD), 13 of the subjects with SBMD and NBMD classified as osteopenic by t-score criterion had higher mean serum levels of PINP and alkaline phosphatase activity, but these increases were not statistically significant at the 95% confidence interval. In osteopenic men, a correlation between SBMD and NTx was detected (r = -0.66, p = 0.01). Within the entire population, the serum NTx level correlated with NBMD (r = -0.26, p < 0.05) and PINP (r = +0.63, p < 0.0001), and the change in the circulating concentration of PINP over the 3 year interval correlated with the magnitude of change in total body BMD (r = -0.28, p = 0.02), NBMD (r = -0.24, p = 0.05), and SBMD (r = -0.36, p = 0. 03) as well as with the change in serum NTx levels (r = 0.43, p < 0. 001). The change in the circulating ICTP level was also related to the change in NBMD (r = -0.24, p = 0.01). Together, weight and the serum PINP level accounted for 25% of total body BMD variance in elderly men. These results indicate that larger populations of men and women should be screened over longer time intervals to explore the value of serial measurement of serum collagen metabolites in predicting bone loss in the spine and hip.