Relation of vitamin D receptor FokI start codon polymorphism to bone mineral density and occurrence of osteoporosis in postmenopausal women in Taiwan

BACKGROUND: Osteoporosis is a common disorder with a strong genetic component. Our aim was to evaluate the correlation of the vitamin D receptor FokI start codon polymorphism to bone mineral density and the occurence of osteoporosis. METHODS: We determined the vitamin D receptor FokI start codon polymorphism using polymerase chain reaction-based restriction analysis in 163 postmenopausal women in Taiwan. The vitamin D receptor gene polymorphism was detected by the restriction enzyme FokI, where the F allele indicated the absence of the cuttable site and the f allele its presence. We then related the genotypes to bone mineral density and the occurence of osteoporosis in these women. RESULTS: The allelic frequencies for 163 postmenopausal women in Taiwan were 59.2% for F and 40.8% for f in FokI restriction fragment length polymorphisms. The prevalence of each genotype in the study population was: 42.3% FF, 33.7% Ff and 24% ff. The three genotypic groups differed significantly in bone mineral density at the lumbar spine (P = 0.029). Bone mineral density was highest in the Ff group and lowest in the ff group at the lumbar spine and the femoral neck. The FokI vitamin D receptor genotype showed a significant effect on the prevalence of osteoporosis in the subjects at the lumbar spine. That is, women with genotype ff had a 2.8 times greater risk for osteoporosis (P < 0.05), and those with genotype FF had a 0.8 times greater risk than women with genotype Ff. CONCLUSION: Our findings indicate that the vitamin D receptor FokI start codon polymorphism is associated with reduced bone mineral density and predisposes women to osteoporosis at the lumbar spine.     

The ALUI calcitonin receptor gene polymorphism (TT) is associated with low bone mineral density and susceptibility to osteoporosis in postmenopausal women

Osteoporosis is a common disorder with a strong genetic component. Our aim was to evaluate the correlation of the ALUI calcitonin receptor gene polymorphism to bone mineral density and their relationship to osteoporosis. We determined the ALUI calcitonin receptor gene polymorphism using polymerase chain reaction-based restriction analysis in 167 postmenopausal women in Taiwan. The polymorphism was detected by the restriction enzyme ALUI, where the C allele indicated the absence of the cuttable site and the T allele indicated its presence. Bone mineral density of the lumbar spine and proximal femur were measured using dual-energy X-ray absorptiometry. The allelic frequencies for the 167 postmenopausal women in Taiwan were 86.5% for C and 13.5% for T in ALUI restriction fragment length polymorphisms. The prevalence of each genotype in the study population was 2.4% TT, 22.2% CT, and 75.4% CC. The three genotypic groups differed significantly in unadjusted and adjusted bone mineral density at the lumbar spine and the femoral neck. Unadjusted and adjusted bone mineral density values were lowest in women with the TT genotype. The ALUI calcitonin receptor genotype showed a positive association with prevalence of osteoporosis in the subjects. That is, women with genotype TT had a greater risk for developing osteoporosis at the lumbar spine and at the femoral neck. The ALUI calcitonin receptor gene polymorphism is associated with reduced bone mineral density and predisposes women to osteoporosis, but should be interpreted with caution because of the small number of subjects in the unfavorable TT genotype.     

The effect of anorexia nervosa on skin thickness, skin collagen and bone density

The effects of anorexia nervosa on skin thickness, skin collagen content and bone density were investigated in a cross-sectional study of 36 women with anorexia nervosa with a 4-year median duration of amenorrhoea and compared with a group of 33 women of comparable age without anorexia and with normal periods. The median skin thickness, assessed radiologically, was significantly reduced (P less than 0.01) from 0.88 mm in the comparison group to 0.70 mm in the anorectic group and the median collagen content was significantly reduced from 209 micrograms/mm2 in the comparison group to 164 micrograms/mm2 in the anorectic group (P less than 0.05). The median bone density in the comparison group was 0.93 gHA/cm2 at the lumbar spine and 0.84 gHA/cm2 at the proximal femur. These values were greatly reduced in the women with anorexia nervosa to 0.77 gHA/cm2 and 0.65 gHA/cm2 respectively (P less than 0.01). Our findings confirm the loss of bone mass with anorexia and demonstrate the coexistent loss of skin thickness and skin collagen content. This association supports the hypothesis that a generalized loss of collagen is a major factor in the causation of osteoporosis following oestrogen deficiency.     

影响绝经后妇女骨密度变化的候选基因研究

目的探讨有关候选基因对绝经后妇女骨密度变化的影响。方法对205例绝经后妇女,应用双能X线骨密度仪测定腰椎和股骨颈骨密度。采用PCR测序法,检测护骨素基因多态性;采用PCR-限制性片段长度多态性方法,检测甲状旁腺激素、降钙素受体、骨钙素及瘦素受体基因多态性;采用PCR-琼脂糖凝胶电泳法,检测瘦素基因多态性。结果在护骨素基因第1外显子中,发现1个G-1181C单核苷酸多态性。在校正年龄及体重指数对骨密度的影响后,携带护骨素基因CC型及甲状旁腺激素基因bb型妇女的腰椎骨密度较高,分别为(1.042±0.142)g/cm2及(1.196±0.133)g/cm2。降钙素受体、骨钙素、瘦素及瘦素受体基因与骨密度之间无相关关系。经多元逐步回归分析,护骨素、甲状旁腺激素及骨钙素基因与腰椎骨密度变异有关,甲状旁腺激素基因与股骨颈骨密度的变异有关。结论护骨素及甲状旁腺激素基因与绝经后妇女骨量变异有一定关系,降钙素受体、骨钙素、瘦素及瘦素受体基因与绝经后妇女骨密度变异无关。护骨素基因可能是绝经后妇女发生骨量减少的遗传性标记。     

Lumbar bone density and serum osteocalcin in pre- and postmenopausal women

The bone mineral density of the lumbar spine (L3) and serum osteocalcin (OC) were measured in 31 pre- and 25 postmenopausal women. Bone density was measured by single energy quantitative computed tomography (QCT value). A significant inverse correlation between the QCT value and age was demonstrated in postmenopausal women but no correlation was found in premenopausal women. Mean QCT value was significantly lower in postmenopausal women than in premenopausal women. Serum OC increases with advancing age and mean serum OC was significantly higher in postmenopausal women than in premenopausal women. A significant inverse correlation between the QCT value and serum OC was demonstrated. These data suggest that there is an association between menopause and accelerated loss of lumbar bone density and that the serum OC level may be useful in evaluating the bone mass.     

Correlations of serum prolidase activity between bone turnover markers and mineral density in postmenopausal osteoporosis

Prolidase is a specific imidodipeptidase involved in collagen degradation. The increase in the enzyme activity is believed to be correlated with the increased intensity of collagen degradation. The aim of this study was to evaluate the serum prolidase activity and its relationship between bone turnover markers and bone mineral density (BMD) in postmenopausal osteoporosis. The study included 45 postmenopausal osteoporotic, 55 postmenopausal nonosteoporotic and 38 premenopausal healthy women. BMD was measured at the femoral neck and lumbar spine with DEXA. T score was more than 2.5 SD below the normal at the lumbar spine or femoral neck in postmenopausal osteoporotic patients. Serum levels of prolidase, C-terminal telopeptide of type I collagen (C-telopeptide), total alkaline phosphatase (ALP), osteocalcin (OC), urinary deoxypyridinoline (Dpd) and urinary creatinine were also assayed. C-telopeptide, total ALP, OC, urinary Dpd levels were significantly higher in postmenopausal osteoporotic group compared with premenopausal women. However, there was no statistical difference in serum prolidase activity between the three groups. There were also no significant correlations between serum prolidase and any biomarkers of bone turnover as well as BMD. To conclude, in postmenopausal osteoporotic women with increased bone turnover, serum prolidase concentration was not correlated with the biomarkers of bone formation or bone resorption and with BMD.     

The relationship of homocyteine,B12 and folic acid with the bone mineral density of the femur and lumbar spine in Turkish postmenopausal women

Objective  The relationship of homocyteine, B12 and folic acid with osteoporosis has already been studied in various populations. We compared the important factors in the metabolism of homocysteine, such as homocysteine, B12 and folic acid levels, of Turkish postmenopausal women, and their relationship with the femur and lumbar spine bone mineral density. Methods  This cross-sectional study was conducted at Gazi University, Department of Obstetrics and Gynecology. The study group consisted of 178 postmenopausal women. Serum homocysteine, folic acid and Vitamin B12 were measured. BMD was measured using DEXA at the right femoral neck and lumbar spine (L1–L4). Results  Upon evaluation of both the femur and lumbar spine, it was determined that osteoporosis could be associated with a homocysteine level above the median and with a B12 value under the lowest quintile value. Conclusion  Plasma Hcy and vitamin B12, but not folate levels, were associated with osteoporosis. Future interventional studies are needed to determine methods to reduce Hcy levels with dietary supplements and extra vitamin B12, which will restore bone health and reduce risk of fractures.     

Comparison of bone mineral density and its variables between premenopausal and postmenopausal women

Objectives

To compare the bone mineral density (BMD) and its variables in premenopausal and postmenopausal women.

Methods

In this cross sectional study, 62 premenopausal and 62 postmenopausal apparently healthy women were evaluated by a questionnaire. The dietary intake of calcium was evaluated by 24 hours recall method and using table for proximate principle of common Indian food by Indian Council of Medical Research (ICMR). BMD at lumbar spine, femoral neck and Ward’s triangle were measured by dual energy X-ray absorptiometry (DXA). A correlation between BMD and various variables were calculated for each of the two groups.

Results

The mean age of premenopausal and postmenopausal women was 32.46±7.8 and 51.74±7.1 years respectively. The body mass index (BMI), height and weight were comparable in both the groups. The daily intake of calcium was significantly higher in premenopausal women (p<0.01). Approximately, 17% of the postmenopausal women and 9.6% of the premenopausal women were having osteoporosis; 28.56% of the postmenopausal women and 43.54% of the premenopausal women were having osteopenia at the lumbar spine. The BMD at lumber spine was found to be statistically significantly higher in premenopausal women than that in postmenopausal women (p=0.03). BMD at lumbar spine, femoral neck and Ward’s triangle were positively correlated with height, weight, BMI in premenopausal as well in postmenopausal women.

Conclusion

A significant number of women had osteopenia during premenopausal period and osteoporosis in postmenopausal phase. By increasing awareness towards bone health in second and third decade, morbidity of osteoporosis can be reduced.     

Effect of non-weight-bearing body fat on bone mineral density before and after menopause

OBJECTIVE: To investigate the difference in the effect of non-weight-bearing body fat mass on bone mineral density between premenopausal and postmenopausal women. METHODS: We studied 252 regularly menstruating premenopausal women and 213 postmenopausal women with right side dominance. Age, years since menopause (in postmenopausal women), height, weight, and body mass index were recorded. Bone mineral density of non-weight-bearing sites (ie, arms), weight-bearing sites (ie, lumbar spine including L2-4 and legs), and body fat mass were measured by whole-body scanning with dual-energy x-ray absorptiometry. Body fat mass was also measured by dual energy x-ray absorptiometry. RESULTS: Body fat mass did not differ between groups. In postmenopausal women, body fat mass correlated positively with bone mineral density of the left leg (r =. 41, P <.001), right leg (r =.36, P <.001), left arm (r =.31, P <. 001), and lumbar spine (r =.27, P <.001). The correlation between body fat mass and bone mineral density of the left arm remained significant after adjusting for age, years since menopause, and height. In premenopausal women, body fat mass correlated positively with bone mineral density of left leg (r =.37, P <.001) and right leg (r = 0.31, P <.001), but correlated weakly with bilateral arms (r < or =.19) and lumbar spine bone mineral density (r = 0.13, P <.05). CONCLUSION: The effect of non-weight-bearing body fat on bone mineral density was greater in postmenopausal than premenopausal women.     

The relationship among serum insulin-like growth factor-I, insulin-like growth factor-I gene polymorphism, and bone mineral density in postmenopausal women in Korea

OBJECTIVE: The objective of this study was to test the hypothesis that the cytosine-adenine polymorphism in the insulin-like growth factor-I gene is associated with serum insulin-like growth factor-I levels and bone mineral density. STUDY DESIGN: The insulin-like growth factor-I cytosine-adenine polymorphism was analyzed in 300 postmenopausal Korean women. Serum insulin-like growth factor-I, bone alkaline phosphatase, and carboxy-terminal cross-linking telopeptide of type I collagen were measured by immunoradiometric assay and enzyme-linked immunosorbent assay. Bone mineral density at the lumbar spine and proximal femur was determined by dual energy radiograph absorptiometry. RESULTS: Serum insulin-like growth factor-I and bone mineral density levels in women who were homozygous for a 194-base pair allele were significantly higher than those levels in the 194-base pair heterozygotes or women who did not possess the 194-base pair allele. A significantly decreased prevalence of the 194/194 genotype was observed in the combined group of women with osteopenia and osteoporosis, compared with normal women. No correlation between insulin-like growth factor-I genotypes and bone turnover markers was found. CONCLUSION: The insulin-like growth factor-I gene cytosine-adenine polymorphism relates with circulating insulin-like growth factor-I levels and bone mineral density at the lumbar spine and proximal femur.     

Comparison of the effects of raloxifene and low-dose hormone replacement therapy on bone mineral density and bone turnover in the treatment of postmenopausal osteoporosis.

OBJECTIVE: The aim of the present study was to compare the effects of raloxifene and low-dose hormone replacement therapy (HRT) on bone mineral density (BMD) and bone turnover markers in the treatment of postmenopausal osteoporosis. METHODS: Forty-two postmenopausal osteoporotic women, who were randomized to receive raloxifene 60 mg or estradiol 1 mg/norethisterone acetate 0.5 mg daily for 1 year, were studied. All women received calcium 600 mg/day and vitamin D 400 IU/day. BMD and markers of bone turnover were measured at baseline and at 12 months. RESULTS: After 12 months of treatment, there were statistically significant increases in BMD in both groups at all sites (all p < 0.05). For the lumbar spine, the increase in BMD was 2.3% for raloxifene compared with 5.8% for low-dose HRT and corresponding values for total body BMD were 2.9% for raloxifene and 4.6% for low-dose HRT; the increases being significantly greater in the low-dose HRT group (p < 0.001 and p = 0.02, respectively). Although the increase in BMD at the hip was significant for both raloxifene (2.1%) and low-dose HRT (3.2%) compared with baseline, the difference between the two regimens did not reach statistical significance. The decrease in serum C-terminal telopeptide fragment of type I collagen and serum osteocalcin levels for the low-dose HRT group (-53% and -47%, respectively) was significantly greater than for the raloxifene group (-23% and -27%, respectively; both p < 0.01). CONCLUSIONS: In postmenopausal women with osteoporosis, low-dose HRT produced significantly greater increases in BMD of the lumbar spine and total body and greater decreases in bone turnover than raloxifene at 12 months.     

Effect of specific exercise training on bone mineral density in women with postmenopausal osteopenia or osteoporosis

Aim.?To analyse the effect of a specific program of weight training exercise with closed kinetic chain in bone mineral density in postmenopausal women with osteopenia or osteoporosis.

Methods.?A total of 59 postmenopausal women with osteoporosis or osteopenia were included in this prospective study. Subjects were divided into two groups: the study group (SG, n = 30; 57.5 ± 5.1 years) and the control group (CG, n = 29; 56.6 ± 4.6 years). In the study group was applied a weight exercise protocol (longitudinal forces in closed kinetic chain) during 12 months, whereas in the control group no weight exercise protocol was applied. Bone mineral density at the lumbar spine and hip was assessed at baseline and at the end of follow-up by dual energy X-ray absorptiometry.

Results.?Although no significant intragroup differences were found, patients in SG showed a 1.17% increase in the lumbar spine whereas in CG a 2.26% decrease in bone density was detected.

Conclusion.?This protocol of weight training exercise did not significantly improve bone mineral density in postmenopausal women with osteopenia or osteoporosis, but in comparison to the control group, the results showed the importance of practising the specific exercise program for maintenance of bone health in postmenopausal women.     

Vitamin K2 treatment for postmenopausal osteoporosis in Indonesia

AIM: To investigate the effect of vitamin K2 (menatetrenone) treatment on bone mineral density (BMD) and a bone metabolic marker (osteocalcin) in postmenopausal women with osteoporosis living in Indonesia. METHODS: A double-blind randomized placebo-controlled study of 63 postmenopausal women with osteoporosis. The vitamin K2 group (n = 33) received 45 mg menatetrenone and 1500 mg calcium carbonate per day and the control group (n = 30) received placebo and 1500 mg calcium carbonate per day for 48 weeks. BMD of lumbal spine (L2-L4), osteocalcin (OC) and undercarboxylated OC were measured before, 24 and 48 weeks after initiation of the treatment. RESULTS: After 48 weeks of treatment, the mean percentage change of lumbar BMD in the vitamin K2 group was significantly higher (P < 0.05) than that of the control group. The undercarboxylated OC level decreased by 55.9% in the menatetrenone group and 9.3% in the control group compared with the baseline level. The difference between the two groups was significant (P < 0.01). The adverse events were three minor gastrointestinal cases, which subsided after temporary cessation of therapy. CONCLUSIONS: Treatment with 45 mg vitamin K2 with 1500 mg calcium per day for postmenopausal women with osteoporosis for 48 weeks resulted in a significant increase in lumbar BMD and a significant decrease in undercarboxylated OC levels.     

The impact of serum FSH and estradiol on postmenopausal osteoporosis related to time since menopause

Aim: To determine the impact on osteopenia/osteoporosis of serum follicle-stimulating hormone (FSH), estradiol levels and time since menopause in a group of Turkish postmenopausal women. Methods: Four hundred and thirty-three healthy postmenopausal women seen at the Marmara University Menopause Outpatient Clinic were enrolled for this prospective cohort study. The women were allocated to one of three groups according to the bone mineral density (BMD) of the lumbar vertebrae and total hip, as measured by dual energy X-ray absorptiometry (DEXA). Serum FSH, estradiol levels, age and time since menopause were compared between the groups. Results: The mean serum FSH, LH, estradiol and testosterone levels for women with normal, osteopenic and osteoporotic BMD at lumbar vertrebra L1-L4 and total hip were comparable. Time since menopause had a stronger predictive value for low BMD (osteopenia or osteoporosis) in the lumbar and hip areas than did serum FSH or estradiol levels. Conclusions: Our study showed that neither FSH nor E2 has a strong impact on postmenopausal BMD. However it appears that time since menopause has a weak non-significant association with postmenopausal osteopenia and osteoporosis.     

Risedronate prevents bone loss in early postmenopausal women: a prospective randomized, placebo-controlled trial.

OBJECTIVES: To assess the efficacy and tolerability of risedronate, a pyridinyl bisphosphonate, in preventing loss of bone mineral density (BMD) of the lumbar spine and proximal femur in early postmenopausal women. METHODS: A total of 383 patients were randomly assigned to receive risedronate 2.5 or 5 mg or placebo once daily for 24 months. All patients received 1 g elemental calcium daily. BMD was measured by dual X-ray absorptiometry at baseline and at 3, 6, 12, 18, and 24 months. RESULTS: Risedronate 5 mg significantly increased BMD at the lumbar spine and femoral neck and trochanter in early postmenopausal women. Significant results were observed as early as 3 months. In the control calcium-supplemented group, BMD decreased steadily at each site throughout the study. The mean percentage change from baseline in BMD in the risedronate 5 mg group was significantly different from that in the control group at each determination at each site. At 24 months, the differences were 4.5 +/- 0.45% at the lumbar spine, 3.3 +/- 0.49% at the femoral neck, and 4.3 +/- 0.67% at the femoral trochanter. Risedronate 2.5 mg maintained BMD at each site, although the effect was less pronounced than that of risedronate 5 mg. Risedronate was well tolerated and was not associated with an increased incidence of overall or upper gastrointestinal adverse events. CONCLUSIONS: Risedronate 5 mg prevents bone loss in early postmenopausal women, is well tolerated, and represents an effective choice to maintain bone mass and prevent osteoporosis.     

Safety and efficacy of drospirenone used in a continuous combination with 17beta-estradiol for prevention of postmenopausal osteoporosis.

OBJECTIVE: To evaluate the combination of 17beta-estradiol and continuous drospirenone for the prevention of postmenopausal osteoporosis. METHODS: A total of 180 (75%) healthy postmenopausal women aged 45-65 years completed a 2-year prospective study. Bone mineral density (BMD) at lumbar spine, hip and total body as well as endometrial thickness, markers of bone turnover and serum lipids were measured regularly. Treatment groups were given placebo or 1 mg 17beta-estradiol combined with 1, 2 or 3 mg drospirenone daily. RESULTS: BMD at the lumbar spine, hip and total body increased by 7, 4 and 3%, respectively, in all hormone groups versus placebo (all p < 0.001). Bone markers all decreased accordingly (serum osteocalcin 52%, serum bone specific alkaline phosphatase 36%, serum CrossLaps 67% and urinary CrossLaps 75% from baseline; all p < 0.001). Total cholesterol and low-density lipoprotein cholesterol decreased by 8% and 13%, respectively (both p < 0.001). High-density lipoprotein cholesterol and triglycerides remained unchanged. No significant dose-related effects were found. Endometrial thickness increased by 1.2 mm only in the 1-mg drospirenone group (p < 0.01 versus placebo). CONCLUSION: The combination of 17beta-estradiol and drospirenone has a positive effect on BMD and a potentially beneficial effect on lipids. Although endometrial thickness increased slightly, the safety of the endometrium was assured, as no cases of hyperplasia or cancer occurred.     

Evaluation of bone metabolic markers as indicators of osteopenia in climacteric women.

Lumbar bone mass (LBM) determination by quantitative computerized tomography in pre-, peri- and postmenopausal women was utilized to identify subjects at risk to develop osteoporosis. The results were related to determinations of bone metabolic markers (serum osteocalcin and urinary calcium excretion). Osteocalcin was the only metabolic marker which underwent significative changes. However, we found very poor correlations between LBM and metabolic markers and it is concluded that bone mass determination remains the method of choice to select women for preventive therapy.     

Oral contraceptives and bone mineral density: A population-based study

OBJECTIVE: We sought to test the hypothesis that exposure to oral contraceptives protects the skeleton. STUDY DESIGN: Multiple regression techniques were used to analyze data for a random sample of 710 Australian women (age range, 20-69 years). Bone mineral density was measured at the lumbar spine, proximal femur, whole body, and distal forearm. Oral contraceptive exposure was assessed by a questionnaire. RESULTS: Women exposed to oral contraceptives had a 3.3% greater mean bone mineral density adjusted for body mass index and age at the lumbar spine (partial r (2) = 0.009; P =.014). Adjusted mean vertebral bone mineral density was 3.3% greater for premenopausal women (partial r (2) = 0.008; P <.05), but the effect did not reach significance among postmenopausal women. Higher bone mineral density was associated with increased duration of exposure, with a mean increase of 3.2% associated with the first 5 years and a further 0.2% with >/=5 years of exposure. No association was detected at other sites. CONCLUSION: Exposure to oral contraceptives may be associated with higher lumbar spine bone mineral density.     

Androgen receptor (AR) gene microsatellite polymorphism in postmenopausal women: correlation to bone mineral density and susceptibility to osteoporosis

OBJECTIVE: To investigate the correlation of the androgen receptor gene microsatellite polymorphism (CAG trinucleotide repeat polymorphism on exon 1) with bone mineral density and their relationship to osteoporosis in postmenopausal women. STUDY DESIGN: A number of 168 of 477 postmenopausal women were randomly recruited. The androgen receptor gene microsatellite polymorphism was determined using polymerase chain reaction-based microsatellite analysis. Bone mineral density of the lumbar spine and proximal femur was measured using dual-energy X-ray absorptiometry. RESULTS: The AR genotype was classified from "9" to "32" according to the number of CAG trinucleotide repeats they contained to represent "signposts". After adjustment for potential confounding factors such as age, height, weight, years since menopause, and daily calcium intake, subjects with genotype 20+ (n=64) had lower bone mineral density values and a significantly greater risk for osteoporosis (OR 4.2, 95% CI 1.0-17.2) when compared with subjects with genotype 20- (n=104) at the femoral neck. CONCLUSION: The present study suggests that the androgen receptor gene microsatellite polymorphism may be a candidate genetic marker for risk of osteoporosis in postmenopausal women.