Relation between obesity and bone mineral density and vertebral fractures in Korean postmenopausal women

Purpose

The traditional belief that obesity is protective against osteoporosis has been questioned. Recent epidemiologic studies show that body fat itself may be a risk factor for osteoporosis and bone fractures. Accumulating evidence suggests that metabolic syndrome and the individual components of metabolic syndrome such as hypertension, increased triglycerides, and reduced high-density lipoprotein cholesterol are also risk factors for low bone mineral density. Using a cross sectional study design, we evaluated the associations between obesity or metabolic syndrome and bone mineral density (BMD) or vertebral fracture.

Materials and Methods

A total of 907 postmenopausal healthy female subjects, aged 60-79 years, were recruited from woman hospitals in Seoul, South Korea. BMD, vetebral fracture, bone markers, and body composition including body weight, body mass index (BMI), percentage body fat, and waist circumference were measured.

Results

After adjusting for age, smoking status, alcohol consumption, total calcium intake, and total energy intake, waist circumference was negatively related to BMD of all sites (lumbar BMD p = 0.037, all sites of femur BMD p < 0.001) whereas body weight was still positively related to BMD of all sites (p < 0.001). Percentage body fat and waist circumference were much higher in the fracture group than the non-fracture group (p = 0.0383, 0.082 respectively). Serum glucose levels were postively correlated to lumbar BMD (p = 0.016), femoral neck BMD (p = 0.0335), and femoral trochanter BMD (p = 0.0082). Serum high density lipoprotein cholesterol (HDLC) was positively related to femoral trochanter BMD (p = 0.0366) and was lower in the control group than the fracture group (p = 0.011).

Conclusion

In contrast to the effect favorable body weight on bone mineral density, high percentage body fat and waist circumference are related to low BMD and a vertebral fracture. Some components of metabolic syndrome were related to BMD and a vertebral fracture.     

Gender differences in fracture risk and bone mineral density

We have investigated gender-related differences of bone mineral density and fracture threshold in 136 males (age, 60.7±9.3 years) and 337 females (age, 59.7±7.8 years) without evidence of secondary osteoporosis. Women and men were examined for total amount of spine fractures and bone mineral density by quantitative computed tomography (QCT) of three non-fractured vertebral bodies L1–L5. Females with lumbar fractures (n=96) when compared with non-fracture women (n=241) were older and had lower bone density at their vertebral sites. Males with vertebral fractures (n=52) were older and had a significantly reduced bone mineral density of the spine when compared with healthy males (n=84). When we compared gender-related vertebral fracture rates, we observed a significantly higher prevalence of vertebral fractures in the male population. After matching males and females for age and bone mineral density to exclude an influence of either variable, we compared the prevalence of vertebral fracture risk in both sexes with logistic regression analysis. Data of estimated fracture risk, differed very significantly for sex and bone density at the vertebral site, indicating that men present fracture at a higher bone density level compared with females; in 10% of study population fractures occurred at a QCT level of 105 mg/cm³ in women and 120 mg/cm³ in men. The estimated odds ratio for sex of 3.1 (95% CI) means a three-fold increased risk for vertebral fractures compared to males at a given density level. These results underline that a decreased bone mineral density leads to the occurrence of spine fractures in females and males as well.     

骨密度影像学测量与椎体骨折率评估结合提高骨质疏松的诊断率

背景：临床上用于诊断骨质疏松症的通用指标：脆性骨折或骨密度T ≤ -2.5标准差,只要满足一个条件即可作出骨质疏松的诊断。在做骨密度检查时同时进行椎体骨折评估,可以避免单一因素的评判造成骨质疏松症的漏诊,有利于提高骨质疏松的诊断率。 目的：评估骨密度结合椎体骨折对骨质疏松症临床诊断率的影响。 方法：对217例年龄≥50岁的绝经后女性患者行髋部骨密度检测,同时进行椎体骨折评估,比较单纯依靠骨密度检查与骨密度结合椎体骨折评估对骨质疏松的诊断率的影响,同时探讨骨密度对椎体骨折率的影响。 结果与结论：92例骨密度T ≤ -2.5,达到骨质疏松诊断阈值,占42.4%;102例骨密度-1 > T > -2.5,为低骨量,占47.0%;23例骨密度在正常范围,骨密度T > -1,占10.6%。158例无椎体骨折;59例(27.2%)椎体骨折,101个骨折椎。骨密度T > -2.5的患者椎体骨折率为21.6%,骨密度T ≤ -2.5的患者椎体骨折率34.8%,两组骨折率比较差异有显著性意义(P < 0.05);骨密度结合椎体骨折评估的骨质疏松诊断率为54.8%,比单纯依靠骨密度检查,骨质疏松诊断率提高12.4%(P=0.01)。说明绝经后女性做骨密度检测的同时进行椎体骨折评估可以提高骨质疏松的诊断率。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

Estrogen receptor alpha polymorphism as a genetic marker for bone loss, vertebral fractures and susceptibility to estrogen

OBJECTIVE: The purpose of the present study was to investigate the possible roles of PvuII and XbaI polymorphisms of the estrogen receptor alpha (ER(alpha)) in bone mineral density (BMD), vertebral fracture, bone loss rate after menopause and response to hormone replacement therapy (HRT). METHODS: All 286 women were grouped according to the genotypes of PvuII or XbaI polymorphisms of the ER(alpha) gene. We compared the BMD Z-score, incidence of vertebral fracture, changes in Z-score after menopause and response of BMD to HRT among the genotypes. RESULTS: Subjects with the PPxx genotype had significantly (P<0.05) lower Z-scores than did subjects with the other genotypes. A negative correlation was observed between the length of time after menopause and the decrease of the Z-score only in women with the pp genotype, suggesting faster bone loss in this group. In the analysis of the ER(alpha) polymorphism with regard to the effect of HRT on BMD, there appears to be a significantly greater increase of BMD (P<0.01 and 0.05) in women with the pp genotype than in those with the Pp or PP genotype. CONCLUSIONS: PvuII and XbaI polymorphisms of the ER(alpha) gene were associated with BMD in postmenopausal Japanese women. Also, the polymorphisms may be useful genetic markers for predicting vertebral fracture in relatively young postmenopausal women. The PvuII polymorphism may be associated with susceptibility to changes in estrogen level.     

Cortical bone loss at the tibia in postmenopausal women with osteoporosis is associated with incident non-vertebral fractures: Results of a randomized controlled ancillary study of HORIZON

Background

In postmenopausal women, yearly intravenous zoledronate (ZOL) compared to placebo (PLB) significantly increased bone mineral density (BMD) at lumbar spine (LS), femoral neck (FN), and total hip (TH) and decreased fracture risk. The effects of ZOL on BMD at the tibial epiphysis (T-EPI) and diaphysis (T-DIA) are unknown.

Methods

A randomized controlled ancillary study of the HORIZON trial was conducted at the Department of Osteoporosis of the University Hospital of Berne, Switzerland. Women with ≥1 follow-up DXA measurement who had received ≥1 dose of either ZOL (n = 55) or PLB (n = 55) were included. BMD was measured at LS, FN, TH, T-EPI, and T-DIA at baseline, 6, 12, 24, and 36 months. Morphometric vertebral fractures were assessed. Incident clinical fractures were recorded as adverse events.

Results

Baseline characteristics were comparable with those in HORIZON and between groups. After 36 months, BMD was significantly higher in women treated with ZOL vs. PLB at LS, FN, TH, and T-EPI (+7.6%, +3.7%, +5.6%, and +5.5%, respectively, p < 0.01 for all) but not T-DIA (+1.1%). The number of patients with ≥1 incident non-vertebral or morphometric fracture did not differ between groups (9 ZOL/11 PLB). Mean changes in BMD did not differ between groups with and without incident fracture, except that women with an incident non-vertebral fracture had significantly higher bone loss at predominantly cortical T-DIA (p = 0.005).

Conclusion

ZOL was significantly superior to PLB at T-EPI but not at T-DIA. Women with an incident non-vertebral fracture experienced bone loss at T-DIA.     

Age-related changes in body composition of healthy and osteoporotic women

Objectives: The study was carried out to assess age-related changes of body composition and to evaluate the influence of lean and fat mass in bone mineral density of healthy and osteoporotic women. Methods: 166 healthy women in premenopause (43.2 ± 6.7 years), 591 healthy postmenopausal women (59.9 ± 8.1 years) and 373 women with established involutive osteoporosis (66.2 ± 7.8 years) were evaluated: bone mineral density (BMD) and soft tissue composition (fat mass, lean mass) were measured by a total body Lunar DPX device. Results: no difference in lean mass was appreciated between the groups. Fat mass was significantly lower in premenopausal women (19.5 ± 6.5 kg) and osteoporotic patients (18.8 ± 5.2 kg) than in postmenopausal healthy women (21.8 ± 5.7 kg). In premenopause weight, soft tissue mass and fat mass increased with age (P < 0.05). In postmenopause, lean mass decreased significantly in healthy women (P < 0.05). Fat mass was lower in the osteoporotics than in normals. Total BMD correlated significantly with fat and lean mass in all groups (P < 0.01). BMD/height ratio correlated significantly with fat mass (P < 0.01), not with lean mass. Conclusions: BMD is closely related to fat mass in healthy premenopausal and postmenopausal women, and in osteoporotic patients; osteoporotic patients and healthy premenopausal women are characterized by a lower fat mass than healthy postmenopausal women; fat mass may be considered one of the determinants of bone mass also in involutive osteoporosis.     

Determinants of one-year response of lumbar bone mineral density to alendronate treatment in elderly Japanese women with osteoporosis

The purpose of this study was to determine factors that could predict the one-year response of the lumbar bone mineral density (BMD) to alendronate treatment in elderly Japanese women with osteoporosis. Eighty-five postmenopausal women with osteoporosis, all of whom were between 55-88 years of age, were treated with alendronate (5 mg daily) for 12 months. Serum calcium, phosphorus, and alkaline phosphatase (ALP) and urinary NTX levels were measured at the baseline and 6 months, and lumbar (L1-L4) BMD was measured by dual energy X-ray absorptiometry at the baseline and 12 months. Multiple regression analysis was used to determine factors that were correlated with the percent change in lumbar BMD at 12 months. Lumbar BMD increased by 8.1 % at 12 months with a reduction in the urinary NTX level by 51.0 % at 6 months. Baseline lumbar BMD (R2=0.226, p < 0.0001) and percent changes in serum ALP and urinary NTX levels (R2=0.044, p < 0.05 and R2=0.103, p < 0.001, respectively) had a negative correlation with the percent change in lumbar BMD at month 12, while the baseline number of prevalent vertebral fractures (R2=0.163, p < 0.001), serum ALP level, and urinary NTX level (R2=0.074, p < 0.05 and R2=0.160, p < 0.001, respectively) had a positive correlation with it. However, baseline age, height, body weight, body mass index, years since menopause, serum calcium and phosphorus levels, and percent changes in serum calcium and phosphorus levels at 6 months did not have any significant correlation with the percent change in lumbar BMD at 12 months. These results suggest that lumbar BMD was more responsive to one-year of alendronate treatment in elderly osteoporotic Japanese women with lower lumbar BMD, more prevalent vertebral fractures, and higher bone turnover, who showed a greater decrease in bone turnover at 6 months, regardless of age, years since menopause, and physique. Alendronate may be efficacious in elderly Japanese women with evident osteoporosis that is associated with high bone turnover, and the percent changes in serum ALP and urinary NTX levels at 6 months could predict the one-year response of lumbar BMD to alendronate treatment.     

Reduced bone mineral density and low parathyroid hormone levels in patients with the adult form of hypophosphatasia

Summary Hypophosphatasia is a heritable metabolic bone disease with characteristically reduced levels of alkaline phosphatase (ALP) in the blood, liver, kidney and bone. ALP levels are normal in the intestine and placenta. About 300 patients have been reported so far in the literature. Three kindreds with 52 known subjects are described here, whereby 12 subjects could be examined osteologically. Four subjects were patients and had clinical signs of the disease: spontaneous fractures of the metatarsals or femora and low ALP serum levels ranging between 8 and 23 U/1 (normal range 40–170 U/1). Four other members without fractures had reduced ALP levels; they might be carriers of the disease and develop symptoms later in life. The four remaining subjects had normal ALP levels and no signs of the disease. Serum levels of intact parathyroid hormone (iPTH) were found to be in the lower normal range and serum calcium levels in the upper normal range. There was a significant (P<0.05) negative correlation between iPTH and serum calcium levels (r=–0.78). Urinary calcium excretion was increased in 3 subjects with fractures. 25-OH-D₃ levels were increased in 6 of 8 subjects without any treatment. The bone mineral density (BMD) was measured using dual X-ray absorptiometry of the lumbar spine, representing mainly trabecular bone, and single-photon absorptiometry of the forearm, measuring mainly cortical bone. Z-scores of the spinal bone mass ranged between 0.38 and –1.95 SD; Z-scores of the forearm bone mass ranged between 0.53 and –2.47 SD with the lowest values in patients with fractures. There was a significant (P<0.05) correlation between serum ALP levels and forearm BMD (r=0.83). We conclude from these data that patients with the adult form of hypophosphatasia have decreased forearm and subnormal spinal bone mass, as well as reduced serum levels of iPTH.Abbreviations BMD bone mineral density - ALP alkaline phosphatase - iPTH intact parathyroid hormone - 25-OHD₃ 25-hydroxyvitamin D₃ - SD standard deviation - PEA phosphoethanolamine - PPi inorganic pyrophosphate - PLP pyridoxal-5-phosphate - cDNA clonal desoxyribonucleic acid - U/S Ca²⁺ urinary/serum calcium - DXA dual X-ray absorptiometry - DPA dual photon absorptiometry - SPAD bone density of distal forearm measured by single photon absorptiometry - SPAP bone density of proximal forearm measured by single photon absorptiometry     

Bone density patterns after normal and premature menopause

Objectives: The investigation of the effect of time and type of menopause on bone mineral density (BMD) at different ages. Methods: Five hundred and fourteen women, who had never received any hormonal substitution were studied in a cross-sectional design: 177 with normal (NMP), 210 with surgical (SUMP) and 127 with premature natural (EMP) menopause. Age at menopause was 49.1±3.9, 38.3±4.7 and 38.1±4.2 years (mean±1 S.D.), respectively. BMD was measured at L2–L4 vertebrae and proximal femur by the DEXA method. Results: EMP women presented significantly lower vertebral BMD than NMP women in the 45–55-years segments (P<0.001), but did not differ from SUMP women. This group exhibited lower vertebral BMD than NMP between 45 and 50 years (P<0.001). Regarding femoral neck, EMP women exhibited lower values than SUMP in the 45–50 and 55–65 age segments (P<0.001) whereas SUMP women presented significantly higher BMD values than NMP women after 55 years of age (P<0.001). The percentages of women with vertebral BMD (T-score values) in the osteoporotic range were significantly greater in EMP compared with either NMP or SUMP groups (both P<0.001) whereas in femoral neck lower in SUMP than the other two categories. Conclusions: Women with either natural or surgical premature menopause exhibit lower BMD of trabecular bone compared with normal menopause women at the age segments 45–55 and 45–50, respectively. However, surgical menopause women exceed normal menopause women in their mixed bone BMD values after 60 years as well as premature natural menopause women at almost all age segments.     

Bone mineral density in older non-Hispanic Caucasian and Mexican-American women: relationship to lean and fat mass

Primary objective: The prevalence of osteoporotic fracture is higher in non-Hispanic Caucasian (NHC) than Mexican-American (MA) women in the USA. The present study examined bone mineral density (BMD) in these two ethnic groups and the association between BMD and body composition.

Research design: Cross-sectional.

Subjects: Sixty-two NHC and 54 MA women, aged 60-86 years, with a body mass index (kgm^-2) of &lt; 30.

Methods: BMD (gcm^-2) of the spine (L_2-4), hip (femoral neck, trochanter, Ward's triangle) and whole body was determined by dual-energy X-ray absorptiometry (DXA). Bone mineral-free lean mass (LM) and fat mass (FM) and several ratios of body fat distribution were also assessed by DXA.

Results: There was no difference in age (NHC, 69.5 ± 0.7; MA 69.5 ± 0.9 years; mean ± SEM) or body mass, but MA women were shorter with a higher truncal adiposity (p < 0.001). There was no significant difference in BMD between groups, however, adjusting for height resulted in higher hip and whole body BMD in MA women (p < 0.01). When volumetric bone density was calculated (bone mineral apparent density; BMAD, g cm^?3), a trend for higher values in MA women was observed at the femoral neck (p = 0.018). LM contributed independently to BMD at the spine and hip in NHC women, with FM also contributing at the femoral neck. In MA women, LM was an independent contributor to lumbar spine and trochanter BMD, and both LM and FM contributed to whole body BMD. However, the effects of LM and FM were removed in both groups when BMD was adjusted for body or bone size, the only exception being at the trochanter in NHC women.

Conclusions: These results indicate that MA women have higher bone density at the proximal femur than NHC women, which may partially account for their lower rate of hip fracture. Further, differences in bone density between the two ethnic groups do not appear to be dependent on soft-tissue composition.     

Calcitonin receptor polymorphism is associated with a decreased fracture risk in post-menopausal women

High bone resorption by the osteoclast results in osteoporosis, a disease affecting 40% of women after the menopause. Calcitonin, used to treat osteoporosis, inhibits bone resorption via receptors located on the osteoclasts. Two alleles of the calcitonin receptor gene ( CTR ) exist: a base mutation T-->C in the third intracellular C-terminal domain changes a proline (CCG) at position 447 to a leucine (CTG). We therefore studied the distribution of these alleles in a cohort of 215 post-menopausal Caucasian women suffering or not from osteoporotic fractures. The region of interest within the point mutation was amplified by PCR and screened for single strand conformation polymorphism. This work was followed by DNA sequencing of the fragments amplified. We found that bone mineral density (BMD) at the femoral neck was significantly higher in heterozygous subjects with the Rr genotype compared with the homozygous leucine (RR) and homozygous proline (rr) genotypes. Also, a decreased fracture risk was observed in heterozygote subjects. In conclusion, our results suggest that polymorphism of CTR could be associated with osteoporotic fractures and BMD in a population of post-menopausal women. CTR heterozygotes could produce both alleles of the receptor. The heterozygous advantage effect of Rr subjects could explain their protection against osteoporosis: higher bone density and decreased fracture risk. Establishing the genotype of the CTR gene in post-menopausal women could be of value in evaluating their risk of developing fractures.      

Prevalence of osteoporosis,vertebral fractures and hypovitaminosis D in postmenopausal women living in a rural environment

Objectives

First, to study the difference between two groups of postmenopausal women living in different population centres (rural vs urban) in the prevalence of osteoporosis, fragility fractures and factors which may influence them: hypovitaminosis D, bone mineral density, coexistence of other diseases which predispose to their appearance; secondly, to observe the influence of low socioeconomic status, categorised as poverty.

Study design

1229 postmenopausal women were studied, of whom 390 (31.7%), were living in rural areas and 839 (68.3%), in urban areas. Data regarding risk factors related to osteoporosis were obtained, and, among other biochemical measures, 25 hydroxyvitamin D and parathyroid hormone were determined. Bone densitometry was carried out in the lumbar spine and proximal femur, as well as lateral X-rays of the dorsal and lumbar spine.

Results

The women who lived in rural areas were older, shorter, heavier and had a higher body mass index than those from urban areas. Among the women from rural areas there was a higher prevalence of poverty, and higher levels of obesity, arterial hypertension and diabetes mellitus were observed, as well as a higher prevalence of densitometric osteoporosis. The rural women had lower values of bone mineral density in the lumbar spine and a higher prevalence of vertebral fractures and hypovitaminosis D. The variables which were associated independently with living in rural areas were poverty, obesity, vertebral fractures, BMD in the lumbar spine and levels of 25 hydroxyvitamin D.

Conclusions

In our study, postmenopausal women who live in rural populations have more poverty, lower values of vitamin D, lower BMD in the lumbar spine and a higher prevalence of vertebral fractures and of osteoporosis. The higher prevalence of obesity, arterial hypertension and diabetes mellitus observed in these women may be adjuvant factors, all fostered by their socioeconomic state of poverty.     

Association of oestrogen receptor alpha gene polymorphisms with postmenopausal bone loss, bone mass, and quantitative ultrasound properties of bone

Background: The gene encoding oestrogen receptor α (ESR1) appears to regulate bone mineral density (BMD) and other determinants of osteoporotic fracture risk.

Objective: To investigate the relation between common polymorphisms and haplotypes of the ESR1 gene and osteoporosis related phenotypes in a population based cohort of 3054 Scottish women.

Results: There was a significant association between a common haplotype "px", defined by the PvuII andXbaI restriction fragment length polymorphisms within intron 1 of the ESR1 gene, and femoral neck bone loss in postmenopausal women who had not received hormone replacement therapy (n = 945; p = 0.009). Annual rates of femoral neck bone loss were ~14% higher in subjects who carried one copy of px and 22% higher in those who carried two copies, compared with those who did not carry the px haplotype. The px haplotype was associated with lower femoral neck BMD in the postmenopausal women (p = 0.02), and with reduced calcaneal broadband ultrasound attenuation (BUA) values in the whole study population (p = 0.005). There was no association between a TA repeat polymorphism in the ESR1 promoter and any phenotype studied, though on long range haplotype analysis subjects with a smaller number of TA repeats who also carried the px haplotype had reduced BUA values.

Conclusions: The ESR1px haplotype is associated with reduced hip BMD values and increased rates of femoral neck bone loss in postmenopausal women. An association with BUA may explain the fact that ESR1 intron 1 alleles predict osteoporotic fractures by a mechanism partly independent of differences in BMD.

     

Association of the MTHFR C677T polymorphism and bone mineral density in postmenopausal women: a meta-analysis

Osteoporosis is a condition characterized by low bone mineral density (BMD) and micro-architectural changes in the bone tissue. The risk of osteoporosis is partly determined by genetic factors. The role of C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene has been investigated in postmenopausal osteoporosis. However, the relationship between MTHFR polymorphism and BMD is still controversial. We carried out a meta-analysis of 5,833 subjects to evaluate the association of MTHFR and BMD in postmenopausal women. Databases of MEDLINE, Web of Science, Scopus and CNKI were retrieved for all publications relating to MTHFR polymorphism and BMD in postmenopausal women. Five eligible studies were selected for meta-analysis. All these articles studied the association of MTHFR polymorphism and BMD of the femoral neck and lumbar spine in postmenopausal women. Our analysis suggested that postmenopausal women with the TT genotype had lower femoral neck BMD than the women with the CC/CT genotype, and the weighted mean difference (WMD) was -0.01 g/cm² [95% confidence interval (CI): (-0.01, -0.01), P < 0.01]. However, BMD of the lumbar spine of postmenopausal women with the TT genotype was not significantly different from that of women with the CC/CT genotype. In the random effects model, the WMD between the TT and TC/CC genotype was -0.01 g/cm² [95% CI: (-0.04, 0.01), P = 0.32]. The C677T polymorphism of the MTHFR gene is associated with BMD of the femoral neck in postmenopausal women. Women with the TT genotype of the MTHFR gene have lower BMD, suggesting that the TT genotype may be a risk factor for postmenopausal osteoporosis.     

High Serum Osteopontin Levels Are Associated with Low Bone Mineral Density in Postmenopausal Women

Osteopontin (OPN) is an acidic, noncollagenous matrix protein produced by the bone and kidneys. It is reportedly involved in bone resorption and formation. We examined the association between serum OPN levels and bone mineral density in postmenopausal women. Premenopausal women (n=32) and postmenopausal women (n=409) participated in the study. We measured serum osteopontin levels and their relationships with bone mineral density and previous total fragility fractures. The postmenopausal women had higher mean serum OPN levels compared to the premenopausal women (43.6±25.9 vs 26.3±18.6 ng/mL; P<0.001). In the postmenopausal women, high serum OPN levels were negatively correlated with mean lumbar bone mineral density (BMD) (r=-0.113, P=0.023). In a stepwise multiple linear regression model, serum OPN levels were associated with BMD of the spine, femoral neck, and total hip after adjustment for age, body mass index, smoking, and physical activity in postmenopausal women. However, serum OPN levels did not differ between postmenopausal women with and without fractures. Postmenopausal women exhibit higher serum OPN levels than premenopausal women and higher serum OPN levels were associated with low BMD in postmenopausal women.     

Lower calcaneal bone mineral density and broadband ultrasonic attenuation,but not speed of sound,in South Asian than white European women

Background: Quantitative ultrasound (QUS) measures of bone predict fracture risk in older white women. South Asian women have low bone mineral density (BMD), perhaps related to smaller body size or vitamin D insufficiency, but it is unknown whether this is accompanied by lower QUS.

Aim: The study compared QUS, BMD and vitamin D status between South Asian and white European women.

Subjects and methods: Participants were 47 postmenopausal women (23 white European, 24 South Asian) aged 55–65 years. BMD was measured at the calcaneus and radius by dual X-ray absorptiometry. The QUS measurements were broadband ultrasound attenuation (BUA) at the calcaneus and speed of sound (SOS) at the calcaneus, radius and tibia. Serum 25-hydroxy vitamin D was determined in late summer.

Results: South Asian women had significantly lower serum 25-hydroxyvitamin D than white Europeans (13.0 ± 5.1 versus 30.3 ± 7.1 ng mL^–1; p < 0.001). Calcaneal BMD and BUA were 14% and 10% lower (p = 0.016 and 0.045), respectively, in South Asian women. Radial BMD, and SOS at all sites, did not differ significantly between groups.

Conclusion: In this study, postmenopausal South Asian women living in the UK had a high prevalence of vitamin D insufficiency and lower calcaneal BMD than white European women, consistent with previous findings. Differences were detected in calcaneal BUA but not SOS. Further research is needed to evaluate fracture risk and its detection in South Asian women.     

Changes in bone markers after once-weekly low-dose alendronate in postmenopausal women with moderate bone loss

BACKGROUND: High bone turnover, with bone resorption exceeding bone formation, is a major mechanism of postmenopausal osteoporosis. Therefore, inhibition of bone resorption is a rational approach for the prevention of bone loss. The objective of the current study was to determine the short-term efficacy of once-weekly low-dose alendronate in the prevention of bone loss, via bone turnover markers, in early postmenopausal Korean women with moderate bone loss. METHODS: This study involved a 12-week, randomized, double-blind clinical trial that compared the effects of placebo with alendronate 20mg once weekly. All subjects received supplemental calcium 600 mg and vitamin D 400IU daily. We recruited 63 postmenopausal women (ranging from 50 to 65 years of age) with the lowest lumbar spine bone mineral density (BMD) at least 2.0 S.D. below the mean value for young healthy adults. BMD was measured at baseline and serum alkaline phosphatase (ALP), osteocalcin, C-terminal telopeptide of type I collagen (CTX), and osteoprotegerin (OPG) were measured at baseline and 12 weeks after treatment. RESULTS: We randomly assigned 63 women to either placebo or alencronate 20 mg once a week for 3 months. Forty-nine women continued and completed all 3 months. After 3 months, bone resorption markers were significantly decreased in the alendronate group than in the placebo group: CTX -47.2% vs. 15% (p<0.01), ALP 1.6% vs. 25.9% (p=0.01), osteocalcin -29.2% vs. -13.6 (p=0.06). Women who received alendronate showed similar results to those who received placebo with regard to adverse events. CONCLUSION: Once-weekly low-dose alendronate may be a cost-effective and safe method of suppressing bone turnover in early postmenopausal women with moderate bone loss.     

Postmenopausal osteoporosis and alendronate

Osteoporosis is a systemic metabolic disorder associated with a decreased bone mass and resistance. Bisphosphonates suppress bone resorption and bone turnover by a mechanism that depends on their structure. They are characterized by low gastrointestinal absorption. In postmenopausal women, alendronate (ALN) reduces bone resorption markers and increases bone mineral density (BMD) in the lumbar spine, femoral neck, and total body. Individuals receiving ALN have been studied for up to 10 years with an apparent linear increase in BMD over that time period estimated at 13.7% at the lumbar spine. Treatment with ALN reduced the risk of both vertebral and non-vertebral fractures, including hip fractures, in postmenopausal women with osteoporosis. Direct comparisons of the results obtained with different antiresortive agents is difficult, because the designs of the respective studies, populations and other factors. However, the meta-analysis of available publications seems to indicate that ALN reduces the relative risk of vertebral fractures in a greater proportion than any other agent. Furthermore, ALN prevents the reduction in BMD after hormone replacement therapy discontinuation.     

Spotlight on Teriparatide in Osteoporosis

Recombinant teriparatide (Forteo®; Forsteo®) is an anabolic (bone-forming) agent. Studies have shown that subcutaneous teriparatide 20 μg/day is effective in women with postmenopausal osteoporosis, men with idiopathic or hypogonadal osteoporosis, and patients with glucocorticoid-induced osteoporosis. Teriparatide improves bone mineral density (BMD) and alters the levels of bone formation and resorption markers; histomorphometric studies have shown teriparatide-induced effects on bone structure, strength, and quality. Subcutaneous teriparatide 20 μg/day administered over a treatment period of 11–21 months was effective in reducing the risk of fractures and improving BMD in men with idiopathic or hypogonadal osteoporosis, women with postmenopausal osteoporosis, and patients with glucocorticoid-induced osteoporosis. Furthermore, the beneficial effects of teriparatide on vertebral fracture prevention and BMD appear to persist following treatment cessation. Teriparatide is generally well tolerated and treatment compliance rates are favorable. However, current limitations on the length of treatment and the high acquisition cost mean that teriparatide is best reserved for the treatment of patients with osteoporosis at high risk of fracture, or for patients with osteoporosis who have unsatisfactory responses to or intolerance of other osteoporosis therapies.     

Treatment of osteoporosis with denosumab

Osteoporosis is a common skeletal disease associated with an imbalance in bone remodeling resulting in a reduction in bone strength and increased fracture risk. The principal regulator of osteoclastic bone resorption is receptor activator of nuclear factor-κB ligand (RANKL), a cytokine member of the tumor necrosis factor family. The binding of RANKL to its receptor on the cell surface of osteoclasts and pre-osteoclasts increases the formation, activity, and survival of osteoclasts. Denosumab is an investigational fully human monoclonal antibody to RANKL. By binding to RANKL, denosumab prevents RANKL from binding to its receptor, resulting in a decrease in bone resorption due to reduction in the formation, activity, and survival of osteoclasts. In postmenopausal women with osteoporosis, denosumab 60 mg by subcutaneous injection every 6 months increased bone mineral density (BMD), reduced bone turnover markers, and reduced the risk of vertebral, hip, and non-vertebral fractures. In postmenopausal women with low BMD, denosumab increased BMD and reduced bone turnover markers. It was well tolerated with a safety profile generally similar to placebo. Denosumab is a promising emerging drug for the prevention and treatment of postmenopausal osteoporosis. It may be particularly useful in clinical practice for the treatment of patients with gastrointestinal contraindications or side effects with oral bisphosphonates and for patients with malabsorption.