Association of FGF23 and Klotho protein with bone mineral density in maintenance hemodialysis patients

Objective To explore the association between serum FGF23 and Klotho protein, and bone mineral density in maintenance hemodialysis (MHD) patients. Methods A total of 125 MHD patients admitted in the Hospital between January 2015 and November 2015 was enrolled. Their bone mineral densities of femur neck and lumbar spine were studied by dual-energy X-ray absorptiometry. These patients were divided into three groups as normal, osteopenic and osteoporotic, according to World Health Organization criteria based on bone mineral density T scores. Levels of serum FGF23, Klotho protein and 1,25(OH)2VitD3 were measured by ELISA. The parameters including calcium, phosphorus, and parathyroid hormone were assessed. Results The incidences of osteopenia and osteoporosis at the femur neck and lumbar spine in MHD patients were 82.40% and 56.00% respectively. No significant difference was found in the levels of serum FGF23 among normal, osteopenic and osteoporotic groups on the basis of femur neck and lumbar spine bone mineral density (P﹥0.05). No correlation was found between FGF23 and bone mineral density. There however were significant differences in the levels of serum Klotho protein among three groups on the basis of femoral neck bone mineral density (P＜0.05). And the levels of Klotho protein in the osteoporotic group [(387.172±54.137) ng/L] were significantly decreased than those in normal group [(429.883±41.776) ng/L] and osteopenic group [(410.598±61.056) ng/L] (P＜0.05). There were also significant differences in the levels of serum Klotho protein among three groups in terms of lumbar spine bone mineral density (P＜0.05), while the levels of Klotho protein in the osteopenic group [(387.263±53.255) ng/L] were significantly decreased than those in normal group [(417.108±56.179) ng/L] (P＜0.05). A positive correlation was found between Klotho protein and bone mineral densities of femur neck and lumbar spine. Multiple linear regression analysis showed that one of the main factors influencing the degree of bone mineral density in MHD patients was Klotho protein. Conclusions CKD-MBD with low BMD is common and widespread in hemodialysis patients. FGF23 has no direct effect on bone mineral density in MHD patients; while Klotho protein is correlated with the severity of bone mineral density. High-level Klotho protein may reduce the severity of CKD-MBD with low BMD in MHD patients.     

Age, body mass index, current smoking history, and serum insulin-like growth factor-I levels associated with bone mineral density in middle-aged Korean men

Osteoporosis is a growing health problem in women and in men. This cross-sectional study examined the association of anthropometric, lifestyle, and hormonal factors with bone mineral density (BMD) in 152 healthy Korean middle-aged men. Smoking habits and alcohol consumption were assessed by interview. Serum testosterone and insulin-like growth factor-I (IGF-I) levels were measured by radioimmunoassay, and serum growth hormone (GH) levels were measured by immunoradiometric assay. GH stimulation tests were performed after the ingestion of 500mg of L-dopa. BMD was measured at the lumbar spine and at the femoral neck by dual-energy X-ray absorptiometry. Of the middle-aged men, 3.9% were osteoporotic and 28.3% were osteopenic at the lumbar spine site, and 5.9% were osteoporotic and 45.4% were osteopenic at the femoral neck site. Lumbar spine BMD correlated significantly with body mass index (BMI), and femoral neck BMD correlated significantly with age, BMI, and serum IGF-I levels. The lowest quartile group for serum IGF-I levels showed the lowest femoral neck BMD. Osteoporotic men by lumbar spine BMD showed significant differences from the normal BMD group in terms of BMI and smoking habits. Also, osteoporotic men by femoral neck BMD were significantly different for mean age, BMI, and serum IGF-I levels compared with the normal BMD group. On multiple regression analysis, BMI was found to be the only independent predictor of lumbar spine BMD, whereas both BMI and serum IGF-I levels were found to be the independent predictors of femoral neck BMD. Overall, 28.3%–45.4% of middle-aged Korean men were osteopenic. We suggest that higher age, a lower BMI, current smoking history, and lower serum IGF-I levels are risk factors for lower BMD in middle-aged Korean men; however, serum testosterone levels and GH secretory capacity were not found to be correlated with BMD.     

Screening for Osteopenia and Osteoporosis: Do the Accepted Normal Ranges Lead to Overdiagnosis?

Osteoporosis is a common disease which causes significant morbidity and mortality and in many cases may be preventable. In the absence of fragility fractures the accepted method of identifying those at high risk is based upon bone mineral density (BMD) measurements with defined cut-off points. To correctly delineate normal from abnormal, reliable reference ranges appropriate to the observed population are required. We have studied the age-dependent changes in mean BMD and standard deviation at the lumbar spine and femoral neck in a normal population extracted from 4280 women screened for osteopenia and compared our findings with the manufacturer's normal range (MNR). The recent World Health Organization criteria for the diagnosis of osteopenia and osteoporosis using the ‘manufacturer's young normal’ (MYN) values and our ‘study young normal’ (SYN) values have been applied. The study normal population (SNP) included 2068 women (mixes social class; mean age 53 years, range 30–79 years). The distribution of mean lumbar spine BMD with age in SNP was generally similar to the MNR. In contrast mean femoral neck bone density from SNP was significantly different from the MNR, ranging from 3% to 12% lower in each 5-year group analysed (p < 0.05). Comparison of standard deviations in spine BMD in SNP against the fixed MNR standard deviation showed a statistically significant increase commencing at 45 years of age. The magnitude of this increase appeared to rise with age and remained significant in the 75-to-79-year group (p < 0.05). In contrast, standard deviation in femoral neck BMD in SNP appeared relatively constant with age except in the group of women at and around the time of the menopause. The SYN value for mean lumbar spine BMD was 0.994 g/cm² (cf. MYN value 1.047, p < 0.0001) with a standard deviation of 0.122 g/cm² (cf. MYN 0.11, p = 0.0005). Similarly our SYN value for femoral neck BMD was 0.787 (cf. MYN value 0.895, p < 0.0001) with a standard deviation of 0.109 (cf. MYN value 0.10, p = 0.0027). Using SYN values 36% (748) for the spine and 33% for the hip of our normal population are classified as osteopenic or osteoporotic. Using MYN values increases the proportion of women classified as osteopenic or osteoporotic to 52% (1078) for the spine and 68% (1409) for the femur. If both sites of measurement are considered simultaneously SYN classifies 46% (952) as either osteopenic or osteoporotic at one or other site, which is increased to 73% (1513) when the MYN values are used. We observe that manufacturer's reference ranges may not be appropriate for the local population and may lead to an erroneously high diagnosis of osteopenia and osteoporosis, which would lead to unnecessary patient anxiety and perhaps errors regarding treatment.     

Polymorphisms in the bone morphogenetic protein 2 (BMP2) gene do not affect bone mineral density in white men or women

Introduction Peak bone mineral density (BMD) achieved during adulthood is a major determinant of osteoporotic fracture in later life. Although environmental factors affect peak BMD, it is a highly heritable trait. Recently, bone morphogenetic protein 2 (BMP2) was reported as a susceptibility gene for osteoporotic fractures and low BMD in Icelandic and Danish populations. Methods To determine whether polymorphisms in the BMP2 gene contribute to BMD variation in our population of healthy American whites, we tested seven single nucleotide polymorphisms (SNPs), four of which were associated with osteoporotic phenotypes in the previous study. BMD at the femoral neck and lumbar spine (L2–L4) were measured by dual energy X-ray absorptiometry (DXA) in 411 men (age 18–61) and 1,291 pre-menopausal women (age 20–50). SNP genotypes/haplotypes were tested for population-based association with BMD using analysis of variance. Results None of the polymorphisms tested reached statistical significance (all p values >0.05) for BMD at the femoral neck or lumbar spine in either gender. Two of the SNP haplotypes spanning the entire BMP2 gene were marginally associated with BMD in men (p values=0.019−0.043). However, these haplotypes would account for only a small, if any, portion of BMD variation and would not be significant after adjustment for multiple comparisons. Conclusions These results demonstrate that genetic variations in BMP2 do not substantially contribute to BMD variation in our population of healthy American whites.     

Bone mineral density and its correlation with clinical and laboratory factors in chronic peritoneal dialysis patients

The aim of this study was to assess the clinical and laboratory correlations of bone mineral density (BMD) measurements among a large population of patients on chronic peritoneal dialysis (PD). This cross-sectional, multicenter study was carried out in 292 PD patients with a mean age of 56 ± 16 years and mean duration of PD 3.1 ± 2.1 years. Altogether, 129 female and 163 male patients from 24 centers in Canada, Greece, and Turkey were included in the study. BMD findings, obtained by dual-energy X-ray absorptiometry (DEXA) and some other major clinical and laboratory indices of bone mineral deposition as well as uremic osteodystrophy were investigated. In the 292 patients included in the study, the mean lumbar spine T-score was −1.04 ± 1.68, the lumbar spine Z-score was −0.31 ± 1.68, the femoral neck T-score was −1.38 ± 1.39, and the femoral neck Z score was −0.66 ± 1.23. According to the WHO criteria based on lumbar spine T-scores, 19.2% of 292 patients were osteoporotic, 36.3% had osteopenia, and 44.4% had lumbar spine T-scores within the normal range. In the femoral neck area, the prevalence of osteoporosis was slightly higher (26%). The prevalence of osteoporosis was 23.3% in female patients and 16.6% in male patients with no statistically significant difference between the sexes. Agreements of lumbar spine and femoral neck T-scores for the diagnosis of osteoporosis were 66.7% and 27.3% and 83.3% for osteopenia and normal BMD values, respectively. Among the clinical and laboratory parameters we investigated in this study, the body mass index (BMI) (P < 0.001), daily urine output, and urea clearance time × dialysis time/volume (Kt/V) (P < 0.05) were statistically significantly positive and Ca × PO₄ had a negative correlation (P < 0.05) with the lumbar spine T scores. Femoral neck T scores were also positively correlated with BMI, daily urine output, and KT/V; and they were negatively correlated with age. Intact parathyroid hormone levels did not correlate with any of the BMD parameters. Femoral neck Z scores were correlated with BMI (P < 0.001), and ionized calcium (P < 0.05) positively and negatively with age, total alkaline phosphatase (P < 0.05), and Ca × P (P < 0.01). The overall prevalence of fractures since the initiation of PD was 10%. Our results indicated that, considering their DEXA-based BMD values, 55% of chronic PD patients have subnormal bone mass—19% within the osteoporotic range and 36% within the osteopenic range. Our findings also indicate that low body weight is the most important risk factor for osteoporosis in chronic PD patients. An insufficient dialysis dose (expressed as KT/V) and older age may also be important risk factors for osteoporosis of PD patients.     

Spine and femur BMD by DXA in patients with varying severity spinal osteoporosis

Summary Bone mineral density (BMD) at the lumbar spine, femoral neck, trochanteric region, and Ward's triangle was measured using dual-energy X-ray absorptiometry (DXA) in 118 women with osteoporotic vertebral collapse (average age 65 years), divided into four groups according to numbers and SD of vertebral deformation below norms: group 1:-3SD deformations only; group 2: one-4SD deformation; group 3: two-four-4SD deformations; and group 4: 5 or more-4SD deformations. There were no significant differences between the groups. Results were compared with those from 80 premenopausal (average age 32 years, range 20–40 years) and 109 postmenopausal normal women (average age 64, range 60–70 years). Mean BMD in osteoporotic group 1 was lower than premenopausal normal women by 32% at the lumbar spine, 31% femoral neck, 30% trochanteric region, and 44% at Ward's triangle, and postmenopausal controls by 17% lumbar spine, 16% femoral neck, 17% trochanter, and 14% Ward's triangle. There was a clear trend to reduction in mean BMD between osteoporotic groups 1 and 4 at all four measured sites with significant differences at the spine of 0.102 g/cm² (P<0.01) and Ward's triangle 0.059 g/cm² (P<0.01). When compared with premenopausal controls, there was a reduction in mean BMD between osteoporotic groups 1 and 4 of 10% at the lumbar spine, 7% femoral neck, 8% trochanteric region, and 13% Ward's triangle. Receiver operating characteristic analysis showed no significant differences in diagnostic sensitivities among the four measured sites for vertebral fractures. We conclude from this crosssectional data that the majority of bone loss in spinal osteoporosis occurs before the onset of fractures.     

Femoral and spinal bone mineral density in Japanese osteoporotics with hip fracture

In the present study, bone mineral density (BMD) of femoral neck and lumbar spine was compared between 38 Japanese female patients with hip fracture (age 63–89 years, mean±SD 76±7 years) and 162 age-matched female controls (age 62–90 years, mean±SD 75±7 years). BMD was measured in the femoral neck and lumbar spine (L2–4) using dual-photon absorptiometry (Norland model 2600). BMD values of femoral neck as well as lumbar spine were significantly lower in patients with hip fracture than in controls (0.504±0.097 v 0.597±0.101,p<0.01, for femoral neck; 0.661±0.146 v 0.720±0.128,p<0.05, for lumbar spine). Patients with hip fracture and controls were stratified according to their BMD levels at two measuring sites, and the ratio of the number of patients and controls at each BMD level was calculated as an indicator of fracture rate. This ratio showed an exponential increase as the femoral neck BMD declined, but only a gradual increase as the lumbar spine BMD declined. Specificity-sensitivity analysis revealed that BMD values of 0.59 and 0.54 g/cm² at the femoral neck provided a specificity of 52% and 68% with a sensitivity of 90% and 75%, respectively. These findings suggest that Japanese patients with hip fracture are more osteoporotic than age-matched controls and that the selective measurement of femoral neck would be useful for predicting the risk of hip fracture.     

An Investigation of the Diagnostic Value of Bilateral Femoral Neck Bone Mineral Density Measurements

This paper describes a study to assess the clinical value of bilateral femoral neck bone mineral density (BMD) measurements. Although a range of factors will determine clinical decisions, the classification of the site with the lowest T-score is likely to have significant bearing on the management of a patient. While it is common practice to measure BMD at the lumbar spine and a single neck of femur, knowledge of the BMD of the second femur may also be of diagnostic value. Using dual-energy X-ray absorptiometry, BMD of the lumbar spine and right and left femoral neck was measured in a group of 2372 white, Caucasian women (mean age ± SD, 56.6 ±13.9 years) routinely referred for bone densitometry. Analysis of the measurements showed a significant (p= 0.02) but small difference between the mean BMD of the right (0.840 ± 0.152 g/cm²) and left (0.837 ± 0.150 g/cm²) femoral neck. Further investigation of femur scans revealed 79 (3.3%) patients in whom one side was osteoporotic while the other side and spine were normal or osteopenic using the World Health Organization diagnostic criteria in combination with manufacturer”s reference data. Patients in whom the femoral neck BMD measurements differed by less than the precision error of the system were then excluded. This left only 51 (2.2%) patients, that is 29 (1.2%) for right femur and spine scan and 22 (0.9%) for left femur and spine scan, in whom knowledge of both femoral neck BMD measurements could have altered the classification of the lowest site assessed to osteoporotic. These data suggest that there is only a small benefit from performing bilateral femoral neck BMD measurements. Since BMD measurements are only one of a range of factors considered as part of a patient”s management, it is suggested that the extra time, cost and radiation dose associated with measurement of the second femur may not be justified. Received: 28 October 1999 / Accepted: 2 February 2000     

Osteoprotegerin and Bone Mass in Squamous Cell Head and Neck Cancer Patients

Osteoprotegerin (OPG) is considered one of the main regulators of bone remodeling. Various patterns of serum OPG levels have been described in different types of tumors. We undertook this study to determine serum OPG levels in patients with squamous cell head and neck cancer (SCHNC), analyzing their relationship with other metabolic bone parameters and bone mineral density (BMD), as well as the possible influence of chemotherapy. Forty male patients with localized SCHNC were studied, and their results were compared with those of 40 healthy male controls. The type of treatment followed by each patient was noted. Age, weight, height, and lifestyle habits were recorded; and OPG, Ca²⁺, intact parathyroid hormone (iPTH), 25-Hydroxyvitamin D (25OHD) and 1,25-Dihydroxyvitamin D (1,25(OH)₂D), bone alkaline phosphatase, osteocalcin, and serum C-terminal cross-links telopeptide of type I collagen (ICTP) were determined. Dual-energy X-ray absorptiometry BMD at the lumbar spine, femoral neck, and hip was also measured. Serum OPG was higher in patients than in controls (91.7 ± 25.8 vs. 77.2 ± 26.3, P = 0.02). ICTP (a bone resorption marker) was 37% higher in patients (P = 0.007). Bone mass was lower in patients at the lumbar spine, femoral neck, and total hip. Lumbar spine Z-score showed a significant progressive decrease in controls, stage I-III patients, and stage IV patients. Logistic regression analysis showed a significant association between the disease and serum OPG levels, the odds ratio per standard deviation increase of this being 1.9 (95% confidence interval 1.1–3.8, P = 0.04) after adjusting for bone mass and ICTP serum levels, as well as for alcohol and smoking history. Adjustment for alcohol intake and tobacco use did not cancel out BMD differences between patients and controls. Patients with SCHNC show increased OPG serum levels, increased bone resorption, and decreased bone mass. The OPG rise appears to be unrelated to the BMD decrease, and the BMD decrease seems to be, at least in part, independent of smoking and drinking habits. No differences in either OPG or BMD were seen between patients with and without chemotherapy. Further studies are needed to clarify the mechanisms responsible for OPG and BMD changes in SCHNC.     

不同性别及年龄因素对原发性骨质疏松症骨代谢指标、血清骨保护素及骨密度影响的研究

目的 研究不同性别及年龄因素对原发性骨质疏松症骨代谢指标、血清骨保护素及骨密度的影响。方法 选择92例原发性骨质疏松症患者为研究对象,根据性别的不同,将本组92例患者分为男性组36例和女性组56例;根据年龄的不同,将92例患者按10岁为一年龄段分组,分为40~50岁组38例,50~60岁组27例,60~70岁组17例,＞70岁组10例。分别对不同性别、不同年龄组患者的骨代谢指标（BGP、ALP）、血清骨保护素（OPG）及骨密度（BMD）进行检测,统计分析不同性别、年龄阶段患者各指标水平的变化趋势。结果 男性组患者平均BGP、ALP、OPG指标水平均低于女性组（P均＜0.05）,平均腰椎正位、右股骨颈BMD均高于女性组（P均＜0.05）。随着患者年龄的增加, BGP、ALP、OPG指标水平逐渐升高（P＜0.05）;同时,随着患者年龄的增加,腰椎正位、右股骨颈BMD指标值逐渐下降（P＜0.05）。结论 性别及年龄是影响原发性骨质疏松症患者的骨代谢指标、血清骨保护素及骨密度指标水平的重要因素,通过其影响机制的分析可为该病的防控提供参考依据。     

The relationship between bone mineral density and ultrasound in postmenopausal and osteoporotic women

The aim of this cross-sectional study was to use a novel method of data analysis to demonstrate that patients with osteoporosis have significantly lower ultrasound results in the heel after correcting for the effect of bone mineral density (BMD) measured in the spine or hip. Three groups of patients were studied: healthy early postmenopausal women, within 3 years of the menopause (n=104, 50%), healthy late postmenopausal women, more than 10 years from the menopause (n=75, 36%), and a group of women with osteoporosis as defined by WHO criteria (n=30, 14%). Broadband ultrasound attenuation (BUA), speed of sound (SOS) and Stiffness were measured using a Lunar Achilles heel machine, and BMD of the lumbar spine and left hip was measured using dual-energy X-ray absorptiometry (DXA). SOS, BUA and Stiffness were regressed against lumbar spine BMD and femoral BMD for all three groups combined. The correlation coefficients were in the range 0.52–0.58, in agreement with previously published work. Using a calculated ratio R, analysis of variance demonstrated that the ratio was significantly higher in the osteoporotic group compared with the other two groups. This implied that heel ultrasound values are proportionately lower in the osteoporotic group compared with the other two groups for an equivalent value of lumbar spine and femoral neck BMD. We conclude that postmenopausal bone loss is not associated with different ultasound values once lumbar spine or femoral neck BMD is taken into account. Ultrasound does not give additional information about patterns of bone loss in postmenopausal patients but is important in those patients with osteoporosis and fractures.     

Bone Mineral Density in French Canadian Women

This cross-sectional study investigated bone mineral density (BMD) at the lumbar spine (L2–4) and femoral neck in French Canadian women residing in the Quebec city area. Data collection was initiated in 1988 and completed in 1994. A total of 747 French Canadian Caucasian women (16–79 years of age) with no metabolic bone disease were evaluated. BMD measurements were obtained using dual-photon absorptiometry (DPA) or dual-energy X-ray absorptiometry (DXA). Anthropometric measures such as weight, height and body mass index (BMI) were recorded. Medical files provided information on demographic characteristics, hormonal profile and lifestyle habits. Results show a curvilinear trend of BMD with aging. Furthermore, the peak BMD at the lumbar spine (L2–4) was reached at 29 years followed by a stable phase until 35 years, after which BMD started to decrease. The pattern of bone evolution at the femoral neck was different, peak BMD being achieved earlier, at 21 years, while after age 26 years a significant decrease was already observed. Women older than 60 years showed the lowest BMD. Regression analysis showed that age, weight and height are determinants of BMD at the lumbar spine and explained 33.9% of inter-individual variation. At the femoral neck, 29.1% of variation was explained by age and height only. In conclusion, our data suggest that French Canadian women have a different pattern of bone loss at the femoral neck compared with the lumbar spine, according to their mean BMD values. Received: 21 July 1997 / Accepted: 15 October 1997     

The use of multiple sites for the diagnosis of osteoporosis

Introduction It has been suggested that bone mineral density (BMD) measurements should be made at multiple sites, and that the lowest T–score should be taken for the purpose of diagnosing osteoporosis. Purpose The aim of this study was to examine the use of BMD measurements at the femoral neck and lumbar spine alone and in combination for fracture prediction. Methods We studied 19,071 individuals (68% women) from six prospective population-based cohorts in whom BMD was measured at both sites and fracture outcomes documented over 73,499 patient years. BMD values were converted to Z-scores, and the gradient of risk for any osteoporotic fracture and for hip fracture was examined by using a Poisson model in each cohort and each gender separately. Results of the different studies were merged using weighted β-coefficients. Results The gradients of risk for osteoporotic fracture and for hip fracture were similar in men and women. In men and women combined, the risk of any osteoporotic fracture increased by 1.51 [95% confidence interval (CI)=1.42–1.61] per standard deviation (SD) decrease in femoral-neck BMD. For measurements made at the lumbar spine, the gradient of risk was 1.47 (95% CI=1.38–1.56). Where the minimum of the two values was used, the gradient of risk was similar (1.55; 95% CI=1.45–1.64). Higher gradients of risk were observed for hip fracture outcomes: with BMD at the femoral neck, the gradient of risk was 2.45 (95% CI=2.10–2.87), with lumbar BMD was 1.57 (95% CI=1.36–1.82), and with the minimum value of either femoral neck and lumbar spine was 2.11 (95% CI=1.81–2.45). Thus, selecting the lowest value for BMD at either the femoral neck or lumbar spine did not increase the predictive ability of BMD tests. By contrast, the sensitivity increased so that more individuals were identified but at the expense of specificity. Thus, the same effect could be achieved by using a less stringent T–score for the diagnosis of osteoporosis. Conclusions Since taking the minimum value of the two measurements does not improve predictive ability, its clinical utility for the diagnosis of osteoporosis is low.     

Bone mineral density of the proximal femur and lumbar spine in glucocorticoid-treated asthmatic patients

The importance of the proximal femur as a site of osteoporotic fractures, the development of techniques for bone mineral density (BMD) measurement at this site and the apparent selectivity of the osteopenic effects of glucorticoids have focused attention on the assessment of proximal femoral BMD in steroid-treated subjects. We have, therefore, measured BMD (Lunar DPX) in the lumbar spine and proximal femur of 31 asthmatic patients receiving long-term glucocorticoid therapy (mean ± SEM dose 16 ± 1 mg prednisone/day, mean duration 10 ± 2 years). BMD values expressed as the percentage of normal age- and sex-appropriate mean values, after weight adjustment, were as follows: lumbar spine 80 ± 2%, femoral neck 83 ± 2%, Ward's triangle 78 ± 3% and trochanter 86 ± 2%. All these values were significantly less than control (p<0.0001) and the decrement in BMD was more marked in Ward's triangle than at the other two femoral sites (p<0.05). In all regions BMD was unrelated to dose or duration of steroid treatment. It is concluded that there are reductions in the BMD of the lumbar spine and proximal femur in glucocorticoid-treated asthmatics, probably reflecting the mixed cortical/trabecular makeup of both regions.     

Polymorphism at an Sp1 Binding Site of COL1A1 and Bone Mineral Density in Premenopausal Female Twins and Elderly Fracture Patients

Polymorphism at an Sp1 binding site in the COL1A1 gene has been reported to be associated with bone mineral density (BMD) and osteoporotic vertebral fracture. We therefore examined for associations and linkage of the Sp1 polymorphism in the COL1A1 gene and BMD at the lumbar spine and femoral neck in 38 monozygotic (MZ) and 40 dizygotic (DZ) twin pairs of white adult women. All twins were premenopausal with an age range of 21–49 years. Sp1 genotypes of 56 patients with idiopathic osteoporotic vertebral fracture were examined for a preponderance of either genotype relative to our normal healthy twin subjects. In the twin sample no significant association was found between Sp1 genotypes and BMD at the spine and femoral neck. No linkage of Sp1 genotype and BMD at the spine or femoral neck was observed in DZ twins discordant for genotype. Frequencies of Sp1 genotypes were similar in our healthy (twin) and fracture population samples. In conclusion, in our American sample of premenopausal twins we found no association or linkage of the Sp1 polymorphism at the COL1A1 gene and BMD at the lumbar spine and femoral neck, and no over-representation of any Sp1 genotype was observed in our sample of patients with osteoporotic vertebral fracture. Taken together these results indicate that the Sp1 polymorphism is not related to BMD in our American sample, and contrasts with the findings in a British population. Received: 16 November 1997 / Accepted: 12 June 1998     

A Prospective Study of Bone Loss in Menopausal Australian-Born Women

Two hundred and twenty-four women (74 pre-, 90 peri-, 60 post-menopausal), aged 46–59 years, from a population-based cohort participated in a longitudinal study of bone mineral density (BMD). BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and femoral neck and the time between bone scans was on average 25 (range 14–41) months. The aim of the study was to assess changes in BMD in relation to changes in normal menopausal status. During the study period women who were between 3 and 12 months past their last menstrual period (n= 22, late perimenopausal) at the time of the second bone scan had a mean (SE) annual change in BMD of 70.9% (0.4%) at the lumbar spine and 70.7% (0.6%) at the femoral neck (both p50.05 compared with women who remained premenopausal). In the women who became postmenopausal (n= 42) the mean annual changes in BMD were 72.5% (0.2%) at the lumbar spine and 71.7% (0.2%) at the femoral neck (both p50.0005), and in the women who remained postmenopausal (n= 60) they were 70.7% (0.2%) per year and 70.5% (0.3%) per year respectively (both p50.05), compared with women who remained premenopausal. In the 1–3 years after the final menstrual period (FMP) there was greater bone loss from the lumbar spine than the femoral neck (p50.05). In women who were menstruating at the time of the second bone scan and whose FMP could be dated prospectively (n= 35), higher baseline oestradiol levels were associated with less lumbar spine bone loss (p50.005). In the women who remained postmenopausal there was an association between baseline body mass index (BMI) and percentage change per year in femoral neck BMD (p50.05), such that women with higher BMI had less bone loss. In conclusion, during the time of transition from peri- to post-menopause, women had accelerated BMD loss at both the hip and spine. Received: 23 June 1997 / Accepted: 5 November 1997     

Quantitative Ultrasound and Symptomatic Vertebral Fracture Risk in Chinese Women

Quantitative ultrasound (QUS) is emerging as a simple, inexpensive and noninvasive method for assessing bone quality and assessing fracture risk. We assessed the usefulness of a contact calcaneal ultrasonometer by studying normal premenopausal women (group I, n= 53), normal postmenopausal women (group II, n= 198), and osteoporotic women without (group III, n= 141) and with vertebral fractures (group IV, n= 53). The osteoporotic subjects had a T-score of the spine or hip neck bone mineral density (BMD) <−2.5 based on the local Chinese peak young mean values. When compared with postmenopausal controls, mean broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI) were 26%, 2.1% and 25% lower in women with vertebral fractures (p all <0.005). The correlation coefficients between QUS parameters and BMD of the spine and hip ranged between 0.4 and 0.5. The ability of the QUS to discriminate between patients groups was determined based on the mean value of normal premenopausal women in group I. The mean T-score for women with fractures was −2.87 ± 1.02 for BUA, −2.54 ± 0.79 for SOS, −3.17 ± 0.70 for QUI, −2.65 ± 0.86 for L2–4 BMD and −2.53 ± 0.66 for hip neck BMD. After adjustment for age and body mass index, the odds ratio of vertebral fracture was 1.71 (95% CI 1.2–2.6) for each 1 SD reduction in BUA, 2.72 (1.3–5.3) for SOS, 2.58 (1.4–4.6) for QUI, 2.33 (1.6–3.3) for L2–4 BMD, 2.09 (1.37–3.20) for femoral neck BMD and 1.88 (1.34–2.92) for total hip BMD. The association between the QUS parameters and vertebral fracture risk persisted even adjustment for BMD. The area under the receiver operating characteristic curve for BUA for vertebral fracture was 0.92, for SOS, QUI, L2–4 BMD and femoral neck BMD was 0.95, and for total hip was 0.91. Received: 7 January 1999 / Accepted: 18 May 1999     

Timing and quantification of bone loss in cardiac transplant recipients

To evaluate osteopenic bone disease in heart transplant patients, we prospectively measured bone mineral density (BMD) in 33 consecutive male recipients before hospital discharge and 1 year later, using dual photon absorptiometry. At hospital discharge BMD measurement at the lumbar spine was only 90% of that expected in healthy age- and sex-matched controls (P=0.005). One year later BMD had further decreased by 8.5% at the lumbar spine and by 10.4% at the femoral neck (P=0.0001). Five patients suffered vertebral compression fractures during the 1st post-operative year. Our results indicate that osteopenia of the lumbar spine is already present at the time of hospital discharge after transplantation and that further bone loss occurs at a considerable rate during the 1st postoperative year at the lumbar spine and at the femoral neck.     

骨密度对骨质疏松性骨折的判断价值

目的研究骨密度对骨质疏松性骨折的判断价值。方法共3组研究对象,398例骨质疏松不伴有骨折的研究对象(A组),胸腰椎骨折患者(B组),骨密度正常的正常组进行研究。研究骨密度的一般情况、不同T值在各组的分配情况,骨质疏松性骨折与骨密度(BMD)的相关性。结果腰椎L2-L4、L2-L4和股颈的BMD值之间,T值人数分配之间,正常组、A组以及B组的差别具有统计学意义(P<0.05)。腰椎L1-L4、L2-L4和股颈的BMD以及总BMD的测定值均与骨质疏松性骨折相关。结论我们认为:本地区所收治的骨质疏松性骨折患者,全部应诊断判定为骨质疏松症。     

Bone diminution of osteoporotic females at different skeletal sites

Summary The bone mineral density (BMD) of the radius and spine was determined by photo absorptiometry in a large number of controls (radius: n=111; spine: n=85; age range: 50–79 years) and osteoporotic women (radius: n=98; spine n=140; age range: 50–79 years) with at least one “atraumatic” vertebral compression fracture. Compared to age-matched controls, the BMD of the osteoporotic women showed the following diminutions: sixth decade: radius:−9.1%; spine:−25%; femur: −33%; seventh decade: radius:−16%; spine: −19%; femur:−23%; eighth decade: radius: −21%; spine:−20%; femur:−24%. The BMD was significantly diminished at all sites in all decades but in contrast to the radius, the difference from controls was bigger in the spine and femur in the sixth decade than in the seventh and eighth decade. In the osteoporotic women there was a significant correlation between radius BMD and age (4=−0.56;P<0.01) but not between spine or femoral BMD and age. The femoral neck BMD was also determined in a subset group of female controls (n=68), patients with crush fractures of the spine without a fracture of the hip (n=46), and in patients with fractures of the proximal femur (n=21). There was no difference among these groups in mean age (64±7, range: 50–79 years). Patients with hip fracture and spine fracture showed bone diminution in all three regions that was significantly below controls (P<0.001). The Ward's triangle region was specially diminished (−35%) and as a consequence the neck BMD was low (−26%). Trochanteric density was lower (−25%) in spine fracture cases than in hip fracture (−16%). The difference between the two groups of osteoporotic women was significant (P<0.05). In the hip fractures cases, spine BMD was reduced only moderately compared to controls (−14%,P<0.01) and slightly elevated compared to spinal osteoporosis where the diminution was greater (−24%,P<0.001). Again, the difference between the two osteoporotic groups was significant (P<0.05). It appeared that spinal osteoporosis involved loss of bone from both the spine and hip, whereas femoral osteoporosis showed a preferential loss of bone from the femur neck region, and a lesser loss from the trochanter or the spine.