Changes in cortical microarchitecture are independent of areal bone mineral density in patients with fragility fractures

Dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) are commonly used to assess the areal bone mineral density (aBMD) and peripheral microstructure, respectively. While DXA is the standard to diagnose osteoporosis, HR-pQCT provides information about the cortical and trabecular architecture. Many fragility fractures occur in patients who do not meet the osteoporosis criterion (i.e., T-score ≤ −2.5). We hypothesize that patients with T-score above −2.5 and fragility fracture may have abnormal bone microarchitecture. Therefore, in this retrospective clinical study, HR-pQCT data obtained from patients with fragility fractures and T-scores ≥ −2.5 (n = 71) were compared to corresponding data from patients with fragility fractures and T-scores ≤ −3.5 (n = 56). Types of secondary osteoporosis were excluded from the study. To verify the dependency of alterations in bone microarchitecture and T-score, the association between HR-pQCT values and aBMD as reflected by the T-score at both proximal femora, was assessed. At the distal tibia, cortical thickness was lower (p < 0.001), cortical porosity was similar (p = 0.61), trabecular number was higher (p < 0.001), and bone volume fraction (BV/TV) was higher (p < 0.001) in patients with T-scores ≥ −2.5 than in patients with T-scores ≤ −3.5. Trabecular number and BV/TV correlated with T-score (r = 0.68, p < 0.001; r = 0.61, p < 0.001), whereas the cortical values did not. Our results thus demonstrate the importance of bone structure, as assessed by HR-pQCT, in addition to the standard DXA T-score in the diagnosis of osteoporosis.     

Vertebral bone quality score predicts fragility fractures independently of bone mineral density

BackgroundCurrent evidence suggests that dual-energy x-ray absorptiometry (DXA) scans, the conventional method defining osteoporosis, is underutilized and, when used, may underestimate patient risk for skeletal fragility. It has recently been suggested that other imaging modalities may better estimate bone quality, such as the magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score which also may assess vertebral compression fracture risk in patients with spine metastases.PurposeTo evaluate whether VBQ score is predictive of fragility fractures in a population with pre-existing low bone density and at high-risk for fracture.Study Design/SettingRetrospective single-center cohort.Patient SamplePatients followed at a metabolic bone clinic for osteopenia and/or osteoporosis.Outcome MeasuresRadiographically-documented new-onset fragility fracture.MethodsPatients with a DXA and MRI scans at the time of consultation and ≥2-year follow-up were included. Details were gathered about patient demographics, health history, current medication use, and serological studies of kidney function and bone turnover. For each patient, VBQ score was calculated using T1-weighted lumbar MRI images. Univariable and multivariable analyses were used to identify the independent predictors of a new fragility fracture. To support the construct validity of VBQ, patient VBQ scores were compared to those in a cohort of 45 healthy adults.ResultsSeventy-two (39.1%) study participants suffered fragility fractures, the occurrence of which was associated with higher VBQ score (3.50 vs. 3.01; p<.001), chronic glucocorticoid use (30.6% vs. 15.2%; p=.014), and a history of prior fragility fracture (36.1% vs. 21.4%; p=.030). Mean VBQ score across all patients in the study cohort was significantly higher than the mean VBQ score in the healthy controls (p<.001). In multivariable analysis, new-onset fracture was independently associated with history of prior fracture (OR=6.94; 95% confidence interval [2.48–19.40]; p<.001), higher VBQ score (OR=2.40 per point; [1.30–4.44]; p=.003), higher body mass index (OR=1.09 per kg/m²; [1.01–1.17]; p=.03), and chronic glucocorticoid use (OR=2.89; [1.03–8.17]; p=0.043). Notably, DXA bone mineral density (BMD) was not found to be significantly predictive of new-onset fractures in the multivariable analysis (p=.081).ConclusionsHere we demonstrate the novel, MRI-derived VBQ score is both an independent predictor of fragility fracture in at-risk patients and a superior predictor of fracture risk than DXA-measured BMD. Given the frequency with which MRIs are obtained by patients undergoing spine surgery consultation, we believe the VBQ score could be a valuable tool for estimating bone quality in order to optimize the management of these patients.     

Age,gender, and body mass effects on quantitative trait loci for bone mineral density: the Framingham Study

A genome-wide scan was performed in participants from the Framingham Osteoporosis Study (1557 members of 330 mostly Caucasian pedigrees), with 401 microsatellite markers spaced on average at 10 cM. Bone mineral density (BMD) was measured at the femoral neck, trochanter, Ward's area, and lumbar spine with DXA. Our recent study (J Bone Mines Res 17 (2002), 1718) reported a number of regions with suggestive linkage to possible quantitative trait loci (QTL). The current study estimates the heterogeneity of linkage in these regions in subsamples of our pedigrees, stratified on the known biological contributors to bone mass of sex, age, and body mass index (BMI). The pedigree sample was stratified into three sets of subgroups by sex [males (age range 35- 96 years), females (29-91 years)], by age [60 or younger (29-60 years) and older than 60 (61-96 years)], and by BMI [stratified into low or high BMI, by median cut-off 27.7 in males (BMI range 17-53) and 25.8 in females (14-54)]. Heritability estimates of BMD (adjusted for age, anthropometry, nutrition, physical activity, and, in females, estrogen use) in subsamples ranged from 0.47 to 0.69. Two-point and multipoint variance component linkage analyses of BMD (using SOLAR) in subsamples supported findings of previously reported suggestive linkage results in the total sample on 8q24.13 and 14q31 (LODs>2.0). However, heterogeneity of linkage was observed on 6p21.2 and 21qter, where findings in the total sample were not supported by subsamples. On the other hand, subsample-specific maxima were found, on 4q34.1 (males), 9q22-9q31 (younger), 16p13.2 (high BMI), and 17p13.3 (older), which were not reflected by the total sample results. In conclusion, heterogeneity of QTL effects was revealed in pedigree members stratified by sex, age, and BMI; in some instances new loci were identified in subgroups. These findings may suggest that effects of genes on the determination of BMD differ between men and women, younger and older, and lean and obese adults. Evaluation of family members stratified in homogeneous groups may be warranted in genetic studies of bone mass.     

Leisure physical activity is associated with quantitative ultrasound measurements independently of bone mineral density in postmenopausal women

The purpose of this study was to assess the magnitude of the relationship between leisure physical activity and bone status as measured either by an Achilles^TM ultrasound bone densitometer (QUS) or dual-energy X-ray absorptiometry (DXA) in postmenopausal women. We studied 1162 French Canadian postmenopausal women, aged 33–84 years (mean age 58 years), for QUS parameters [broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness index (SI)] measured at the right calcaneus, and bone mineral density (BMD) measured at the lumbar spine and femoral neck. Multivariate regression analyses revealed that leisure physical activity level was an independent predictor of the heel QUS parameters and of femoral neck BMD. No such association was observed for BMD of the lumbar spine. Heel QUS parameters (BUA, SOS, SI) and femoral neck BMD adjusted for interfering covariables showed a statistically significant difference between sedentary (less than three sessions/month) and active women (three or more sessions/week) (P 0.001). Furthermore, after adjusting each heel QUS parameters for the mean lumbar spine BMD value, the association observed between leisure physical activity and QUS remained significant. These results suggest that regular leisure physical activity could influence QUS parameters, independently of BMD, and that quantitative ultrasound could be a suitable outcome measure in exercise studies in postmenopausal women.     

Quantitative ultrasound and bone mineral density are equally strongly associated with risk factors for osteoporosis.

Because resources do not allow all women to be screened for osteoporosis, clinical risk factors are often used to identify those individuals at increased risk of fracture who are then assessed by bone densitometry. The aim of this study was to compare calcaneal quantitative ultrasound (QUS) and axial bone mineral density (BMD) T and Z scores in a large group of women, some with no clinical risk factors and others with one or more risk factors for osteoporosis. The study population consisted of 1115 pre- and postmenopausal women. A subgroup of 530 women was used to construct reference data for calculating T and Z scores. A total of 786 women was found to have one or more of the following risk factors: (i) atraumatic fracture since the age of 25 years, (ii) report of X-ray osteopenia, (iii) predisposing medical condition or use of therapy known to affect bone metabolism, (iv) premature menopause before the age of 45 years or a history of amenorrhea of longer than 6 months duration, (v) family history of osteoporosis, (vi) body mass index (BMI) <20 kg/m2, and (vii) current smoking habit. Calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS) measurements were performed on a Hologic Sahara and a DTUone and BMD was measured at the spine and hip using dual-energy X-ray absorptiometry (DXA). The Z score decrements associated with the seven risk factors calculated using multivariate regression analysis were similar for QUS and BMD measurements. Z score decrements (mean of BMD and QUS measurements combined) associated with a history of atraumatic fracture (-0.67), X-ray osteopenia (-0.36), a family history of osteoporosis (-0.23), and a low BMI (-0.53) were all statistically significant compared with women with no risk factors. Z score decrements associated with a medical condition or use of therapy known to affect bone metabolism, a premature menopause or prolonged amenorrhea, or those who were current smokers were not significantly different from zero. As the number of risk factors present in each individual increased, the mean Z score decrements became more negative, increasing from -0.28 for women with one risk factor to -1.19 for those with four or more risk factors. QUS and BMD measurements yielded similar mean Z scores for women with one, two, three, or more than four risk factors. Using the World Health Organization (WHO) criteria to diagnose osteoporosis for BMD measurements and revised diagnostic criteria for QUS, approximately one-third of postmenopausal women aged 50+ years with clinical risk factors were classified as osteoporotic compared with only 12% of women without clinical risk factors. Over two-thirds of postmenopausal women with risk factors were classified as osteopenic or osteoporotic and approximately 28% were classified as normal. The proportion of women classified into each diagnostic category was similar for BMD and QUS. In conclusion, clinical risk factors for osteoporosis affected calcaneal BUA and SOS Z score measurements to the same extent as axial BMD Z score measurements. Provided revised diagnostic criteria are adopted for QUS, similar proportions of postmenopausal women are identified as osteopenic or osteoporotic as with BMD.     

Monitoring alendronate and estradiol therapy with quantitative ultrasound and bone mineral density.

Few studies have compared quantitative ultrasound with bone mineral density (BMD) in monitoring response to therapy in osteoporosis. The aim of our study was to compare finger ultrasound variables and BMD for monitoring alendronate and estradiol therapy in postmenopausal women. We recruited 26 women aged 50 to 79 yr (mean: 65 yr) with osteoporosis; 18 patients received 10 mg/d of alendronate and 500 mg/d of calcium carbonate and 8 patients received 500 mg/d of calcium carbonate only. We recruited 21 hysterectomized postmenopausal women who were randomized to treatment or control. The treatment group received a 25-mg estradiol implant, which was replaced every 6 mo. The control group had a sham procedure. In the alendronate group, there were significant changes at 1 yr at the lumbar spine (p<0.05), bone transmission time (p<0.01), and pure speed of sound (p<0.001) and the changes continued into the second year. In the estradiol implant group, there were significant changes at 1 yr at the lumbar spine (p<0.001), the femoral neck (p<0.05), and the pure speed of sound (p<0.01). For alendronate, the signal-to-noise ratio was similar between the lumbar spine and bone transmission time (1.8 and 1.4) and greater than for the pure speed of sound and femoral neck (0.8 and 0.7); for estradiol, the signal-to-noise ratio was similar between the lumbar spine and femoral neck (2.0 and 1.5) and greater than for the pure speed of sound and bone transmission time (1.1 and 0.6).These results indicated that changes in finger ultrasound are similar in clinical utility to dual-energy X-ray absorptiometry measurements at the femoral neck for the monitoring of antiresorptive treatments for osteoporosis.     

Apolipoprotein E4 is associated with reduced calcaneal quantitative ultrasound measurements and bone mineral density in elderly women

Some studies have reported an association between the apolipoprotein E4 (APOE4) allele and reduced bone density and increased propensity to fracture, but this remains controversial as other studies have not found an association between APOE4 and bone density or fracture. No information is available concerning the effect of the APOE4 allele on quantitative ultrasound (QUS) parameters. We therefore examined this issue in a population-based study of 1332 healthy elderly women, examining the effect of the APOE4 allele on QUS parameters at the calcaneus and comparing this to dual-energy X-ray absorptiometry (DEXA) bone mineral density (BMD) at the hip. In addition, we examined the effect of the APOE4 allele on fracture. Subjects who had at least one APOE4 allele (n = 308) had lower calcaneal QUS parameters and lower hip BMD at the total hip, trochanter, and intertrochanter, but not the femoral neck, compared to subjects without an APOE4 allele (n = 1024) after adjustment for age, body mass index (BMI), and smoking. The decrement in QUS parameters and BMD was approximately 2%. Those subjects having an APOE4 allele were also more likely to fall into a low bone density group, defined by a T score of <1 SD below the young normal range (odds ratio [OR] 1.55, 95% confidence interval [CI] 1.08-2.22). We compared both prevalent and incident nontraumatic fractures over 2 years in the APOE4-present group compared with the APOE4-absent group. There were 354 subjects who entered the study with a history of one or more prevalent fractures, and 104 subjects sustained a nontraumatic fracture during the study. These fractures were not associated with the presence of the APOE4 allele, but a 2% decrement in BMD was unlikely to be associated with a statistically observable increase in fractures in this study. The APOE4 allele was not associated with a difference in any biochemical measures of bone formation or resorption, or in estrogen concentration, nor was it associated with a difference in BMI. Therefore, we conclude that the APOE4 allele is associated with a consistent decrease in both QUS parameters at the calcaneus and BMD at the clinically important hip site, and that this is not associated with differences in biochemical measures of bone formation or resorption.     

Age, gender, and race/ethnic differences in total body and subregional bone density

Summary  Total body bone density of adults from National Health and Nutrition Examination Survey (NHANES) 1999–2004 differed as expected for some groups (men>women and blacks>whites) but not others (whites>Mexican Americans). Cross-sectional age patterns in bone mineral density (BMD) of older adults differed at skeletal sites that varied by degree of weight-bearing. Introduction  Total body dual-energy X-ray absorptiometry (DXA) data offer the opportunity to compare bone density of demographic groups across the entire skeleton. Methods  The present study uses total body DXA data (Hologic QDR 4500A, Hologic, Bedford MA, USA) from the NHANES 1999–2004 to examine BMD of the total body and selected skeletal subregions in a wide age range of adult men and women from three race/ethnic groups. Total body, lumbar spine, pelvis, right leg, and left arm BMD and lean mass from 13,091 adults aged 20 years and older were used. The subregions were chosen to represent sites with different degrees of weight-bearing. Results  Mean BMD varied in expected ways for some demographic characteristics (men>women and non-Hispanic blacks>non-Hispanic whites) but not others (non-Hispanic whites>Mexican Americans). Differences in age patterns in BMD also emerged for some characteristics (sex) but not others (race/ethnicity). Differences in cross-sectional age patterns in BMD and lean mass by degree of weight-bearing in older adults were observed for the pelvis, leg, and arm. Conclusion  This information may be useful for generating hypotheses about age, race, and sex differences in fracture risk in the population.

The T869C TGF beta polymorphism is associated with fracture,bone mineral density,and calcaneal quantitative ultrasound in elderly women

Osteoporosis is a disease that is strongly genetically determined and polymorphisms present in a range of candidate genes may be involved. A number of previous studies have shown an association between the T869C functional polymorphism of the gene for transforming growth factor beta (TGF beta) and bone mineral density (BMD) and fracture, but these studies have been limited to relatively small studies of selected subjects. In a population-based study of 1337 white women over age 70 we examined the TGF beta T869 polymorphism in relation to BMD, calcaneal quantitative ultrasound (QUS), and prevalent and incident fracture. The TGF beta C allele was observed in 50% of the subjects and was associated with reduced hip BMD at all sites (2.8% total hip, 2.4% femoral neck, 2.6% intertrochanter, and 3.4% trochanter) compared to the TGF beta TT genotype. The TGF beta C allele was also associated with a reduction in the QUS parameters BUA, SOS, and stiffness of 0.87%, 0.26%, and 2.4%, respectively, compared to the TGF beta TT genotype. After adjustment for body mass index in an analysis of variance model, the effect of the TGF beta C allele remained significant at the total hip, the femoral neck, and the trochanter, and for the QUS SOS and stiffness parameters. The TGF beta C allele was associated with an increase in osteoporosis [T score < or =-2.5 SD; odds ratio (OR) 2.07; 95% confidence interval (CI) 1.19-3.60] and prevalent fracture (1.37; 95% CI 1.06-1.75). After adjustment for BMD and QUS stiffness, the association of the TGF beta C allele with prevalent fracture was still present (OR 1.40; 95% CI 1.04-1.89), suggesting that the effect of the C allele on fracture was independent of a reduction in BMD and QUS stiffness. Subjects with normal BMD and a TGF beta C allele had an increased risk of incident fracture over 3 years compared to subjects with normal BMD and a TGF beta TT genotype (relative risk 3.95; 95% CI 1.52-10.29). This association was not found in osteopenic or in osteoporotic subjects, indicating a BMD-TGF beta C allele interaction in relation to the association of the TGF beta C allele with fracture risk. These findings are of potential clinical usefulness, as the TGF beta T869C genotype could be used, in conjunction with other genetic and clinical information, to determine an individual's risk of osteoporosis.     

Habitual flavonoid intakes are positively associated with bone mineral density in women

Dietary flavonoids exert bone-protective effects in animal models, but there is limited information on the effect of different flavonoid subclasses on bone health in humans. The aim of this observational study was to examine the association between habitual intake of flavonoid subclasses with bone mineral density (BMD) in a cohort of female twins. A total of 3160 women from the TwinsUK adult twin registry participated in the study. Habitual intakes of flavonoids and subclasses (flavanones, anthocyanins, flavan-3-ols, polymers, flavonols, and flavones) were calculated from semiquantitative food frequency questionnaires using an updated and extended U.S. Department of Agriculture (USDA) database. Bone density was measured using dual-energy X-ray absorptiometry. In multivariate analyses, total flavonoid intake was positively associated with higher BMD at the spine but not at the hip. For the subclasses, the magnitude of effect was greatest for anthocyanins, with a 0.034 g/cm² (3.4%) and 0.029 g/cm² (3.1%) higher BMD at the spine and hip, respectively, for women in the highest intake quintile compared to those in the lowest. Participants in the top quintile of flavone intake had a higher BMD at both sites; 0.021 g/cm² (spine) and 0.026 g/cm² (hip). At the spine, a greater intake of flavonols and polymers was associated with a higher BMD (0.021 and 0.024 g/cm², respectively), whereas a higher flavanone intake was positively associated with hip BMD (0.008 g/cm²). In conclusion, total flavonoid intake was positively associated with BMD, with effects observed for anthocyanins and flavones at both the hip and spine, supporting a role for flavonoids present in plant-based foods on bone health. © 2012 American Society for Bone and Mineral Research.     

Physical training preserves bone mineral density in postmenopausal women with forearm fractures and low bone mineral density

Summary One hundred and twelve postmenopausal women with low bone mineral density (BMD) and forearm fractures were randomized to physical training or control group. After one year the total hip BMD was significantly higher in the women in the physical training group. The results indicate a positive effect of physical training on BMD in postmenopausal women with low BMD. Introduction The fivefold increase in hip fracture incidence since 1950 in Sweden may partially be due to an increasingly sedentary lifestyle. Our hypothesis was that physical training can prevent bone loss in postmenopausal women. Methods One hundred and twelve postmenopausal women 45 to 65 years with forearm fractures and T-scores from −1.0 to −3.0 were randomized to either a physical training or control group. Training included three fast 30-minute walks and two sessions of one-hour training per week. Bone mineral density (BMD) was measured in the hip and the lumbar spine at baseline and after one year. Results A per protocol analysis was performed, including 48 subjects in the training group and 44 subjects in the control group. The total hip BMD increased in the training group +0.005 g/cm2 (±0.018), +0.58%, while it decreased −0.003 g/cm2 (±0.019), −0.36%, (p = 0.041) in the control group. No significant effects of physical training were seen in the lumbar spine. A sensitivity intention to treat analysis, including all randomized subjects, showed no significant effect of physical training on BMD at any site. Conclusions The results indicate a small but positive effect of physical exercise on hip BMD in postmenopausal women with low BMD.     

Comparison of bone mineral density at various skeletal sites with quantitative ultrasound parameters of the calcaneus for assessment of vertebral fractures

This study investigated the role of quantitative ultrasound (QUS) for evaluation of fracture risk in comparison with bone mineral density (BMD) measurement. Our subjects were postmenopausal Japanese women (n = 260; age, 67 ± 6.1 years) who were examined for bone densitometry, QUS, and spinal X-ray examination at our department between 1992 and 1996. The subjects were categorized into three groups by the number of atraumatic fractured vertebrae: NF, no vertebral fractures; F1, one vertebral fracture; F2, two or more vertebral fractures. We compared the measured parameters to determine their association with the number of fractured vertebrae. Differences among groups were compared and analyzed by Student's t-test. Odds ratios were also calculated after age adjustment, as well as age and lumbar or calcaneal parameters. Between NF and F1, lumbar BMD and BMD of the Ward's triangle showed more significant differences than other values, while between F1 and F2, whole-body BMD and QUS parameters showed more significant differences. Lumbar BMD also showed the highest age-adjusted odds ratio in differentiating F1 from NF. Although QUS parameters showed no power to differentiate between NF and F1, these values showed higher odds ratios than other measurements for discriminating between F1 and F2. Adjustment for bone density did not totally abolish the association between QUS parameters and vertebral fracture. Additionally, the combination of lumbar BMD and QUS ("stiffness") clearly showed a high power to discriminate NF from F1 + F2. In conclusion, we showed that QUS measurement is effective in evaluating fracture risk in advanced osteoporosis, while lumbar dual X-ray absorptiometry is effective in evaluating risk in early osteoporosis. Received: Sept. 7, 1998 / Accepted: Nov. 27, 1998     

Genistein effects on quantitative ultrasound parameters and bone mineral density in osteopenic postmenopausal women

Summary  

This study aimed at evaluating the effects of genistein (54 mg/die) on calcaneus and phalanges ultrasound (QUS) parameters and bone mineral density in osteopenic postmenopausal women. We concluded that genistein prevented bone loss in the osteopenic postmenopausal women and improves QUS parameters at the calcaneus and phalanges.     

Altered distributions of bone tissue mineral and collagen properties in women with fragility fractures

Heterogeneity of bone tissue properties is emerging as a potential indicator of altered bone quality in pathologic tissue. The objective of this study was to compare the distributions of tissue properties in women with and without histories of fragility fractures using Fourier transform infrared (FTIR) imaging. We extended a prior study that examined the relationship of the mean FTIR properties to fracture risk by analyzing in detail the widths and the tails of the distributions of FTIR properties in biopsies from fracture and non-fracture cohorts. The mineral and matrix properties of cortical and trabecular iliac crest tissue were compared in biopsies from women with a history of fragility fracture (+ Fx; n = 21, age: mean 54 ± SD 15 y) and with no history of fragility fracture (− Fx; n = 12, age: 57 ± 5 y). A subset of the patients included in the − Fx group were taking estrogen-plus-progestin hormone replacement therapy (HRT) (− Fx + HRT n = 8, age: 58 ± 5 y) and were analyzed separately from patients with no history of HRT (− Fx − HRT n = 4, age: 56 ± 7 y). When the FTIR parameter mean values were examined by treatment group, the trabecular tissue of − Fx − HRT patients had a lower mineral:matrix ratio (M:M) and collagen maturity (XLR) than that of − Fx + HRT patients (− 22% M:M, − 18% XLR) and + Fx patients (− 17% M:M, − 18% XLR). Across multiple FTIR parameters, tissue from the − Fx − HRT group had smaller low-tail (5th percentile) values than that from the − Fx + HRT or + Fx groups. In trabecular collagen maturity and crystallinity (XST), the − Fx − HRT group had smaller low-tail values than those in the –Fx + HRT group (− 16% XLR, − 5% XST) and the + Fx group (− 17% XLR, − 7% XST). The relatively low values of trabecular mineral:matrix ratio and collagen maturity and smaller low-tail values of collagen maturity and crystallinity observed in the − Fx − HRT group are characteristic of younger tissue. Taken together, our data suggest that the presence of newly formed tissue that includes small/imperfect crystals and immature crosslinks, as well as moderately mature tissue, is an important characteristic of healthy, fracture-resistant bone. Finally, the larger mean and low-tail values of mineral:matrix ratio and collagen maturity noted in our − Fx + HRT vs. − Fx − HRT biopsies are consistent with greater tissue age and greater BMD arising from decreased osteoclastic resorption in HRT-treated patients.     

Chronic hemodialysis is associated with lower trabecular bone score,independent of bone mineral density: a case-control study

Summary

We measured trabecular bone score (TBS) in 98 patients on permanent hemodialysis (HD) and 98 subjects with similar bone mineral density and normal kidney function. TBS was significantly lower in HD patients, indicating deteriorated bone microarchitecture, independent of bone mass. This might partially explain the increased fracture risk in HD.

Purpose

In the general population, trabecular bone score (TBS) was shown to predict fracture independent of bone mineral density (BMD). In end-stage renal disease patients on hemodialysis (HD), the value of TBS is beyond that of BMD in currently unclear. Our aim was to assess lumbar spine (LS) TBS in HD patients compared with subjects with normal kidney function matched for age, sex, and LS BMD.

Methods

We assessed TBS and LS and femoral neck (FN) BMD in 98 patient on permanent HD (42.8% males; mean age 57.5?±?11.3 years; dialysis vintage 5.5?±?3.8 years) and 98 control subjects (glomerular filtration rate?>?60 mL/min) using DXA. We simultaneously controlled for sex, age (±?3 years), and LS BMD (±?0.03 g/cm²).

Results

HD patients had significantly lower LS TBS (0.07 [95% CI 0.03–0.1]; p?=?0.0004), TBS T-score (0.83 SD [95% CI 0.42–1.24]; p?=?0.0001)) and TBS Z-score (0.81 SD [95% CI 0.41–1.20]; p?=?0.0001) than matched controls. TBS significantly correlated with LS BMD in both HD patients (r?=?0.382; p?=?0.001) and controls (r?=?0.36; p?=?0.002). The two regression lines had similar slopes (0.3 vs. 0.28; p?=?0.84) with different intercepts (0.88 vs. 0.98). TBS adjustment significantly increased the 10-year fracture risk from 3.7 to 5.3 for major osteoporotic fracture and from 0.9 to 1.5 for hip fracture.

Conclusions

HD patients have lower TBS than controls matched for LS BMD, indicating altered bone microarchitecture. Also, the magnitude of TBS reduction in HD patients is constant at any LS BMD. Adjustment for TBS partially corrects the absolute 10-year fracture risk.

     

Alleles of RUNX2/CBFA1 gene are associated with differences in bone mineral density and risk of fracture.

The aim of this study was to determine if DNA polymorphism within runt-related gene 2 (RUNX2)/core binding factor A1 (CBFA1) is related to bone mineral density (BMD). RUNX2 contains a glutamine-alanine repeat where mutations causing cleidocranial dysplasia (CCD) have been observed. Two common variants were detected within the alanine repeat: an 18-bp deletion and a synonymous alanine codon polymorphism with alleles GCA and GCG (noted as A and G alleles, respectively). In addition, rare mutations that may be related to low BMD were observed within the glutamine repeat. In 495 randomly selected women of the Geelong Osteoporosis Study (GOS), the A allele was associated with higher BMD at all sites tested. The effect was maximal at the ultradistal (UD) radius (p = 0.001). In a separate fracture study, the A allele was significantly protective against Colles' fracture in elderly women but not spine and hip fracture. The A allele was associated with increased BMD and was protective against a common form of osteoporotic fracture, suggesting that RUNX2 variants may be related to genetic effects on BMD and osteoporosis.