Site-specific differential effects of once-yearly zoledronic acid on the hip assessed with quantitative computed tomography: results from the HORIZON Pivotal Fracture Trial

Summary

We used new approaches to the analysis of diagnostic scans to detect changes in bone density in different regions of the hip after 3 years of treatment with the zoledronic acid. We showed that the drug significantly increases hip bone density compared to placebo at regions where hip fractures usually occur.

Introduction

This study aims to identify whether treatment with zoledronic acid exerts site-specific differential effects on volumetric bone mineral density (vBMD) at the hip.

Methods

We analysed quantitative computed tomography scans of the hip obtained at baseline and 36 months in 179 women participating in the HORIZON Pivotal Fracture Trial. Cortical, trabecular and integral BMDs were determined at three main regions of interest—the femoral neck (FN), trochanter (TR) and total hip (TH)—and several sub-regions of interest, namely the proximal, middle, distal, anterior, posterior, inferomedial and superolateral FN, and the middle and distal TR.

Results

Volumetric BMD increased significantly (p?<?0.05) from baseline with zoledronic acid compared to placebo. Trabecular vBMD increased as follows: FN, 5.4 %; FN sub-regions, 6.0 % (proximal), 4.4 % (middle), 5.6 % (distal), 7.5 % (anterior), 7.0 % (superolateral) and 5.4 % (posterior); TR, 6.5 % and TH, 5.7 %. Cortical vBMD increased as follows: FN sub-regions, 5.0 % (proximal FN) and 2.3 % (anterior); TR, 4.6 %; middle TR, 2.7 % and TH, 3.8 %.

Conclusions

The effects on vBMD of annual infusion of 5 mg of zoledronic acid are site-specific and dominated by trabecular changes.     

Predictors of new and severe vertebral fractures: results from the HORIZON Pivotal Fracture Trial

Summary  

We examined prevalent and recent vertebral fractures in 1 year as predictors of new vertebral fractures over subsequent 2 years using data from RCT placebo patients. We found that prevalent and recent vertebral fractures strongly and independently predicted subsequent vertebral fractures including those which were severe.     

Once‐yearly zoledronic acid and days of disability,bed rest,and back pain: Randomized,controlled HORIZON Pivotal Fracture Trial

The objective of this study was to determine the effect of once‐yearly zoledronic acid on the number of days of back pain and the number of days of disability (ie, limited activity and bed rest) owing to back pain or fracture in postmenopausal women with osteoporosis. This was a multicenter, randomized, double‐blind, placebo‐controlled trial in 240 clinical centers in 27 countries. Participants included 7736 postmenopausal women with osteoporosis. Patients were randomized to receive either a single 15‐minute intravenous infusion of zoledronic acid (5 mg) or placebo at baseline, 12 months, and 24 months. The main outcome measures were s elf‐reported number of days with back pain and the number of days of limited activity and bed rest owing to back pain or a fracture, and this was assessed every 3 months over a 3‐year period. Our results show that although the incidence of back pain was high in both randomized groups, women randomized to zoledronic acid experienced, on average, 18 fewer days of back pain compared with placebo over the course of the trial (p = .0092). The back pain among women randomized to zoledronic acid versus placebo resulted in 11 fewer days of limited activity (p = .0017). In Cox proportional‐hazards models, women randomized to zoledronic acid were about 6% less likely to experience 7 or more days of back pain [relative risk (RR) = 0.94, 95% confidence interval (CI) 0.90–0.99] or limited activity owing to back pain (RR = 0.94, 95% CI 0.87–1.00). Women randomized to zoledronic acid were significantly less likely to experience 7 or more bed‐rest days owing to a fracture (RR = 0.58, 95% CI 0.47–0.72) and 7 or more limited‐activity days owing to a fracture (RR = 0.67, 95% CI 0.58–0.78). Reductions in back pain with zoledronic acid were independent of incident fracture. Our conclusion is that in women with postmenopausal osteoporosis, a once‐yearly infusion with zoledronic acid over a 3‐year period significantly reduced the number of days that patients reported back pain, limited activity owing to back pain, and limited activity and bed rest owing to a fracture. © 2011 American Society for Bone and Mineral Research.     

Thoracic bone mineral density measured by quantitative computed tomography in patients undergoing spine surgery

BACKGROUND CONTEXTThe thoracic spine is a common location for vertebral fractures as well as instrumentation failure after long spinal fusion procedures. The association between those complications and bone mineral density (BMD) are well recognized. Due to the overlying sternum and ribs in the thoracic spine, projectional BMD assessment tools such as dual energy x-ray absorptiometry (DXA) are limited to the lumbar spine. Quantitative computed tomography circumvents several shortcomings of DXA and allows for level-specific BMD measurements. Studies comprehensively quantifying BMD of the entire thoracic spine in patients undergoing spine surgery are limited.PURPOSEThe objective of this study was: (1) to assess the reliability of thoracic QCT measurements, (2) to determine possible level-specific BMD variation throughout the thoracic spine and (3) to assess the correlation between BMDs of the T1-T12 spinal levels.STUDY DESIGN/SETTINGCross-sectional observation study.PATIENT SAMPLEPatients undergoing spine surgery from 2016–2020 at a single, academic institution with available preoperative CT imaging of the thoracic spine were included in this study.OUTCOME MEASURESThe outcome measure was BMD measured by QCT.METHODSPatients undergoing spine surgery from 2016–2020 at a single, academic institution with available preoperative CT imaging of the thoracic spine were included in this study. Subjects with previous instrumentation at any thoracic level, concurrent vertebral fractures, a Cobb angle of more than 20 degrees, or incomplete thoracic spine CT imaging were excluded. Asynchronous quantitative computed tomography (QCT) measurements of T1-T12 were performed. To assess inter- and intra-observer reliability, a validation study was performed on 120 vertebrae in 10 randomly selected patients. The interclass correlation coefficient (ICC) was calculated. A pairwise comparison of BMD was conducted and correlations between each thoracic level were evaluated. The statistical significance level was set at p<.05.RESULTS60 patients (men, 51.7%) met inclusion criteria. The study population was 90% Caucasian with a mean age of 62.2 years and a mean BMI of 30.2 kg/m². The inter- and intra-observer reliability of the thoracic QCT measurements was excellent (ICC of 0.97 and 0.97, respectively). The trabecular BMD was highest in the upper thoracic spine and decreased in the caudal direction (T1 = 182.3 mg/cm³, T2 = 168.1 mg/cm³, T3 = 163.5 mg/cm³, T4 = 164.7 mg/cm³, T5 = 161.4 mg/cm³, T6 = 152.5 mg/cm³, T7 = 143.5 mg/cm³, T8 = 141.3 mg/cm³, T9 = 143.5 mg/cm³, T10 = 145.1 mg/cm³, T11 = 145.3 mg/cm³, T12 = 133.6 mg/cm³). The BMD of all thoracic levels cranial to T6 was statistically higher than the BMD of all levels caudal to T6 (p < .001). Nonetheless, significant correlations in BMD among all measured thoracic levels were observed, with a Pearson's correlation coefficient ranging from 0.74 to 0.97.CONCLUSIONSThere is significant regional BMD variation in the thoracic spine depending on spinal level. This BMD variation might contribute to several clinically relevant phenomena. First, vertebral fractures occur most commonly at the thoracolumbar junction including T12. In addition to mechanical reasons, these fractures might be partially attributed to thoracic BMD that is lowest at T12. Second, the optimal upper instrumented vertebra (UIV) for stopping long fusions to the sacrum and pelvis is controversial. The BMD of surgically relevant upper thoracic stopping points (T2-T4) was significantly higher than the BMD of lower thoracic stopping points (T10-T12). Besides stress concentration at the relatively mobile lower thoracic segments, the low BMD at these levels might contribute to previously suggested higher rates of junctional failures with short fusions.     

The Interaction of Acute-Phase Reaction and Efficacy for Osteoporosis After Zoledronic Acid: HORIZON Pivotal Fracture Trial

Zoledronic acid (ZOL) as a yearly infusion is effective in reducing fracture risk. An acute-phase reaction (APR), consisting of flu-like symptoms within 3 days after infusion, is commonly seen. The objective of this analysis was to investigate whether APR occurrence influences drug efficacy. This analysis uses data from the 3-year randomized clinical trial, Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT). APRs were identified as adverse events within 3 days of first infusion with higher frequency in ZOL than placebo. To compare mean 3-year change in bone mineral density (BMD) in ZOL versus placebo, among women with and without APR, t tests were used. Logistic regression was used to examine the relationship between APR occurrence and odds of incident morphometric vertebral fracture. Cox regression was used to determine the risk of nonvertebral and hip fractures for women with versus without APR. Logistic and Cox models were used to determine the risk of incident fracture in ZOL versus placebo for women with and without an APR. The analysis included 3862 women in the ZOL group and 3852 in placebo, with 42.4% in ZOL versus 11.8% in placebo experiencing an APR. The difference in BMD mean change for ZOL versus placebo was similar for women with and without an APR (all p interaction >0.10). Among ZOL women, those with APR had 51% lower vertebral fracture risk than those without (odds ratio [OR] = 0.49, p < 0.001). A similar but nonsignificant trend was observed for nonvertebral and hip fracture (relative hazard [RH] = 0.82, p = 0.10; RH = 0.70, p = 0.22, respectively). There was a greater treatment-related reduction in vertebral fracture risk among women with APR (OR = 0.19) than those without (OR = 0.38) (p interaction = 0.01). Our results suggest that women starting ZOL who experience an APR will have a larger reduction in vertebral fracture risk with ZOL. © 2021 American Society for Bone and Mineral Research (ASBMR).     

应用双能CT与定量CT对椎体骨密度测量的对照研究

目的应用双能CT(DECT)及定量CT(QCT)测量腰椎骨密度,评价利用双能CT测量骨密度(BMD)的可行性。方法对56名志愿者采用DECT检查,获得钙值图,测量骨钙CT值及骨髓CT值,同时应用QCT测量骨密度(BMD),分析骨钙CT值及骨髓CT值与BMD值的相关性。结果腰椎椎体骨钙CT值与BMD值呈显著正相关(L1-5椎体Pearson相关系数分别为:r=0.715,0.692,0.739,0.673,0.686,P0.01);骨髓CT值与BMD值呈正相关(L1-5椎体Pearson相关系数分别为r=0.343、0.315、0.439、0.440、0.456,L5椎体P0.05,其余椎体P0.01)。结论 DECT所测量腰椎骨钙CT值及骨髓CT值与QCT所测BMD值密切相关,可定量反映腰椎BMD变化。     

Regional bone mineral density differences measured by quantitative computed tomography in patients undergoing anterior cervical spine surgery

BACKGROUND CONTEXTClinically, the association between bone mineral density (BMD) and surgical instrumentation efficacy is well recognized. Although several studies have quantified the BMD of the human lumbar spine, comprehensive BMD data for the cervical spine is limited. The few available studies included young and healthy patient samples, which may not represent the typical cervical fusion patient. Currently no large scale study provides detailed BMD information of the cervical and first thoracic vertebrae in patients undergoing anterior cervical spine surgery.PURPOSEThe objective of this study was to determine possible trabecular BMD variations throughout the cervical spine and first thoracic vertebra in patients undergoing anterior cervical discectomy and fusion (ACDF) and to assess the correlation between BMDs of the spinal levels C1–T1.STUDY DESIGN/SETTINGThis is a retrospective case series.PATIENT SAMPLEPatients undergoing ACDF from 2015 to 2018 at a single, academic institution with available preoperative CT imaging were included in this study.OUTCOME MEASURESThe outcome measure was BMD measured by QCT.METHODSPatients that underwent ACDF from 2015 to 2018 at a single, academic institution were included in this study. Subjects with previous cervical instrumentation or missing/incomplete preoperative cervical spine CT imaging were excluded. Asynchronous quantitative computed tomography (QCT) measurements of the lateral masses of C1 and the C2-T1 vertebral bodies were performed. For this purpose, an elliptical region of interest that consisted exclusively of trabecular bone was selected. Any apparent sclerotic levels that might affect trabecular QCT measurements were excluded from the final analysis. Interobserver reliability of measurements was assessed by calculating the interclass correlation coefficients (ICC). Pairwise comparison of BMD was performed and correlations between the various cervical levels were evaluated. The statistical significance level was set at p<.05.RESULTSIn all, 194 patients (men, 62.9%) met inclusion criteria. The patient population was 91.2% Caucasian with a mean age of 55.9 years and mean BMI of 28.2 kg/m². The ICC of cervical QCT measurements was excellent (ICC 0.92). The trabecular BMD was highest in the mid-cervical spine (C4) and decreased in the caudal direction (C1 average=253.3 mg/cm³, C2=276.6 mg/cm³, C3=272.2 mg/cm³, C4=283.5 mg/cm³, C5=265.1 mg/cm³, C6=235.3 mg/cm³, C7=216.8 mg/cm³, T1=184.4 mg/cm³). The BMD of C7 and T1 was significantly lower than those of all other levels. Nonetheless, significant correlations in BMD among all measured levels were observed, with a Pearson's correlation coefficient ranging from 0.507 to 0.885.CONCLUSIONSTo the authors’ knowledge this is the largest study assessing trabecular BMD of the entire cervical spine and first thoracic vertebra by QCT. The patient sample consisted of patients undergoing ACDF, which adds to the clinical relevance of the findings. Knowledge of BMD variation in the cervical spine might be useful to surgeons utilizing anterior cervical spine plate and screw systems. Due to the significant variation in cervical BMD, procedures involving instrumentation at lower density caudal levels might potentially benefit from a modification in instrumentation or surgical technique to achieve results similar to more cephalad levels.     

Relationship of changes in total hip bone mineral density to vertebral and nonvertebral fracture risk in women with postmenopausal osteoporosis treated with once-yearly zoledronic acid 5 mg: the HORIZON-Pivotal Fracture Trial (PFT)

Measurements of change in bone mineral density (BMD) are thought to be weak predictors of treatment effect on the reduction of fracture risk. In this study we report an alternative year-on-year approach for the estimation of treatment effect explained by BMD in which we examine the relationship between fracture risk and the most recent change in BMD. We studied 7736 postmenopausal women (ages 65 to 89 years) who were participants in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT) and were randomized to either intravenous administration of zoledronic acid or placebo. The percentage of treatment effect explained by change in total hip BMD was estimated using the alternative year-on-year approach and the standard approach of looking at change over 3 years. We also studied a subset of 1132 women in whom procollagen type 1 amino-terminal propeptide (PINP) was measured at baseline and 12 months, to estimate the percentage of treatment effect explained by change in PINP. Regardless of the method used, the change in total hip BMD explained a large percentage of the effect of zoledronic acid in reducing new vertebral fracture risk (40%; 95% CI, 30% to 54%; for the 3-year analysis). The treatment effects for nonvertebral fracture were not statistically significant for the year-on-year analysis but 3-year change in BMD explained 61% (95% CI, 24% to 156%) of treatment effect. Change in PINP explained 58% (95% CI, 15% to 222%) of the effect of zoledronic acid in reducing new vertebral fracture risk. We conclude that our estimates of the percentage of treatment effect explained may be higher than in previous studies because of high compliance with zoledronic acid (due to its once-yearly intravenous administration). Previous studies may have underestimated the relationship between BMD change and the effect of treatment on fracture risk.     

Compact and trabecular components of the spine using quantitative computed tomography

Summary A computer algorithm was employed to quantify separately cortical and trabecular bone mineral density (BMD) from single energy computed tomography (CT) scans of 139 vertebrae (L1–L3) of 50 normal female subjects. In addition, the trabecular-to-integral and cortical-to-integral mass ratios were determined using digital image segmentation techniques. They showed that for the central 8-mm vertebral slice, the mass of integral bone consists of about one-fifth trabecular and four-fifth cortical bone. The trabecular-to-integral volume ratios were 0.37±0.08 and 0.63±0.08, respectively. Based on cross-sectional data from this subject group, the average annual loss was -2.21±0.15 mg/cm³ or-1.84±0.12% for trabecular bone, -3.15±0.25 mg/cm³ or-1.01±0.08% for cortical bone, and -2.60±0.20 mg/cm³ or -1.09±0.09% for the integral bone. The proportions of the age-related los of BMD from the integral bone which originated from trabecular and cortical bone were 29.5 and 70.5%, respectively.     

Pelvic body composition measurements by quantitative computed tomography: association with recent hip fracture

INTRODUCTION: Loss of subcutaneous fat, decreased muscle cross-sectional area (CSA) and increased muscle adiposity are related to declining physical function and disability in the elderly, but there is little information about the relationship of these tissue changes to hip fracture. Thus we have compared body composition measures in women with hip fractures to age-matched controls, using quantitative computed tomography (QCT) imaging of the hip to characterize total adiposity, muscle CSA and muscle attenuation coefficient, a measure of adiposity. MATERIALS AND METHODS: 45 Chinese women (mean age 74.71+/-5.94) with hip fractures were compared to 66 healthy control subjects (mean age 70.70+/-4.66). Hip QCT scans were analyzed to compute total adipose CSA as well as CSA and attenuation values of muscle groups in the CT scan field of view, including hip extensors, abductors, adductors and flexors. The total femur areal BMD (aBMD) was estimated from the QCT images. Logistic regression was employed to compare body composition measures between fracture subjects and controls after adjustment for age, height, BMI and aBMD. Receiver-operator curve (ROC) analyses determined whether combinations of aBMD and body composition had higher area under curve (AUC) than aBMD alone. RESULTS AND CONCLUSIONS: Fracture subjects had lower fat CSA (p<0.0001) than controls but had higher muscle adiposity as indicated by lower attenuation in the adductor, abductor and flexor groups (0.00001相似文献   

Proximal femoral density and geometry measurements by quantitative computed tomography: association with hip fracture

INTRODUCTION: Bone mineral density and geometry measurements by volumetric quantitative computed tomography (vQCT) have been utilized in clinical research studies of aging, pharmacologic intervention and mechanical unloading, but there is relatively little information about the association of these measures with hip fracture. To address this issue, we have carried out a study comparing vQCT parameters in elderly Chinese women with hip fractures with measurements in age-matched controls. MATERIALS AND METHODS: Forty-five women (mean age 74.71+/-5.94) with hip fractures were compared to 66 age-matched control subjects (mean age 70.70+/-4.66). vQCT was employed to characterize the volumetric bone mineral density in cortical, trabecular, and integral volumes of interest in the proximal femur. In addition to the volume of interest measurements, we computed the cross-sectional areas of the femoral neck and intertrochanteric planes, the femoral neck axis length, indices of femoral neck bending and compressive strength, and measures of femoral neck cortical geometry. To determine if cortical geometry measures were associated with hip fracture independently of trabecular vBMD, we carried out multi-variate analyses including these parameters in a logistic regression model. RESULTS AND CONCLUSIONS: All vQCT measurements discriminated between fractured subjects and age-matched controls. There was no significant difference in predictive strength between volumetric and areal representations of BMD and trabecular and integral vBMD showed comparable discriminatory power, although both of these measures were more correlated to fracture status than cortical vBMD. We found that fractured subjects had larger femoral neck cross-sectional areas, consistent with adaptation to lower BMD in these osteoporotic subjects. The larger neck cross-sectional areas resulted in bending strength indices in the fractured subjects that were comparable or larger than those of the control subjects. In multi-variate analyses, reduced femoral neck cortical thickness and buckling ratio indices were associated with fracture status independently of trabecular vBMD.     

Forearm BMD as measured by peripheral quantitative computed tomography (pQCT) in a German reference population

Low bone mass as estimated by decreased bone mineral density (BMD) is an established predictor of osteoporotic fractures. One of the latest developments in bone densitometry is peripheral quantitative computed tomography (pQCT) of the forearm. In Germany, the CT bone scanner XCT 900 has already been widely used; however, interpretation of measurements with respect to osteoporosis risk assessment can be improved by better defined and validated reference data. In the present study, this device was used to measure BMD at the distal radius in a well-defined healthy population of 179 German adults (91 men, 88 women) aged 20–79 years. In vivo precision was 1.67% for trabecular and 0.81% for total BMD measurements. Peak values of trabecular and total BMD were observed at the ages 40–50 years in women and 30–40 years in men. Beyond these ages, both trabecular and total BMD showed a linear decline with age, decreasing by 0.85% and 1.08% per year in women and by 0.59% and 0.54% in men, respectively. Measures of BMD were not influenced by weight, height or body mass index (BMI). In both sexes, trabecular and total radial BMD showed a positive and significant correlation with femoral BMD measures obtained by dual X-ray absorptiometry (DXA). Weaker correlations were observed with DXA measures of the lumbar spine. Compared with the 95% reference range provided by the manufacturer, the distribution of age- and sex-specific values of trabecular BMD of the distal radius was shifted to lower values by up to 1 standard deviation. Thus, 17% (30 of 179) of our apparently healthy population had BMD values falling short of the suggested lower reference limit. On the other hand, the distribution of total BMD values was shifted to higher values by up to 2 standard deviations in the younger age groups. We conclude that pQCT of the radius is a precise method for measuring BMD, but that its use for osteoporosis risk assessment crucially depends on both well-defined reference data and the results of prospective studies.     

Growth rate of abdominal aortic aneurysms as measured by computed tomography

The risk of rupture of an abdominal aortic aneurysm increases with size. It has thus been recommended that small aneurysms be continuously followed with some type of imaging technique to detect when aneurysm size constitutes an indication for surgery. The present study focuses on the growth rate of abdominal aortic aneurysms in 35 patients who were subjected to repeated computerized tomographic examinations of their abdominal aortic aneurysms. Several aneurysms were measured more than twice resulting in 57 different examinations. The mean growth rate of the transverse diameter was 0.52 cm/year. The individual growth rates were, however, variable. Aneurysms with an initial transverse diameter exceeding 6 cm showed a slightly but not significantly faster increase in size compared with smaller aneurysms. No correlation between initial size and growth rate could be established. Six patients died during the study period, two from myocardial infarction, three after elective aneurysm operations and one, refused for elective operation, died after rupture. It is concluded that the growth rate measured with computed tomography agrees well with previously reported estimates obtained with ultrasonography. It is recommended that small aneurysms particularly in patients with relative contraindications to surgery be followed with repeated examinations of size.     

Fracture prevention in patients with cognitive impairment presenting with a hip fracture: secondary analysis of data from the HORIZON Recurrent Fracture Trial

Summary

Patients with cognitive impairment (CI) often do not receive secondary fracture prevention. Use of zoledronic acid led to a similar reduction in re-fracture risk but the survival benefit was limited to those without CI.

Introduction

We tested whether the effects of zoledronic acid (Zol) on re-fracture and mortality differed in patients presenting with a hip fracture by cognitive status.

Methods

We used data from the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Recurrent Fracture Trial, of yearly intravenous 5 mg Zol vs. placebo in patients presenting with a hip fracture. Primary outcome was new fracture and secondary outcome mortality. Short Portable Mental Status Questionnaire (SPMSQ) with a cut-point of >2 was used to identify CI. Fine–Gray models for competing events were fitted to study the effect of Zol on re-fracture and Cox regression for death. A multiplicative term was introduced to study a potential interaction between treatment and cognitive status on outcomes.

Results

Baseline SPMSQ of 1,966/2,127 (92.4 %) patients was measured. Three hundred fifty (17.8 %) had CI, balanced between treatment arms. In the placebo arm, there was similar fracture incidence between those with and without CI (15.4 vs. 12.3 %, p?=?0.26). There was no significant interaction for the effect of CI on Zol and re-fracture (p?=?0.66). CI was associated with higher 1-year mortality (12.6 vs. 4.3 %, p?<?0.001) and the interaction was bordering significance (interaction, p?=?0.066). Zol prolonged survival only in patients with normal cognitive status [HR 0.56 (95 % CI 0.40–0.80)] and not in those with CI [HR 0.90 (95 % CI 0.59–1.38)].

Conclusions

While these results require confirmation, the findings support the use of bisphosphonates in patients with osteoporotic fracture and CI expected to live for more than 6 months.     

Intracapsular hip fracture and the region-specific loss of cortical bone: analysis by peripheral quantitative computed tomography.

Generalized bone loss within the femoral neck accounts for only 15% of the increase in intracapsular hip fracture risk between the ages of 60 and 80 years. Conventional histology has shown that there is no difference in cancellous bone area between cases of intracapsular fracture and age and sex-matched controls. Rather, a loss of cortical bone thickness and increased porosity is the key feature with the greatest change occurring in those regions maximally loaded during a fall (the inferoanterior [IA] to superoposterior [SP] axis). We have now reexamined this finding using peripheral quantitative computed tomography (pQCT) to analyze cortical and cancellous bone areas, density, and mass in a different set of ex vivo biopsy specimens from cases of intracapsular hip fracture (female, n = 16, aged 69-92 years) and postmortem specimens (female, n = 15, aged 58-95 years; male, n = 11, aged 56-86 years). Within-neck location was standardized by using locations at which the ratio of maximum to minimum external diameters was 1.4 and at more proximal locations. Cortical widths were analyzed using 72 radial profiles from the center of area of each of the gray level images using a full-width/half-maximum algorithm. In both male and female controls, cancellous bone mass increased toward the femoral head and the rate of change was gender independent. Cancellous bone mass was similar in cases and controls at all locations. Overall, cortical bone mass was significantly lower in the fracture cases (by 25%; p < 0.001) because of significant reductions in both estimated cortical area and density. These differences persisted at locations that are more proximal. The mean cortical width in the cases was significantly lower in the IA (22.2%;p = 0.002) and inferior regions (19%;p < 0.001). The SP region was the thinnest in both cases and controls. These data confirm that a key feature in the etiology of intracapsular hip fracture is the site-specific loss of cortical bone, which is concentrated in those regions maximally loaded during a fall on the greater trochanter. An important implication of this work is that the pathogenesis of bone loss leading to hip fracture must be by a mechanism that varies in its effect according to location within the femoral neck Key candidate mechanisms would include those involving locally reduced mechanical loading. This study also suggests that the development of noninvasive methodologies for analyzing the thickness and estimated densities of critical cortical regions of the femoral neck could improve detection of those at risk of hip fracture.     

Anatomy of the abductor muscles of the hip as studied by computed tomography

Computed tomography provides a non-invasive method for studying anatomy in live subjects. The abductor muscles of the hip were studied by using computed tomography to describe their position, size, and orientation. The outlines of the muscles were clearly identifiable; patterns that are associated with trauma, arthritis, and so on, differed from normal. The patterns in eighteen normal hips in twelve adults were mapped in detail. The cross-sectional areas of the abductor muscles were measured and vectors representing the total pull of the abductor muscle in the frontal and sagittal planes were constructed for each hip. The variations in individual and composite muscular anatomy were recorded. The inclination of the axis of the abductor muscle ranged from 17 to 26 degrees (standard deviation, 2.9 degrees) in the frontal plane and from -2 to 14 degrees (standard deviation, 4.2 degrees) in the sagittal plane.     

Treatment with raloxifene for 2 years increases vertebral bone mineral density as measured by volumetric quantitative computed tomography

Volumetric quantitative computed tomography (vQCT), using multiple thin-slice acquisition, measures three-dimensional volumetric bone mineral density (BMD, mg/cm3). vQCT is often used to measure BMD of lumbar vertebrae and may detect early changes in trabecular, cortical, or integral BMD that extend beyond the technical limits of areal dual X-ray absorptiometry (DXA) BMD measurements. The objective of this study was to determine the effect of 2 years of raloxifene (RLX) treatment on several volumetric BMD measures in a subset of postmenopausal women (n=58) enrolled in the Multiple Outcomes of Raloxifene Evaluation (MORE) trial. Patients in this study were randomized to one of three treatment groups: placebo (n=21), RLX 60 mg/day (n=17), or RLX 120 mg/day (n=20), and all patients received daily calcium (500 mg) and vitamin D (400-600 IU) supplementation. Data from the raloxifene treatment groups were pooled for each analysis. Following 2 years of raloxifene treatment, there was a significant percent change from baseline in the vQCT regions of interest (ROIs) of midintegral BMD, total trabecular BMD, and total integral BMD (P<0.05) compared to placebo, while there was no significant change in the spinal DXA BMD measurement. These data provide the first longitudinal assessment by vQCT of changes in vertebral bone density after 2 years of treatment with raloxifene. vQCT appears to be a valuable technique for measuring the effects of raloxifene treatment in this population of postmenopausal women with osteoporosis.     

In vivo discrimination of hip fracture with quantitative computed tomography: Results from the prospective European Femur Fracture Study (EFFECT)

In assessing osteoporotic fractures of the proximal femur, the main objective of this in vivo case‐control study was to evaluate the performance of quantitative computed tomography (QCT) and a dedicated 3D image analysis tool [Medical Image Analysis Framework—Femur option (MIAF‐Femur)] in differentiating hip fracture and non–hip fracture subjects. One‐hundred and seven women were recruited in the study, 47 women (mean age 81.6 years) with low‐energy hip fractures and 60 female non–hip fracture control subjects (mean age 73.4 years). Bone mineral density (BMD) and geometric variables of cortical and trabecular bone in the femoral head and neck, trochanteric, and intertrochanteric regions and proximal shaft were assessed using QCT and MIAF‐Femur. Areal BMD (aBMD) was assessed using dual‐energy X‐ray absorptiometry (DXA) in 96 (37 hip fracture and 59 non–hip fracture subjects) of the 107 patients. Logistic regressions were computed to extract the best discriminates of hip fracture, and area under the receiver characteristic operating curve (AUC) was calculated. Three logistic models that discriminated the occurrence of hip fracture with QCT variables were obtained (AUC = 0.84). All three models combined one densitometric variable—a trabecular BMD (measured in the femoral head or in the trochanteric region)—and one geometric variable—a cortical thickness value (measured in the femoral neck or proximal shaft). The best discriminant using DXA variables was obtained with total femur aBMD (AUC = 0.80, p = .003). Results highlight a synergistic contribution of trabecular and cortical components in hip fracture risk and the utility of assessing QCT BMD of the femoral head for improved understanding and possible insights into prevention of hip fractures. © 2011 American Society for Bone and Mineral Research.     

Regional bone mineral density differences measured by quantitative computed tomography: does the standard clinically used L1-L2 average correlate with the entire lumbosacral spine?

BACKGROUND CONTEXT

Quantitative computed tomography (QCT) of the lumbar spine is used as an alternative to dual-energy X-ray absorptiometry in assessing bone mineral density (BMD). The average BMD of L1-L2 is the standard reportable metric used for diagnostic purposes according to current recommendations. The density of L1 and L2 has also been proposed as a reference value for the remaining lumbosacral vertebrae and is commonly used as a surrogate marker for overall bone health. Since regional BMD differences within the spine have been proposed, it is unclear if the L1-L2 average correlates with the remainder of the lumbosacral spine.