Ignite Creation Date:
2024-05-05 @ 11:50 AM
Last Modification Date:
2024-10-26 @ 9:14 AM
Study NCT ID:
NCT00145977
Status:
COMPLETED
Last Update Posted:
2018-09-11
First Post:
2005-09-01
Brief Title:
Texture Analysis for Postmenopausal Osteoporosis
Sponsor:
University of Chicago
Organization:
University of Chicago
Study Overview
Official Title:
Changes in Bone Density Radiographic Texture Analysis and Bone Turnover During Two Years of Antiresorptive Therapy for Postmenopausal Osteoporosis
Status:
COMPLETED
Status Verified Date:
2018-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to determine if a new test for osteoporosis can be useful in monitoring treatment We are studying a new method for examining the quality of bone by an experimental method of computerized analysis of radiographic images x-ray pictures of the heel
Detailed Description:
The study proposed in this application is a part of a larger project entitled Clinical utility of radiographic texture analysis in diagnosing and treating osteoporosis The overall goal of the larger project is to determine whether computerized texture analysis of digitized high-resolution images of trabecular bone texture analysis improves our ability to diagnose bone fragility and follow natural history andor response to pharmacological therapy of osteoporosis In the study proposed here we plan to examine changes in the results of texture analysis during two years of pharmacological therapy for osteoporosis
Role of densitometry in osteoporosis
Measurement of bone mineral density is the principal diagnostic method used in clinical practice and in research studies both to identify patients who have the disease and to follow their response to therapeutic agents The technique used most widely is dual-energy X-ray absorptiometry DXA which has advantages of low cost and radiation exposure and high precision and accuracy of 1-2 and 4-8 respectively Garner 1996 and Melton 1990 Based on the association between the low BMD and increased risk of fracture BMD-based treatment guidelines have been developed Melton 1993 and National Osteoporosis Foundation 1999 There is however a considerable overlap between BMD of patients who sustain fragility fractures and those who do not Cummings 1993 Marshall 1996 Melton 1989 Ross 1990 and Wasnich 1990 The problem arises because the fragility is determined not only by the quantity of the bone measured as bone density but also by its quality which is believed to be related to the preservation of the normal trabecular pattern Parfitt 1987 Bone quality is not specifically assessed using current diagnostic methods Information about bone quality however would be of substantial clinical and scientific value as it would complement the BMD measurement when selecting patients for therapy and when studying bone loss or assessing effects of therapeutic agents
Texture analysis
A novel approach to noninvasive and practical assessment of bone structure is to analyze the texture of high resolution radiographs of trabecular bone Link 1999 Dr Giger has developed a method for characterizing bone structure by computerized texture analysis of digitized high-resolution radiographs Jiang 1999 Caligiuri 1993 Caligiuri 1994 Chinander 1999 and Chinander 2000 In this approach the texture is analyzed in several ways including Fourier based analysis which yields root mean square RMS as a measure of magnitude of trabecular bone texture pattern and the first moment of power spectrum FMP which characterizes the texture patterns frequency and Minkowski dimension fractal analysis Caligiuri 1993 Chinander 1999 Chinander 2000 Benhamou 1994 Jiang 1999 Majumdar 1993 and Maragos 1994 Radiographic texture analysis has been studied in vivo on lumbar spine radiographs and found to predict presence of vertebral fractures elsewhere in the spine more reliably than did the BMD of the spine Caligiuri 1993 and Caligiuri 1994 In addition in an in vitro study texture features as well as BMD were analyzed in femoral neck specimens obtained during surgical hip replacement Mechanical loading crush test was then performed on cubes of trabecular bone machined from these specimens to determine their bone strength It was found that the combination of BMD and texture analysis predicted bone strength better than BMD alone Jiang 1999 Chinander 1999 and Chinander 2000
Biochemical markers of bone turnover
In studies of osteoporosis the bone mass is assessed by measuring BMD while the metabolic activity of the bone is assessed by measuring the biochemical markers of bone turnover Looker 2000 These markers have limited utility in individual patients because they have high within-person variability low precision and because it is not clear which markers are useful in which clinical situation Looker 2000 and Bauer 1999 In contrast comparing biochemical markers between groups of patients in clinical studies has been found to be useful in two settings Firstly it has been found that high levels of biochemical markers of bone resorption predict fractures independent of BMD Garnero 1996 and van Daele 1996 Secondly early changes in bone markers at 3-6 months during anti-resorptive therapy predict later changes in BMD and fracture rates Ravin 1999 Greenspan 1998 Chesnut 1997 and Bjarnason 1997 The mechanisms underlying these observations have not been elucidated to date It is speculated that increased bone resorption which is reflected in elevation of biochemical markers of bone turnover increases fragility by weakening trabecular structure prior to or independent of measurable BMD changes Similarly decreased bone resorption during pharmacological therapy is likely to improve the trabecular structure before or independent of its effects on BMD Since the aim of our research is to indirectly examine the trabecular structure by performing the radiographic texture analysis we plan to determine whether the changes in biochemical markers of bone turnover during antiresorptive therapy will correlate with changes in the results of texture analysis
Rationale for the study
Anti-resorptive therapy reduces bone fragility and increases bone density It is likely that the trabecular structure of the bone also changes during treatment Peripheral densitometry has not been used so far to monitor response to therapy If the combination of texture analysis and peripheral BMD change reproducibly during treatment it may be possible to employ this combination to monitor therapeutic response In so doing one could avoid the need to use the central densitometry and biochemical markers of bone turnover since the former is cumbersome while the latter suffers from low precision
Potential advantages of using a portable peripheral densitometer The texture analyses described above were developed for high-resolution radiographs which were digitized and subjected to computer analysis The new DXA imaging systems such as GELunar PIXI which will be used in our research provide digital images with resolution sufficient for computerized texture analysis 200 micron pixels Furthermore PIXI can generate the image in a shorter time seconds vs minutes and at a fraction of radiation dose of conventional radiographs Finally since this is a portable densitometer the methodology developed in this proposal has the potential to be widely applicable to large segments of the population including frail elderly who have limited mobility and high prevalence of osteoporosis
STUDY PROCEDURES
The studies will be performed in the outpatient facility of the University of Chicago Every 3 months for the first 6 months and every 6 months for the remainder of 2 years the subjects will come in the morning in the fasting state provide a urine sample second morning void and blood sample for measurement of biochemical markers of bone turnover Height and weight will be recorded at each visit and any change in health status including fractures ascertained We will also assess other factors known to influence bone turnover such as diet and physical activity Every 12 months the subjects will fill out Block food frequency questionnaire from Berkley Nutrition Services In addition every 6 months they will fill out a calcium intake questionnaire which will be analyzed by the nutritionist and a short physical activity questionnaire which was used in PEPI trial for assessment of physical activity Medication compliance will be assessed by questioning the patients and counting the number of calcium and alendronate tablets remaining from the previous visit
After these tests are completed the subjects will go to the densitometry suite of the Endocrinology clinic where BMD will be measured and heel images obtained for texture analysis The left heel will be scanned twice using the PIXI densitometer GELunar corporation for measurement of BMD of the heel and texture analysis If there is a deformity of the left heel right heel will be used for all examinations In addition every 6 months BMD of the lumbar spine and proximal femur will be measured using the central densitometer Prodigy GELunar corporation The same instrument will be used for lateral vertebral assessment a method used for detecting vertebral deformities on images of the lateral spine from the densitometer which will be performed every 12 months
Role of densitometry in osteoporosis
Measurement of bone mineral density is the principal diagnostic method used in clinical practice and in research studies both to identify patients who have the disease and to follow their response to therapeutic agents The technique used most widely is dual-energy X-ray absorptiometry DXA which has advantages of low cost and radiation exposure and high precision and accuracy of 1-2 and 4-8 respectively Garner 1996 and Melton 1990 Based on the association between the low BMD and increased risk of fracture BMD-based treatment guidelines have been developed Melton 1993 and National Osteoporosis Foundation 1999 There is however a considerable overlap between BMD of patients who sustain fragility fractures and those who do not Cummings 1993 Marshall 1996 Melton 1989 Ross 1990 and Wasnich 1990 The problem arises because the fragility is determined not only by the quantity of the bone measured as bone density but also by its quality which is believed to be related to the preservation of the normal trabecular pattern Parfitt 1987 Bone quality is not specifically assessed using current diagnostic methods Information about bone quality however would be of substantial clinical and scientific value as it would complement the BMD measurement when selecting patients for therapy and when studying bone loss or assessing effects of therapeutic agents
Texture analysis
A novel approach to noninvasive and practical assessment of bone structure is to analyze the texture of high resolution radiographs of trabecular bone Link 1999 Dr Giger has developed a method for characterizing bone structure by computerized texture analysis of digitized high-resolution radiographs Jiang 1999 Caligiuri 1993 Caligiuri 1994 Chinander 1999 and Chinander 2000 In this approach the texture is analyzed in several ways including Fourier based analysis which yields root mean square RMS as a measure of magnitude of trabecular bone texture pattern and the first moment of power spectrum FMP which characterizes the texture patterns frequency and Minkowski dimension fractal analysis Caligiuri 1993 Chinander 1999 Chinander 2000 Benhamou 1994 Jiang 1999 Majumdar 1993 and Maragos 1994 Radiographic texture analysis has been studied in vivo on lumbar spine radiographs and found to predict presence of vertebral fractures elsewhere in the spine more reliably than did the BMD of the spine Caligiuri 1993 and Caligiuri 1994 In addition in an in vitro study texture features as well as BMD were analyzed in femoral neck specimens obtained during surgical hip replacement Mechanical loading crush test was then performed on cubes of trabecular bone machined from these specimens to determine their bone strength It was found that the combination of BMD and texture analysis predicted bone strength better than BMD alone Jiang 1999 Chinander 1999 and Chinander 2000
Biochemical markers of bone turnover
In studies of osteoporosis the bone mass is assessed by measuring BMD while the metabolic activity of the bone is assessed by measuring the biochemical markers of bone turnover Looker 2000 These markers have limited utility in individual patients because they have high within-person variability low precision and because it is not clear which markers are useful in which clinical situation Looker 2000 and Bauer 1999 In contrast comparing biochemical markers between groups of patients in clinical studies has been found to be useful in two settings Firstly it has been found that high levels of biochemical markers of bone resorption predict fractures independent of BMD Garnero 1996 and van Daele 1996 Secondly early changes in bone markers at 3-6 months during anti-resorptive therapy predict later changes in BMD and fracture rates Ravin 1999 Greenspan 1998 Chesnut 1997 and Bjarnason 1997 The mechanisms underlying these observations have not been elucidated to date It is speculated that increased bone resorption which is reflected in elevation of biochemical markers of bone turnover increases fragility by weakening trabecular structure prior to or independent of measurable BMD changes Similarly decreased bone resorption during pharmacological therapy is likely to improve the trabecular structure before or independent of its effects on BMD Since the aim of our research is to indirectly examine the trabecular structure by performing the radiographic texture analysis we plan to determine whether the changes in biochemical markers of bone turnover during antiresorptive therapy will correlate with changes in the results of texture analysis
Rationale for the study
Anti-resorptive therapy reduces bone fragility and increases bone density It is likely that the trabecular structure of the bone also changes during treatment Peripheral densitometry has not been used so far to monitor response to therapy If the combination of texture analysis and peripheral BMD change reproducibly during treatment it may be possible to employ this combination to monitor therapeutic response In so doing one could avoid the need to use the central densitometry and biochemical markers of bone turnover since the former is cumbersome while the latter suffers from low precision
Potential advantages of using a portable peripheral densitometer The texture analyses described above were developed for high-resolution radiographs which were digitized and subjected to computer analysis The new DXA imaging systems such as GELunar PIXI which will be used in our research provide digital images with resolution sufficient for computerized texture analysis 200 micron pixels Furthermore PIXI can generate the image in a shorter time seconds vs minutes and at a fraction of radiation dose of conventional radiographs Finally since this is a portable densitometer the methodology developed in this proposal has the potential to be widely applicable to large segments of the population including frail elderly who have limited mobility and high prevalence of osteoporosis
STUDY PROCEDURES
The studies will be performed in the outpatient facility of the University of Chicago Every 3 months for the first 6 months and every 6 months for the remainder of 2 years the subjects will come in the morning in the fasting state provide a urine sample second morning void and blood sample for measurement of biochemical markers of bone turnover Height and weight will be recorded at each visit and any change in health status including fractures ascertained We will also assess other factors known to influence bone turnover such as diet and physical activity Every 12 months the subjects will fill out Block food frequency questionnaire from Berkley Nutrition Services In addition every 6 months they will fill out a calcium intake questionnaire which will be analyzed by the nutritionist and a short physical activity questionnaire which was used in PEPI trial for assessment of physical activity Medication compliance will be assessed by questioning the patients and counting the number of calcium and alendronate tablets remaining from the previous visit
After these tests are completed the subjects will go to the densitometry suite of the Endocrinology clinic where BMD will be measured and heel images obtained for texture analysis The left heel will be scanned twice using the PIXI densitometer GELunar corporation for measurement of BMD of the heel and texture analysis If there is a deformity of the left heel right heel will be used for all examinations In addition every 6 months BMD of the lumbar spine and proximal femur will be measured using the central densitometer Prodigy GELunar corporation The same instrument will be used for lateral vertebral assessment a method used for detecting vertebral deformities on images of the lateral spine from the densitometer which will be performed every 12 months
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 1K23AR048205 | NIH | NIH | httpsreporternihgovquickSearch1K23AR048205 |
| NIH AR42739 | OTHER_GRANT | None | None |
| NIH AR42739-S1 | OTHER_GRANT | None | None |