The Accuracy of DEXA
The DEXA test, which is considered the gold standard for measuring bone mineral density and diagnosing osteoporosis, is a poor predictor of actual fracture risk, which is the real issue.
In Health
Jeff
A new perspective on the causal influence of soft tissue composition on DXA-measured in vivo bone mineral density. J Bone Miner Res. 1998 Nov;13(11):1739-46.
Abstract
An extensive series of quantitative simulation studies replicating ideal dual-energy X-ray absorptiometric (DXA) bone mineral density (BMD) measurements of typical and realistic in vivo lumbar vertebral and proximal femoral sites has been carried out to quantitatively assess the extent of inherent systematic inaccuracies in such measurements. The results for these bone sites indicate that BMD inaccuracies as high as 20% or more can be anticipated clinically, particularly in cases of osteopenic, osteoporotic, and elderly patients. It is found that the most important soft-tissue anthropometric determinants of the extent of bone site-specific systematic in vivo BMD inaccuracies reflected in DXA measurements are the ratio of the areal density of extraosseous fat to that of lean muscle tissue immediately surrounding the interrogated bone site and the specific yellow/red marrow mix within the scanned bone. As such, the present findings focus directly on the question of whether or not the strong, positive correlations and associations between soft tissue compositional parameters and DXA-measured in vivo BMD determined in a large number of previous clinical investigations are, in toto or in part, biologically causal. The present results are seen to be quantitatively and qualitatively in conformity with the many clinical studies that have found marked general decreases (increases) in measured BMD as body weight and/or body fat mass decreases (increases). It is concluded that the clinically observed correlations between DXA-measured BMD and these anthropometric parameters are artefacts of the systematic errors (inaccuracies) inherent in planar DXA methodology and are unlikely to be of biological genesis.
PMID: 9797483
Inaccuracies inherent in dual-energy X-ray absorptiometry in vivo bone mineral densitometry may flaw osteopenic/osteoporotic interpretations and mislead assessment of antiresorptive therapy effectiveness. Bone. 2001 May;28(5):548-55.
Abstract
New, anatomically realistic simulation studies based on a cadaveric lumbar vertebra and a broad range of soft tissue anthropometric representations have quantitatively delineated inaccuracies inherent in dual-energy X-ray absorptiometry (DXA) in vivo bone mineral density (BMD) methodology. It is found that systematic inaccuracies in DXA BMD measurements may readily exceed +/-20% at typical in vivo lumbar vertebral sites, especially for osteopenic/osteoporotic, postmenopausal, and elderly patients. These findings are quantitatively compared with extensive clinical evidence of strong, positive correlations between soft tissue anthropometrics and DXA in vivo BMD upon which prior significant bone biology interpretations and implications have been based. The agreement is found to be both qualitatively and quantitatively excellent. Moreover, recent extensive multicenter clinical studies have also exposed new facets of strong linkages between body mass/percent body fat/body mass index (BMI) and DXA-measured BMD that are particularly relevant to osteopenia/osteoporosis and remedial effectiveness of antiresorptive drug therapy. These seemingly disparate and unrelated diagnostic and prognostic aspects of clinically observed associations between soft tissue anthropometrics and measured vertebral BMD are, in this study, self-consistently shown to share the common origin of being manifestations of systematic inherent inaccuracies in DXA in vivo BMD methodology, without the need to invoke any underlying biologically causal mechanism(s). These inaccuracies arise principally from absorptiometric disparities between the intra- and extraosseous soft tissues within the DXA scan region of interest. The present evaluative comparisons are based exclusively on an incisive and diverse body of clinical data that appears difficult to dismiss or discount. Previous invocations of biologically causal mechanisms responsible for this broad range of observations linking body mass, percent body fat, and/or BMI to measured BMD now appear questionable. This doubtful status has also been extended in the present work to previously reported relationships between antiresorptive therapies and observed changes in DXA-derived BMD. These findings strongly indicate that critical and insightful reassessments of diagnostic/prognostic imputations underpinned by DXA in vivo BMD measurements are warranted. It is suggested that a good deal of what is known of bone fragility, bone densitometry, antiresorptive drug efficacy, and/or other therapeutic regimens, if based on patient-specific in vivo DXA methodology, may prove to be equivocal and tenuous. PMID: 11344055
Wilkin TJ, Devendra D. Bone densitometry is not a good predictor of hip fracture. BMJ. 2001 Oct 6;323(7316):795-7. No abstract available. PMID: 11588087
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1121341/The significant effects of bone structure on inherent patient-specific DXA
in vivo bone mineral density measurement inaccuracies.
Med Phys. 2004 Apr;31(4):774-88.
An extended analytic exposition is developed of the effects bone structure has on the form and extent of systematic inaccuracies in planar dual-energy x-ray absorptiometry (DXA) in vivo bone mineral density (BMD) measurements. Explicit expressions for absolute and percentage BMD inaccuracies are derived and criteria governing these BMD inaccuracies delineated. It is shown that the effect of bone structure is to introduce a scale factor which modulates the sizable and unavoidable DXA in vivo/in situ BMD inaccuracies that arise directly from patient-specific anthropometric and x-ray absorptiometric disparities among the several soft tissues present within the scan region of interest of any given bone site (i.e., lean muscle tissue, interposed and admixed fat, and red/yellow marrow combinations). Different magnitudes and patterns of BMD inaccuracies are shown to pertain for bone structures that are (i) essentially wholly trabecular, (ii) wholly cortical, and (iii) those containing both cortical and trabecular bone. Over the range of soft tissue anthropometrics typical of adult patients, the overall percentage inaccuracies in DXA-measured BMD are shown to be quite sizable and to vary considerably for different bone structures. For a typical lumbar vertebral bone site, BMD inaccuracies are found to be as large as approximately 25% for normal patients, to exceed approximately 35% for osteopenics, and to approach 50% for osteoporotic individuals. For bone sites with non-negligible cortical surrounds of trabecular structures (e.g., distal radius, some segments of proximal femur, etc.), it is shown that BMD percentage inaccuracies range up to approximately 20% for normal, approximately 25% osteopenic, and approximately 35% for osteoporotic patients. The BMD % inaccuracies associated with wholly cortical bone (trabecular-free) sites (e.g., mid-shaft femur, mid-shaft radius, etc.) are comparatively small, being less than approximately 2%. Depending on bone structure, bone size and shape, and patient-specific intra- and extra-osseous soft tissue particulars of any given adult patient, DXA in vivo BMD measurements can be grossly inaccurate, and can severely under- or over-estimate the true value of BMD and mask or exaggerate true changes in BMD in ways not previously elucidated. It is concluded that in vivo DXA-measured and actual BMD cannot be considered to be synonymous, and clinical reliance upon the two being the same may readily conduce to seriously flawed and misleading diagnostic, prognostic, and prospective results.
Relationship of body surface area with bone density and its risk of osteoporosis at various skeletal regions in women of mainland China.
Osteoporos Int. 2004 Sep;15(9):751-9. Epub 2004 Jun 3.
Abstract
The aim of this study was to investigate the relationship between body surface area (BS) and bone mineral density (BMD) and the associated osteoporosis risk at various skeletal regions in women from mainland China. BMD was measured at the posteroanterior (PA) spine (L1-L4), supine lateral spine (L2-L4) including volumetric BMD (vBMD), hip including femoral neck, trochanter and total hip, and forearm, including radius + ulna ultradistal (R + UUD), 1/3 site (R + U1/3) and total region (R + UT) using a dual-energy X-ray absorptiometry (DXA) fan-beam bone densitometer (Hologic QDR 4500A) in 3418 females aged from 18 to 75 years. Data analysis revealed a positive correlation between BS and BMD at the various skeletal regions (r = 0.114-0.373, all P = 0.000), but no correlation with vBMD (r = 0.000, P = 0.934). Using the stepwise regression model, BMDs at various skeletal regions were dependent variables while height, weight, body mass index (BMI), BS and projective bone area (BA) were independent variables; BS was determined to be the most important variable that affected the PA spine, hip and forearm BMDs. Subjects were divided into three groups according to size: large BS group (LBSG), intermediate BS group (IBSG) and small BS group (SBSG). The BMD at different skeletal regions of subjects between groups exhibited a significant gradient difference, with LBSG > IBSG > SBSG, but this was not seen for vBMD. On the fitting curves where BMD varied with age at the PA spine, femoral neck, total hip and R + UUD, BMDs of LBSG were 6.93-9.29% higher than those of IBSG and 12.1-16.9 % higher than those of SBSG, whereas those of SBSG were 6.12-9.59% lower than those of IBSG at various skeletal regions, respectively. The prevalence rates and risks of osteoporosis of LBSG were significantly lower than those of SBSG and IBSG, whereas those of IBSG were obviously lower than those of SBSG at various skeletal regions, respectively, presenting a gradient difference among the three study groups, LBSG < IBSG < SBSG. Our study shows that the relationship between BS and BMD exceeds that between BMD and height or weight in women in mainland China. When areal BMD is employed, those with a larger BS have higher areal BMD and lower risks of osteoporosis while, conversely, those with a smaller BS have lower areal BMD, and therefore higher risk for osteoporosis. However, when vBMD is used, these differences diminish or even disappear.
PMID: 15175842
Dual-energy x-ray absorptiometry measurements of total-body bone mineral during weight change. J Clin Densitom. 2005 Spring;8(1):31-8.
Abstract
Bone mineral measurements were made using dual-energy X-ray absorptiometry during a multicenter diet trial. There were five centers, two using Hologic QDR4500 fan-beam scanners, two using Lunar Prodigy fan-beam scanners,and one using a pencil-beam Lunar DPX. Measurements were made at 0, 2.5, and 6 mo. The mean weight loss was 7.9 kg, but there was a wide range. With the Lunar instruments, the total-body bone mineral density reduced with weight loss, but with the Hologic scanners, it appeared to increase. This anomaly is similar to that observed previously with a Hologic QDR1000 pencil-beam scanner. It was shown that changes of fat distribution can lead to alterations in bone measurement without any real change in the skeleton. With all of the scanners, there was a strong correlation between the change in the bone mineral content and bone area, with some values of the latter being quite implausible. There was an associated worsening of long-term precision compared with that derived from short-term duplicated scans, more marked with the Lunar scanners. It is concluded that measurement artifacts preclude the valid assessment of total-body bone mineral during weight change.
PMID: 15722585
Disease expands through marriage of marketing and machines
By Susan Kelleher
Seattle Times staff reporter
June 28, 2005
http://seattletimes.com/html/health/sick3.htmlEvery day in clinics and doctors' offices across the country, healthy middle-age women slide their wrists into portable X-ray machines that calculate bone density. If they get a low enough density score, they walk out with a prescription that's supposed to prevent a hip fracture late in life by adding bone tissue now. But there's a big problem with this familiar exercise, according to some top osteoporosis experts: Most of these women don't need the drug. They are wasting money and risking side effects for little benefit.
DXA in vivo BMD methodology: an erroneous and misleading research and clinical gauge of bone mineral status, bone fragility, and bone remodeling. Bone. 2007 Jul;41(1):138-54. Epub 2007 Mar 1. PMID: 17481978
The seemingly unqualified reliance and near-universal dependence upon in vivo dual-energy X-ray absorptiometric (DXA) methodology to provide accurate, quantitative, and meaningful in vivo (in situ cadaveric) bone mineral areal density ("BMD") determinations are proven to be unwarranted and misplaced. The underlying systematics of sizable, inherently unavoidable and un-correctable inaccuracies in the DXA output values of in vivo "BMD" are shown to be quantitatively consistent with being the root cause of unreliable, misdirected, and misinterpreted aspects of consensual knowledge of bone fragility, osteoporotic diagnostics/prognostics, and remodeling therapies. The "BMD" label that DXA ascribes to the output values of in vivo (in situ cadaveric) bone densitometry scans is shown to be a misnomer and an erroneous and invalid measure of bone mineral material. The DXA-derived "BMD" value does not correctly represent the areal density of bone mineral material, as it is contaminated by sizable, unavoidable, inextricable, independent soft tissue contributions. Due to intra- and extra-osseous soft tissue X-ray absorptiometric effects, it is unknown (and unknowable) exactly what DXA in vivo "BMD" is a measure of in any given case, or what proportion of the "BMD" value represents the actual bone mineral material areal density present in the DXA scan region of interest (ROI) of any predominantly trabecular bone-site (e.g., lumbar vertebrae, proximal femora). This inherent fundamental defect in DXA in vivo bone mineral areal density methodology adversely compromises both the validity and reliability of patient-specific diagnostic/prognostic evaluations, cross sectional and prospective studies, and DXA-based interpretations of bone quality and bone fragility. It further undermines the WHO characterizations (and definitions) of 'normal', 'osteopenic', and 'osteoporotic' classifications. It is also seen to make equivocal the qualitative and quantitative epidemiological estimates of the proportion of the population that is, or is deemed to become, osteoporotic. The present quantitative exposition shows DXA-measured in vivo "BMD" methodology to be an intrinsically flawed and misleading indicator of bone mineral status and an erroneous gauge of relative fracture risk.
Osteoporosis and Fractures
Missing the Bridge?
Angela M. Cheung; Allan S. Detsky.
JAMA. 2008;299(12):1468-1470.
On August 1, 2007, a bridge on interstate 35W collapsed during rush-hour traffic near Minneapolis, Minnesota, with tragic consequences. Engineers commissioned by the National Transportation Safety Board are still investigating the cause of this structural failure, and the final report is expected by fall 2008. The bridge buckled because its load exceeded the strength of its structure. Was the bridge collapse caused by an external force such as extra weight on the bridge, or was it due to structural deficiencies such as corrosion and deterioration of the truss gusset plates joining the beams? Although current evidence suggests that the collapse was due to a design flaw (the gusset plates were too thin) coupled with the 300 tons of extra construction equipment and gravel, the collapse could have been caused by one of many elements. These general principles and possible explanations for structural failure apply not only to the collapse of bridges, but also to the fracture of bones.
What Are Bones and Bone Strength?
Bones are designed to support and protect vital organs while being light and allowing for mobility. Humans are born with approximately 300 bones that fuse to become 206 bones by age 25 years. Some bones, such as the skull and ribs, support and protect the brain, heart, and lungs. Other bones provide attachment sites for muscles and allow humans to perform motor activities. However, bone is a complex organ with multiple functions. It makes blood cells, stores minerals, and plays a key role in calcium homeostasis and possibly energy metabolism.1
Fragility fractures-fractures sustained with minimal trauma such as falling from standing height-are the hallmark of osteoporosis. They occur when the load on a bone exceeds its strength. Fractures are more common than heart disease or cancer in women, affecting 1 in 2 women and 1 in 6 men older than 50 years in North America.2 Vertebral fractures are the most common osteoporotic fracture in postmenopausal women; two-thirds of these fractures are not clinically recognized.3 Postmenopausal women who have sustained multiple vertebral fractures can develop restrictive lung disease, early satiety, chronic pain, and low self-esteem. Even asymptomatic vertebral fractures are associated with decreased quality of life, increased hospitalization, and mortality.4-5 Women and men who sustain a hip fracture have pain, decreased mobility, fear of falling, and loss of independence.6 Hip fractures contribute to significant excess mortality; more than half of patients who have a hip fracture die within 5 years.7
Prior to 1993, osteoporosis was defined by the presence of a fragility fracture. With the invention of dual-energy x-ray absorptiometry machines to measure bone mineral density (BMD), the World Health Organization (WHO) established a new definition of osteoporosis in 1993 based on BMD T scores (the number of standard deviations from the mean peak BMD in young sex-matched adults).8 The goal of this change in definition was to identify and treat at-risk individuals before they developed a fragility fracture. In 2001, the National Institutes of Health amended this BMD-based definition of osteoporosis to recognize that bone strength is a combination of both BMD
and "bone quality."9 However, bone quality is a vague entity that is difficult to measure clinically. As a result, clinicians still rely on BMD
for fracture risk assessment and treatment decisions. In addition, pharmaceutical companies use BMD as a surrogate outcome in the development of drugs to reduce fracture risk.
*However, BMD is only 1 determinant of bone strength. Applying principles from engineering, bone strength depends on a combination of its structural and material properties, both of which are modulated by bone turnover.10 Structural properties depend on the size and shape of the bone, the microarchitecture of the bone (such as cortical thickness and porosity, and trabecular thickness, number, and separation), and the amount of accumulated damage (microcracks). Material properties depend on the degree of mineralization, the crystal size of the minerals, the amount and type of collagen cross-links, other proteins, and fat. The measure of BMD by dual-energy x-ray absorptiometry is the amount of bone mineral mass within a user-defined area but is confounded by bone size, which is a strong
determinant of bone strength. Bone mineral density is higher if the bone is bigger, even if the degree of mineralization of the bone is the same. Bone mineral density assumes a homogenous distribution of mineral and density and does not reflect the anisotropy (variability) of bone micro architecture. Thus, many factors that contribute to bone strength are not captured by BMD.*
How Does the Body Protect Bones From Trauma?
Bone strength, in turn, is only one determinant of fracture risk. The ability to avoid injury to the bones is another. A major function of bones is to help humans stay upright and move. Maintaining an upright stance and avoiding falls are important protectors of bones. The ability to avoid falls is a complex activity involving the coordination of bones, muscles, tendons, nerves, and the brain. When an unexpected encounter occurs, such as missing a step, stepping on a slippery surface, or receiving a glancing blow from someone walking in the opposite direction, good coordination, quick reflexes, strong muscles, and excellent balance are required to avoid a
fall. In addition, all individuals experience minor injuries to the muscles, tendons, and bones on one side of the body or the other, and the rest of the structures have to compensate to stay upright and maintain mobility. When a fall occurs, the direction and the force of the impact on bone, the degree of padding around the impact site, the muscular coordination to absorb the impact of the fall, and the strength of the bone itself determine whether a fracture occurs.
Recent data suggest that falls are a stronger predictor of fractures than BMD.11 Falls increase in frequency with advancing age and account for at least 95% of hip fractures in the elderly.12 More than a third of community-dwelling elderly people will fall each year and approximately 10% will sustain a significant injury.13 The reasons for falls are multifactorial: oversedation with drugs, orthostatic hypotension, impaired gait or balance, poor eyesight and hearing, neurological problems, arthritis, sarcopenia (age-related loss of muscle mass), and environmental hazards such as slippery floors or uneven ground. Elderly individuals tend to fall sideways or backward in a manner that applies a load in a direction very different from the usual load-bearing axis of the involved bone. Because of the anisotropy of bone microarchitecture, a bone is more susceptible to fracture when the impact is in such a direction. Thus, the
load of a person's own weight can lead to a femoral neck fracture in a sideways fall.
How Can Bone Fractures Be Predicted?
Experts in osteoporosis are highly cognizant of the limitations of using BMD for the prediction of fracture risk. For example, epidemiological studies have shown that for a given BMD T score (eg, T score of -2.5), a 50-year-old woman has a much lower fracture risk than an 80-year-old woman.14 Also, an individual with a history of fragility fracture after the age of 45 years has a higher risk of a bone fracture than an individual without such a history, all other factors such as age and T score being equal.15 In response to these limitations, WHO and other organizations recently have recommended using an individual's 10-year fracture risk to guide therapy
decisions,16-18 a concept similar to the Framingham cardiovascular risk assessment. The risk calculation algorithm FRAX has been derived from large prospective cohort studies conducted around the world and takes into account clinical risk factors for fractures.19
Although this long-awaited WHO instrument is a substantial improvement over using BMD as the sole criterion for initiating therapy, it still has limitations. Few large prospective cohort studies that have identified risk factors for osteoporosis and fractures examined muscle strength, sarcopenia, gait, balance, history of falls, and other risk factors for falls in methodologically rigorous ways. As a result, these important factors are not included in the WHO model. In addition, the model is only applicable to treatment-naive patients and cannot be used for patients who are already undergoing therapy.
How Can Bone Fractures Be Prevented?
Bisphosphonates, in addition to calcium and vitamin D, are the current mainstay of osteoporosis therapies and have been shown to increase BMD and decrease fractures and mortality.20-21 However, in 2 well-designed randomized controlled trials in which elderly individuals were enrolled on the basis of being at increased risk of hip fracture because of factors other than low BMD, treatment with bisphosphonates did not decrease the risk of hip fractures, the primary outcome in these studies.22-23 These 2 large negative drug trials should serve as a cautionary note that current drug therapies may not address non-BMD related determinants of fracture risk.
Thus, bisphosphonates may not be the most effective therapy for at least some individuals at increased risk of fractures. For these persons, interventions directed at other determinants of fracture risk, such as tai chi exercises to improve balance and muscle strength, may have a greater benefit.
In the effort to prevent fractures, does attention focus too heavily on BMD to the exclusion of other vital factors? Just as hypercholesterolemia is but one of many risk factors for coronary artery disease, low BMD is one of a number of risk factors for osteoporotic fractures. Reasons that some osteoporotic patients sustain fractures and others do not must be examined. To advance the field of osteoporosis and fractures to the next level, the current paradigm must be broadened to include the study of how muscle,
nerves, and bone work together as a unit for coordination, mobility, balance, and strength. Other properties that determine bone strength besides BMD and bone size must be investigated. Assessing the risk of falls using orthostatic blood pressure measurements and validated tools, such as the timed up-and-go, functional reach, and physiological profile assessment tests, should be a routine component of assessing fracture risk.24 Exercise training and multifactorial intervention to maintain muscle strength, gait, balance, and function should be used more often in the clinical setting, and more research is needed in this area. Drug development efforts should be broadened to include drugs that can halt or slow the development of sarcopenia.
Engineering and kinesiology colleagues should be included in understanding the role of muscle function, balance, and sarcopenia in determining fracture risk. In the clinical arena, fracture prevention needs to move beyond the realm of endocrinologists and rheumatologists to include neurologists, physiatrists, physiotherapists, engineers, and muscle activation therapists. The system is only as strong as its weakest link; at times the weakest link is BMD, but often other factors require attention to avert a fracture. Like
investigators for I-35W seeking to prevent the collapse of another bridge, the focus should not be solely on the density of the steel; all links in the chain that determine the integrity of the structure as a whole must be examined.
Resisting the Broken Bone Businesses: Bone Mineral Density Tests and the Drugs That Follow
http://www.nealhendrickson.com/mcdougal ... uosteo.htm