Overview of dual-energy x-ray absorptiometry

INTRODUCTION — Osteoporosis or low bone mass (osteopenia) occurs in approximately 54 million American adults, and approximately 50 percent of women and 20 percent of men at least 50 years of age will sustain an osteoporotic fracture over their lifetime [1]. Osteoporosis is defined as "a skeletal disease characterized by compromised bone strength predisposing a person to an increased risk of fracture" [2].

Approximately two million fragility fractures occur in the United States each year: 547,000 vertebral fractures (VFs), 297,000 hip fractures, 397,000 wrist fractures, and 675,000 at other skeletal sites [3]. Fractures of the spine and hip are associated with chronic pain, deformity, depression, disability, and death. Approximately 50 percent of patients with hip fractures will never be able to walk without assistance and 25 percent will require long-term care [4]. The mortality rate five years after a fracture of the hip or a clinical VF is approximately 20 percent greater than expected [5]. The direct cost of incident osteoporotic fractures in the United States is estimated to be USD $25.3 billion per year in 2025 [3].

This topic review will discuss the clinical applications and interpretation of dual-energy x-ray absorptiometry (DXA) in evaluating osteoporosis. Other aspects of screening for osteoporosis are reviewed elsewhere. (See "Screening for osteoporosis in postmenopausal women and men".)

BONE QUALITY — Bone strength is determined by bone mineral density (BMD) and other properties of bone that are often collectively called "bone quality" [6]. Non-BMD determinants of bone strength include bone turnover, architecture (size and shape, or bone geometry), microarchitecture (eg, trabecular thickness, trabecular connectivity, trabecular perforation, cortical thickness, and cortical porosity), damage accumulation, matrix properties, mineralization, and mineral properties (eg, crystal size and orientation).

Investigation of bone quality has provided insight into the pathogenesis of osteoporosis and a better understanding of the mechanism of action of medications used to treat osteoporosis, but with the exception of bone turnover markers, it is not yet possible to measure these routinely in clinical practice. Technologies such as high-resolution peripheral quantitative computed tomography (HR-pQCT) and micro-magnetic resonance imaging (micro-MRI) can be used to assess trabecular microarchitecture, but at the present time, these are largely used for research, with no established clinical applications. Trabecular bone score (TBS) is a gray-level textural measurement that can be extracted from a dual-energy x-ray absorptiometry (DXA) image of the lumbar spine with proprietary software; it captures information related to bone microarchitecture that provides an assessment of fracture risk that is independent of bone density [7]. In the absence of a fragility fracture, bone density is the best predictor of fracture risk.

BMD testing — Bone mineral density (BMD) testing is a widely available clinical tool to diagnose osteoporosis, predict fracture risk, and monitor response to therapy. BMD testing at any skeletal site with a variety of technologies can predict fracture risk [8]; however, the only methods for diagnosis of osteoporosis in the absence of a fragility fracture are [9]:

●DXA T-scores of the lumbar spine, total hip, femoral neck, and one-third radius

●T-scores of the total hip and femoral neck calculated from 2D projections of quantitative computed tomography (QCT) data

DXA is the best method for monitoring changes in BMD over time for the following reasons [9]:

●Biomechanical studies have shown a strong correlation between mechanical strength and BMD measured by DXA [10].

●In prospective cohort studies, there is a strong relationship between fracture risk and BMD measured by DXA [8].

●The World Health Organization (WHO) criteria for the diagnosis of osteoporosis are based on reference data obtained by DXA [11]. (See "Clinical manifestations, diagnosis, and evaluation of osteoporosis in postmenopausal women", section on 'Bone mineral density' and "Clinical manifestations, diagnosis, and evaluation of osteoporosis in men", section on 'Diagnosis of osteoporosis'.)

●The fracture risk algorithm (Fracture Risk Assessment Tool [FRAX]) uses femoral neck BMD measured by DXA. (See "Osteoporotic fracture risk assessment", section on 'Fracture risk assessment tool'.)

●Randomized, clinical trials showing a reduction in fracture risk with drug therapy have selected subjects based on BMD measured by DXA [12].

●There is a strong relationship between decreased fracture risk with drug therapy and the magnitude of BMD increase measured by DXA [13,14].

●Accuracy and precision are excellent [15]; radiation exposure is very low [16].

DXA TECHNOLOGY — A typical dual-energy x-ray absorptiometry (DXA) instrument consists of a padded table on which the patient lies and a movable C-arm with a radiograph tube below the patient and a detector above the patient (figure 1). The radiograph tube generates photon beams of two different energy levels, thus the term "dual-energy." A collimator below the table limits the scatter of the photons and directs them toward the area of interest. The difference in attenuation (reduction in intensity) of the two photon beams as they pass through body tissue of variable composition distinguishes bone from soft tissue and allows quantification of bone mineral density (BMD). Denser and thicker tissue contains more electrons and allows fewer photons to pass through to the detector. A computer with specially designed proprietary software designed by each manufacturer completes the DXA "system."

Radiation exposure to the patient is very small, usually of a similar magnitude to daily background radiation. Radiation scatter beyond the edge of the DXA table is negligible. No shielding of the technologist or the room is necessary. As a safety precaution, the technologist should typically not sit within three feet of the table edge while the patient is being scanned.

DXA measures bone mineral content (BMC, in grams) and bone area (BA, in square centimeters), then calculates "areal" BMD in g/cm² by dividing BMC by BA. T-score, the value used for diagnosis of osteoporosis, is calculated by subtracting the mean BMD of a young adult reference population from the patient's BMD and dividing by the standard deviation (SD) of young adult population. Z-score, used to compare the patient's BMD to a population of peers, is calculated by subtracting the mean BMD of an age, ethnicity, and sex-matched reference population from the patient's BMD and dividing by the SD of the reference population. The mean BMD and SD of the reference populations used for these calculations are critical variables in the determination of T-scores and Z-scores. (See "Clinical manifestations, diagnosis, and evaluation of osteoporosis in postmenopausal women", section on 'T-score' and "Clinical manifestations, diagnosis, and evaluation of osteoporosis in postmenopausal women", section on 'Z-score'.)

There are significant differences in the technologies used by different manufacturers and sometimes different models of DXA made by the same manufacturer. Manufacturers use different methods for creating dual photon beams (eg, K-edge filtering and voltage switching), different bone edge detection algorithms, different assumptions on body size and tissue composition, different calibration, and different types of photon detectors. Photon beams have different configurations, eg, pencil beam and fan beam. The bone regions of interest (ROI) measured may be different, especially so with the femoral neck. The reference databases used to calculate T-scores and Z-scores may be different. For all of these reasons, it is not possible to make quantitative comparisons of BMD measured on different instruments, especially those made by different manufacturers, unless a cross-calibration study has been done [9].

CLINICAL APPLICATIONS OF DXA — Dual-energy x-ray absorptiometry (DXA) is used to diagnose osteoporosis or low bone mineral density (BMD), estimate the future risk of fracture, and monitor changes in BMD over time.

Indications — Guidelines or evidence-based reviews on the indications for BMD testing have been published by many organizations and are reviewed in detail separately. (See "Screening for osteoporosis in postmenopausal women and men", section on 'Recommendations by expert groups'.)

The guidelines vary according to the populations addressed, clinical risk factors considered, definition of fragility fracture, methodologies used, and weighting of levels of medical evidence versus expert opinion. The Bone Health and Osteoporosis Foundation (BHOF; formerly the National Osteoporosis Foundation [NOF]) guide provides comprehensive recommendations for adults that are useful in clinical practice (table 1) [1]. The International Society for Clinical Densitometry (ISCD) Official Positions include recommendations for BMD testing in special populations, such as children, transgender and gender nonconforming individuals, spinal cord injury patients, and patients scheduled for elective orthopedic and spine surgery [9].

Contraindications — DXA should not be done in individuals who are pregnant or may be pregnant because ionizing radiation, albeit it in very small doses, is used. DXA should be postponed until pregnancy is completed. As with any medical test, DXA should not be done unless the results are likely to play a role in the management of the patient. It may not be possible to do a DXA of the hip and spine in some patients due to inability to get on the table. BMD measurement may not be valid in some situations due to skeletal structural abnormalities, such as severe osteoarthritis, surgical hardware, or scoliosis.

Skeletal site selection — The World Health Organization (WHO) recommends that the international standard for diagnosis of osteoporosis be made using the T-score measured by DXA at the femoral neck [17]. However, the BHOF and the International Society for Clinical Densitometry (ISCD) suggest that the diagnosis of osteoporosis in clinical practice be made by DXA using the lowest T-score of the lumbar spine (ideally L1-L4), total proximal femur, or femoral neck [1,9]. The hip, Ward's area, trochanter, and other regions of interest (ROIs) should not be used for diagnosis. If the forearm is measured, then the 33 percent radius (one-third radius) may be used for diagnostic purposes if it is the lowest of the relevant skeletal sites measured.

The rationale for using the lowest T-score of these skeletal sites is that all are good predictors of fracture risk, and the use of the lumbar spine, hip, and forearm BMD is consistent with the original WHO diagnostic classification of 1994 [11].

We suggest following BHOF recommendations (DXA of the lumbar spine and hip). We make the diagnosis according to the lowest T-score measured. Skeletal site selection is discussed in more detail separately. (See "Osteoporotic fracture risk assessment", section on 'Skeletal site to measure'.)

Reference databases — The WHO and the ISCD recommend calculation of T-score with a uniform, standardized reference database in adults of all racial and ethnic groups, using the National Health and Nutrition Examination Survey (NHANES) III database for femoral neck measurements in young adult, White females [9,17]. It should be noted, however, that application of ISCD recommendation may vary according to local requirements and that many DXA systems currently in clinical use continue to report T-scores in males using a male reference database. Some DXA facilities may choose to continue to report T-scores in this manner despite the ISCD recommendation. DXA manufacturers should use the NHANES III database as the reference standard for femoral neck and total hip T-scores, while continuing to use their own databases for the lumbar spine as the reference standard for T-scores. If local reference data are available, they should be used to calculate only Z-scores but not T-scores. The reference database for calculation of Z-score is matched for age, ethnicity, and sex.

Diagnosis of osteoporosis — A clinical diagnosis of osteoporosis may be made in the presence of a fragility fracture, regardless of BMD. A fragility fracture has been defined variously as one that occurs after a fall from the standing position or one that is associated with low BMD and increases in incidence with age [18,19]. The National Bone Health Alliance recommends a clinical diagnosis of osteoporosis in patients with elevated risk for future fracture. This includes patients with a hip fracture, regardless of BMD; with vertebral, proximal humerus, pelvis, or some wrist fractures when the T-score is between -1.0 and -2.5; or with a Fracture Risk Assessment Tool [FRAX] 10-year probability of major osteoporotic fracture 20 percent or greater, or 10-year probability of hip fracture 3 percent or greater (United States only) [19]. It is preferable to diagnose osteoporosis before the first fracture occurs, just as it is preferable to diagnose hypertension before a stroke or hypercholesterolemia before a myocardial infarction. The WHO has established a classification of BMD according to T-score that has been adapted for clinical use by the ISCD (table 2) [9,11]. (See "Clinical manifestations, diagnosis, and evaluation of osteoporosis in postmenopausal women", section on 'Diagnosis' and "Clinical manifestations, diagnosis, and evaluation of osteoporosis in men", section on 'Diagnosis of osteoporosis'.)

Postmenopausal females — The WHO classification of BMD may be applied to perimenopausal and postmenopausal females of all ethnicities [9]. The WHO selected a T-score of -2.5 or less to define osteoporosis because this identified approximately 30 percent of postmenopausal White females as having osteoporosis, which is approximately the same as the lifetime risk of fragility fracture in this population [20]. (See "Clinical manifestations, diagnosis, and evaluation of osteoporosis in postmenopausal women".)

Premenopausal females — The WHO classification should not be used in healthy premenopausal females, because the relationship between BMD and fracture risk is not well established in this population. Z-scores, not T-scores, should be used in premenopausal females [9]. A clinical diagnosis of osteoporosis may be made in the presence of a fragility fracture, or when there is low BMD and risk factors for fracture, such as long-term glucocorticoid therapy or hyperparathyroidism. (See "Epidemiology and etiology of premenopausal osteoporosis".)

Males — The WHO classification may be used in males age 50 years and older [17]. In younger males, as with premenopausal females, Z-scores (not T-scores) should be used, and a clinical diagnosis of osteoporosis should not be made in males under age 50 on the basis of BMD alone [9]. In males below age 50 years with low BMD (Z-score ≤-2.0), we diagnose osteoporosis if there is a history of a fragility fracture and, possibly, if other risk factors for osteoporosis (such as glucocorticoid therapy, hypogonadism, or hyperparathyroidism) are present. (See "Clinical manifestations, diagnosis, and evaluation of osteoporosis in men".)

Children — The WHO classification should not be used in children and adolescents. The diagnosis of osteoporosis in children and adolescents cannot be made based on densitometric criteria alone.

●A diagnosis of osteoporosis may be made in the presence of one or more vertebral fractures with the absence of local disease or high-energy trauma. In such children and adolescents, measuring BMD adds to the overall assessment of bone health.

●In the absence of vertebral fractures, the diagnosis of osteoporosis may be made in the presence of both a clinically significant fracture history and Z-score less than or equal to -2.0. Z-scores, not T-scores, should be used since it is not appropriate to compare the BMD of someone who has not yet achieved peak bone mass to an adult who has.

A clinically significant fracture history is one or more of the following [9]:

●Two or more long bone fractures by age 10 years

●Three or more long bone fractures at any age up to age 19 years

BMD measurement in children and adolescents is confounded by factors that include the lack of standardized reference databases for calculating Z-scores [9], changes in bone size with growth, and variability in the relationships between BMD and chronological age, sexual maturation, and bone age. When technically feasible, patients should have measurements of spine and total body less head (TBLH) BMC and areal BMD prior to initiation of bone active treatment [9]. Proximal femur DXA measurements can be used, if reference data are available, for assessing children with reduced weightbearing and mechanical loading of the lower extremities or in children at-risk for bone fragility who would benefit from continuity of DXA measurements through the transition into adulthood [9]. DXA measurements at the 33 percent radius (also called one-third radius) may be used clinically in ambulatory children who cannot be scanned at other skeletal sites, provided adequate reference data are available. Lateral distal femur DXA measurements, if reference data are available, correlate well with increased lower extremity fragility fracture risk in nonambulatory children. An appropriate reference data set for calculation of Z-score must include a sample of the general healthy population sufficiently large to characterize the normal variability in bone measures that takes into consideration sex, age, and race/ethnicity [9].

Repeat BMD testing — Repeat bone mineral density (BMD) testing should be performed when the results are expected to inform management decisions.

Repeat BMD testing may be used in the following settings:

●To monitor the effectiveness of osteoporosis pharmacotherapy.

●To inform decisions about initiation of osteoporosis pharmacotherapy in untreated patients [9].

●To assess patients who sustain a fracture or develop additional risk factors for fracture. In patients who sustain a fracture, repeat BMD testing should not delay the initiation of treatment to reduce fracture risk.

●To monitor patients taking bisphosphonate therapy before and during a planned treatment interruption (drug holiday) [9].

Repeat BMD tests provide helpful clinical information, assuming the comparisons are technically valid and the clinician is knowledgeable regarding clinical implications. (See 'Validity of comparisons' below and 'Interpretation of BMD changes' below.)

Whenever possible, the same instrument at a high-quality DXA facility should be used for repeat DXA studies. If the previous DXA is poor quality (eg, measurement of invalid vertebral bodies, incorrect labeling of vertebral bodies, poor placement of femoral neck box, lack of instrument calibration), then BMD measurement at a high-quality DXA facility is appropriate. Comparison of BMD measured with different instruments made by the same manufacturer or by a different manufacturer is discouraged for the reasons noted above. It is not possible to quantify BMD changes on measurements made on different instruments unless a cross-calibration study has been done. Comparison should be done using BMD in g/cm², not T-score, since changes in reference databases with software upgrades may cause spurious T-score changes.

Precision assessment — The least significant change (LSC) with a 95 percent level of confidence should be established at each bone densitometry center for each technologist by in-vivo precision assessment according to well-established guidelines [9]. LSC is defined as a change that is 2.77 times the precision error for each measured skeletal site, for each technologist, and it is best expressed as an absolute value (g/cm²). Values for precision error supplied by the manufacturer of the DXA instrument are generally better than what is achievable in bone densitometry centers and should not be used for the calculation of LSC.

Time interval for repeating DXA — The intervals for repeat BMD testing with dual-energy x-ray absorptiometry (DXA) must be individualized based on factors including patient age, baseline BMD, type of pharmacologic treatment, and clinical risk factors for bone loss [9]. A shorter interval for repeat DXA may be appropriate when more rapid change in BMD is expected. Rapid change in BMD may occur with anabolic osteoporosis pharmacotherapies; use of other medications including glucocorticoids, aromatase inhibitors, or androgen deprivation therapy; or clinical settings including prolonged immobilization or surgical menopause.

Skeletal site to monitor — The best skeletal site to monitor is one that responds quickly to therapy or lack of therapy and has a low LSC. Usually this is the lumbar spine or the total proximal femur. If the lumbar spine is not evaluable, as may occur with degenerative arthritis in older patients, then the total proximal femur is preferred.

Validity of comparisons — Quantitative comparison of BMD measured with different instruments made by the same manufacturer or by a different manufacturer is discouraged for the reasons noted above. Comparison should be done using BMD in g/cm², not T-score, since changes in reference databases may cause spurious T-score changes [21]. Images of the skeletal site being compared should be carefully examined to assure correct positioning, labeling, and identification of bone edges. If the lumbar spine is being compared, then the vertebral levels must be labeled in the same way. If hip or forearm is being compared, the same ROI on the same side must be used, with reproducible positioning of the limbs. Bone area being compared must be similar.

Interpretation of BMD changes — In treated patients who are adherent to therapy, stability or an increase in BMD is consistent with a skeletal response to therapy. A response to therapy is necessary but may not be sufficient in achieving an acceptable level of fracture risk. Since larger increases in BMD are associated with greater reduction in fracture risk [14], consideration should be given to treating to a target T-score (eg, at least >-2.5), as suggested by a working group of the American Society of Bone and Mineral Research and BHOF [22]. A post hoc analysis of data in 2984 women from the Fracture Intervention Trial (FIT) of alendronate showed that the greatest fracture reduction occurred in those who gained BMD, although those with stable BMD still had fewer fractures than those who lost BMD [23]. Meta-regression analyses of multiple clinical trials with many different pharmacological agents have shown robust correlations between the magnitude of BMD increase and reduction of fracture risk [14,24]. Loss of BMD more than the LSC is cause for clinical concern and may be associated with poor adherence to therapy [25-28], previously unrecognized contributing factors that require additional intervention, or development of a new condition or use of new medication that is harmful to bone [29]. (See "Overview of the management of low bone mass and osteoporosis in postmenopausal women", section on 'Monitoring response to initial pharmacotherapy'.)

Vertebral fracture assessment — Vertebral fractures (VFs) are a strong predictor of future fractures of all types [9]. VFs are the most common type of fragility fracture, yet approximately two-thirds of VFs are not clinically detected [30]. Vertebral fracture assessment (VFA) by DXA is a method of visualizing the spine to detect VFs [31]. This can be done at the time of BMD testing, at greater patient convenience, less cost, and lower radiation exposure than conventional radiography of the spine [32].

VFA compares favorably with spine radiographs in detecting moderate and severe VFs, but it does not perform as well for diagnosing mild VFs [33,34]. In one study of women age 65 years and older, the sensitivity and specificity of VFA for detecting moderate and severe VFs was 87 to 93 percent and 93 to 95 percent, respectively [33].

Identification of previously undetected VFs may change the diagnostic classification, fracture risk profile, and clinical management. The ISCD has published guidelines addressing the potential indications for VFA (table 3) [9].

NOMENCLATURE — DXA, not DEXA, is the preferred acronym for dual-energy x-ray absorptiometry. T-score should be used with no italics, not T score, t-score, or t score. Similarly, Z-score with no italics, not Z score, z-score, or z score, should be used. These should be expressed to one decimal digit, eg, -2.3, not -2 or -2.31. Bone mineral density (BMD) should be expressed to three decimal digits, eg, 0.946 g/cm² [35].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Clinical densitometry".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Bone density testing (The Basics)" and "Patient education: Osteoporosis (The Basics)" and "Patient education: Calcium and vitamin D for bone health (The Basics)")

●Beyond the Basics topics (see "Patient education: Bone density testing (Beyond the Basics)" and "Patient education: Osteoporosis prevention and treatment (Beyond the Basics)" and "Patient education: Calcium and vitamin D for bone health (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Clinical application of DXA – Dual-energy x-ray absorptiometry (DXA) is the best available clinical tool for the diagnosis of osteoporosis and monitoring changes in bone mineral density (BMD) over time. (See 'Clinical applications of DXA' above.)

●Diagnosis of osteoporosis – The World Health Organization (WHO) has established a classification of BMD according to T-score that is the worldwide standard for diagnosis of osteoporosis (table 2). The WHO criteria should be used for diagnostic classification in postmenopausal females, perimenopausal females, and for males aged 50 years and older. They should not be used for premenopausal females, males under age 50 years, or children. In these populations, Z-scores rather than T-scores should be used. (See 'Diagnosis of osteoporosis' above.)

•Skeletal site selection – The Bone Health and Osteoporosis Foundation (BHOF) and the International Society for Clinical Densitometry (ISCD) recommend that the diagnosis of osteoporosis be made using the lowest T-score measured by DXA of the lumbar spine (L1-L4), total proximal femur, femoral neck, or one-third radius. (See 'Skeletal site selection' above.)

•Reference database – The WHO and the ISCD recommend the use of the National Health and Nutrition Examination Survey (NHANES) III young adult reference database for calculation of T-score at the hip, using a White female database for females and for males. Application of this recommendation may vary according to local requirements. (See 'Reference databases' above.)

●Repeat BMD testing – The same DXA instrument should be used for repeat BMD testing whenever possible. It is not possible to quantify BMD changes on measurements made on different instruments unless a cross-calibration study has been done. (See 'Repeat BMD testing' above.)

●Vertebral fracture assessment – Identification of previously undetected vertebral fractures (VFs) may change the diagnostic classification, fracture risk assessment, and clinical management. Vertebral fracture assessment (VFA) by DXA is a method of visualizing the spine to detect VFs (table 3). VFA compares favorably with spine radiographs in detecting moderate and severe VFs, but it does not perform as well for diagnosing mild VFs. (See 'Vertebral fracture assessment' above.)