An Update on Dual-Energy X-Ray Absorptiometry Glen M. Blake, PhD, and Ignac Fogelman, MD Dual-energy x-ray absorptiometry (DXA) scans to measure bone mineral density at the spine and hip have an important role in the evaluation of individuals at risk of osteoporosis, and in helping clinicians advise patients about the appropriate use of antifracture treat- ment. Compared with alternative bone densitometry techniques, hip and spine DXA exam- inations have several advantages that include a consensus that bone mineral density results should be interpreted using the World Health Organization T score definition of osteoporosis, a proven ability to predict fracture risk, proven effectiveness at targeting antifracture therapies, and the ability to monitor response to treatment. This review dis- cusses the evidence for these and other clinical aspects of DXA scanning. Particular attention is directed at the new World Health Organization Fracture Risk Assessment Tool (FRAX) algorithm, which uses clinical risk factors in addition to a hip DXA scan to predict a patient’s 10-year probability of suffering an osteoporotic fracture. We also discuss the recently published clinical guidelines that incorporate the FRAX fracture risk assessment in decisions about patient treatment. Semin Nucl Med 40:62-73 © 2010 Elsevier Inc. All rights reserved. steoporosis is widely recognized as an important public porosis before fractures occur and the development of effec- Ohealth problem because of the significant morbidity, tive treatments. Measurements of bone mineral density mortality, and costs associated with its complications, (BMD) played a crucial role in both these developments. namely, fractures of the hip, spine, forearm, and other skel- Until the mid-1980s, bone-density measurements were used etal sites.1 The incidence of fragility fractures is highest mainly for research, and it was only with the introduction of among elderly white women, with 1 in every 2 women suf- dual-energy x-ray absorptiometry (DXA) scanners in 1987 fering an osteoporosis-related fracture in their lifetime.2 Each that they entered routine clinical practice.8 Further mile- year in the United States an estimated 2 million people suffer stones included the first publication showing that bisphos- a fragility fracture, with hip fractures alone causing hospital- phonate treatment prevents bone loss,9 the publication of the ization, disability, and loss of independence for 300,000 in- World Health Organisation (WHO) report defining osteopo- dividuals.3 Hip fractures are often the focus of attention be- rosis in postmenopausal white women as a BMD T score at cause 20% of patients die in the first year after a fracture, and the spine, hip, or forearm of ՅϪ2.5,10,11 and the Fracture they also incur the greatest morbidity and medical costs.4 Intervention Trial confirming that bisphosphonate treatment However, fractures at other sites also cause significant mor- can prevent fractures.12 Since then, several large trials have bidity and costs,5 and vertebral fractures as well as hip frac- provided evidence of the effectiveness of bisphospho- tures are associated with an increased risk of death.6,7 In the nates,13-17 selective estrogen receptor modulators,18 recombi- year 2005, osteoporotic fractures in the United States were nant human parathyroid hormone,19 and strontium rane- responsible for estimated costs of $19 billion.3 Due to the late20-22 in the prevention of fragility fractures. The most aging population the annual number of fractures as a result of significant recent development is the Fracture Risk Assess- osteoporosis is expected to increase to more than 3 million by ment Tool (FRAX) initiative, which enables physicians to use 2025.3 information about a patient’s clinical risk factors in combina- Although for many years there was an awareness of the tion with a hip DXA scan to assess the 10-year probability of morbidity and mortality associated with fragility fractures, fracture for individual patients.23 actual progress only came with the ability to diagnose osteo- The Clinical Role of King’s College London, Guy’s Campus, London, United Kingdom. Bone Density Measurements Address reprint requests to Glen M. Blake, PhD, Osteoporosis Research Unit, 1st Floor, Tower Wing, Guy’s Hospital, London SE1 9RT, United King- Today, BMD measurements have an important role in the dom. E-mail: [email protected] evaluation of patients at risk of osteoporosis and in the ap- 62 0001-2998/10/$-see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1053/j.semnuclmed.2009.08.001 Dual-energy x-ray absorptiometry 63 Figure 1 (A) Scan printout of a spine dual-energy x-ray absorptiometry (DXA) examination. The printout shows (left) scan image of the lumbar spine; (top right) patient’s age and bone mineral density (BMD) plotted with respect to the manufacturer’s reference range; (bottom right) BMD figures for individual vertebrae and total spine (L1-L4), together with the interpretation in terms of T and Z scores. (B) Scan printout of a hip DXA examination. The printout shows (left) scan image of the hip; (top right) patient’s age and total hip BMD plotted with respect to the National Health and Nutrition Examination Survey (NHANES III) reference range28; (bottom right) BMD figures for the femoral neck and total hip regions of interest, together with the interpretation in terms of T and Z scores using the NHANES III reference range. (Color version of figure is available online.) propriate use of antifracture treatment.24-27 In general, the patients for scanning, low radiation dose, and good measure- preferred method of testing is to use DXA scans to measure ment precision (Table 2). BMD of the lumbar spine and hip (Fig. 1).28 DXA examina- Patients’ DXA results are usually presented as T and Z tions have 3 major roles, namely, the diagnosis of osteoporo- scores (Fig. 1). T scores are calculated by taking the differ- sis, the assessment of patients’ risk of fracture, and monitor- ence between a patient’s measured BMD and the mean BMD ing response to treatment. The reasons for using DXA include in healthy young adults, matched for gender and ethnic the fact that hip BMD is the most reliable measurement for group, and expressing the difference relative to the young 29-31 predicting hip fracture risk, the use of spine BMD for adult population standard deviation (SD): monitoring treatment,32,33 and the consensus that in post- menopausal white women and older men spine and hip DXA scans should be interpreted using the WHO T score defini- Measured BMD Ϫ Young adult mean BMD 11,25,34 T score ϭ (1) tion of osteoporosis (Table 1). Other important advan- Young adult population SD tages of DXA include the short scan times, easy set up of 64 G.M. Blake and I. Fogelman Table 1 The WHO Definitions of Osteoporosis and Osteope- Ca10(PO4)6(OH)2) and soft tissue. Provided that the object nia Used to Interpret Spine, Hip, and Forearm DXA Scan under study is composed solely of the 2 reference materials, 10,11 Results in Postmenopausal White Women the computed areal densities will accurately reflect the true Terminology T Score Definition densities. Normal T > 1.0 As a measurement technique, DXA has 2 important limi- (Osteopenia ؊2.5 < T < ؊1.0 tations. First, because the scan is a two-dimensional (2D -Osteoporosis T < ؊2.5 projection image, the measurements of areal density are af Established osteoporosis T < ؊2.5 in the presence of fected by bone size as well as the true 3D volumetric density one or more fragility fractures of the bone tissue.35 This is the basic difficulty with the in- terpretation of pediatric DXA scans discussed above. How- ever, to a certain extent it affects adult scans as well, causing Z scores are similar to T scores except that instead of com- differences between men and women, black people, and paring the patient’s BMD with the young adult mean, it is white people, as well as less obvious effects due to different compared with the mean BMD expected for the patient’s bone sizes in different individuals. peers (eg, for a healthy subject matched for age, gender, and The second limitation of the DXA technique is that for the ethnic group): purpose of x-ray transmission the human body is composed of 3 basic types of tissue, bone, lean, and fat.39-42 The limita- Measured BMD Ϫ Age matched mean BMD tion of only being able to distinguish 2 types of tissue arises Z score ϭ (2) Age matched population SD from the fact that there are only 2 x-ray attenuation processes involved—Compton scattering and the photoelectric ef- Spine and hip DXA scan results in postmenopausal women fect.38 Because these 2 processes have different dependencies and men over the age of 50 years are interpreted using T on photon energy and atomic number, DXA measurements scores in accordance with the WHO definition of osteoporo- can distinguish bone from soft tissue because of the higher sis (Table 1). The International Society for Clinical Densitom- atomic number of the calcium (Z ϭ 20) and phosphorous etry recommends using the lowest T score figure between the (Z ϭ 15) atoms in bone compared with the carbon, nitrogen, 34 lumbar spine, femoral neck, and total hip sites. T scores for and oxygen atoms in the soft tissue (Z ϭ 6, 7, 8). Fat is largely black and Asian patients should be calculated using the white composed of repeated methylene units ((CH2)n), whereas the Caucasian reference range.34 Before reporting DXA results it x-ray attenuation of lean tissue is similar to water (H2O). The is always important to carefully scrutinize the scan image to difference in x-ray attenuation between fat and lean tissue is ensure the scan is correctly analyzed and there are no artifacts therefore equivalent to the atomic number difference be- over the bone or soft tissue that might affect the interpreta- tween carbon and oxygen.