Four DXA systems are available in the laboratory: two are pencil beam DXA systems (Lunar DPX and DPX-L) and two are fan-beam systems (GE Lunar Prodigy and Hologic Delphi-A). All 4 systems have been cross-calibrated on volunteer subjects so that results for bone mineral and body composition measured by any system can be translated to results on any of the other three systems. The laboratory has provided measurements of total and regional bone mineral and body composition to more than 50 investigators from the local region in more than 100 research projects and in many clinical trials. It has carried out more than 15,000 subject studies in the past 17 years with more than 50% of these for research purposes. It is also a major center for bone density evaluation for physicians for clinical purposes from pediatric to geriatric patients. The laboratory has served as a QC and reading center in several projects involving multi-center investigations. The laboratory also provides teaching programs to investigators or laboratory staff who are interested in learning DXA techniques for bone mineral and body composition measurements. One of the systems, a Lunar DPX, is available for animal studies in the Animal Research laboratory under the supervision of Dr. Joe Vasselli at the NYORC. The telephone number for human study is 212 523-BONE (2663). The telephone number for animal study is 212 523-3574. Background and Application of Dual-Energy X-Ray Absorptiometry History Anthropologists and health care workers in the field of metabolic bone disease required a method of quantifying bone mass. The selected approach was to expose one side the wrist to a photon-emitting radioactive source and a scintillation counter was positioned on the other side of the wrist. The number of detected counts was related to the amount of attenuating calcium or bone present. The wrist was usually selected for measurement as bone is the main attenuating tissue, unlike conditions at the hip or spine in which soft tissue is also present. Later investigators explored means of evaluating hip and spine as these are clinically important bone areas involved in osteoporosis. The single photon system evolved to a dual-photon system, now based on a filtered x-ray source and referred to as dual-energy x-ray absorptiometry (DXA). DXA systems required information about soft tissue composition in order to quantify bone mineral within a soft-tissue containing pixel. The capability of quantifying the fat and lean soft tissue content of a pixel evolved into DXA’s central role in modern body composition analysis. Application DXA systems all operate on similar principals, although important technical details prevail. An x-ray source provides a broad photon beam that is usually filtered, yielding two main energy peaks. Some systems produce the two energy peaks using a pulsating voltage source. The emitted photons traverse the subject’s tissues and are attenuated to an extent dependent upon the tissue’s elemental make-up. Low atomic weight elements, such as hydrogen, minimally attenuate photons while elements such as calcium are highly attenuating. Additionally, the difference in attenuation between the two energy peaks is characteristic for each element and thus each tissue. The characteristic attenuation signature for fat, lean, and bone mineral allows development of pixel-by-pixel composition estimates using a series of assumptions and reconstruction algorithms. Some systems use a simple “pencil-beam” configuration as the patient is scanned and others have a “fan-beam” configuration of x-ray source and detector. Fan beam systems tend to be faster, requiring only several minutes for each scan compared to longer scan times for pencil beam models. Accuracy varies with system design and software. Calibrations are carried out by the manufacturer that allow resolution of the three molecular level components, bone mineral, fat, and lean soft tissue. System calibration and function is also carried out once systems are operational on a regular basis. DXA x-ray exposure is minimal (<1 mrem), allowing longitudinal studies in children and adults. Current DXA systems designed for body composition analysis can provide estimates for the three components of the whole body and for specific regions such as the arms, legs, and trunk. This unique capability of DXA provides several important opportunities: regional or total-body fat mass can be quantified using standard system settings or for investigator-initiated specific anatomic sites; appendicular lean soft tissue can be quantified and used as a measure of regional or total-body skeletal muscle mass ; and acquired bone mineral can be applied not only to the study of osteoporosis, but to development of more complex multicomponent models. DXA measurements provide valuable insights in longitudinal studies as measurement precision is very high. Many studies have now validated DXA body composition estimates against other reference methods with good overall agreement for body fat estimates. Some variation in fat and bone mineral estimates is usually observed when different instruments are compared, necessitating close scrutiny of the selected instrument with respect to calibration and accuracy. Although providing regional “total” fat estimates, unlike CT and MRI DXA is not capable of estimating visceral adipose tissue. DXA systems are increasingly available, are accurate when properly calibrated and applied, and relatively safe to use in the majority of subjects. As a result, DXA is becoming the method of choice for accurately measuring fat and bone mineral mass at research centers lacking IVNA systems. Disadvantages are that DXA cannot be used in pregnant women, cost is reasonably high, and very large or obese subjects cannot be easily accommodated on most presently available systems. An important feature of DXA is that it provides investigators with an estimate of bone mineral mass. Combining measured bone mineral with estimates of body volume by underwater weighing/air plethysmography and total-body water by isotope dilution allows development of “multi-component” models. The best recognized of these is the family of models based on body volume estimates, beginning with the classic two-component model and advancing to three components with addition of total-body water, and four components with addition of bone mineral estimates. The main advantage of multicomponent models, in addition to providing more compartmental estimates of biological interest, is that fewer assumptions are made regarding component relationships that are assumed stable or constant across subjects (e.g., fat-free mass hydration). Accordingly, multicomponent methods are usually applied as the reference against which other techniques are validated or compared.