The cornerstone for making a diagnosis of osteoporosis or of low bone mass (osteopenia) is BMD measurement. Approximately 80% of bone strength in vivo and in vitro is accounted for by bone mass (8). Moreover, there is now extensive prospective data in diverse populations, using a number of different techniques for bone mass assessment, that consistently shows that BMD accurately predicts the risk of osteoporotic fractures. In fact, compared with serum cholesterol measurements, BMD is a stronger predictor of clinical events: for each standard deviation (SD) decrease in BMD, fracture risk increases by 1.5 to 2.0 fold (Table 4), compared to the comparable value of about 1.3 for risk of cardiovascular disease events per SD increase in serum cholesterol (4). In addition, the relationship between BMD and the risk of spine or hip fractures is also stronger than that seen between blood pressure measurements and stroke mortality (9).

A variety of techniques for bone mass measurement are available (Table 5), each with its own advantages and limitations. It should be noted, however, that standard x-rays are not reliable in assessing bone mass or in predicting fracture risk (10). Rather, they should only be used to evaluate the presence or absence of vertebral deformities in a patient with known or suspected osteoporosis.

SPA (Single-Photon Absorptiometry) and SXA (Single X-Ray Absorptiometry) are older techniques that are not widely used at present. While relatively precise and easy to perform, the major limitation of these techniques is that they are limited to peripheral sites, such as the radius and calcaneus. Since the major fractures of concern from the standpoint of morbidity and mortality are vertebral and hip fractures, these older techniques have largely been supplanted by methods that utilize either dual photon absorptiometry (DPA) or more commonly, dual x-ray absorptiometry (DXA), which allow accurate and precise determinations of BMD at central sites.

DXA is currently the gold standard for bone mass measurements, and has significant advantages over the other methods, although it, too, is not without some limitations. It provides reasonable accuracy and precision, short scan times, and relatively low radiation exposure (Table 5). As such, it is the most widely used method both in research studies and in clinical practice. Its two major limitations are that it does not provide a true volumetric bone density and it is also subject to artifacts due to extraneous calcifications that may be in the path of the x-rays.

DXA provides an "areal BMD", expressed as gm/cm2, since the bone mineral content is divided by the projected (2-dimensional) area to calculate a "BMD". As such, it fails to account for the depth of the bones, and inherent in this technique is the caveat that individuals with bigger bones will have higher BMD values by DXA, despite having the same volumetric BMDs as individuals with smaller bones. The prime example of this is that men consistently have higher BMDs using DXA compared to women, but this difference disappears when a true volumetric BMD is either calculated or actually measured using CT scanning (11). Nonetheless, at least in the vertebrae, bone size also appears to impact on fracture risk (12), and DXA measurements (despite this limitation) remain excellent predictors of fracture risk.

The second limitation to DXA is that aortic calcifications or spinal osteophytes and hypertrophic degenerative changes may artifactually increase the measured BMD at the spine (13). While this is a problem when the spine is scanned in the AP direction, it is not an issue if a lateral spine scan is obtained, although most current clinical densitometers are not geared to provide this measurement. If this is a concern in a given patient and the lateral spine measurements are not available, greater reliance is often placed on the hip BMD measurements, since these are not influenced to any significant extent by arthritic changes.

Since, as noted earlier (7, 7a) an existing osteoporotic fracture greatly increases the risk of a subsequent osteoporotic fracture, there has been considerable interest recently in the development of methods using the lateral spine DXA to evaluate the presence of vertebral fractures (vertebral fracture assessment, VFA) (13a). This is cheaper and requires less radiation than spine x-rays, and also appears to be a relatively cost-effective way to identify unrecognized vertebral fractures in otherwise asymptomatic patients (13a).

Quantitative computed tomography (QCT) is attractive at many institutions and community hospitals since it does not require the purchase of specialized equipment, but rather simply the adaptation of an existing CT scanner to perform the BMD measurements. QCT also provides a true volumetric BMD, and is not subject to the problems of extraneous calcifications noted above for the AP spine DXA measurements. The major disadvantage of current QCT measurements is the relatively lower precision and accuracy as compared to DXA (Table 5), as well as the significantly higher radiation doses needed. For that reason, DXA has remained the method of choice over QCT for most clinical purposes.

Radiographic Absorptiometry (RA) is based on obtaining a hand x-ray with an aluminum step wedge placed on the film as a standard against which density can be determined. Subsequently, a computer-assisted densitometric measurement is made of the X-ray image of the bones. While reasonably accurate and precise, this technique suffers from the same limitations as the SPA and SXA methods, in that only peripheral sites (in this case the hand) can be assessed.

Not listed in Table 5, but gaining some popularity, is bone mass assessment using ultrasound. These techniques are based on measuring the speed of ultrasound at the calcaneus or patella, or ultrasound attenuation at these sites. While BMD measurements by ultrasound correlate only modestly with assessments of BMD in the same patients (14), they do appear to predict fracture risk (15). At this point, however, the precise role of ultrasound measurements in the evaluation of the patient with known or suspected osteoporosis remains to be clearly defined.

In summary, while a number of techniques for assessment of bone mass are available, the most widely used method currently is DXA. For most patients, this is likely the single BMD test to use. In general a spine and hip measurement is obtained, with greatest reliance placed on either the femoral neck or total hip measurement. Under certain circumstances, a forearm measurement may be necessary, as in a patient with spinal degenerative changes and bilateral hip replacements. In addition, patients with primary hyperparathyroidism often have disproportionate losses of cortical bone (16), and forearm measurements are recommended in these patients to help define their fracture risk and possible indications for parathyroid surgery. If possible, the addition of VFA to DXA in order to evaluate the patient for the presence of existing vertebral fractures may help identify individuals with existing fractures who should be treated.

Having obtained a bone mass measurement, the clinician needs to be aware of the current criteria for making a diagnosis of osteoporosis or osteopenia. Absolute BMD measurements (unlike blood pressure readings or serum cholesterol levels) cannot be used, since BMD measurements obtained on densitometers made by different manufacturers often give different results in gm/cm2. In part to circumvent this problem and more importantly, in order to define osteoporosis on the basis on bone density (without requiring the presence of fragility fractures), the World Health Organization (WHO) convened an expert panel to help formulate the criteria for making a diagnosis of osteoporosis. The recommendations of this panel have now been widely accepted, and are summarized in Table 6 (17).

The cornerstone of these criteria is to define osteoporosis on the basis of comparisons with peak adult bone mass, using T-scores (or SD deviations compared to young normal individuals). The WHO criteria were formulated for women, so the normative data are based on peak bone mass as measured in healthy young women. The issue of how to define osteoporosis in men was not addressed by the WHO panel, and remains somewhat contentious. As noted above, since men have higher "areal" BMD by DXA than women, using female normative data would result in very few men being defined as having osteoporosis (considerably lower, in fact, than the estimated lifetime risk of fracture in men (18)). As such, the WHO criteria are being applied to men based on gender specific normative data (i.e. using T-scores based on BMD in young normal men). This seems to be a reasonable approach at present, pending more definitive data on the relationship between BMD and fracture risk in men.

In addition to the T-score, a Z-score (or SD units the patient is above or below the mean age-matched BMD at that site) is often also provided. The main utility of the Z-score is that if it is below -2.0, the clinician should be aware that the patient has a disproportionate amount of bone loss relative to her or his peers, and likely warrants a more thorough evaluation for possible secondary causes.

It is also important to note that a world-wide effort currently underway involves the use of a combination of BMD with clinical risk factors in order to provide the physician and patient with absolute fracture risks (e.g., in % per 5 or 10 years). This is being led by a number of organizations, and once implemented, may help further in cost-effective decision making.