Bone Densitometry: The Best Way to Detect Osteoporosis and to Monitor Therapy

The development of objective, noninvasive, and highly sensitive techniques to quantitate bone mineral density (BMD) has provided the clinician with a powerful diagnostic tool. Bone mass measurement is the best way to make the diagnosis of osteoporosis, one of the major diseases of our time. Using this technology, osteoporosis can now be detected well before it is obvious by conventional x-rays or when fractures eventuate. The definition of osteoporosis by the World Health Organization (WHO) is a BMD that is 2.5 sd or more below the mean of a young, normal reference population (1). This definition offers the practitioner an objective standard by which to make a diagnosis and to make subsequent management decisions. It has also profound therapeutic implications. Fortuitously, the advent of this technology has been accompanied by an exciting array of new, effective therapies to prevent and treat osteoporosis. The therapeutic optimism resulting from these pharmacological breakthroughs has fueled discussions about the potential widespread applicability of bone mass measurement to the entire population at risk. It has sparked controversy over how widely bone mass measurement modalities should be applied to detect the population at risk and what devices should be used to this end. In this article we provide a perspective on these issues. The aging population is inevitably going to become more osteoporotic unless we intervene first with diagnostic tools and then with preventive therapy. The National Osteoporosis Foundation has estimated that the number of postmenopausal women in this country will double from 40 to 80 million over the next 20 yr (2). Projections also call for a tripling of the number of osteoporotic fractures by 2040 from current annual estimates of 1.3 million. Staggering costs are surely going to exceed the 1995 figure of 13.8 billion dollars by countless billions more. The need is clear both to discover the population with osteoporosis and, more importantly, to identify those at risk for the disease. Measurement of bone mass is the single best predictor of fracture risk (3–5). The advent of this technology into the clinical arena over the past 15 years is similar in importance to the development of the sphygmomanometer and assays for serum cholesterol. As blood pressure and cholesterol determinations are predictors of stroke and cardiovascular disease, so bone density predicts fracture risk (2, 3–5). In fact, the measurement of bone mass is a much more powerful indicator of fracture risk than cholesterol determination is a predictor of myocardial infarction. Epidemiological studies indicate that the totality of risk for fracture, as represented by bone mass measurement, is 60–70% (6). Because of its predictive power, it is, thus, the most important information to gain about fracture risk. Other independent predictors of fractures are readily known, such as age, history of previous fracture, and low body weight. Together, the risk profile of an individual can be rather accurately determined as long as the BMD is known. The most widely used technique is dual energy x-ray absorptiometry (DXA). DXA can measure central sites, such as lumbar spine and hip, as well as peripheral sites, such as distal forearm, heel, and phalanges. DXA is noninvasive, rapid, accurate, and safe. The high precision of the technique usually allows DXA testing of central sites (not peripheral sites) to be used for monitoring as well as diagnosis. The effectiveness of therapy with bisphosphonates is well correlated with changes in bone mass (7). Most of the recent literature with respect to treatment response is based upon central measurements (8–10). It is the gold standard with which all other technologies are compared. Other approaches to bone mass measurement have been developed (11). Quantitative computed tomography (QCT) measures lumbar spine (12) and more recently has been adapted to measure peripheral sites as well (13). The potential advantage of QCT over DXA is in its ability to measure true volumetric density (grams per cm3) compared with DXA, which gives an areal density (grams per cm2). Moreover, QCT measures cancellous bone of the lumbar spine exclusively, devoid of the cortical envelope. It is less likely, therefore, to detect artifacts of aging, such as osteophytes and aortic calcifications, than DXA. On the other hand, changes in the bone marrow space with aging can confound the lumbar spine density measurement by QCT. Other disadvantages of QCT are the cost of the machines, poor availability, cost of the test, and, to a certain extent, radiation exposure, the latter of which becomes a consideration when patients are monitored. Fracture prediction by QCT is as good as but no better than that by DXA (14). A number of less costly and more portable devices that measure peripheral sites have been developed and approved by the FDA (15). The rationale to develop these densitometers rests with the fact that central machines are relatively expensive and, in some settings, not readily accessible. Some believe that central densitometers are unlikely to proliferate sufficiently or to be distributed proportionately throughout the United States so as to be accessible to all who are in need of bone mass measurement. There are currently about 5000 central DXA machines in the United States. As noted, DXA and QCT have been adapted to peripheral sites. In addition, the radius can be measured by single energy absorptiometry (16), and the phalanges can be measured by radiogrammetric absorptiometry (17) and DXA. In addition to machines that use ionizing radiation, the technique of ultrasound has been developed to measure bone mass (18). Ultrasound can measure the speed of sound as well as broadband ultrasonic attenuation of the site in question. These indexes give a measure of bone mass, although it is still not clear whether ultrasound may also detect certain qualitative aspects of bone. The machines available