Osteoporosis is an insidious disease characterized by reduced bone mass, deterioration of bone structure, and fractures. The consequences of osteoporosis for the individual and for the cost of health care in the United States are enormous, and rising. This year, according to estimates from the National Osteoporosis Foundation (NOF), the disease will result in more than 1.5 million fractures, including 300,000 hip fractures and 700,000 vertebral fractures. The estimated cost to the nation in direct expenditures for osteoporosis and associated fractures in 1995 alone was about $14 billion. Because the US population is aging, the NOF has estimated that the number of women with osteoporosis will top 80,000,000 by 2020, with associated health care costs predicted to total $30 billion or more. Clearly, early detection of and appropriate therapy for osteoporosis could substantially reduce morbidity and secondary mortality and decrease the economic burden for this country.
Because osteoporosis is characterized by loss of bone structure, the measurement of bone mineral density (BMD) is a linchpin in diagnosis. Bone mineral densitometry can be used to make or confirm the diagnosis of osteoporosis and can also predict the future risk of fracture. In addition, BMD is useful in monitoring the efficacy of therapy. Unfortunately, there remains considerable confusion regarding the most appropriate densitometry technique to employ for BMD testing. A number of methods of bone densitometry exist, each with advantages and drawbacks. Moreover, while each of the various densitometry methods can provide the clinician with an estimate of bone density, results differ among the various techniques and can be puzzling.
Through the Bone Mass Measurement Act of 1998, Medicare has been required by law to reimburse for densitometry when it is performed for women and men who meet certain criteria. At least every 2 years, Medicare will pay for a BMD determination that is made by any method approved by the FDA. It therefore behooves every health professional who deals with patients at risk to understand the diagnostic criteria for osteoporosis and the methods that are most useful in diagnosing the disease and in evaluating treatment.
The World Health Organization (WHO) has established criteria for bone density based on the consensus of experts with respect to data for normal people throughout the world. The WHO criteria are intended to provide a reasonable standard for evaluation of individual BMD values in comparison to existing databases. Comparisons are stated as standard deviation (SD) from normal BMD values obtained from young, healthy persons of the same sex, race, and age. These young normal scores, or T-scores, can then be used to decide whether a patient has a reduced BMD consistent with osteoporosis or osteopenia. Most densitometry equipment contains software that calculates T-scores automatically.
The WHO has defined osteoporosis as a BMD of 2.5 or more SD below that of young, normal individuals, specifically a T-score of < -2.5. Low bone mass, or osteopenia, is defined as a BMD between 1 and 2.5 SD below that of young, normal people, or a T-score between -1 and -2.5. Normal is defined as a BMD not less than 1 SD below young normals.
Despite these standard values, a number of difficulties have been identified regarding BMD. The body sites evaluated in the WHO report were the spine and femoral neck (so-called central sites), but the WHO criteria for central sites have been widely applied for screening regardless of whether other skeletal sites such as the forearm or calcaneus, rather than the spine or hip, were actually being tested. Also, BMD values are being obtained for women who do not fall within the population identified in the WHO document. Leonard Avecilla, MS, director of site accreditation for the International Society of Clinical Densitometry, Vancouver, Wash, points out that such a practice is inherently fraught with error. “The WHO criteria were originally derived for one population and one population only: postmenopausal Caucasian women. As one’s population diverges from that group, the applicability of the WHO criteria can be considered only quasi-valid.” If one tests a Hispanic woman in her thirties, for example, there is no real way to be certain of the meaning of the data obtained. Although there is reason to believe that the WHO criteria for the spine are applicable to populations other than postmenopausal women and to skeletal sites other than the hip and spine, clear-cut data to confirm that belief do not exist. What is clear is that to predict fracture at any particular site, bone density measurement at that site will provide a good estimate of risk, in a properly chosen individual.
Another difficulty is differing T-score values obtained with different equipment. According to Daniel Baran, MD, an endocrinologist at the University of Massachusetts Medical Center in Worcester, each manufacturer has employed somewhat different populations as a standard. “Even if you have the same types of machine, not every manufacturer has the same reference population,” Baran notes. “So the standard deviations of the young normals might change. And as the precision of different instruments changes, the standard deviation might also change. You cannot use the same T-score of -2.5 for all of the various instruments, because that number represents the lowest 20% of the reference population for a particular device. Instead you would have to find out what the lowest 20% is with quantitative computed tomography (QCT), or you would have to find out what the lowest 20% is with ultrasound, etc.”
Finally, while the definition of osteoporosis based on the WHO criteria for BMD seems clear, the bone density of a site such as the heel may be significantly different from that of the spine or hip. To compound the issue, it has even been shown that bone density can vary substantially between hips in the same individual.
Methods of BMD Determination
The most common methods in current use for BMD are dual energy x-ray absorptiometry (DXA), QCT, and ultrasound densitometry. Other methods include single energy x-ray absorptiometry (SXA) and radiographic absorptiometry. The latter two methods are variously employed and may one day come into wider use, but it is DXA, QCT, and ultrasound that are most commonly used.
Dual energy x-ray absorptiometry is currently considered to be the “gold standard” for assessing bone mass. DXA usually means central skeletal measurements, but it can also be employed to measure BMD peripherally. This method emits high and low x-ray energy and measures the difference in tissue attenuation of each, in turn allowing separation of soft-tissue density from bone density. The attenuation of x-rays is also distinctly different between normal bone and osteoporotic bone. While DXA is not an imaging technique, an image is produced that can also provide evidence of fractures. In addition, DXA has the advantages of being relatively rapid and painless. Although a typical DXA may take several minutes, another advantage is a low dose of ionizing radiation. The total radiation exposure during DXA is minimal, perhaps one-twentieth that of a chest radiograph. These units have the disadvantages of being large, nonportable, and relatively expensive. But the cost of DXA equipment is coming down. A fully equipped unit can cost well over $130,000, but recently introduced units priced under $40,000 are capable of performing accurate BMD.
Quantitative computed tomography is another useful method for determining BMD, but computed tomography has the significant drawback of being relatively expensive, and somewhat more difficult to use. QCT, like DXA, is also predictive of subsequent fracture risk, whether used for central or peripheral BMD determinations. QCT is also the only BMD technology that enables physicians to view a spine with degenerative bone disease. Again, like DXA, CT equipment is large and nonportable. But the phantom and calibration software is half the cost of a low-end tabletop DXA unit.
Ultrasound measurement is employed to evaluate bone density only at peripheral skeletal sites. Peripheral ultrasound units have the distinct advantages of portability and lower cost compared to DXA and QCT, but their results are less sensitive and specific. Importantly, though, heel measurements have been shown to predict hip fracture, as have measurements at the forearm, although forearm measurements are less sensitive than either DXA of the spine or measurements of the heel.
NOF GUIDELINES CLARIFY
As a consequence of the current confusion, the National Osteoporosis Foundation has recently issued guidelines (available on the Internet at www.nof.org) for prevention and treatment of osteoporosis. The NOF guidelines focus not only on BMD measurement but also on assessment of fracture risk based on the presence or absence of specific risk factors. The more risk factors present in an individual woman, the greater her risk of fracture. Included are modifiable risk factors, including current cigarette smoking, low body weight, estrogen deficiency, low calcium intake over a lifetime, alcoholism, impaired eyesight despite adequate correction, recurrent falls, inadequate physical activity, and generally poor health. Nonmodifiable risk factors include an adult history of fracture in the patient or a first-degree relative, Caucasian race, advanced age, female gender, dementia, and general poor health. Based on the presence of risk factors, the possibility of osteoporosis and fracture must be considered in all postmenopausal women. Combining BMD measurement with risk factors can help the clinician determine whether treatment is needed. Bone mineral density carries a clear-cut, inverse relationship with the risk of fracture.
The NOF states flatly that whenever a postmenopausal woman suffers a hip or vertebral fracture, the presumptive diagnosis should be osteoporosis. This in turn should trigger a measurement of BMD, although women over 70 with multiple risk factors are at sufficiently high risk that treatment may be instituted without BMD evaluation. The decision to test for BMD must be based on the individual’s risk profile and should not be done unless the results will influence treatment. Currently, the NOF recommends BMD measurement on all postmenopausal women under age 65 who have one or more risk factors (besides menopause); all women 65 or older regardless of additional risk factors; postmenopausal women with fractures; women who might need therapy for osteoporosis if BMD will help make the decision; and women who have been on long-term hormone replacement therapy.
The decision regarding the need for BMD testing is fairly straightforward based on the NOF guidelines, but given the disagreement and confusion concerning the commonly employed methods, the question remains concerning which BMD method to use and which sites to test.
On the basis of current data, Kenneth Faulkner, PhD, director of osteoporosis research at Synarc, a Portland, Ore, pharmaceutical research consortium, asserts that central DXA is still the best way to assess patients for fracture risk. “If you can,” says Faulkner, who is also an associate professor at the Oregon Health Sciences University, “measure spines and hips. Use the NOF guidelines. You need to take into account the patient’s age, risk factors, and the method of BMD determination.” Although available data show clearly that there is a strong relationship between bone density at both central and peripheral sites and subsequent risk of fracture, the WHO criteria are based on central BMD determinations using DXA, making T-score interpretation relatively straightforward. Faulkner is not opposed, however, to the use of peripheral densitometry. “If you don’t have access [to DXA], use peripheral densitometry, as long as you are going to trust it, because the NOF guidelines do apply to peripheral densitometry.” The T-scores from peripheral studies may be substantially different from those obtained by DXA, he cautions, and the careful clinician must take that fact into account. “With peripheral densitometry, a T-score of, say, -1.5 may correlate with an increased fracture risk. So if you get a -1.5 [T-score] at the forearm or at the heel, would you consider treating that woman? If you say no, then you don’t believe in peripheral densitometry and you’re wasting your time. If you say yes, or will consider treating based on peripheral densitometry alone, then I would say that’s good use of that technology.”
Avecilla agrees, citing the very real possibility that DXA might not be available for everyone. “Patients for whom peripheral densitometry is most advantageous are those who have limited access to central skeletal measurement and/or who may never have undergone any quantitative measurement.” Despite the burgeoning of central skeletal DXA, Avecilla says, the technology is not available in small towns or suburbs and the investment is often too much for small group practices. Avecilla, whose society has been a driving force in education, certification, and BMD site accreditation, adds that the increased complexity of performance and interpretation of central skeletal DXA requires more of an investment in time and money than a practice might be able to make. He believes that in those cases, physicians can do their patient population a lot of good by having a peripheral device available.
While agreeing that if access to DXA equipment is limited one should use a peripheral device, Baran is more cautious regarding its use since BMD is employed not only for screening and for diagnosis, but also to evaluate the patient’s response to therapy. “The advantage of DXA is that diagnostic categories are based on it, and you also can use central DXA to monitor therapy. There are no good data showing that you can use peripheral instruments to monitor the response to therapy.” Also, if pharmacotherapy is being considered, precise BMD values are, in his estimation, mandatory due to the potential for drug side effects and complications and the long-term cost of medication. He notes that one recently published clinical study performed to evaluate treatment of osteoporosis showed that during therapy, women gained bone mass at the spine and hip but lost bone mass at the forearm over the 2 years of the study. That worries him. “If you are only monitoring the forearm and bone mass is going down, you are going to conclude that the therapy is not working.” Although he has done a great deal of research with peripheral ultrasound, Baran concludes, “if there is easy access to a central DXA, that is the way to go.”
Although there are differences among the technologies available for evaluation of bone density, several key points are paramount. First, the currently available guidelines from the National Osteoporosis Foundation supply an excellent rationale for BMD measurement that should be reviewed by every clinician that deals with patients who might have osteoporosis. A careful determination of those risk factors will allow the practitioner to decide whether BMD evaluation is needed. Although both peripheral and central BMD are predictive of fracture risk, whether obtained by ultrasound or by DXA or QCT, central DXA is currently more easily interpreted and can be used with confidence to monitor subsequent therapies.
Gary L. Hoff, DO, is a contributing writer for Decisions in Axis Imaging News.