SYMPOSIUM ON OSTEOPOROSIS

Preview

Dual-energy x-ray absorptiometry (DXA) is the method of choice to measure bone mineral density in elderly patients and others at risk for osteoporosis. Early detection is important because fractures represent an enormous health burden. In this article, the authors discuss the application and interpretation of DXA scans as well as limitations and conditions that can affect results.

Osteoporosis, a preventable and treatable bone disorder that occurs with aging, is a growing challenge to primary care physicians. In the United States alone, 28 million people have either osteopenia or osteoporosis. Each year there are 1.5 million osteoporotic fractures, 800,000 emergency department visits, 2,600,000 physician office visits, and 180,000 nursing home admissions from osteoporotic complications, which add up to an annual direct cost of nearly $18 billion.1

Osteoporosis is a systemic skeletal disease characterized by compromised bone strength and a consequent increase in bone fragility and susceptibility to fractures.2 Although a wide variety of devices are available for quantifying bone density?\including dual-energy x-ray absorptiometry (DXA), quantitative computed tomography (QCT), peripheral DXA, peripheral QCT, and peripheral quantitative ultrasound3?|5?\central bone mineral density (BMD) measurement using DXA is currently the ?ggold standard?h for the diagnosis of osteoporosis.6,7 A DXA measurement can be completed in about 15 to 20 minutes with minimal radiation exposure (about one tenth that of a standard chest x-ray).

Peripheral DXA scans are inexpensive and are useful in screening large populations such as at health fairs. The peripheral DXA device is simple to operate. However, the sensitivity of peripheral DXA for detecting osteoporosis is lower than that of central DXA. Moreover, issues such as a lack of consensus on how results from peripheral sites are interpreted, poor correlation among different machines, and precision errors prohibiting monitoring of patients who are receiving osteoporosis therapy limit the clinical utility of this technology.

Indications for obtaining a DXA scan
Menopausal women should be evaluated clinically for osteoporosis risk in order to determine the need for BMD testing. All women aged 65 or older, younger postmenopausal women with risk factors, and men aged 70 or older should undergo bone density testing. Risk factors include dementia, poor health, recent falls, prolonged immobilization, smoking, alcohol abuse, low body weight (<127 lb), history of fragility fracture in a first-degree relative, estrogen deficiency at an early age (<45 years), and steroid use for more than 3 months.8?|13

Adults who have a history of fragility fractures, have diseases associated with bone loss, or take medications that cause bone loss14 should also have DXA scans. DXA scans are also appropriate for monitoring a patient's response to osteoporosis therapy.13

Site of measurement of BMD

The International Society for Clinical Densitometry recommends obtaining BMD measurements of the posteroanterior spine and hip.13 The lateral spine and Ward's triangle region of the hip should not be used for diagnosis, because these sites overestimate osteoporosis and results can be false-positive. T-scores represent the standard deviations (SDs) comparing a patient's BMD to that of a young adult (control), whereas Z-scores compare a pa-tient's BMD to that of age-matched controls. The World Health Organization (WHO) defines osteoporosis as a T-score of ?|2.5 or below7,15 in either the spine or the hip.

In the spine, the BMD of L1 through L4 should be reported unless there are vertebrae affected by severe degenerative changes or compression fractures. These should be excluded from the analysis because they falsely increase BMD. Most DXA devices measure and report BMD of the total hip, femoral neck, and trochanter. The diagnostic classification of a patient is based on the lowest T-score of any of these hip sites.

Evidence suggests that the femur is the optimum site for predicting the risk of hip fracture16?|18 and the spine is the optimum site for monitoring response to treatment.19 In very obese patients, those with primary hyperparathyroidism, or those in whom the hip or the spine, or both, cannot be measured or interpreted, BMD may be measured in the forearm, using a 33% radius on the nondominant forearm.13

Interpretation of DXA scans

Primary care physicians are usually not directly involved in the performance and interpretation of DXA scans but should be familiar with the information on DXA scan reports and how it applies to patient management.8 T-scores are used to diagnose osteoporosis, and Z-scores give the physician a sense of the age-appropriateness of bone loss. A Z-score of ?|2.0 or lower suggests a secondary cause and should trigger the search for underlying causes.9 In our practice, patients with a Z-score below ?|1.0 are frequently found to have secondary causes, and such a score initiates a comprehensive search for these causes.

Although postmenopausal osteoporosis is clearly the most common bone disease, secondary causes of osteoporosis are also quite common (table 1). Physicians need to actively look for these causes, either by thorough history taking or with biochemical studies. Common secondary causes include primary hyperparathyroidism, vitamin D deficiency, hyperthyroidism, liver and renal disease, malabsorption from celiac disease or inflammatory bowel disease, and use of medications that cause bone loss.

Physicians must be aware that a low BMD may indicate osteomalacia rather than osteoporosis in patients with severe vitamin D deficiency, and appropriate testing is necessary to differentiate between these two diseases. Patients with osteomalacia usually have very low 25-hydroxyvitamin D3 levels, hypocalciuria, elevation in total or bone-specific alkaline phosphatase, and secondary hyperparathyroidism.

Initiation of treatment

Evidence showing an unacceptably high risk of fracture with T-scores of ?|2.5 and below and a significant reduction in fracture risk with treatment has made this threshold the initial criterion for the diagnosis of osteoporosis.8,9 However, the National Osteoporosis Foundation12 recommends initiating treatment to reduce fracture risk in women with T-scores below ?|2.0, even in the absence of risk factors, and in women with T-scores below ?|1.5 in the presence of one or more risk factors. Regardless of the T-score, patients with previous vertebral or hip fractures are classified as severely osteoporotic and should be treated. Recently, the National Osteoporosis Risk Assessment study20 found osteoporotic fractures among patients who were classified as osteopenic on the basis of the WHO criteria. There is now a move toward establishing a global fracture risk score that includes risk factors and BMD as a possible basis for initiating therapy.

Monitoring response to treatment

DXA scans are useful in determining response to osteoporosis therapy. Under ideal conditions, the same technologist should perform DXA scans on the same densitometer and under similar circumstances.

It is important to note that antiresorptive drug therapy leads to significant reduction of fracture risk, which can be obtained with very little improvement in BMD. Moreover, in interpreting serial DXA scans, the actual BMD (in gm/cm2) should be compared and not the T-scores.

The percentage of change is calculated using the following formula: current BMD ?| old BMD/old BMD ?~ 100%. This number must then be compared with the least significant change of the machine, a number that reflects both the accuracy and the precision of the machine. In general, this is about 3% for the spine and about 4% for the hip. Any change that exceeds this number is a significant or true change and is not simply due to machine measurement variability.

BMD remains the best and most useful marker for fracture risk reduction in clinical practice. The interval between BMD testing should be determined according to each patient's clinical status. BMD measurements to monitor response to osteoporosis therapy should generally be obtained every year until stability is established, then at longer intervals, such as every 2 years.13 The posteroanterior lumbar spine is the optimum site to monitor therapy, and significant changes may be seen in a year or more, depending on the therapy used.19 Medicare permits physicians to repeat DXA scans every 2 years12 or, in patients who are being monitored while on therapy, every year.

Osteoporosis in men

The focus of osteoporosis management has been on postmenopausal women. However, osteoporosis in men is not rare.21 The estimated lifetime risk of fracture ranges from 13% to 25%.22 The three major causes of osteoporosis in men are alcohol abuse, glucocorticoid excess (from either endogenous Cushing's syndrome or long-term glucocorticoid therapy), and hypogonadism.22,23 Bone density testing should be considered in men with fragility fractures; those taking drugs that may cause bone loss, such as androgen deprivation therapy for prostrate cancer24; and men with multiple risk factors.

The International Society for Clinical Densitometry recommends that in men aged 65 years or older, osteoporosis should be diagnosed if T-scores are at or below ?|2.5. Between age 50 and 65 years, osteoporosis should be diagnosed if T-scores are at or below ?|2.5 and other risk factors for fracture are identified. In men under age 50 years, diagnosis of osteoporosis should not be made on the basis of T-scores. Osteoporosis may be diagnosed clinically in men at any age with secondary causes of low BMD supported by the finding of low BMD.

It is important to know that the WHO classification, with its associated implications for fracture risk, was derived from a database composed purely of postmenopausal white women. Most densitometry devices now use the third National Health and Nutrition Examination Survey (NHANES III) database, which provides appropriate sex-matched controls for hip BMD.

Artifacts

Certain conditions can artificially elevate the BMD, obscuring osteoporosis and leading to underestimation of fracture risk.25 These include degenerative changes seen in osteoarthritis and ankylosing spondylitis, structural abnormalities such as compression fractures26 and scoliosis,27 aortic calcification, high-density objects on clothing, surgical implants,27 laminectomy,26 and retained radiopaque contrast agents.26 Vertebrae with abnormal conditions should be excluded from the spine analysis. Similarly, BMD at the proximal femur can be altered by degenerative arthritis, degree of internal rotation, placement of soft tissue gluteal silicon implants,28 and overlying soft tissue thickness or fat.29 Patient positioning and appropriate placement of region of interest are paramount for precision and reproducibility.27

Physicians should visually assess DXA scans for artifacts that could affect BMD values. Going down the spine, the vertebrae become larger and have greater BMD (L1<L2<L3??L4), and the T-scores of individual vertebra should be within approximately 1 SD of each other. This observation does not apply to the hip, where differences greater than 1 SD between regions may occur because of different rates of loss of cancellous and cortical bone from different hip sites.8

Automated analysis of spine scans is enhanced with the introduction of computer-aided densitometry, a software feature that assists physicians in the identification of concealed osteoporosis or osteopenia in spine scans adversely affected by conditions that cause an artificial elevation in BMD.27 Common DXA artifacts and errors affecting BMD are shown in figures 1 through 4.

Referral

According to guidelines of the American Association of Clinical Endocrinologists,9 referral to a specialist is appropriate if the patient has osteoporosis that is unexpectedly severe, has unusual features at the time of initial assessment, or has a suspected condition that may underlie the osteoporosis (eg, hyperthyroidism, hyperparathyroidism, hypercalciuria, Cushing's syndrome, hypogonadism). Patients should also be referred if they are intolerant of approved therapies, fail to respond to treatment, or are a candidate for combination therapy.

Conclusion

Primary care physicians are and should be the main providers for osteoporosis prevention and treatment. Early recognition and treatment of osteoporosis can significantly decrease morbidity, mortality, and healthcare costs associated with this disease. DXA scans continue to increase the identification and influence the management of osteoporosis. It is important that physicians are knowledgeable in the interpretation and pitfalls of this technology.

Dr Agarwal is resident physician, University of Illinois at Chicago/Christ Medical Center. Dr Camacho is assistant professor of medicine, division of endocrinology and metabolism, Loyola University, Chicago.
Correspondence: Monica Agarwal, MD, 4211 W 95th St, Apt Unit 2C, Oaklawn, IL 60453. E-mail: agarwalm@uic.edu.

References

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