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Menopause Matters

Clinical Use of Bone Density Testing

E. Michael Lewiecki, MD, CCD; James A. Simon, MD

Combined with clinical risk factors for fracture, bone density testing can identify patients at high risk for fracture who are likely to benefit from pharmacologic intervention.

Osteoporosis is a disease of low bone strength that increases the risk of fractures with minimal trauma. There are no symptoms until the time of fracture. Osteoporosis or low bone mass (osteopenia) is estimated to occur in about 44 million American women and men, accounting for 55% of the population aged 50 years and older.1 Fractures of the spine and hip may cause chronic pain, deformity, depression, disability, and death. About 50% of patients with hip fractures will never be able to walk again without assistance, and 25% will require long-term care.2 The 5-year mortality after a hip or vertebral fracture is about 20% greater than that for an age-matched, nonosteoporotic population.3 The direct cost of osteoporotic fractures in the United States was about $17 billion per year as of 2001.4 The US Surgeon General’s “Report on Bone Health and Osteoporosis”5 and the National Osteoporosis Foundation’s “Physician’s Guide to Prevention and Treatment of Osteoporosis” identify osteoporosis as a major public health concern, and note that bone mineral density (BMD) testing is the best clinical tool for diagnosing patients at high risk of fracture before the first fracture occurs.6

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MEASUREMENT

Dual-energy X-ray absorp-tiometry (DXA) is the “gold standard” for measuring BMD because:

• There is a strong correlation between BMD and bone strength
• Accuracy and precision are excellent
• Radiation exposure is very low
• Diagnostic classification is based on DXA measurement
• Patients shown to benefit from pharmacologic intervention in most clinical trials were selected by DXA-measured BMD.

The use of DXA to measure BMD involves ionizing radiation with photon beams of two different energy levels. The differences in attenuation of the beams passing through body tissues of variable composition allow the instrument to provide a quantitative measurement of bone density, expressed as g/cm2. Other technologies, such as quantitative ultrasound (QUS), measure properties of bone strength at peripheral skeletal sites (eg, the calcaneus). Although QUS-derived values correlate well with fracture risk, at this time they cannot be used with the World Health Organization (WHO) criteria for diagnosing osteoporosis and are not clinically useful for monitoring changes in response to therapy.7

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INDICATIONS

Anyone at risk for fracture should be considered for BMD testing, provided the results are likely to influence patient- management decisions. Of the many guidelines for ordering a BMD test, those of the International Society for Clinical Densitometry8 (ISCD) are the most comprehensive (Table 1). Most guidelines agree that women over age 65 years, and those under age 65 years with risk factors for osteoporosis, should be considered for BMD testing.

Table not available online

Table 1. Indications for Bone Mineral Density Testing8

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INTERPRETATION

Results of DXA testing are reported as standardized values expressed as T-scores and Z-scores. Both of these rely on SD variability—ie, the patient’s BMD compared with the mean BMD of a young-adult reference (T-score) and an age-matched population (Z-score) (Figure). The T-score is then used with the WHO criteria9 to classify the patient as having a normal BMD, low bone mass (osteopenia), osteoporosis, or severe osteoporosis (Table 2). The ISCD recommends that patients undergoing DXA be routinely measured at the lumbar spine and hip, and at the nondominant forearm if indicated (eg, obesity exceeding weight limit of table, hyperparathyroidism, spine or hip invalid for measuring BMD).10 The lowest T-score of the lumbar spine, total proximal femur, femoral neck, or 33% radius (if measured) should be used for diagnostic classification.

Figure not available online

Figure. Standardized reporting of BMD measurement. BMD = bone mineral density; WHO = World Health Organization; SD = standard deviation; ISCD = International Society for Clinical Densitometry.

Table not available online

Table 2. World Health Organization Classification of Bone Mineral Density9

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PREDICTING FRACTURE RISK

Clinical Risk Factors

The prediction of fracture risk is greatly enhanced by combining BMD results with clinical risk factors for fracture. Many clinical risk factors for hip fracture have been identified, including personal history of any type of fracture after age 50 years, maternal history of hip fracture, self-rated fair or poor health, and difficulty rising from a chair.11 The best validated risk factors for vertebral fractures are low BMD, advanced age, and previous fracture of any type.12 Methodologies are being developed that will combine T-scores with clinical risk factors to estimate the 10-year probability of fracture, which may then be considered with the DXA findings to help determine whether the patient is likely to benefit from pharmacologic therapy.

Vertebral Fracture Assessment

Vertebral fracture assessment (VFA) is a spinal image that can be obtained by DXA at the same time as BMD is measured. Compared with standard spinal radiography, it exposes the patient to a lower dose of ionizing radiation, costs less, is more convenient for the patient, and offers good diagnostic sensitivity and specificity. Interpretation of VFA requires special training—especially for nonradiologists—which is provided by organizations such as the ISCD. Previously unrecognized vertebral fractures may be detected by VFA, possibly altering the patientês diagnostic classification, fracture-risk level, and management.13

Bone-turnover Markers

Bone-turnover markers (BTMs) are laboratory tests that measure byproducts of bone metabolism in the blood and urine. They cannot be used to diagnose osteoporosis, but have been very helpful in the research setting to provide a better understanding of the pathogenesis of osteoporosis and the mechanism of action of therapeutic agents. In clinical practice, BTMs potentially play a role in the assessment of fracture risk and in monitoring the effects of therapy on bone remodeling. An elevated value suggests a high bone-turnover rate, which is a fracture risk factor that is independent of BMD. Failure to suppress BTMs with antiresorptive drugs suggests poor patient compliance, inadequate drug absorption, or the presence of a disorder/disease that is increasing bone turnover and overwhelming the drugês effect. The BTMs most commonly used in clinical practice are markers of bone resorption, N-telopeptide and C-telopeptide, which can be measured in serum or urine. The preferred method for measuring these is with a fasting serum specimen, which is easier to collect than a timed urine specimen and has less variability. Procollagen type 1 intact N-terminal peptide is a serum marker of bone formation that may have clinical utility in predicting BMD response to treatment with the anabolic agent teriparatide.

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TREATMENT

Regular weight-bearing exercise, adequate intake of calcium and vitamin D, and avoidance of cigarette smoking and excess alcohol intake should be recommended to minimize the adverse skeletal effects of estrogen deficiency and aging. If BMD findings and clinical evaluation suggest that a patient is at high risk for fracture, pharmacologic therapy may be indicated. Although many agents have been approved for treatment and/or prevention of osteoporosis (eg, alendronate, estrogen, ibandronate, raloxifene, risedronate, salmon calcitonin, teriparatide), long-term adherence to therapy is typically poor, with less than 50% of patients still using the drug 1 year after starting. Strategies to improve adherence include the development of agents with longer intervals between dosing and injectable administration. Perhaps the best clinical approach to optimizing adherence is regular contact with a health care professional to reinforce the importance of continuing to take medication correctly and to address patient concerns. Repeat BMD testing 1 to 2 years after starting therapy with the goal of stabilizing or increasing BMD, and follow-up measurement of BTMs in some patients may also help to improve compliance. A significant loss of BMD during therapy is a cause for concern and warrants investigation for factors that could produce a suboptimal response.

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CONCLUSION

Bone mineral density testing is a clinical tool that can diagnose osteoporosis or bone weakness before the first fracture occurs. Estimation of fracture risk is best achieved by combining BMD with clinical risk factors for fracture. Patients with the greatest risk of fracture are most likely to benefit from pharmacologic intervention.

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E. Michael Lewiecki, MD, CCD, is director, New Mexico Clinical Research & Osteoporosis Center, Albuquerque. James A. Simon, MD, is clinical professor, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, The George Washington University School of Medicine, Washington, DC; and medical director, Womenês Health & Research Consultants, Washington, DC.

References

1. National Osteoporosis Foundation. Americaês Bone Health: The State of Osteoporosis and Low Bone Mass in Our Nation. Washington, DC: National Osteoporosis Foundation; 2002.
2. Riggs BL, Melton LJ 3rd. The worldwide problem of osteoporosis: insights afforded by epidemiology. Bone. 1995;17(5 suppl):505S-511S.
3. Cooper C, Atkinson EJ, Jacobsen SJ, OêFallon WM, Melton LJ 3rd. Population-based study of survi-val after osteoporotic fractures. Am J Epidemiol. 1993;137(9): 1001-1005.
4. Ray NF, Chan JK, Thamer M, Melton LJ 3rd. Medical expenditures for the treatment of osteoporotic fractures in the United States in 1995: report from the National Osteoporosis Foundation. J Bone Miner Res. 1997;12(1):24-35.
5. US Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, Md: US Department of Health and Human Services, Office of the Surgeon General; 2004.
6. National Osteoporosis Foundation. Physicianês Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2003.
7. Lewiecki EM, Richmond B, Miller PD. Uses and misuses of quantitative ultrasonography in managing osteoporosis. Cleve Clin J Med. 2006;73(8):742-752.
8. The Writing Group for the ISCD Position Development Conference. Indications and reporting for dual-energy x-ray absorptiometry. J Clin Densitom. 2004;7(1):37-44.
9. World Health Organization. Assessment of Fracture Risk and Its Application to Screening for Postmenopausal Osteoporosis. Geneva, Switzerland: World Health Organization; 1994.
10. Hamdy RC, Petak SM, Lenchik L; International Society for Clinical Densitometry Position Development Panel and Scientific Advisory Committee. Which central dual X-ray absorptiometry skeletal sites and regions of interest should be used to determine the diagnosis of osteoporosis? J Clin Densitom. 2002;(5 suppl):S11-S18.
11. Cummings SR, Nevitt MC, Browner WS, et al. Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med. 1995;332(12):767-773.
12. Van der Klift M, De Laet CE, McCloskey EV, et al. Risk factors for incident vertebral fractures in men and women: the Rotterdam Study. J Bone Miner Res. 2004;19(7):1172-1180.
13. Lewiecki EM, Laster AJ. Clinical review: clinical applications of vertebral fracture assessment by dual-energy x-ray absorptiometry. J Clin Endocrinol Metab. 2006;91(11):4215-4222.

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