Assessing Fracture Risk in Individual Patients

Assessing Fracture Risk in Individual Patients

Combining BMD with other clinical risk factors provides a more accurate estimate of fracture risk.

Osteoporosis is chiefly characterized by increased fracture risk; thus, the primary goal of therapy is to minimize the occurrence of fractures.¹ Several agents have been shown to reduce fracture rates in patients who are at moderate-to-high risk. However, demonstrating therapeutic efficacy in low-risk populations is difficult, and treatment of low-risk individuals is not cost-effective.² Patients should be selected for treatment with osteoporosis medications, based on absolute fracture risk.

BMD AND FRACTURE RISK

Low BMD is an established and strong predictor of fracture risk in older adults, with the relation described by a gradient of increasing risk with decreasing BMD.³ For every one standard deviation decrease in age-adjusted BMD, fracture risk increases about twofold.⁴ The current designation of postmenopausal osteoporosis is based on a BMD threshold defined by a T-score of –2.5 (the T-score is the number of standard deviations below the average BMD of a young, healthy adult of the same sex).⁵ This diagnostic threshold is a modestly specific, but relatively insensitive, predictor of fracture risk. For example, in one study of women 65 and older, more than half the women who experienced hip fractures did not have osteoporosis by BMD criteria.⁶

COMBINING BMD AND OTHER RISK FACTORS

Estimates of fracture risk gain accuracy when BMD is combined with other risk factors, particularly age and history of fracture.⁷ Age is a strong BMD-independent risk factor for fracture: At any BMD value, older adults are at much higher risk for fracture than are younger adults.³ A history of fracture at the spine, hip, or wrist increases the relative risk for subsequent fracture at these sites.⁸^,⁹ Table 1 lists various combinations of risk factors and their effect on fracture probability in postmenopausal women.

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Table 1. Ten-Year Probability of Fracturing the Hip, Spine, Forearm, or Shoulder in Postmenopausal Women (Relative Risk Attributable to Prior Fracture, 1.74)³^,⁹

Note that fracture probability in a 65-year-old woman with a T-score of –1.5 and a prior fracture (Example D) is comparable to that in a 65-year-old woman with osteoporosis but no prior fracture (Example C). These examples demonstrate that, although BMD threshold is useful for making the diagnosis of osteoporosis, other factors must also be considered when determining the level of risk at which treatment is appropriate.

CURRENT CLINICAL GUIDELINES

Various clinical guidelines for managing patients who have or are at risk for osteoporosis are available.¹⁰^,¹¹^,¹² The general agreement is that older adults with osteoporosis are candidates for treatment, and all guidelines recognize that some patients who do not have osteoporosis would benefit from treatment. The guidelines also suggest that postmenopausal women who have less-pronounced reductions in BMD (i.e., T-scores of –1.5 or –2.0) but who have other risk factors for fracture should be treated. However, the guidelines differ regarding specific BMD levels and risk factors that warrant therapy, leading to uncertainty about which patients should be treated.¹³

A particularly confusing aspect of fracture risk assessment centers on the diagnostic category known as osteopenia. According to the World Health Organization, osteopenia (low bone mass) is defined as a T-score between –1.0 and –2.5 in postmenopausal women, but this diagnostic category is not meant to be used in clinical practice.⁵ Although the major guidelines do not recommend treating all women with osteopenia, this diagnosis has been misinterpreted as implying increased or moderate fracture risk. However, as shown in Examples A and G in Table 1, women at low risk and those at high risk fit the definition of osteopenia, emphasizing that the diagnosis itself has little clinical significance.

WHO FRACTURE RISK ALGORITHM

In a collaborative project with the WHO, Kanis and colleagues are developing a model for assessing absolute fracture risk based on combined information from many large observational studies evaluating risk factors in populations worldwide.⁷ This project has provided important information on the predictive strength of many risk factors and on the interplay among the risk factors. The model includes risk factors that are easily assessed in clinical offices: age, history of fracture, femoral neck BMD, BMI (when BMD is not available), parental history of hip fracture, current smoking, alcohol intake, history of glucocorticoid therapy, and secondary causes of bone loss such as rheumatoid arthritis.⁷ This information can be used to estimate the probability that older men and women will experience a fracture related to osteoporosis. The estimate can then be used to determine the level of risk at which treatment would be appropriate. The risk-based treatment threshold will vary from country to country and among healthcare systems, depending on the availability of resources and the rank held by osteoporosis among healthcare priorities.

Basing treatment decisions on risk-based treatment thresholds instead of T-scores has important clinical implications. Recommendations for therapy will shift from low-risk young postmenopausal women (primarily healthy women with osteopenia) toward older men and women without osteoporosis who are at moderate or high risk on the basis of non-BMD risk factors.

CONCLUSION

To improve management of patients at risk for fracture, distinguishing between the BMD-based diagnostic threshold for osteoporosis and risk-based intervention thresholds is important. The updating of osteoporosis treatment guidelines based on the WHO risk model will be a key step forward for clinicians and their patients. Although the diagnosis of osteoporosis will still be based on BMD measurements, a sophisticated, validated model that combines BMD and other clinical risk factors will be available to assess fracture probability in individual women and men. This will allow recommendations for treatment to be based on estimates of fracture risk, not just on BMD, and will permit therapy to be directed toward the patients who need it most.

— Michael R. McClung, MD, FACP

Dr. McClung is Founding Director, Oregon Osteoporosis Center, Portland.

Published in Journal Watch Women's Health August 30, 2007

Citation(s):

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2. Schousboe JT et al. Cost-effectiveness of alendronate therapy for osteopenic postmenopausal women. Ann Intern Med 2005 May 3; 142:734-41.

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3. Kanis JA et al. Ten year probabilities of osteoporotic fractures according to BMD and diagnostic thresholds. Osteoporos Int 2001 Dec; 12:989-95.

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4. Marshall D et al. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996 May 18; 312:1254.

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5. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser 1994; 843:1-129.

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6. Wainwright SA et al. Hip fracture in women without osteoporosis. J Clin Endocrinol Metab 2005 May; 90:2787-93.

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7. Kanis JA et al. The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women. Osteoporos Int 2007 Aug; 18:1033-46.

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9. Kanis JA et al. A meta-analysis of previous fracture and subsequent fracture risk. Bone 2004 Aug; 35:375-82.

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10. National Osteoporosis Foundation. Physician’s guide to prevention and treatment of osteoporosis. 2003. Accessed on August 28, 2007 at http://www.nof.org.

11. Hodgson SF et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the prevention and treatment of postmenopausal osteoporosis: 2001 edition, with selected updates for 2003. Endocr Pract 2003 Nov/Dec; 9:544-64. [Erratum in: Endocr Pract 2004 Jan/Feb; 10:90.]

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12. North American Menopause Society. Management of osteoporosis in postmenopausal women: 2006 position statement of The North American Menopause Society. Menopause 2006 May/Jun; 13:340-67.