Skeletal health prognostications.

  "Prophesy is a good line of business, but it is full of risks."
--Mark Twain (1835-1910)

The National Health and Nutrition Examination Survey (NHANES) is an ongoing cross-sectional population survey conducted by the National Center for Health Statistics, which is part of the Centers for Disease Control and Prevention (CDC). The objective of NHANES is to assess the health and nutrition of adults and children throughout the USA by doing in-home interviews and health examinations. The examinations are performed in a mobile examination center made of four linked trailers containing high-tech medical equipment. One of the many measurements taken is bone mineral density (BMD) testing of the proximal femur by dual-energy x-ray absorptiometry (DXA). NHANES data provide a benchmark for public health policymakers and epidemiologists to evaluate the health status of Americans. These data have been used to formulate healthcare policy, evaluate health trends, and perform extensive epidemiologic research. NHANES III (1988-1994) values have become the reference standard for calculating T-scores at the hip in the USA, and may soon be officially recognized as the international reference standard. In addition, NHANES provides an abundance of information about the association, or lack of association, of many variables with BMD.

In this issue of the Journal, Bass et al report on their analysis of 7,532 women over the age of 20 in the NHANES III database to study potential risk factors for low hip BMD. (1) They conclude that there is an association between low hip BMD and advancing age, low body weight, low level of exercise, and smoking. These findings are not at all surprising, and are consistent with data from other studies. Low calcium intake was associated with low BMD at the trochanter, but not other hip regions of interest. The authors suggest that modification of risk factors may reduce the risk of osteoporosis and fragility fractures, and that guidelines for calcium intake be reassessed. The use of clinical risk factors in the management of osteoporosis is well established, but fraught with difficulties. It behooves all clinicians to have a thorough understanding of risk factors to optimize their clinical utility.

Clinical risk factors for osteoporosis are not a substitute for BMD testing. In the absence of a fragility fracture, BMD testing by DXA is the only way to currently diagnose osteoporosis. In a study of about 7,000 women without known osteoporosis, about 50% of those with risk factors did not have osteoporosis, and about 50% of those with osteoporosis did not have risk factors. (2) Risk factors can be helpful in selecting patients for BMD testing. For example, the National Osteoporosis Foundation (NOF) guidelines recommend BMD testing for postmenopausal women under age 65 with risk factors and for those age 65 and older regardless of risk factors. (3) The NOF identifies major risk factors as personal history of fracture as an adult, history of fragility fracture in a first degree relative, low body weight (less than about 127 lbs.), current smoking, and use of oral glucocorticoids for more than 3 months.

There is a distinction between risk factors for osteoporosis and risk factors for fracture, and between skeletal risk factors and nonskeletal risk factors. This distinction is important in clinical practice because different types of risk factors may require different therapeutic approaches. For example, poor vision is a nonskeletal risk factor for fracture that is independent of BMD. Treatment with a bone-active agent cannot be expected to alter this risk factor, while improvement of vision with cataract surgery may. Vitamin D deficiency has both skeletal and nonskeletal adverse effects. It is associated with osteoporosis and osteomalacia that increases the risk of fracture, and with impaired balance and muscle strength that may increase fracture risk independently of BMD. (4) Osteoporosis itself is a risk factor for fracture, with the risk of fracture approximately doubling for every 1 standard deviation decrease in BMD. (5)

It has been suggested by some that BMD testing can be bypassed when clinical risk factors suggest a very high risk of fracture. (6) This may at times be an effective strategy, but runs the risk of inappropriate therapy for some. The 3-year risedronate hip fracture trial did not show a significant reduction in hip fractures in treated patients in the group of 3,886 women age 80 and older who were selected primarily on the basis of nonskeletal risk factors for hip fracture. (7) In contrast, women aged 70 to 79 selected on the basis of a femoral neck T-score of -3.0 or below did show reduction in hip fracture risk with treatment.

The best strategy for estimating fracture risk uses a combination of BMD and clinical risk factors for fracture that are independent of BMD. The World Health Organization (WHO) is developing a standardized methodology to quantify fracture risk expressed as 10-year probability. (8) When cost-utility analysis is applied to these data, using many country-specific economic assumptions and efficacy of treatment assumptions, then cost-effective intervention thresholds can be calculated. (9) This allows patients with the greatest risk of fracture, who are most likely to benefit from pharmacologic therapy, to be identified and treated.

References

1. Bass MA, Ford MA, Mauromoustakos A. et al. Variables for the Prediction of Femoral Bone Mineral Status in American Women. South Med J 2006;99:115-122.

2. Watts NB, Pols H, Ringe JD, et al. Detection of "unexpected" osteoporosis: insights from the "IMPACT" trial. Arthritis Rheum 2001;44:S256.

3. Physician's Guide to Prevention and Treatment of Osteoporosis. 2003. Washington DC, National Osteoporosis Foundation. 2003.

4. Pfeifer M, Begerow B, Minne HW, et al. Vitamin D status, trunk musele strength, body sway, falls, and fractures among 237 postmenopausal women with osteoporosis. Exp Clin Endocrinol Diabetes 2001;109:87-92.

5. Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996;312:1254-1259.

6. Kanis JA, Borgstrom F, De Laet C, et al. Assessment of fracture risk. Osteoporos Int 2005;16:581-589.

7. McClung MR, Geusens P, Miller PD, et al. Effect of risedronate on the risk of hip fracture in elderly women. N Engl J Med 2001;344:333-340.

8. Kanis JA, Johnell O, Oden A, et al. Ten-year risk of osteoporotic fracture and the effect of risk factors on screening strategies. Bone 2002;30:251-258.

9. Kanis JA, Johnell O, Oden A, et al. Intervention thresholds for osteoporosis in men and women: a study based on data from Sweden. Osteoporos Int 2005;16:6-14.</p> <pre> I'd rather regret the things I've done, than the things I didn't do. --Russell Crowe </pre> <p>E. Michael Lewiecki, MD, FACP 

From the New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM.

Reprint requests to E. Michael Lewiecki, MD, Osteoporosis Director, New Mexico Clinical Research & Osteoporosis Center, 300 Oak Street NE, Albuquerque, NM 87106. Email: [e-mail]

Accepted August 26, 2005.