Is Bone Mineral Density Predictive of Fracture Risk Reduction?

Charles A. Cefalu


Curr Med Res Opin. 2004;20(3) 

In This Article

Summary and Introduction

Bone mineral density (BMD) measurement is a widely available noninvasive means of identifying individuals with osteoporosis and, possibly, those at high risk for fracture. This nonsystematic review examines the relationship between BMD increase and fracture risk reduction in clinical trials evaluating osteoporosis therapy. The trials examined here are predominantly in postmenopausal women. BMD increase correlates poorly with fracture risk reduction in clinical trials of osteoporosis therapy conducted in postmenopausal women. Although BMD may increase with therapy, the increase is not measurable until later, and the overall increase is too small to account for the timing and magnitude of fracture risk reduction. BMD is only one of many contributors to bone strength and fracture risk reduction. Bone strength is derived from bone quantity, which consists of density and size, and bone quality, which, in turn, consists of structure (micro-and macroarchitecture), material properties, and turnover. Data are beginning to accrue suggesting that changes in bone turnover markers may be an accurate predictor of fracture risk reduction. Future research will elucidate the link between changes in bone turnover markers and bone architecture as a measure of osteoporosis treatment efficacy. Until then, physicians will continue to rely on fracture risk reduction data from well-designed clinical trials when judging the efficacy of different treatments for osteoporosis.

Bone mineral density (BMD) measurement by dual energy X-ray absorptiometry (DXA) is widely used to diagnose osteoporosis.[1,2,3] The World Health Organization (WHO) defines osteoporosis as a BMD value that is 2.5 standard deviations (SDs) or more below the mean of a young adult of the same sex (T-score).[4]

BMD is a useful tool for the diagnosis of osteoporosis because fracture risk is increased when BMD is decreased. Monitoring changes in BMD over time can be used to estimate an individual's rate of bone loss.[5] BMD can confirm response to treatment; however, the predictive precision of BMD for determining a change in fracture risk appears to be compromised by two factors: (1) errors of accuracy inherent in the testing methods and the normal variance of BMD in the population mean requires that a prolonged interval of time is usually needed to assess change in BMD with a satisfactory degree of accuracy [6]; (2) BMD is not the only physiological factor that contributes to bone strength and fracture risk.[7] The lack of predictive precision of BMD for change in fracture risk means that the usefulness of BMD as a surrogate for efficacy (fracture risk reduction) in clinical trials may be limited.

This article reviews the relationship between BMD increase and fracture risk reduction observed in clinical studies of osteoporosis therapies, and discusses additional physiological mechanisms that may impact fracture risk. Data included in this review are from a MEDLINE literature search conducted of articles published since 1990 using the terms 'osteoporosis', 'bone mineral density', 'fracture risk', and the generic names of available osteoporosis therapies. Data from clinical trial reports and meta-analyses were included in the review. Recent data (since the year 2000) from published abstracts presented at relevant scientific meetings, including the International Osteoporosis Foundation World Congress and the American Society for Bone and Mineral Research, were also discussed. The patients evaluated in these studies were predominantly white postmenopausal women. The literature search did not identify studies evaluating osteoporotic therapies in other ethnic groups or in men.


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