Changes in Bone Density, Radiographic Texture Analysis and Bone Turnover During Two Years of Antiresorptive Therapy for Postmenopausal Osteoporosis

The study proposed in this application is a part of a larger project entitled "Clinical utility of radiographic texture analysis in diagnosing and treating osteoporosis". The overall goal of the larger project is to determine whether computerized texture analysis of digitized high-resolution images of trabecular bone (texture analysis) improves our ability to diagnose bone fragility and follow natural history and/or response to pharmacological therapy of osteoporosis. In the study proposed here we plan to examine changes in the results of texture analysis during two years of pharmacological therapy for osteoporosis.

Role of densitometry in osteoporosis:

Measurement of bone mineral density is the principal diagnostic method used in clinical practice and in research studies, both to identify patients who have the disease and to follow their response to therapeutic agents. The technique used most widely is dual-energy X-ray absorptiometry (DXA), which has advantages of low cost and radiation exposure, and high precision and accuracy of 1-2% and 4-8%, respectively [Garner, 1996 and Melton, 1990]. Based on the association between the low BMD and increased risk of fracture, BMD-based treatment guidelines have been developed [Melton, 1993 and National Osteoporosis Foundation, 1999]. There is, however, a considerable overlap between BMD of patients who sustain fragility fractures and those who do not [Cummings, 1993; Marshall, 1996; Melton, 1989; Ross, 1990 and Wasnich, 1990]. The problem arises because the fragility is determined not only by the quantity of the bone (measured as bone density), but also by its "quality" which is believed to be related to the preservation of the normal trabecular pattern [Parfitt, 1987]. Bone quality is not specifically assessed using current diagnostic methods. Information about bone quality, however, would be of substantial clinical and scientific value, as it would complement the BMD measurement when selecting patients for therapy and when studying bone loss or assessing effects of therapeutic agents.

Texture analysis:

A novel approach to noninvasive and practical assessment of bone structure is to analyze the texture of high resolution radiographs of trabecular bone [Link, 1999]. Dr. Giger has developed a method for characterizing bone structure by computerized texture analysis of digitized high-resolution radiographs [Jiang, 1999; Caligiuri, 1993; Caligiuri, 1994; Chinander, 1999 and Chinander, 2000]. In this approach, the texture is analyzed in several ways, including Fourier based analysis, which yields root mean square (RMS) as a measure of magnitude of trabecular bone texture pattern, and the first moment of power spectrum (FMP) which characterizes the texture pattern's frequency; and Minkowski dimension fractal analysis [Caligiuri, 1993; Chinander, 1999; Chinander, 2000; Benhamou, 1994; Jiang, 1999; Majumdar, 1993 and Maragos, 1994]. Radiographic texture analysis has been studied in vivo, on lumbar spine radiographs and found to predict presence of vertebral fractures elsewhere in the spine more reliably than did the BMD of the spine [Caligiuri, 1993 and Caligiuri, 1994;]. In addition, in an in vitro study texture features as well as BMD were analyzed in femoral neck specimens obtained during surgical hip replacement. Mechanical loading (crush test) was then performed on cubes of trabecular bone machined from these specimens to determine their bone strength. It was found that the combination of BMD and texture analysis predicted bone strength better than BMD alone [Jiang, 1999; Chinander, 1999 and Chinander, 2000].