One and a half million Americans suffer from fragility fractures of the hip, spine or wrist, subjecting them to pain, deformities and disability, and resulting in health care costs in excess of $10 billion annually. Based on the assumption that fragility fractures are caused by low bone mass, the World Health Organization (WHO) has defined individuals at risk for these fractures based on their areal bone mineral density relative to that of a normal young adult, as measured by dual energy X-ray absorptiometry (DXA).
However, fracture predictions based on areal bone mineral density have been shown to be neither sensitive nor specific. Areal bone mineral density, a two-dimensional projection of a three-dimensional construct, is not representative of the volumetric bone mineral density and is incapable of distinguishing between changes in the two main determinants of bone strength, its material and geometric properties. This distinction is essential for the proper diagnosis and treatment of skeletal diseases associated with low bone mass.
While it is assumed that most fragility fractures are caused by osteoporosis, where decreased bone volume is viewed as the main culprit; 50 percent of postmenopausal women who fracture their hip and have no other cause for low bone mass are diagnosed with vitamin D deficiency. Vitamin D deficiency can result in osteomalacia, where both bone mineral composition and volume are decreased. Indeed, up to 33 percent of patients with low bone mass who have suffered a hip fracture have been diagnosed with osteomalacia (hypo-mineralized osteoid) upon subsequent histologic evaluation. Thus, accurate assessment of the underlying causes of osteopenia, whether osteoporosis or osteomalacia, is important, as the treatment protocols for these conditions are very different.
Therefore, we propose to develop a new non-ionizing approach capable of measuring bone mineral and matrix composition and structure to properly quantify changes in bone material and geometric properties altered by different pathologic conditions. Toward this end, our group has demonstrated that the organic matrix component of bone can be measured using water and fat suppressed proton magnetic resonance (MR) imaging (WASPI) (which cannot otherwise be measured non-invasively), and that the mineral component of bone can be measured using P-31 solid state MR imaging (P-31 SMRI). Further, our group and others have established that bone volume fraction (BV/TV), trabecular microstructure and cross-sectional bone geometry can also be measured using liquid state MR imaging. Thus, we hypothesize that combined liquid and solid (WASPI and P-31 SMRI) state MR imaging can be used to (a) differentiate metabolic bone diseases on the basis of bone tissue mineral composition and structural properties; and (b) estimate the load capacity of normal and pathologic bones.
Our ultimate goal is to establish liquid+solid state MR imaging as a method to perform a "virtual bone biopsy" in humans to non-invasively assess the organic matrix and inorganic mineral composition of bone to diagnose skeletal diseases, predict fracture risk and guide treatment. However, first we must prove that liquid+solid state MR imaging can be used to evaluate the range of metabolic bone diseases that may be encountered clinically using well established rat models in a controlled environment. We understand that rat bones undergo minimal secondary remodeling. Therefore, they are only used for basic validation of techniques outlined here and not as a substitute for human bone/pathology.
Relevant Publications: 7 , 23