The mechanical competence of bone is determined by the amount of bone per unit volume (also referred to as apparent density), its structural arrangement and its chemical make-up. Age and osteoporosis-related deterioration of the bone has typically been attributed to a net loss of bone mass and architectural impairment but it has been widely assumed that the bone's intrinsic material properties remain invariant. This notion is in conflict with a substantial body of literature indicating significant decreases in the degree of mineralization of bone (DMB) following ovariectomy and increased DMB in response to antiresorptive treatment. Such a behavior is plausible since the bone turnover rate determines the average age of the bone and younger bone is known to be hypomineralized. Paralleling changes in DMB are the bone's biomechanical properties in that decreased DMB is associated with decreased static strength and Young's modulus. The extent to which mechanical failure in the form of fractures is related to changes in the bone's mineral content is not known. Unfortunately, DMB cannot currently be measured noninvasively. However, since DMB is related to the bone's osteoid water content, information on mineral density can be obtained indirectly. There is evidence that during mineralization some of the matrix water is displaced and its space taken by mineral in such a manner that osteoid volume remains constant. In this proposal we advance the hypothesis that there is an inverse relationship between osteoid water and bone mineral volume and that a measure of DMB can be obtained indirectly by quantitative proton magnetic resonance of solid bone. We provide evidence in preliminary work that decreased mineralization is associated with higher water content and that the matrix water can be imaged with appropriate imaging techniques in intact bone. In two disease models in which DMB is expected to be altered (rabbit osteomalacia and rat ovariectomy) we test the hypothesis using proton and 31P NMR that changes in DMB occur at the expense of a commensurate change in bone water and further that increased bone water decreases static strength and elastic modulus. The long-term goal of this project is to provide a noninvasive method for probing the intrinsic properties of bone in laboratory animals and ultimately in humans.
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