An NIH consensus development panel concluded in 2001 that in the United States alone, 10 million people already have osteoporosis, and 18 million more have low bone mass. Patients with low bone mass due to osteomalacia usually remain for many years misdiagnosed as only having osteoporosis, since radiographs plus blood and urine measurements frequently fail to distinguish the two conditions. Patients with osteomalacia have impaired bone mineralization, and may in addition have a reduced amount of bone tissue, whereas patients with osteoporosis have a reduced amount of bone which is normally-mineralized. At present an invasive bone biopsy is the only way to discriminate osteomalacia from osteoporosis with confidence. Confounding osteomalacia with osteoporosis in individual patients leads to inappropriate therapy. The purpose of the proposed 31P/1H solid state magnetic resonance imaging (SMRI) measurement of bone mineralization is to provide critically needed information about the relative proportions of bone mineral and bone matrix in a given volume of bone substance that is unattainable by any other noninvasive methods including CT and high resolution liquid state MRI. The SMRI method targets a so-called soft solid regime. The 31P NMR signals of bone mineral and some portion of the 'H NMR signals of solid bone matrix fall in this regime. Quantitative 31P SMRI yields a good representation of the mineral density in bone, and quantitative water and fat suppressed [H projection MRI (WASPI) provides the measurement of the matrix density of bone. Combining these two measurements yields the degree of bone mineralization. In the proposed project, this novel MRI technology will be further developed and implemented in a whole body MRI scanner. It will be evaluated first in live swine with osteomalacia and controls, then in human subjects with osteoarthritis, all against gold standard chemical and gravimetric analyses of the associated bone specimens harvested from the animals or resected during total knee replacement. Finally, the proposed SMRI will be evaluated in patients who have been clinically diagnosed with osteoporosis and/or osteomalacia. If this technology is successful, it would identify osteomalacia non-invasively in patients with low bone density and benefit their medical care, because treatment of osteomalacia is dramatically effective, and increases bone mineral density and bone strength much more than any available treatment for osteoporosis.
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|Cao, Haihui; Nazarian, Ara; Ackerman, Jerome L et al. (2010) Quantitative (31)P NMR spectroscopy and (1)H MRI measurements of bone mineral and matrix density differentiate metabolic bone diseases in rat models. Bone 46:1582-90|
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