On the Trail of Osteoporosis

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Even as adults, our bones are not static. The processes of bone building and bone demolishing are silently going on in our bodies all the time. In healthy adults, these two bone-remodeling processes are balanced so that the net effect is neither addition nor loss of bone mass. But in post-menopausal women, and in the case of certain diseases, the balance shifts, and more bone is resorbed than rebuilt. The net effect is called osteoporosis, and it leads to fragile bones that can easily crack or break.

Osteoporosis is a major public health problem. More than 40 million people in the U.S. are affected by the disorder. And the societal costs resulting from fractures of the femur alone--the long bone in the leg--exceed $10 billion annually in the U.S. Researchers around the world are searching for new preventive measures, new treatments, and improved diagnostic methods for the condition.

In 1985, UW professor David Eyre developed a method for spotting the tell-tale signs present when bone is resorbed by the body. Eyre, who holds the Ernest M. Burgess Professorship of Orthopedic Research, developed a method to detect a specific protein fragment excreted in the urine when bone is resorbed. Until that time, there were no easy-to-use and accurate methods available to measure the rate of bone resorption.

In 1989, Eyre's discoveries were exclusively licensed by the University to Ostex International, Inc., a Seattle-based start-up company launched to commercialize the technology. Ostex has developed a quick and inexpensive urine test called Osteomark® which may be used to identify those at risk for bone loss, as well as to monitor the effectiveness of treatments for the disorder.

Eyre's method resulted from long-term basic research studies to understand the molecular mechanisms of the protein cross-linking in bone. Bone is resorbed when special cells called osteoclasts contact the normal mineralized bone and begin to remove the mineral components while degrading the bone's collagen protein matrix by means of enzymes called proteases. The degradation products are protein fragments that can be targeted by a monoclonal antibody and quantified by immunoassay.

The protein fragment, or peptide, which Eyre abbreviates as NTx, is present in postmenopausal women in concentrations that are, on average, 2.5 times higher than in premenopausal women, evidence of the accelerated rate of bone loss after menopause.

Bisphosphonates are chemical compounds that inhibit the activity of osteoclasts. In a collaborative effort involving clinical trials, Eyre has demonstrated that the NTx assay is a highly specific monitor for the effects of bisphosphonate on the rate of bone resorption. After a six-week treatment with the compound, patients showed a marked reduction in the amount of NTx peptide excreted in the urine compared to levels before the treatment. When the treatment with bisphosphonate is stopped, the amount of NTx peptide gradually returns to what it was before treatment started. The measurements were highly responsive and dose-dependent. Eyre is continuing studies to determine to what degree the test may be used to predict, for women at the time of menopause, the risk of future bone fractures.

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