Prediction of Skeletal Response to HRT using the NTx Test

Osteoporosis is recognized as a significant contributor to morbidity and mortality to postmenopausal women. Several effective strategies, including calcium supplementation, exercise and, most importantly hormone replacement therapy, have been developed to prevent or decrease clinically significant bone loss.

For over 20 years, physicians who specialize in metabolic bone diseases have used biochemical markers in conjunction with bone mineral density (BMD) measurements to determine how rapidly a patient is losing bone mass and whether that patient is receiving clinical benefit from a given therapeutic regimen.

However, the traditional markers of bone metabolism have often been criticized for lacking sensitivity and/or specificity when used to characterize the relativity subtle changes in bone remodeling that accompany osteoporosis. New biochemical bone markers for bone resorption, such as the collagen crosslink NTx has become available in recent years which seems to be a powerful tool to monitor the rate of bone loss.

They detect highly specific products of bone breakdown in urine or serum. When the level of bone marker is high, it indicates rapid rate of bone loss. If antiresorptive therapy is effective, the rate of bone loss should be slower and the level of bone marker should be decreased from baseline.

By learning how to use urinary bone marker testing in postmenopausal women, clinicians will be able to predict who is a greatest risk of rapid bone loss, and whether patients are responding to therapy within a few months.

"These tests have untapped potential in the evaluation of patients with documented low bone mass or patients with documented low bone mass or patients at risk for accelerated boneloss. . . Biochemical markers of bone resorption and formation will be a necessary adjunct to bone mass measurement in evaluating the future risk of osteoporosis and in identifying individuals in greatest need of intervention to preserve current bone mass," said Laurence Demers, PhD, Distinguished Professor of Pathology and Medicine at The Pennsylvania State University College of Medicine and Michael Kleerekoper,MD, professor of endocrinology at Wayne State University.

The FDA has already cleared collagen crosslink assays (including the NTx and CTx) for a number of indications, including identification of osteoporotic individuals with elevated bone resorption in whom response to treatment is being monitored; predicting response as assessed by bone mass measurements to antiresorptive therapies in postmenopausal women; and assessing effectiveness of osteoporosis treatment which includes FDA approved therapies in postmenopausal women and individuals with osteoporosis.'

NTx results can be used to:

• Predict skeletal response to hormone replacement therapy (HRT) in postmenopausal women.
• Determine probability for decrease in bone mass in postmenopausal women on HRT.
• Counsel patients about initiation and continuation of therapy.
• Monitor response to therapy as early as three months after initiation.

Summary

In summary, both the bone mineral density and NTx tests can offer physicians important, complementary information. The BMD test is the gold standard to assess current skeletal status. The NTx test, however, predicts what the future skeletal status will be if the correct preventative steps are taken or not taken. A 3 month follow up NTx test also assesses the adequacy of whatever therapy had been elected by the physician.

Using BMD alone, this assessment would take significantly longer to determine, perhaps 2 - 3 years. In some instances, this retrospective interval may be long enough such that a highly significant additional amount of bone may be lost before the true situation is appreciated and rectified. Employing BMD and NTx tests in a complementary fashion can help prevent this problem.

graphic - Changes in NTx and BMD among Women on HRT + Calcium (N=109)

Changes in NTx values and bone mineral density among women on hormone replacement and calcium. Adopted from Chestnut et al.

References

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3. Rosen, C. et al. The Predictive Value of Biochemical Markers of bone Turnover for Bone Mineral Density in Early Postmenopausal Women Treated with Hormone Replacement of Calcium Supplementation. J. Clin Endocrinol Metab. 1997; 82: 1904 1910.
4. Zackson DA, MA. The Complementary Role of NTx and BMD in the Prevention and Treatment of Osteoporosis. Ostex Int'1, Technical Bulletin No 8. 1998.
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