1997 by Excerpta Medica, Inc. 0002-9343/97/$17.00 29 All rights reserved. PII S0002-9343(96)00387-7 / 220a 0281 Mp 29 Sunday Dec 29 11:04 PM EL–AJM (v. 102, no. 1) 0281 Hormone Replacement Therapy in Postmenopausal Women: Urinary N-Telopeptide of Type I Collagen Monitors Therapeutic Effect and Predicts Response of Bone Mineral Density Charles H. Chesnut III, MD, Seattle, Washington, Norman H. Bell, MD, Charleston, South Carolina, Guy S. Clark, MD, Santa Barbara, California, Barbara L. Drinkwater, PhD, Seattle, Washington, Susan C. English, MD, Billings, Montana, C. Conrad Johnston Jr., MD, Indianapolis, Indiana, Morris Notelovitz, MD, PhD, Gainesville, Florida, Clifford Rosen, MD, Bangor, Maine, Daniel F. Cain, BS, Karen A. Flessland, BS, Nancy J. S. Mallinak, BS, Seattle, Washington PURPOSE: To assess the ability of the urinary N- telopeptide of type I collagen (NTx) to monitor and predict therapeutic effects of hormone replacement therapy (HRT) in postmenopausal women. PATIENTS AND METHODS: To assess the relationship between baseline or change in NTx (predictive variable), and change in lumbar and hip bone mineral density (BMD; outcome variable), we conducted a 2-year randomized controlled study at academic university and private practice medical centers in 236 healthy women 1 to 3 years postmenopausal; 227 women completed the study. Women received estrogen plus progesterone plus calcium (treated group) or calcium alone (control group). RESULTS: In the treated group NTx significantly (P õ0.0001) decreased, and spine and hip BMD significantly (P õ0.00001 and P õ0.005, respectively) increased; in the control group NTx did not change but BMD decreased significantly (P õ0.01). Subjects in the highest quartiles for baseline NTx (67 to 188 units) or decreasing NTx (066% to 087%) through 6 From the University of Washington Medical Center, Seattle, Washington (CHC); VA Medical Center and Medical University of South Carolina, Charleston, South Carolina (NHB); Osteoporosis Center of Santa Bar- bara, Santa Barbara, California (GSC); Pacific Medical Center, Seattle, Washington (BLD); Deaconess Research Institute, Billings, Montana (SCE); Indiana University Medical Center, Indianapolis, Indiana (CCJ); Women’s Medical and Diagnostic Center, Gainesville, Florida (MN); St. Jo- seph Hospital, Bangor, Maine (CR); and Ostex International, Inc., Seattle, Washington (DFC, KAF, NJSM). Ostex International, Seattle, Washington, provided financial grants to each investigative site for conduct of the study. Presented in part at the 17th and 18th Annual Meetings of the Ameri- can Society for Bone and Mineral Research, Baltimore, Maryland, 1995, and Seattle, Washington, 1996. Requests for reprints should be addressed to Dr. Charles H. Chesnut, III, University of Washington Medical Center, Nuclear Medicine Box 356113, Seattle, Washington 98195-6113. Manuscript submitted June 14, 1996 and accepted in revised form Oc- tober 21, 1996. months demonstrated the greatest gain in BMD in response to HRT (P õ0.05 and P õ0.005). For every increase of 30 units in baseline NTx, the odds of gain in BMD in response to HRT increased by a factor of 5.0 (95% confidence interval [CI] 1.9 to 13.3); for every 30% decrease in NTx through 6 months, the odds of gaining BMD in response to HRT increased by a factor of 2.6 (95% CI 1.6 to 4.4). In the control group an increase of 30 units in mean NTx across the study indicated a higher odds of losing BMD by a factor of 3.2 (95% CI 1.6 to 6.5). A high baseline NTx (ú67 units) indicated a 17.3 times higher risk of BMD loss if not treated with HRT. CONCLUSION: These data support the clinical utility of NTx to monitor the antiresorptive effect of HRT in recently postmenopausal women, and to predict changes in BMD in response to HRT. 1997 by Excerpta Medica, Inc. Am J Med. 1997;102:29–37. E strogen depletion in postmenopausal women is associated with increased bone resorption, a de- cline in bone mass, and subsequent increased risk for osteoporosis and fractures. 1–3 Although com- monly used to relieve vasomotor symptoms, estro- gen replacement therapy (ERT) is an effective anti- resorptive treatment that increases bone mass and reduces the incidence of fractures. 4–6 Clinical usage of ERT, or of any osteoporosis ther- apy, optimally requires a means of monitoring treat- ment response, and of predicting who should be treated. In this regard, measurement of bone mineral density (BMD) with dual energy x-ray absorptiome- try (DXA) technology has been utilized. However, this technique is an integral but static assessment of all biological and physical factors previously affect- ing the measured skeletal site rather than an assess- ment of the current status of bone turnover. In ad- dition, DXA may require up to 2 years to detect a significant therapeutic response, 7 is comparatively