1997 by Excerpta Medica, Inc. 0002-9343/97/$17.00 291 All rights reserved. PII S0002-9343(97)00130-7 / 2212 5095 Mp 291 Tuesday Sep 23 12:34 PM EL–AJM (v. 103, no. 3) 5095 Increments in Bone Mineral Density of the Lumbar Spine and Hip and Suppression of Bone Turnover Are Maintained after Discontinuation of Alendronate in Postmenopausal Women John L. Stock, MD, Worcester, Massachusetts, Norman H. Bell, MD, Charleston, South Carolina, Charles H. Chesnut III, MD, Seattle, Washington, Kristine E. Ensrud, MD, Minneapolis, Minnesota, Harry K. Genant, MD, Steven T. Harris, MD, San Francisco, California, Michael R. McClung, MD, Portland, Oregon, Frederick R. Singer, MD, Santa Monica, California, Robert A. Yood, MD, Worcester, Massachusetts, Suzanne Pryor-Tillotson, MS, L. Wei, PhD, Arthur C. Santora II, MD, PhD, Rahway, New Jersey PURPOSE: Previously we have reported a significant increase in bone mineral density (BMD) of the spine and the hip and reductions in biochemical indices of bone turnover in postmenopausal women with osteoporosis treated with alendronate at various doses over 1 to 2 years. We have followed BMD and biochemical parameters in these patients for 1 or 2 years after discontinuation of alendronate to determine resolution of alendronate effects. PATIENTS AND METHODS: Participants received daily oral doses of placebo, 5 or 10 mg of alendronate for 2 years, or 20 or 40 mg of alendronate for 1 year followed by 1 year of placebo. No treatment was given in the third year of study. RESULTS: Lumbar spine BMD changes in the 5- and 10-mg groups (01.4 and 00.4%) were similar to those in the placebo group (01.2%) 1 year after discontinuation of drug and lumbar spine BMD changes in the 20- and 40-mg groups (01.2% and 0.8%) were similar to those in the placebo group (00.9%) 2 years after discontinuation of drug. BMD of the total hip From Memorial Health Care and the University of Massachusetts Medi- cal School (JLS), Worcester, Massachusetts; VA Medical Center and the Medical University of South Carolina (NHB), Charleston, South Carolina; University of Washington (CHC), Seattle, Washington; Minneapolis VA Medical Center and Healthspan, Inc. (KEE), Minneapolis, Minnesota; Uni- versity of California (HKG, STH), San Francisco, California; Providence Medical Center (MRM), Portland, Oregon; and St. John’s Hospital and Health Center (FRS), Santa Monica, California; St. Vincent Hospital (RAY), Worcester, Massachusetts; and Merck Research Laboratories (SP-T, LW, ACS), Rahway, New Jersey. This work was supported by a grant from Merck Research Laborato- ries, Rahway, New Jersey. Presented in part at the 17th Annual Meeting of the American Society for Bone and Mineral Research, Baltimore, MD, September, 1995, and the 1996 World Congress on Osteoporosis, Amsterdam, The Netherlands. Requested for reprints should be addressed to John L. Stock, MD, Me- morial Health Care, 119 Belmont Street, Worcester, Massachusetts 01605. Manuscript submitted December 16, 1996 and accepted in revised form March 24, 1997. followed the same pattern of resolution. The difference in BMD between alendronate and placebo groups at the end of alendronate treatment was maintained up to 2 years. Residual reductions in the bone resorption markers urinary deoxypyridinoline (D-Pyr) and collagen type 1 cross-linked N telopeptides and the bone formation markers serum bone- specific alkaline phosphatase and osteocalcin remained for 1 year after discontinuation of 5 and 10 mg of alendronate and for 2 years after discontinuation of 20 and 40 mg of alendronate, other than return of D-Pyr to baseline 1 year after cessation of treatment with the 5- and 10-mg doses. CONCLUSIONS: A residual decrease in bone turnover may be found up to 2 years after discontinuation of alendronate. Accelerated bone loss is not observed when treatment is discontinued. However, continuous therapy with alendronate is required to achieve a continuous gain in BMD. Am J. Med. 1997;103:291– 297.  1997 by Excerpta Medica, Inc. T he amino-bis-phosphonate alendronate sodium is a potent selective inhibitor of osteoclast-me- diated bone resorption. 1–3 Alendronate increases bone mass and strength in animal models of osteo- porosis, 4 reduces the incidence of vertebral and hip fractures in postmenopausal women with osteopo- rosis, 5,6 and recently received approval for the treat- ment of postmenopausal osteoporosis in the United States. Previously, we have reported an increase in bone mineral density (BMD) of the spine and hip, and re- ductions in biochemical indices of bone turnover in a double-blind, randomized, placebo-controlled study of 188 postmenopausal women with low spinal BMD treated with alendronate at various doses for 1 to 2 years. 7 Bisphosphonates have a long half-life in bone and previous studies provide evidence for continued efficacy once dosing has stopped. 8–11 We