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Alendronate Prevents Postmenopausal Bone Loss in Women without Osteoporosis: A Double-Blind, Randomized, Controlled Trial

Michael McClung, MD; Bjorg Clemmesen, MD; Anastasia Daifotis, MD; Nigel L. Gilchrist, MB, ChB; John Eisman, MD; Robert S. Weinstein, MD; Ghada El Hajj Fuleihan, MD; Celia Reda, BS; A. John Yates, MD; and Pernille Ravn, MD
[+] Article, Author, and Disclosure Information

for the Alendronate Osteoporosis Prevention Study Group. For affiliations and current author addresses, see end of text. For members of the Alendronate Osteoporosis Prevention Study Group, see Appendix. Grant Support: By Merck Research Laboratories in the form of research grants to the individual study sites. Requests for Reprints: Michael R. McClung, MD, Oregon Osteoporosis Center, Providence Health System, 5050 NE Hoyt Street, Suite 651, Portland, OR 97213. Current Author Addresses: Dr. McClung: Oregon Osteoporosis Center, Providence Health System, 5050 NE Hoyt Street, Suite 651, Portland, OR 97213.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1998;128(4):253-261. doi:10.7326/0003-4819-128-4-199802150-00001
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Background: Preventing bone loss associated with menopause and aging and maintaining the normal microarchitecture of bone provide important opportunities for the prevention of osteoporosis and fractures.

Objective: To determine the safety and efficacy of alendronate, an aminobisphosphonate, for preventing postmenopausal bone loss.

Design: 3-year double-blind, randomized, placebo-controlled trial.

Setting: 15 osteoporosis centers throughout the world.

Participants: 447 women who had recently experienced menopause (6 to 36 months before study entry).

Intervention: Participants were randomly assigned to one of five regimens: oral placebo; oral alendronate, 1, 5, or 10 mg/d; or oral alendronate, 20 mg/d for 2 years followed by placebo during the third year (20/0 mg/d).

Measurements: Bone mineral density was measured by dual-energy x-ray absorptiometry. Bone turnover and bone quality were assessed with biochemical markers and bone histomorphometry.

Results: Alendronate at 5, 10, and 20/0 mg/d increased bone mineral density from baseline at the lumbar spine, femoral neck, and trochanter by 1% to 4% and in the total body by 0.3% to 1.0%; placebo led to losses of 2% to 4% at these sites. Alendronate, 1 mg/d, attenuated losses relative to those seen with placebo. Alendronate decreased markers of bone resorption to a new steady state by 3 months and decreased markers of bone formation by 6 to 12 months. Bone quality remained normal. At all dosages studied, alendronate had a safety and tolerability profile similar to that of placebo.

Conclusions: In early postmenopausal women, alendronate given for 3 years at dosages of 5 mg/d or greater prevented the loss of bone mineral density at the spine and hip and in the total body. Alendronate seems to be a safe and effective nonhormonal option for prevention of postmenopausal bone loss.


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Figure 1.
Mean changes from baseline in bone mineral density of the spine, femoral neck, trochanter, and total body in the placebo and alendronate groups.

All women also received 500 mg of calcium (as carbonate) daily. Bars represent SEs.

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Figure 2.
Mean changes from baseline in biochemical markers and indices of mineral metabolism with time in the placebo and alendronate groups.

Dashed lines designate the period during which women who received 20 mg of alendronate per day for 2 years and placebo for 1 year (the 20/0-mg/d group) were receiving placebo. Numbers of participants per group for each variable are 43 to 53 for deoxypyridinoline excretion, 23 to 42 for N-telopeptide crosslinks excretion, 44 to 55 for serum bone-specific alkaline phosphatase, and 43 to 50 for serum osteocalcin.

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Figure 3.
Histomorphometric variables (osteoid thickness [top] and mineralizing surface [bottom]) at 3 years.

Values are expressed as the mean ± SE. Each plot provides the median (center line of each box), 25th and 75th percentiles (bottom and top of each box), 10th and 90th percentiles (caps of error bars), and individual points outside those limits.

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