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Early Changes in Biochemical Markers of Bone Turnover Are Associated with Long-Term Changes in Bone Mineral Density in Elderly Women on Alendronate, Hormone Replacement Therapy, or Combination Therapy: A Three-Year, Double-Blind, Placebo-Controlled, Randomized Clinical Trial

Divisions of Endocrinology and Metabolism (S.L.G.) and Geriatric Medicine (S.L.G., N.M.R.), Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213; and Center for Biostatistics in AIDS Research (R.A.P.), Harvard School of Public Health, Boston, Massachusetts 02215

Address all correspondence and requests for reprints to: Susan L. Greenspan, M.D., University of Pittsburgh, Osteoporosis Prevention and Treatment Center, Kaufmann Medical Building, Suite 1110, 3471 Fifth Avenue, Pittsburgh, Pennsylvania 15213-3221. E-mail: griffithsd{at}msx.dept-med.pitt.edu.

Elderly women on combination therapy with alendronate and hormone replacement for osteoporosis have greater gains in bone mass than those on monotherapy. It is not known whether early changes in markers can predict the long-term changes in bone density with therapy. We assessed bone density and biochemical markers of bone turnover [urine N-telopeptide cross-linked collagen type 1 (NTx), serum bone-specific alkaline phosphatase, and osteocalcin] every 6 months for 3 yr in a double-blind, placebo-controlled, randomized clinical trial. After a 3-month run-in phase, 373 community-dwelling, elderly women were randomized to 1) alendronate, 2) hormone replacement therapy, 3) combination therapy with alendronate and hormone replacement therapy, or 4) placebo. Women on active treatment with the greatest decrease in markers of bone turnover at 6 months had the greatest increases in spine and hip bone density at 3 yr. The response to alendronate was generally associated with greater reductions in markers than the response to hormone replacement and was associated with greater increases in bone density at the spine and hip. Those in the tertile with the greatest decrease in urinary NTx had a 10.1% increase in spine bone density and a 6.1% increase in hip bone density compared with those in the lowest tertile, who had a 5.9% increase in spine bone density and a 2.1% increase in hip bone density. In women on active treatment, the area under the receiver operator curve for a 6-month change in markers to predict a response in bone mineral density at 3 yr was highest for urine NTx (range, 75–78%) and lowest for osteocalcin (range, 60–66%). We conclude that short-term changes in biochemical markers of bone turnover at 6 months predict bone density changes at the spine and hip at 3 yr in elderly women on alendronate, hormone replacement therapy, or combination therapy.

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