Abstract
Journal of Bone and Mineral Research, Journal of Bone and Mineral Research July 2005:20:1244-1253 (doi: 10.1359/JBMR.050309)

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Differential Effects of Teriparatide and Alendronate on Bone Remodeling in Postmenopausal Women Assessed by Histomorphometric Parameters

Monique Arlot, 1   Pierre J Meunier, 1   Georges Boivin, 1   Lillian Haddock, 2   Juan Tamayo, 3   Ricardo Correa-Rotter, 4   Salomón Jasqui, 4   David W Donley, 5   Gail P Dalsky, 5   Javier San Martin, 5   Erik Fink Eriksen5  

1Laboratoire d'Histodynamique Osseuse and INSERM Unit 403, Faculty of Medicine R. Laennec, Lyon, France;

2University of Puerto Rico School of Medicine, San Juan, Puerto Rico;

3COMOP AC, Av Insurgentes Sur 299 Mezzanine México D.F., Mexico;

4Department de Nefrologia y Metabolismo, Mineral Instituto Nacional de Ciencias Medicas, Y Nutricion “Salvador Zubiran,” Mexico DF, Mexico;

5Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.

Address reprint requests to: Monique Arlot, MD Laboratoire d'Histodynamique Osseuse INSERM Unit 403 Faculty of Medicine R. Laennec rue Guillaume Paradin Lyon 69372 Cedex 08, France E-mail:




An 18-month randomized double-blind study was conducted in postmenopausal women with osteoporosis to compare the effects of once-daily teriparatide 20 μg with alendronate 10 mg on bone histomorphometry. Biopsies were obtained from 42 patients. Indices of bone formation were significantly higher after 6 or 18 months of teriparatide compared with alendronate treatment.

Introduction: Alendronate and teriparatide increased BMD, assessed by DXA, by different mechanisms of action, supported by changes in biochemical markers of bone turnover. The purpose of this cross-sectional study was to explore the differential effects of these two osteoporosis treatments at the bone tissue level by examining bone histomorphometric parameters of bone turnover after either 6 or 18 months of treatment.

Materials and Methods: Patients were a cohort from a randomized parallel double-blind study conducted to compare the effects of once-daily teriparatide 20 μg and alendronate 10 mg in postmenopausal women with osteoporosis. Transiliac crest bone biopsies were obtained after tetracycline double labeling from 42 patients treated for 6 months (n = 23) or 18 months (n = 14); 5 additional patients were biopsied from contralateral sides at 6 and 18 months. Biopsy specimens adequate for quantitative analysis were analyzed by 2D histomorphometry from 17 patients at 6 months (teriparatide, n = 8; alendronate, n = 9) and 15 patients at 18 months (teriparatide, n = 8; alendronate, n = 7). Data were analyzed by two-sample tests.

Results: Histomorphometric indices of bone formation were significantly and markedly greater in the teriparatide group than in the alendronate group at 6 and 18 months, whereas indices of bone resorption were only significantly greater in the teriparatide group than in the alendronate group at 6 months. Bone formation and activation frequency were significantly lower at 18 months compared with 6 months in the teriparatide group, returning to levels comparable with untreated postmenopausal women. In the teriparatide group, the peak in histomorphometric bone formation indices coincided with peak levels for N-terminal propeptide of type I collagen, a biochemical marker of bone formation. The degree of mineralization was lower at 18 months than at 6 months with treatment in both groups but was not different between groups.

Conclusions: These results confirm the opposite mechanisms of action of teriparatide and alendronate on bone remodeling and confirm the bone formation effect of teriparatide.

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Authors:
Monique Arlot,
Pierre J Meunier,
Georges Boivin,
Lillian Haddock,
Juan Tamayo,
Ricardo Correa-Rotter,
Salomón Jasqui,
David W Donley,
Gail P Dalsky,
Javier San Martin,
Erik Fink Eriksen
Keywords:
teriparatide
histomorphometry
bone remodeling
bone formation
osteoporosis