Drs Ma, Zeng, Donley, Dalsky, and Marcus are employees of Eli Lilly and Company;
Teriparatide Increases Bone Formation in Modeling and Remodeling Osteons and Enhances IGF-II Immunoreactivity in Postmenopausal Women With Osteoporosis†
Version of Record online: 8 MAY 2006
Copyright © 2006 ASBMR
Journal of Bone and Mineral Research
Volume 21, Issue 6, pages 855–864, June 2006
How to Cite
Ma, Y. L., Zeng, Q., Donley, D. W., Ste-Marie, L.-G., Gallagher, J. C., Dalsky, G. P., Marcus, R. and Eriksen, E. F. (2006), Teriparatide Increases Bone Formation in Modeling and Remodeling Osteons and Enhances IGF-II Immunoreactivity in Postmenopausal Women With Osteoporosis. J Bone Miner Res, 21: 855–864. doi: 10.1359/jbmr.060314
This paper was previously presented at the 1st Joint Meeting of the International Bone and Mineral Society/Japanese Society of Bone and Mineral Research, June 3–7, 2003, Osaka, Japan, the 9th Bath Conference on Osteoporosis, National Osteoporosis Society, June 23–26, 2003, Bath, United Kingdom, the 30th European Symposium on Calcified Tissues, May 8–12, 2003, Rome, Italy, and Advances in Skeletal Anabolic Agents and the Treatment of Osteoporosis, May 24–25, 2004, Bethesda, MD, USA.
- Issue online: 4 DEC 2009
- Version of Record online: 8 MAY 2006
- Manuscript Accepted: 28 MAR 2006
- Manuscript Revised: 27 FEB 2006
- Manuscript Received: 13 JUN 2005
- transiliac bone biopsy;
- bone formation;
Transiliac bone biopsies were obtained from 55 women treated with teriparatide or placebo for 12–24 months. We report direct evidence that modeling bone formation at quiescent surfaces was present only in teriparatide-treated patients and bone formation at remodeling sites was higher with teriparatide than placebo.
Introduction: Recombinant teriparatide [human PTH(1-34)], a bone formation agent for the treatment of osteoporosis when given once daily subcutaneously, increases biochemical markers of bone turnover and activation frequency in histomorphometry studies.
Materials and Methods: We studied the mechanisms underlying this bone-forming action of teriparatide at the basic multicellular unit by the appearance of cement lines, a method used to directly classify surfaces as modeling or remodeling osteons, and by the immunolocalization of IGF-I and IGF-II. Transiliac bone biopsies were obtained from 55 postmenopausal women treated with teriparatide 20 or 40 μg or placebo for 12–24 months (median, 19.8 months) in the Fracture Prevention Trial.
Results: A dose-dependent relationship was observed in modeling and mixed remodeling/modeling trabecular hemiosteons. Trabecular and endosteal hemiosteon mean wall thicknesses were significantly higher in both teriparatide groups than in placebo. There was a dose-dependent relationship in IGF-II immunoreactive staining at all bone envelopes studied. The greater local IGF-II presence after treatment with teriparatide may play a key role in stimulating bone formation.
Conclusions: Direct evidence is presented that 12–24 months of teriparatide treatment induced modeling bone formation at quiescent surfaces and resulted in greater bone formation at remodeling sites, relative to placebo.