Teriparatide increases bone formation in modeling and remodeling osteons and enhances IGF-II immunoreactivity in postmenopausal women with osteoporosis

Yanfei L. Ma, Qingqiang Zeng, David W. Donley, Louis Georges Ste-Marie, John Christopher G. Gallagher, Gail P. Dalsky, Robert Marcus, Erik Fink Eriksen

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

Transiliac bone biopsies were obtained front 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.

Original languageEnglish
Pages (from-to)855-864
Number of pages10
JournalJournal of Bone and Mineral Research
Volume21
Issue number6
DOIs
StatePublished - Jun 2006

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Haversian System
Teriparatide
Insulin-Like Growth Factor II
Osteogenesis
Osteoporosis
Placebos
Bone and Bones
Biopsy
Bone Remodeling
Parathyroid Hormone
Insulin-Like Growth Factor I
Therapeutics
Biomarkers
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Surgery

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Teriparatide increases bone formation in modeling and remodeling osteons and enhances IGF-II immunoreactivity in postmenopausal women with osteoporosis. / Ma, Yanfei L.; Zeng, Qingqiang; Donley, David W.; Ste-Marie, Louis Georges; Gallagher, John Christopher G.; Dalsky, Gail P.; Marcus, Robert; Eriksen, Erik Fink.

In: Journal of Bone and Mineral Research, Vol. 21, No. 6, 06.2006, p. 855-864.

Research output: Contribution to journalArticle

Ma, Yanfei L. ; Zeng, Qingqiang ; Donley, David W. ; Ste-Marie, Louis Georges ; Gallagher, John Christopher G. ; Dalsky, Gail P. ; Marcus, Robert ; Eriksen, Erik Fink. / Teriparatide increases bone formation in modeling and remodeling osteons and enhances IGF-II immunoreactivity in postmenopausal women with osteoporosis. In: Journal of Bone and Mineral Research. 2006 ; Vol. 21, No. 6. pp. 855-864.
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AU - Zeng, Qingqiang

AU - Donley, David W.

AU - Ste-Marie, Louis Georges

AU - Gallagher, John Christopher G.

AU - Dalsky, Gail P.

AU - Marcus, Robert

AU - Eriksen, Erik Fink

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AB - Transiliac bone biopsies were obtained front 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.

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