Early changes in biochemical markers of bone formation correlate with improvements in bone structure during teriparatide therapy

Harald Dobnig, Adrien Sipos, Yebin Jiang, Astrid Fahrleitner-Pammer, Louis Georges Ste-Marie, John Christopher G. Gallagher, Imre Pavo, Jingyuan Wang, Erik F. Eriksen

Research output: Contribution to journalArticle

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Abstract

Context: Biochemical markers of bone turnover may reflect bone structure during anabolic treatment. Objective: The objective was to evaluate associations between changes in biochemical markers and structural and dynamic bone parameters during teriparatide treatment. Design: This study was a randomized, multicenter, double-blind, placebo-controlled fracture prevention trial, with 20-month median treatment duration for biopsy subset. Setting: The trial was conducted at 11 clinical study sites. Patients: Sixty-one postmenopausal women with osteoporosis who had paired transiliac biopsy specimens participated in the study. Interventions: Once-daily sc injections of either placebo or teriparatide (20 or 40 μg) were administered. Main outcome measures: The study measured: 1) serum and urinary biochemical markers of bone formation [bone alkaline phosphatase and procollagen I C-terminal propeptide (PICP)] and resorption (N-telopeptide and deoxypyridinoline); and 2) structural and dynamic analyses of bone biopsies, including two-dimensional (2D) histomorphometry and three-dimensional (3D) micro-computed tomography evaluations measured at baseline (n = 57) and 12 (n = 21) or 22 (n = 36) months. Results: U-N-telopeptide/creatinine and serum-PICP correlated with bone structure and dynamic indices at baseline, respectively. Changes in bone alkaline phosphatase at 1 month correlated with changes at 22 months in 2D wall thickness (r = 0.73; P = 0.001), trabecular bone volume (trabecular bone volume per total volume, BV/TV) (r = 0.58; P <0.05), marrow star volume (r = -0.51; P = 0.05); 3D trabecular thickness (r = 0.49; P <0.05), and BV/TV (r = 0.54; P <0.05). Changes in PICP at 1 month correlated with changes in wall thickness (r = 0.60; P = 0.01), and 2D BV/TV (r = 0.51; P <0.05) at 22 months. Changes in markers at 6 or 12 months were not associated with changes in structural or dynamic parameters. Conclusions: Early (1-month) changes in biochemical markers of bone formation, but not resorption, correlated with improvements in bone structure after 22 months of teriparatide therapy.

Original languageEnglish
Pages (from-to)3970-3977
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume90
Issue number7
DOIs
StatePublished - Jul 2005

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Teriparatide
Osteogenesis
Bone
Biomarkers
Bone and Bones
Therapeutics
Biopsy
Alkaline Phosphatase
Placebos
Bone Remodeling
Serum
Osteoporosis
Creatinine
Bone Marrow
Tomography
Outcome Assessment (Health Care)

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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Early changes in biochemical markers of bone formation correlate with improvements in bone structure during teriparatide therapy. / Dobnig, Harald; Sipos, Adrien; Jiang, Yebin; Fahrleitner-Pammer, Astrid; Ste-Marie, Louis Georges; Gallagher, John Christopher G.; Pavo, Imre; Wang, Jingyuan; Eriksen, Erik F.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 90, No. 7, 07.2005, p. 3970-3977.

Research output: Contribution to journalArticle

Dobnig, Harald ; Sipos, Adrien ; Jiang, Yebin ; Fahrleitner-Pammer, Astrid ; Ste-Marie, Louis Georges ; Gallagher, John Christopher G. ; Pavo, Imre ; Wang, Jingyuan ; Eriksen, Erik F. / Early changes in biochemical markers of bone formation correlate with improvements in bone structure during teriparatide therapy. In: Journal of Clinical Endocrinology and Metabolism. 2005 ; Vol. 90, No. 7. pp. 3970-3977.
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title = "Early changes in biochemical markers of bone formation correlate with improvements in bone structure during teriparatide therapy",
abstract = "Context: Biochemical markers of bone turnover may reflect bone structure during anabolic treatment. Objective: The objective was to evaluate associations between changes in biochemical markers and structural and dynamic bone parameters during teriparatide treatment. Design: This study was a randomized, multicenter, double-blind, placebo-controlled fracture prevention trial, with 20-month median treatment duration for biopsy subset. Setting: The trial was conducted at 11 clinical study sites. Patients: Sixty-one postmenopausal women with osteoporosis who had paired transiliac biopsy specimens participated in the study. Interventions: Once-daily sc injections of either placebo or teriparatide (20 or 40 μg) were administered. Main outcome measures: The study measured: 1) serum and urinary biochemical markers of bone formation [bone alkaline phosphatase and procollagen I C-terminal propeptide (PICP)] and resorption (N-telopeptide and deoxypyridinoline); and 2) structural and dynamic analyses of bone biopsies, including two-dimensional (2D) histomorphometry and three-dimensional (3D) micro-computed tomography evaluations measured at baseline (n = 57) and 12 (n = 21) or 22 (n = 36) months. Results: U-N-telopeptide/creatinine and serum-PICP correlated with bone structure and dynamic indices at baseline, respectively. Changes in bone alkaline phosphatase at 1 month correlated with changes at 22 months in 2D wall thickness (r = 0.73; P = 0.001), trabecular bone volume (trabecular bone volume per total volume, BV/TV) (r = 0.58; P <0.05), marrow star volume (r = -0.51; P = 0.05); 3D trabecular thickness (r = 0.49; P <0.05), and BV/TV (r = 0.54; P <0.05). Changes in PICP at 1 month correlated with changes in wall thickness (r = 0.60; P = 0.01), and 2D BV/TV (r = 0.51; P <0.05) at 22 months. Changes in markers at 6 or 12 months were not associated with changes in structural or dynamic parameters. Conclusions: Early (1-month) changes in biochemical markers of bone formation, but not resorption, correlated with improvements in bone structure after 22 months of teriparatide therapy.",
author = "Harald Dobnig and Adrien Sipos and Yebin Jiang and Astrid Fahrleitner-Pammer and Ste-Marie, {Louis Georges} and Gallagher, {John Christopher G.} and Imre Pavo and Jingyuan Wang and Eriksen, {Erik F.}",
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T1 - Early changes in biochemical markers of bone formation correlate with improvements in bone structure during teriparatide therapy

AU - Dobnig, Harald

AU - Sipos, Adrien

AU - Jiang, Yebin

AU - Fahrleitner-Pammer, Astrid

AU - Ste-Marie, Louis Georges

AU - Gallagher, John Christopher G.

AU - Pavo, Imre

AU - Wang, Jingyuan

AU - Eriksen, Erik F.

PY - 2005/7

Y1 - 2005/7

N2 - Context: Biochemical markers of bone turnover may reflect bone structure during anabolic treatment. Objective: The objective was to evaluate associations between changes in biochemical markers and structural and dynamic bone parameters during teriparatide treatment. Design: This study was a randomized, multicenter, double-blind, placebo-controlled fracture prevention trial, with 20-month median treatment duration for biopsy subset. Setting: The trial was conducted at 11 clinical study sites. Patients: Sixty-one postmenopausal women with osteoporosis who had paired transiliac biopsy specimens participated in the study. Interventions: Once-daily sc injections of either placebo or teriparatide (20 or 40 μg) were administered. Main outcome measures: The study measured: 1) serum and urinary biochemical markers of bone formation [bone alkaline phosphatase and procollagen I C-terminal propeptide (PICP)] and resorption (N-telopeptide and deoxypyridinoline); and 2) structural and dynamic analyses of bone biopsies, including two-dimensional (2D) histomorphometry and three-dimensional (3D) micro-computed tomography evaluations measured at baseline (n = 57) and 12 (n = 21) or 22 (n = 36) months. Results: U-N-telopeptide/creatinine and serum-PICP correlated with bone structure and dynamic indices at baseline, respectively. Changes in bone alkaline phosphatase at 1 month correlated with changes at 22 months in 2D wall thickness (r = 0.73; P = 0.001), trabecular bone volume (trabecular bone volume per total volume, BV/TV) (r = 0.58; P <0.05), marrow star volume (r = -0.51; P = 0.05); 3D trabecular thickness (r = 0.49; P <0.05), and BV/TV (r = 0.54; P <0.05). Changes in PICP at 1 month correlated with changes in wall thickness (r = 0.60; P = 0.01), and 2D BV/TV (r = 0.51; P <0.05) at 22 months. Changes in markers at 6 or 12 months were not associated with changes in structural or dynamic parameters. Conclusions: Early (1-month) changes in biochemical markers of bone formation, but not resorption, correlated with improvements in bone structure after 22 months of teriparatide therapy.

AB - Context: Biochemical markers of bone turnover may reflect bone structure during anabolic treatment. Objective: The objective was to evaluate associations between changes in biochemical markers and structural and dynamic bone parameters during teriparatide treatment. Design: This study was a randomized, multicenter, double-blind, placebo-controlled fracture prevention trial, with 20-month median treatment duration for biopsy subset. Setting: The trial was conducted at 11 clinical study sites. Patients: Sixty-one postmenopausal women with osteoporosis who had paired transiliac biopsy specimens participated in the study. Interventions: Once-daily sc injections of either placebo or teriparatide (20 or 40 μg) were administered. Main outcome measures: The study measured: 1) serum and urinary biochemical markers of bone formation [bone alkaline phosphatase and procollagen I C-terminal propeptide (PICP)] and resorption (N-telopeptide and deoxypyridinoline); and 2) structural and dynamic analyses of bone biopsies, including two-dimensional (2D) histomorphometry and three-dimensional (3D) micro-computed tomography evaluations measured at baseline (n = 57) and 12 (n = 21) or 22 (n = 36) months. Results: U-N-telopeptide/creatinine and serum-PICP correlated with bone structure and dynamic indices at baseline, respectively. Changes in bone alkaline phosphatase at 1 month correlated with changes at 22 months in 2D wall thickness (r = 0.73; P = 0.001), trabecular bone volume (trabecular bone volume per total volume, BV/TV) (r = 0.58; P <0.05), marrow star volume (r = -0.51; P = 0.05); 3D trabecular thickness (r = 0.49; P <0.05), and BV/TV (r = 0.54; P <0.05). Changes in PICP at 1 month correlated with changes in wall thickness (r = 0.60; P = 0.01), and 2D BV/TV (r = 0.51; P <0.05) at 22 months. Changes in markers at 6 or 12 months were not associated with changes in structural or dynamic parameters. Conclusions: Early (1-month) changes in biochemical markers of bone formation, but not resorption, correlated with improvements in bone structure after 22 months of teriparatide therapy.

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