Long-term risedronate treatment normalizes mineralization and continues to preserve trabecular architecture: Sequential triple biopsy studies with micro-computed tomography

B. Borah, T. E. Dufresne, E. L. Ritman, S. M. Jorgensen, S. Liu, P. A. Chmielewski, R. J. Phipps, Xiaojie Zhou, J. D. Sibonga, R. T. Turner

Research output: Contribution to journalArticle

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Abstract

The objective of the study was to assess the time course of changes in bone mineralization and architecture using sequential triple biopsies from women with postmenopausal osteoporosis (PMO) who received long-term treatment with risedronate. Transiliac biopsies were obtained from the same subjects (n = 7) at baseline and after 3 and 5 years of treatment with 5 mg daily risedronate. Mineralization was measured using 3-dimensional (3D) micro-computed tomography (CT) with synchrotron radiation and was compared to levels in healthy premenopausal women (n = 12). Compared to the untreated PMO women at baseline, the premenopausal women had higher average mineralization (Avg-MIN) and peak mineralization (Peak-MIN) by 5.8% (P = 0.003) and 8.0% (P = 0.003), respectively, and lower ratio of low to high-mineralized bone volume (BMR-V) and surface area (BMR-S) by 73.3% (P = 0.005) and 61.7% (P = 0.003), respectively. Relative to baseline, 3 years of risedronate treatment significantly increased Avg-MIN (4.9 ± 1.1%, P = 0.016) and Peak-MIN (6.2 ± 1.5%, P = 0.016), and significantly decreased BMR-V (-68.4 ± 7.3%, P = 0.016) and BMR-S (-50.2 ± 5.7%, P = 0.016) in the PMO women. The changes were maintained at the same level when treatment was continued up to 5 years. These results are consistent with the significant reduction of turnover observed after 3 years of treatment and which was similarly maintained through 5 years of treatment. Risedronate restored the degree of mineralization and the ratios of low- to high-mineralized bone to premenopausal levels after 3 years of treatment, suggesting that treatment reduced bone turnover in PMO women to healthy premenopausal levels. Conventional micro-CT analysis further demonstrated that bone volume (BV/TV) and trabecular architecture did not change from baseline up to 5 years of treatment, suggesting that risedronate provided long-term preservation of trabecular architecture in the PMO women. Overall, risedronate provided sustained benefits on mineralization and architecture, two key determinants of bone strength, over 5 years lending support for its long-term efficacy in fracture risk reduction.

Original languageEnglish (US)
Pages (from-to)345-352
Number of pages8
JournalBone
Volume39
Issue number2
DOIs
StatePublished - Aug 2006

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Tomography
Postmenopausal Osteoporosis
Biopsy
Bone and Bones
Therapeutics
Risedronate Sodium
Physiologic Calcification
Fracture Fixation
Synchrotrons
Bone Remodeling
Risk Reduction Behavior
Radiation

Keywords

  • Architecture
  • Bone turnover
  • Mineralization
  • Osteoporosis
  • Risedronate

ASJC Scopus subject areas

  • Physiology
  • Hematology

Cite this

Long-term risedronate treatment normalizes mineralization and continues to preserve trabecular architecture : Sequential triple biopsy studies with micro-computed tomography. / Borah, B.; Dufresne, T. E.; Ritman, E. L.; Jorgensen, S. M.; Liu, S.; Chmielewski, P. A.; Phipps, R. J.; Zhou, Xiaojie; Sibonga, J. D.; Turner, R. T.

In: Bone, Vol. 39, No. 2, 08.2006, p. 345-352.

Research output: Contribution to journalArticle

Borah, B, Dufresne, TE, Ritman, EL, Jorgensen, SM, Liu, S, Chmielewski, PA, Phipps, RJ, Zhou, X, Sibonga, JD & Turner, RT 2006, 'Long-term risedronate treatment normalizes mineralization and continues to preserve trabecular architecture: Sequential triple biopsy studies with micro-computed tomography', Bone, vol. 39, no. 2, pp. 345-352. https://doi.org/10.1016/j.bone.2006.01.161
Borah, B. ; Dufresne, T. E. ; Ritman, E. L. ; Jorgensen, S. M. ; Liu, S. ; Chmielewski, P. A. ; Phipps, R. J. ; Zhou, Xiaojie ; Sibonga, J. D. ; Turner, R. T. / Long-term risedronate treatment normalizes mineralization and continues to preserve trabecular architecture : Sequential triple biopsy studies with micro-computed tomography. In: Bone. 2006 ; Vol. 39, No. 2. pp. 345-352.
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AU - Ritman, E. L.

AU - Jorgensen, S. M.

AU - Liu, S.

AU - Chmielewski, P. A.

AU - Phipps, R. J.

AU - Zhou, Xiaojie

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AU - Turner, R. T.

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N2 - The objective of the study was to assess the time course of changes in bone mineralization and architecture using sequential triple biopsies from women with postmenopausal osteoporosis (PMO) who received long-term treatment with risedronate. Transiliac biopsies were obtained from the same subjects (n = 7) at baseline and after 3 and 5 years of treatment with 5 mg daily risedronate. Mineralization was measured using 3-dimensional (3D) micro-computed tomography (CT) with synchrotron radiation and was compared to levels in healthy premenopausal women (n = 12). Compared to the untreated PMO women at baseline, the premenopausal women had higher average mineralization (Avg-MIN) and peak mineralization (Peak-MIN) by 5.8% (P = 0.003) and 8.0% (P = 0.003), respectively, and lower ratio of low to high-mineralized bone volume (BMR-V) and surface area (BMR-S) by 73.3% (P = 0.005) and 61.7% (P = 0.003), respectively. Relative to baseline, 3 years of risedronate treatment significantly increased Avg-MIN (4.9 ± 1.1%, P = 0.016) and Peak-MIN (6.2 ± 1.5%, P = 0.016), and significantly decreased BMR-V (-68.4 ± 7.3%, P = 0.016) and BMR-S (-50.2 ± 5.7%, P = 0.016) in the PMO women. The changes were maintained at the same level when treatment was continued up to 5 years. These results are consistent with the significant reduction of turnover observed after 3 years of treatment and which was similarly maintained through 5 years of treatment. Risedronate restored the degree of mineralization and the ratios of low- to high-mineralized bone to premenopausal levels after 3 years of treatment, suggesting that treatment reduced bone turnover in PMO women to healthy premenopausal levels. Conventional micro-CT analysis further demonstrated that bone volume (BV/TV) and trabecular architecture did not change from baseline up to 5 years of treatment, suggesting that risedronate provided long-term preservation of trabecular architecture in the PMO women. Overall, risedronate provided sustained benefits on mineralization and architecture, two key determinants of bone strength, over 5 years lending support for its long-term efficacy in fracture risk reduction.

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KW - Bone turnover

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KW - Osteoporosis

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