Modeling and simulation of bone mineral density in Japanese osteoporosis patients treated with zoledronic acid using tartrate-resistant acid phosphatase 5b, a bone resorption marker

Y. Mori, H. Kasai, A. Ose, M. Serada, M. Ishiguro, M. Shiraki, Yusuke Tanigawara

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Summary: Annual intravenous administration of zoledronic acid is used in the treatment of osteoporosis. A mathematical model was developed to predict bone mineral density up to 2 years after two annual doses of zoledronic acid from the early values of a bone resorption marker in osteoporosis patients. Introduction: The measurement of bone mineral density (BMD) has been used as a surrogate marker instead of the observation of incident fractures to detect the efficacy of treatment. However, this method requires a long time to obtain significant changes. On the other hand, bone resorption markers respond to bone resorption inhibitors within a few weeks. Therefore, the aim of this study was to develop a mathematical model predicting long-term BMD after two annual doses of zoledronic acid (ZOL) using the early response of a bone resorption marker in osteoporosis patients. Methods: The model was constructed using 3410 tartrate-resistant acid phosphatase 5b (TRACP-5b) serum concentrations and 1146 lumbar spine (L2-L4) BMD values from 306 patients with primary osteoporosis. A mathematical model was developed to describe the time-dependent profiles of TRACP-5b and BMD. Results: The percentage changes from baseline of the BMD (%BMD) at up to 2 years were predicted from patients’ baseline BMD and baseline and 12-week TRACP-5b values by the model obtained. The simulated 90% prediction interval almost covered the observed %BMD distribution at each time point, and the predictions were comparable to the observed %BMD. Conclusions: This is the first model to predict BMD for up to 2 years following two annual doses of ZOL using patients’ background characteristics and the early response of TRACP-5b. This model allows us to inform patients at the initial stage of ZOL treatment of their predicted response to treatment.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalOsteoporosis International
DOIs
Publication statusAccepted/In press - 2018 Feb 8

Fingerprint

zoledronic acid
Bone Resorption
Bone Density
Osteoporosis
Theoretical Models
Tartrate-Resistant Acid Phosphatase
Hand Bones
Bone Density Conservation Agents

Keywords

  • Bone mineral density
  • Bone resorption marker
  • Modeling and simulation
  • Osteoporosis
  • Tartrate-resistant acid phosphatase 5b (TRACP-5b)
  • Zoledronic acid

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

@article{a82e9c6b8f174368b13319e34f97bd45,
title = "Modeling and simulation of bone mineral density in Japanese osteoporosis patients treated with zoledronic acid using tartrate-resistant acid phosphatase 5b, a bone resorption marker",
abstract = "Summary: Annual intravenous administration of zoledronic acid is used in the treatment of osteoporosis. A mathematical model was developed to predict bone mineral density up to 2 years after two annual doses of zoledronic acid from the early values of a bone resorption marker in osteoporosis patients. Introduction: The measurement of bone mineral density (BMD) has been used as a surrogate marker instead of the observation of incident fractures to detect the efficacy of treatment. However, this method requires a long time to obtain significant changes. On the other hand, bone resorption markers respond to bone resorption inhibitors within a few weeks. Therefore, the aim of this study was to develop a mathematical model predicting long-term BMD after two annual doses of zoledronic acid (ZOL) using the early response of a bone resorption marker in osteoporosis patients. Methods: The model was constructed using 3410 tartrate-resistant acid phosphatase 5b (TRACP-5b) serum concentrations and 1146 lumbar spine (L2-L4) BMD values from 306 patients with primary osteoporosis. A mathematical model was developed to describe the time-dependent profiles of TRACP-5b and BMD. Results: The percentage changes from baseline of the BMD ({\%}BMD) at up to 2 years were predicted from patients’ baseline BMD and baseline and 12-week TRACP-5b values by the model obtained. The simulated 90{\%} prediction interval almost covered the observed {\%}BMD distribution at each time point, and the predictions were comparable to the observed {\%}BMD. Conclusions: This is the first model to predict BMD for up to 2 years following two annual doses of ZOL using patients’ background characteristics and the early response of TRACP-5b. This model allows us to inform patients at the initial stage of ZOL treatment of their predicted response to treatment.",
keywords = "Bone mineral density, Bone resorption marker, Modeling and simulation, Osteoporosis, Tartrate-resistant acid phosphatase 5b (TRACP-5b), Zoledronic acid",
author = "Y. Mori and H. Kasai and A. Ose and M. Serada and M. Ishiguro and M. Shiraki and Yusuke Tanigawara",
year = "2018",
month = "2",
day = "8",
doi = "10.1007/s00198-018-4376-1",
language = "English",
pages = "1--9",
journal = "Osteoporosis International",
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T1 - Modeling and simulation of bone mineral density in Japanese osteoporosis patients treated with zoledronic acid using tartrate-resistant acid phosphatase 5b, a bone resorption marker

AU - Mori, Y.

AU - Kasai, H.

AU - Ose, A.

AU - Serada, M.

AU - Ishiguro, M.

AU - Shiraki, M.

AU - Tanigawara, Yusuke

PY - 2018/2/8

Y1 - 2018/2/8

N2 - Summary: Annual intravenous administration of zoledronic acid is used in the treatment of osteoporosis. A mathematical model was developed to predict bone mineral density up to 2 years after two annual doses of zoledronic acid from the early values of a bone resorption marker in osteoporosis patients. Introduction: The measurement of bone mineral density (BMD) has been used as a surrogate marker instead of the observation of incident fractures to detect the efficacy of treatment. However, this method requires a long time to obtain significant changes. On the other hand, bone resorption markers respond to bone resorption inhibitors within a few weeks. Therefore, the aim of this study was to develop a mathematical model predicting long-term BMD after two annual doses of zoledronic acid (ZOL) using the early response of a bone resorption marker in osteoporosis patients. Methods: The model was constructed using 3410 tartrate-resistant acid phosphatase 5b (TRACP-5b) serum concentrations and 1146 lumbar spine (L2-L4) BMD values from 306 patients with primary osteoporosis. A mathematical model was developed to describe the time-dependent profiles of TRACP-5b and BMD. Results: The percentage changes from baseline of the BMD (%BMD) at up to 2 years were predicted from patients’ baseline BMD and baseline and 12-week TRACP-5b values by the model obtained. The simulated 90% prediction interval almost covered the observed %BMD distribution at each time point, and the predictions were comparable to the observed %BMD. Conclusions: This is the first model to predict BMD for up to 2 years following two annual doses of ZOL using patients’ background characteristics and the early response of TRACP-5b. This model allows us to inform patients at the initial stage of ZOL treatment of their predicted response to treatment.

AB - Summary: Annual intravenous administration of zoledronic acid is used in the treatment of osteoporosis. A mathematical model was developed to predict bone mineral density up to 2 years after two annual doses of zoledronic acid from the early values of a bone resorption marker in osteoporosis patients. Introduction: The measurement of bone mineral density (BMD) has been used as a surrogate marker instead of the observation of incident fractures to detect the efficacy of treatment. However, this method requires a long time to obtain significant changes. On the other hand, bone resorption markers respond to bone resorption inhibitors within a few weeks. Therefore, the aim of this study was to develop a mathematical model predicting long-term BMD after two annual doses of zoledronic acid (ZOL) using the early response of a bone resorption marker in osteoporosis patients. Methods: The model was constructed using 3410 tartrate-resistant acid phosphatase 5b (TRACP-5b) serum concentrations and 1146 lumbar spine (L2-L4) BMD values from 306 patients with primary osteoporosis. A mathematical model was developed to describe the time-dependent profiles of TRACP-5b and BMD. Results: The percentage changes from baseline of the BMD (%BMD) at up to 2 years were predicted from patients’ baseline BMD and baseline and 12-week TRACP-5b values by the model obtained. The simulated 90% prediction interval almost covered the observed %BMD distribution at each time point, and the predictions were comparable to the observed %BMD. Conclusions: This is the first model to predict BMD for up to 2 years following two annual doses of ZOL using patients’ background characteristics and the early response of TRACP-5b. This model allows us to inform patients at the initial stage of ZOL treatment of their predicted response to treatment.

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KW - Bone resorption marker

KW - Modeling and simulation

KW - Osteoporosis

KW - Tartrate-resistant acid phosphatase 5b (TRACP-5b)

KW - Zoledronic acid

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