TY - JOUR
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, Y.
N1 - Funding Information:
The authors would like to thank Rika Oishi and Satoshi Tanaka for their fruitful comments and suggestions and Risa Tanaka and Yuri Ota for their technical support. This study was conducted in compliance with the World Medical Association Declaration of Helsinki?Ethical Principles for Medical Research Involving Human Subjects and Good Clinical Practice. The protocol was approved by the institutional review board at each study site. Written, informed consent was obtained from all subjects before enrollment in the study.
PY - 2018/5/1
Y1 - 2018/5/1
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.
KW - Bone mineral density
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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U2 - 10.1007/s00198-018-4376-1
DO - 10.1007/s00198-018-4376-1
M3 - Article
C2 - 29423715
AN - SCOPUS:85041514404
VL - 29
SP - 1155
EP - 1163
JO - Osteoporosis International
JF - Osteoporosis International
SN - 0937-941X
IS - 5
ER -