Open AccessMathematical modeling of the effects of CK2.3 on mineralization in osteoporotic bone
Author(s) -
Lisberg A,
Ellis R,
Nicholson K,
Moku P,
Swarup A,
Dhurjati P,
Nohe A
Publication year - 2017
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1002/psp4.12154
Subject(s) - osteoporosis , mineralization (soil science) , physiologically based pharmacokinetic modelling , bone mineral , bone morphogenetic protein 2 , medicine , bone formation , chemistry , endocrinology , bone morphogenetic protein , pharmacokinetics , biochemistry , in vitro , gene , organic chemistry , nitrogen
Osteoporosis is caused by decreased bone mineral density (BMD) and new treatments for this disease are desperately needed. Bone morphogenetic protein 2 (BMP2) is crucial for bone formation. The mimetic peptide CK2.3 acts downstream of BMP2 and increases BMD when injected systemically into the tail vein of mice. However, the most effective dosage needed to induce BMD in humans is unknown. We developed a mathematical model for CK2.3‐dependent bone mineralization. We used a physiologically based pharmacokinetic (PBPK) model to derive the CK2.3 concentration needed to increase BMD. Based on our results, the ideal dose of CK2.3 for a healthy individual to achieve the maximum increase of mineralization was about 409 µM injected in 500 µL volume, while dosage for osteoporosis patients was about 990 µM. This model showed that CK2.3 could increase the average area of bone mineralization in patients and in healthy adults.