Mathematical modeling of the effects of CK2.3 on mineralization in osteoporotic bone.
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.
Department of Biomedical Engineering, University of Delaware, Newark, Delaware, USA.
A
A
Lisberg
Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware, USA.
R
R
Ellis
Department of Mathematical Sciences, University of Delaware, Newark, Deleware, USA.
K
K
Nicholson
Department of Biological Sciences, University of Delaware, Newark, Delaware, USA.
P
P
Moku
Department of Biological Sciences, University of Delaware, Newark, Delaware, USA.
A
A
Swarup
Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware, USA.|Department of Mathematical Sciences, University of Delaware, Newark, Deleware, USA.|Department of Biological Sciences, University of Delaware, Newark, Delaware, USA.
P
P
Dhurjati
Department of Biomedical Engineering, University of Delaware, Newark, Delaware, USA.|Department of Biological Sciences, University of Delaware, Newark, Delaware, USA.
A
A
Nohe
D000328:Adult; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D006801:Humans; D008954:Models, Biological; D008962:Models, Theoretical; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage*; D016896:Treatment Outcome
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D010446:Peptide Fragments