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.

Current methods for drug development and discovery involve pre-clinical analyses that are extremely expensive and time consuming. Animal models are not the best precedent to use, when comparing to human models as they are not synonymous with the human response, thus, alternative methods for drug development are needed. One of which could be the use of an ex vivo human organ where drugs could be tested and the effects of those drugs could be observed. Finding a viable human organ to use in these preliminary ex vivo studies is difficult due to the availability, cost, and viability. Bone tissue and marrow contain a plethora of both bone and stem cells, however, these cells need constant perfusion to be viable over a longer time range. Here we maintain bone cell sustainability in an ex vivo model, through the use of human femoral heads in a novel bioreactor. This bioreactor was designed to directly perfuse cell culture media (DMEM) through the vasculature of a femoral head, providing ideal nutrients and conditions required for maintaining organ viability. We show, for the first time, that cells within a femoral head can stay alive up to 12 h. Further development could be used to determine the effects of drugs on a human organ system and could aid in the understanding of the progression of bone diseases and pathologies.

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