Which characteristic most strongly limits distribution of a drug into bone tissue?

• A. Low perfusion and a dense bone matrix requiring diffusion and binding
• B. High perfusion of bone
• C. Dense hydroxyapatite matrix increasing diffusion
• D. Small molecular weight only

Answer: (C)

Bone distribution is governed by how easily a drug can move through the mineralized matrix and how strongly it binds to this matrix. The bone matrix is dense and rich in hydroxyapatite, which creates a tight diffusion barrier. Drugs must diffuse through this mineralized network and then often bind to hydroxyapatite, which reduces the amount that can diffuse deeper and can trap the drug for extended periods. Because of this diffusion barrier and binding, the hydroxyapatite-rich matrix is the main factor that limits how widely and quickly a drug distributes into bone tissue. (Perfusion and molecular size matter too, but the dense matrix is the dominant limiter of bone distribution.)