The present disclosure is directed to protocells or nanoparticles, which are optionally coated with a lipid bilayer, which can be used for targeting bone tissue for the delivery of bioactive agents useful in the treatment and/or diagnosis of bone cancer, often metastatic bone cancer which often occurs secondary to a primary cancer such as prostate cancer, breast cancer, lung cancer and ovarian cancer, among numerous others. These protocells or nanoparticles target bone cancer especially metastatic bone cancer with bioactive agents including anticancer agents and/or diagnostic agents for purposes of treating, diagnosing and/or monitoring the therapy of the bone cancer. Osteotropic protocells or nanoparticles, pharmaceutical compositions comprising a population of osteotropic protocells or nanoparticles and methods of diagnosing, treating and/or monitoring therapy of bone cancer are representative aspects.