Bone biology and physiology: implications for novel osteoblastic osteosarcoma treatments?

Healthy bone undergoes a continuous cycle of bone resorption by osteoclasts and formation by osteoblasts. These processes are in turn regulated by developmental sequences involved in differentiation of bone marrow puripotent mesenchymal cells into osteoblasts and mononuclear hemaotpoitic stem cells into osteoclasts. A variety of growth factors and receptors are involved in these maturation sequences. Osteoblast proliferation and inhibition, for example, are highly dependent not only on such factors as bone morphogenic protein and core binding factor a1 (CBFa1), but on intracellular levels of calcium and cAMP. Therefore, agents that affect concentrations of these two compounds may hypothetically play a role in osteoblastic osteosarcoma treatment. Osteoblast proliferation is also under neural control; in particular, the activity of the N-methyl-d-aspartate (NMDA) and alpha adrenergic 1 receptors. Antagonists to these receptors may also hypothetically play a role in osteoblastic osteosarcoma therapy. This article reviews the basic science supporting the putative roles of common, relatively safe but disparate agents-ranging from caffeine and theophylline to dextromethorphan and econazole-in the potential treatment of osteoblastic osteosarcoma.