Pamidronate decreases tumor-induced osteoclastogenesis in osteopetrotic mice.

Recent studies indicate that the bisphosphonate pamidronate reduces skeletal complications caused by tumor osteolysis. In this investigation, the cellular mechanism through which pamidronate affects tumor-induced osteoclastogenesis is studied in osteopetrotic mice. A unique animal model is employed which studies the effect of pamidronate on a tumor (2472 sarcoma) which induces osteoclastogenesis in osteoclast-deficient mice (oplop). This model provides opportunity to specifically study effects on osteoclast formation and findings suggest that pamidronate decreases the number of osteoclasts at sites of 2472 tumor by decreasing the number of osteoclast precursor cells at the level of myeloid precursors.

Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord.

Bone cancer pain is common among cancer patients and can have a devastating effect on their quality of life. A chief problem in designing new therapies for bone cancer pain is that it is unclear what mechanisms drive this distinct pain condition. Here we show that osteoprotegerin, a secreted 'decoy' receptor that inhibits osteoclast activity, also blocks behaviors indicative of pain in mice with bone cancer. A substantial part of the actions of osteoprotegerin seems to result from inhibition of tumor-induced bone destruction that in turn inhibits the neurochemical changes in the spinal cord that are thought to be involved in the generation and maintenance of cancer pain. These results demonstrate that excessive tumor-induced bone destruction is involved in the generation of bone cancer pain and that osteoprotegerin may provide an effective treatment for this common human condition.