Multiple myeloma is one of the most painful and debilitating cancers, arising from cancerous plasma cells in the bone marrow. These cells alter the chemistry and signaling of the skeletal system's remodeling, and lytic bone lesions may form anywhere in the skeletal system. Other than aches and pains, there are very few initial symptoms of this cancer. The radiographic presence of lesions is a telltale sign of multiple myeloma, and because the dental office is the only place people routinely get x-rays taken, this cancer is often diagnosed by dentists. These lesions are the source of significant debilitation for affected patients, and so preventing them or lessening their severity would be an important step in both palliative and therapeutic care.
Recently, researchers published a study which detailed their investigation into potential ways of blocking this massive, lytic bone destruction. If light could be shed on this mechanism, perhaps this knowledge could be used to stop other cases of bone resorption, such as peri-implantitis and periodontitis.
Previous research indicated that an enzyme called thymidine phosphorylase was expressed in many kinds of cancer, including multiple myeloma. This enzyme promotes ingrowths of blood vessels to tumors, and inhibits self-destruction of cancerous cells. As it turns out, it is also a potent agent in the bio-signaling of bone remodeling. Thymidine phosphorylase initiates a chemical cascade that releases a molecule called 2DDR, which inhibits the bone-depositing osteoblasts. Osteoclasts are not as strongly affected by this signal, and continue to degrade bone. As the bone erodes, excess calcium leaches into the blood stream and can cause kidney failure, heart problems and neurological symptoms.
But is this the sole cause of the bone destruction? Researchers aimed to find out. Using mice injected with multiple myeloma cells, the team investigated the impact of blocking thymidine phosphorylase, and by extension its downstream products like 2DDR. They found that mice given the inhibitor suffered significantly less bone resorption than mice who were not, although they did not experience complete protection. This discovery excites cancer researchers, as it deprives the cancerous cells of blood flow, which may make them more vulnerable to other anti-cancer agents, while also preserving the patient's quality of life.
Dentists are also eagerly awaiting further research on this topic, as thymidine phosphorylase inhibition represents an exciting new method to prevent bone resorption, and could possibly be integrated into therapeutic treatments to encourage the success of bone grafts, implants, and complex oral surgeries.
Saey, T. H. (2016, August 24). Weapon of bone destruction identified. Cancer,Cells. Retrieved from https://www.sciencenews.org/article/weapon-bone-destruction-identified
MedScape (2016). Hypercalcaemia. In MedScape Clinical Reference.