Novel Therapies For Myeloma Bone Disease

by
Published: Jan 14, 2009 12:23 am

The majority of myeloma patients develop bone disease, which is caused by two main factors: stimulation of cells that break down bone and suppression of cells that make bone. Drugs that alter these processes have therapeutic potential for bone disease.

A biological pathway called RANKL is known to increase break down of bone. Scientists have developed an antibody called denosumab, which decreases bone destruction by blocking the RANKL pathway. One dose of denosumab reduces bone resorption for 90 days. Denosumab is currently in clinical trials; however, it is unclear whether it is effective in all myeloma patients.

Another novel therapy acts on a biological pathway that increases bone mass, called the Wnt signaling pathway. Studies have shown that an inhibitor of the pathway is found in excess in myeloma patients and is correlated to bone disease.

Researchers have been working to enhance the Wnt signaling pathway in order to increase bone formation.  They have also increased bone growth in mice by blocking chemicals that inhibit this pathway. Nonetheless, further studies are needed before these treatments can be tested in clinical trials, because Wnt signaling also promotes the growth of myeloma cells.

Several drugs approved to treat myeloma also effect myeloma bone disease. These agents include Velcade (bortezomib) and thalidomide (Thalomid) analogs.

Thalidomide and its analog, Actimid (CC-4047), have been shown to prevent bone resorption. Thalidomide in combination with dexamethasone has been shown to reduce the amount of bone breakdown for at least six months.

Another promising study showed that myeloma patients who took Velcade had a 25 percent increase in bone formation. Additionally, Velcade significantly increased bone nodule formation, an important step in the formation of new bone.

Scientists have also found that Velcade reduced the concentration of chemicals that inhibit bone formation and inhibited pathways like RANKL that cause bone to break down.

The majority of patients who showed a bone growth response to Velcade also showed an antitumor response to the drug.  Hence, it is still unclear if the results from Velcade are due to the drug alone or from the antitumor response.

For more information about bone disease, see the full article in the American Society of Hematology’s 2008 Education Program Book, Hematology, and related Beacon articles about the use of imaging and bisphosphonates for the treatment of myeloma bone disease.

Tags: , , , , ,

Related Articles: