The United States of Pharma is a strange place where companies can take lab discoveries that seem simple and really screw real people up. Today’s entry is a drug called Prolia that I have encountered before. When I looked it up back then, I was astounded and disturbed at how this drug worked. Now it looks like I was right: this stuff is bad news.
Prolia (denosumab) is a drug for osteoporosis that works by blocking a receptor ligand called RANKL. It was approved in 2010 by the FDA with much fanfare because it’s a monoclonal antibody that targets the “key” (RNKL) that fits into the receptor “lock” (RANK). When the body inserts the RANKL keys into the RANK locks on the cells that break down bone (osteoclasts), they can’t perform their job. Hence, the cells that break down bone are inactivated, and thus bone density increases because there is less bone breakdown. Simple, right? Not so fast…
It turns out that the RANK receptor lives on lots of cell types, including skeletal muscle, liver, colon, small intestine, adrenal gland, bone, breast glands, skin cells, prostate, and pancreas! Hence, injecting an antibody to deactivate the RANK receptors on all of these cells just sounds like a really bad idea. In addition, the RANK receptor also plays a role in immunity!
About a year ago, I had a patient on Prolia who had been having good results managing her severe ankle arthritis by going to our licensed advanced stem cell site in Grand Cayman. She was coming down for another treatment and had been placed on Prolia for osteoporosis. I looked it up and soon learned that the RANK receptor also lived on mesenchymal stem cells (MSCs). I had misgivings about how it could impact her stem cells, so I told her to get off it. Despite getting off it, the Cayman lab was unable to grow her stem cells that trip when they had no issues before. We eventually did get her cells to culture after more time had passed since discontinuing the drug.
The new research concerns the cases of nine women who had taken Prolia and then stopped the drug. They then had between them some 50 vertebral fractures in short order that the paper blamed on a rebound effect from the drug. Yikes!
Why could this be happening? We saw that the drug didn’t do great things to bone marrow stem cells. Hence, it’s possible that in addition to turning off the cells that break down bone, it may also be hurting the cells that create the cells that make bone (mesenchymal stem cells).
The upshot? There is no cell-surface-receptor free lunch! If you break one thing in the body, it usually has many workarounds. So antibodies that target receptors on many cells are a really dumb idea. As far as Prolia is concerned, how did this stuff get approved? In the meantime, if you’re on Prolia, definitely consult your physician before getting off.
About the Author
Christopher J. Centeno, M.D. is an international expert and specialist in regenerative medicine and the clinical use of mesenchymal stem cells in orthopedics. He is board certified in physical medicine as well as rehabilitation and in pain management through The American Board of Physical Medicine and Rehabilitation.…