Bisphosphonates beware. Now, I am not saying there isn’t a major place for these medications which reduce the breaking down of our bones, but for those who have used these for a long period of time, well, we just shouldn’t make any bones about it. In my case, and others, the long term use of these drugs cause more problems than the disease, itself.

Bisphosphonates come in many different forms, but the essential purpose is to reduce the generation of enzymes, called osteoclasts, which break down bones. For all of us with bone-involved myeloma, that is a good thing. Also, it seems that the myeloma cells grow when osteoclasts are more productive. It is like positive feedback, or a painful vicious cycle.  The myeloma generates more osteoclasts which help feed an increase in cancer cells, and those in turn, generate additional osteoclasts. And I noticed in my own diary that after three months of Aredia treatments in early 1997, my back was feeling much better. So bisphosphonates, such as Aredia and Zometa, would seem to be two wonderful drugs available to myeloma patients.

But as the years passed, other developing novel myeloma medications seemed to reduce my myeloma to next to nothing. First thalidomide, then revlimid, and over the past three years, revlimid and dexamethasone. My latest protein reading is between 0.5 and 0.9 – record low for me. Yet, the back pain returned and is at times severe, and I seem to continue shrinking. I call myself the incredible shrinking meteorologist. The attacks of pain have led my doctors to try additional therapies, and one of the thoughts by Dennis Cooper, my doctor at a Yale, was that the myeloma may not be responsible for all of this discomfort. Something else was going on.

I then undertook a series of test through the endocrinology department, and something real interesting soon surfaced. I had a very simple urine test which just required that I didn’t eat before it, and the lab came back with a report that showed no evidence of collagen. That chemical would be present if osteoclasts were generated and my bones were being dissolved. My treatment was working, but maybe, too well. Unfortuantely the suspicion by the doctors was that the bones were not building up, either – there was simply none of the normal turn over of bone. The osteoblasts which build up the bone were probably non-existent, too. My bones were frozen, some called it “frozen bone syndrome,” others, more scientifically, called it “adynamic bone.” Sure, tests showed no breaking down of the bone, but because none were building up or turning over, those bones could just shatter, and that is what has been happening.

What to do? Well, I took other tests to confirm the diagnosis. This was an invasive one, and required an biopsy of a small sample(about 1 cm.) of my hip. I debated going through the procedure. One who has so much trouble with bones really is not anxious to give up any, even if it is under a half inch. Also, the bone biopsy, not the common bone marrow biopsy,  required full sedation. It was a real operation. But I had to find out because I knew that so many other patients seem to have the same problem – reduced myeloma cells, but a modest to a high level of pain.

I went forward with it during the summer of 2005. The sample was sent to Johns Hopkins where there has been some pretty good experience with adynamic bone issues, and they came back with a mixed report. First, one of the doctors said to my Yale endocrinologist, “Are you sure this guy has cancer?” They could not find even a trace of myeloma cells in the bone, but then added, “He does have the worst case of adynamic bone that we have ever seen.”The suspicion was that the 9 years of taking aredia and then zometa have taken quite a toll by completely shutting down the normal bone turn over.

It was suggested that I take a sabbatical from bisphosphonates and see what happens. If my myeloma cells began to increase, then the suggestion was to gradually increase the bisphosphonate use, after all, those drugs do seem to have a positive effect on reducing the level of myeloma. Any increase in cancer cells is easy to monitor for most myeloma patients through a simple blood test. The doctors felt that it would take a year, or more, for these drugs to be flushed out of my system. That’s a long wait.

But now, approaching a year later, I find that my level of pain is the lowest it has been in the 10 years of my cancer diagnosis. I have never felt better. During this period, the protein level was reduced to its all-time low. Sometimes, it shows a very small increase, but there has been no trend in that direction. So, the elimination of Zometa and Aredia has not caused an increase in cancer, and perhaps for other reasons, my cancer level has reached record lows. Importantly, I even bought a Steinway piano – my dream that was definitely soft-pedalled in recent years because of back pain. Now I can play for as much as an hour at a time. One year ago, I couldn’t play for more than five minutes before excruciating pain developed.

Evidently, I am not the only person having problems with these bisphosphonates. In December, 2004, a group at the University of Texas, found that some patients who took Fosamax over a number of years for osteoporosis developed adynamic bone . The original write up of this can be found at:  http://jcem.endojournals.org/cgi/content/full/90/3/1294 . Also, myeloma patients have had documented instances of jaw problems, osteonecrosis of the jaw, which could lead to teeth falling out and serious infection. We are told to eliminate the use of Aredia or Zometa well in advance of any dental work. You can read more about it at: http://www.myeloma.org/main.jsp?type=article&tab_id=1&menu_id=0&id=1259 .