Dear Debbie -
The worst of my pain used to be the sensation that my feet were participating in a crucifixion: that spikes were being driven through the front of my feet, breaking apart the ankle joints. The Zometa (zoledronic acid) infusions, a "3rd generation" biphosphonate, entered my life and that all went away.
There have already been a few threads in this forum on biphosphonates in the treatment of CRPS. See, Biphosphonate infusion for RSD? (the FDA approved U.S. prescribing information sheet for Zometa is attached to my post # 4)
http://neurotalk.psychcentral.com/sh...eta#post663177 and concern noted re long-term use of bisphosphonates, unclear what patients at risk
http://neurotalk.psychcentral.com/sh...ghlight=Zometa
I will not repeat here a recitation of the studies on biphosphonates and CRPS that were included in the prior posts.
The whole class of biphosphonates was initially developed to treat multiple myeloma, by inhibiting the uptake of bone material into the blood stream that, if left unchecked, would contribute to kidney failure in short order. But what I really hadn’t focused on until now was the specific mechanism of action, which is interesting.
Essentially, our bone mass is kept in balance by two types of cells. Osteoblasts, which are responsible for bone formation
http://en.wikipedia.org/wiki/Osteoblast and osteoclasts, that removes bone tissue by attacking its mineralized matrix and breaking up the organic bone, a process that is known as bone resorption.
http://en.wikipedia.org/wiki/Osteoclast As the osteoclasts “digest” the mineralized portion of the matrix, calcium and phosphate ions are absorbed into the cells and eventually are released into the extracellular fluid, and from there into the blood.
While the mechanism of biphosphonates is not entirely known, Zometa is thought to inhibit osteoclastic activity in two ways. First, through a process called
apoptosis, aka programmed cell death, it actually kills osteoclasts through the fragmentation of its nuclear DNA. Secondly, it appears that Zometa also blocks bone resorption by binding directly to the bone surface.
Two quick observations. Biphosphonates entered the world of RSD patients the same way as (since discontinued for our purposes) Thalidomide: they were being given as treatments to multiple myeloma (MM) patients who happened to also have RSD, when it was anecdotally noted that a number of these patients saw their RSD suddenly improve. Now, at a personal level, a careful review of my blood work – beginning about 2 years into my CRPS/RSD – revealed an abnormal protein spike that was later diagnosed as Monoclonal Gammopathy of Uncertain Significance (MGUS), a necessary but not necessarily a sufficient condition for subsequently developing MM, with an average annual risk of “progressing” of 1%. With that background, I couldn't help but wonder if it was purely a coincidence that there was something of a stock of “co-morbid” RSD/MM patients, in whom doctors could see the effects of their MM medications. That said, in discussing this with my hematologist, it's clear that a basic understanding of some of this stuff is going to be beyond me, and the best I can do is hope that someone can clearly show whether we can in fact connect the dots, and then is able to get the results published, especially if the question of any relationship between the two conditions is answered in the negative.
Second point, as soon as the osteoporosis community – and those concerned about acquiring osteoporosis - heard about biphosphonates, they ran with it, and in large numbers. Hence when some unexplained thigh fractures started showing up, it concerned a great many people, leading to the most carefully couched “black box” warning I have ever seen.
http://www.nlm.nih.gov/medlineplus/d...s/a605023.html
Now, the stuff has some known toxicity issues, but its pretty clear that much of the fear, especially that it would lead to thigh bone fractures has not been supported by recent studies. But one thing is clear, PEOPLE IN NEED OF SIGNIFICANT DENTAL WORK, E.G. TOOTH EXTRACTIONS, ROOT CANAL, ETC., OR WITH ANY RENAL (KIDNEY) IMPAIRMENT CANNOT USE ZOMETA. By example, the first time I got an infusion, my pain mgt. doctor required a "dental clearance" letter from my dentist, that I was in overall good dental health: the downside being a charming condition called "jaw necrosis," which is just what it sounds like. Similarly, unless your kidneys are in good shape, it can cause some real damage. As such, for each and every infusion - which I now need only once a year or so - I have to have a metabolic panel drawn not more than 10 days before the scheduled infusion, and if there would be any significant elevation in my creatinine level, there would be no infusion.
And as far as the risk of fractures is concerned, that may be best answered by a recent epidemiological study out of Australia, which showed that as the number of prescriptions for biphosphonates in the Australian Capital Territory (Canberra) dropped by 14% between 2007 and 2008, in response to concerns about fractures, the level of hip fractures rose significantly! Bisphosphonate use and hip fracture epidemiology: ecologic proof from the contrary, Alex Fisher, Jodie Martin, Wichat Srikusalanukul, Michael Davis,
Clinical Interventions in Aging, November 2010 , Volume 2010:5 Pages 355 - 362, ONLINE TEXT @
https://www.dovepress.com/getfile.php?fileID=8159
Bottom line: unless you know you would be excluded due to dental or renal issues, I think it’s certainly worth discussing Zometa infusions with your physicians.
Mike