In the "Spread Thread" the other day, I included the following information about Zometa, which can be linked to here: http://neurotalk.psychcentral.com/sh...t=24167&page=2 (There are a couple of articles attached to that post which are worth checking out.)

In conversation with Frogga on that thread, I made the point that it didn't work for me until the third monthly infusion, and that the drug is not for everyone, specifically for those needing significant dental work. However, response to her additional inquiries I have done some more work. Turns out that Zometa is in fact a new and improved pamidromate, approximately two to three times more effective than the original. That and the infusion time is a fraction of the original model:

Bisphosphonates

Bisphosphonates are analogues of inorganic pyrophosphate that inhibit osteoclast activity and, consequently, reduce bone resorption in a variety of illnesses. The analgesic efficacy of these compounds, particularly pamidronate (Aredia®; Novartis Pharmaceuticals Corp.), has been well established.

Pamidronate has been extensively studied in populations with bone metastases [108]. Its analgesic effects have been shown in breast cancer [109-111] and multiple myeloma [112]. The dose usually recommended is 60-90 mg i.v. (infused over 2-4 hours) every 3-4 weeks [111]. There are dose-dependent effects, and a poor response at 60 mg can be followed by a trial of 90 or 120 mg. The reduction of skeletal morbidity (pathological fractures, need for bone radiation or surgery, spinal cord compression, hypercalcemia)described with the administration of pamidronate in multiple myeloma and breast cancer patients is another incentive to use it as an adjuvant [113-114]. Adverse effects, including hypocalcemia and a flu-like syndrome, are dose related and typically transitory. Nephrotoxicity occurs rarely, usually following relatively rapid infusions, and typically is transitory; the drug can be used in those with impaired renal function.

Zoledronic acid (Zometa®; Novartis Pharmaceuticals Corp.) is a new bisphosphonate that is approximately two to three times more potent than pamidronate. It has been shown to reduce pain and the occurrence of skeletalrelated events in breast cancer [112, 115, 116], prostate cancer [117], and multiple myeloma [112], as well as a variety of solid tumors, including lung cancer [118]. It is effective in both osteoblastic and osteolytic lesions [116]. It is as effective as pamidronate [112, 116], and its use is more convenient, as it can be infused safely over 15 minutes at a dose of 4 mg every 3 weeks. The side effects are similar to those encountered with pamidronate, and the dose does not have to be adjusted in patients with mild-to moderate renal failure [119].

Data on the analgesic effect of clodronate are conflicting, but it has been shown to be effective in prostate cancer and multiple myeloma [108]. The main advantage of clodronate over pamidronate is its good oral bioavailability, which avoids the need for i.v. administration. An oral dose of 1,600 mg daily seems to be optimal [108]. Clodronate is not available in the U.S.

Scarce data exist on the efficacy of the other newer bisphosphonates alendronate (Fosamax®; Merck and Company, Inc.; West Point, PA) and ibandronate (Boniva™; Hoffman-La Roche Inc.). These drugs, which are very potent, are likely to be analgesic.

"Adjuvant analgesics in cancer pain management," Lussier D, Huskey AG, Portenoy RK, Oncologist, 2004; 9(5): 571-91 at 583. A copy of that article is attached.

Moral of the story: accept no substitutes. That, and it might be worthwhile talking to your doctors about Fosamax and Boniva as well. (I am sending the article on to my pain guy for what it's worth.)

Mike

Attached Files

Adjuvant Analgesics in Cancer Pain Management.pdf (165.5 KB, 970 views)

A quick follow up. Attached is the U.S. prescribing information for Boniva. Unfortunately, the Fosamax and Zometa sheets are too large to post, but you can download them here:

[Zometa] http://www.pharma.us.novartis.com/pr...pdf/Zometa.pdf
[Fosamex] http://www.rocheusa.com/products/Bon...jection_PI.pdf

Especially for folks with RSD-induced osteoporisis, I think it's important that people get on this stuff sooner rather than later.

Mike

Attached Files

Boniva - prescribing information.pdf (190.8 KB, 159 views)

mike, could you explain exactly how you are better? less pain? less swelling? just wondering what the improvements are for you. this is very interesting information. thank you, joan

Hi Joan -

Zometa has substantially relieved what may have been the single worst symptom I had: that a spike was being driven - crucifixion style - through the ankle joints of both feet.

It also appears to have produced maybe a 50% reduction in the sense that someone was taken a hammer to my toes. (The rest I've been able to control with Xanax (Alprazolam) a benzodiazepine that does wonders for shooting neuropathic pain a lot of folks experience, even though a couple of studies the literature didn't find empirical support for the claim, but that's another story.)

That said, Zometa has given me no relief of any kind from really nasty compression pain around my ankles, which is often triggered by stress. And the swelling is still about the same. Nor has there been any overall improvement in cramping, although a fair amount of Baclofen seems to work more effectively than had Zanaflex, and since I'm no longer practicing law, I put up with a little amnesia as the price of admission. And I'm blessed not to have sensitivity to light touch, so I can't speak to that one.

By coincidence, I just came across the following abstract tonight, following up on Anne Louise Oaklander's work a year or two ago, tying small fiber neuropathy to CRPS:

"Concordance between epidermal nerve fiber density and sensory examination in patients with symptoms of idiopathic small fiber neuropathy," Walk D, Wendelschafer-Crabb G, Davey C, Kennedy WR, J. Neurol Sci., 2007 Apr 15; 255(1-2): 23-6:

Quantitation of epidermal nerve fiber (ENF) density is an objective diagnostic test of small fiber neuropathy (SFN). For a diagnostic test to be clinically useful it should correspond well with clinically meaningful physical findings. We performed a retrospective analysis of the concordance between foot ENF density and clinical findings in all patients seen at our institution with possible idiopathic SFN who underwent skin biopsy for ENF density determination. We found a high concordance between reduced foot ENF density and loss of pinprick sensitivity in this patient population. Our findings indicate that ENF density determination is a clinically relevant objective test in patients undergoing evaluation for possible SFN.

What's interesting in this context is that in the almost 22 months I've been on Zometa my "pin-prick sensitivity" has grown markedly worse, suggesting that even though although the underlying disease may be growing more entrenched, at least some of my symptoms have improved.

Bottom line: the stuff seems to work really well, at least for "deep bone pain."

Mike

ps A copy of "Concordance between epidermal nerve fiber density, etc." article is now attached.

Attached Files

Concordance between epidermal nerve fiber density.pdf (150.6 KB, 228 views)

Just saw my pain dr. at U.S.C. this morning for another Zometa infusion. He tells me that there's every reason to believe that Zometa and other bisphosphonates work directly on the nerves, where not every RSD patient experiences a loss in bone density: I certainly did not.

He also tells me that based upon what he understands through the literature and speaking with colleagues, although his personal experience in treating this patient population with Zometa is somewhat limited, that these drugs should work for burning RSD skin pain and touch sensitivity.

In any event, this is something that those of us fortunate enough to not need major dental work in the near term should be discussing with our doctors. (And to the extent everyone else can get their dental work done before trying the stuff, so much the better.)

Mike

Heya..

Very interesting - will forward to my pain guy.. who knows.. he might get the point!!!

Especially as with my last set of X rays and scans it looks like I will need something along that line... and looks better than Fosemax...

Thankyou so much!

Love

Frogga xxxxxxxxx

I spoke with my PM doc about this Mike and he is hip to this.
He is going to look into this exciting treatment for RSD.

Although not an option for me for several reasons I am really glad it is working for you

Talk soon

GnP

mike, thank you for the specifics on the pain control. i asked because so many people have such different problems. this sounds like it could be helpful to many. i'm so glad to hear you are getting some relief. joan

I am just basically a lay person. When reading all the above, I just do not understand what it is I am reading. The medical jargon is way over my head. With that said, how would I go about presenting this to my PM Doctor to see what he thinks of it all. For all I know, this could be a huge answer for me & could be exactly a treatment that would do me way more good than not. But not understanding what I read, but understanding that it could be helpful, just exactly how would I present this?? I do swear also that the longer I have this syndrome, the less I am able to understand whether my brain function is less due to RSD or due to the medications I am on, I just don't know. But I am less able to understand what I read now than I was 4 years ago.

DebbyV

Hey Debby,

I began intensively researching RSD ten years ago, and since then built up a definitions file of about 450 words that I must still constantly refer to. I can't understand most of the med-speak in research posted here; and looking up definitions is frequently not too useful, as the definitions include words I've never seen before, and then I have to look them up !!!

And if that isn't enough: most of the links posted here are cluttered with statistical stuff that I didn't understand 1/2 hour after passing statistics finals in college, and they come along faster than speed-bumps at mobile home parks. I keep losing my place in the text.

It isn't RSD or meds or pot or aging; it's trying to read a foreign language. I'll try to read it, but I give up easily. Just call me "Lazy"...Vic