Biphosphonate infusion for RSD?
 

I was wondering if anyone has tried a biphosponate infusion for RSD. The 2 types I've heard about are Zometa and Pamidronate. I'm wondering if they help with the burning and sensitivity that come with RSD. I have it all over and nothing has been helpful, including ketamine. I'd love to hear from anyone who has benefited from this treatment. Thanks!!

I've been having Zometa infusions for the last few years. Initially in three monthly infusions, where it didn't really take unti the 3rd one, but then it
has eliminated maybe 60% of my "deep, bone crunching pain." Since then I have a single bouster infusions every 10 months or so.

2 caveats: it cannot be taken if any serious dental work is in the offing, so a dental "re-clearance" is often required, where root canals have led to a charming condition called "jaw necrosis."

Secondly, because the stuff can play havoc with weakened kidneys, my pain doc. requires a basic metabolic panel to be drawn no earlier than a week before each infusion.

Hope this is useful.

Mike

Thank you for the info! Could you tell me what type of doctor you go to for the infusion? I've been to a lot of doctors but no one's mentioned it. My pain doc is an anesthesiologist, but he's very conservative. Many thanks,
Becky

Becky -

I am treated by a pain specialist as well ("double-boarded" in anesthesiology and psychiatry), but perhaps someone more familiar with current literature, where he is the chief of pain medicine at a local medical school and at any time is training a number of clinical fellows in pain medicine, doctors who have already completed residencies in fields such as anesthesiology, neurology, etc.

Perhaps the best overall review of biphosphonates in the contexts of other treatments appears in

Treatment of complex regional pain syndrome: a review of the evidence.
Tran de QH, Duong S, Bertini P, Finlayson RJ, Can J Anaesth. 2010 Feb;57(2):149-66 FREE FULL TEXT @ http://www.rsds.org/2/library/articl..._Finlayson.pdf

Abstract
PURPOSE: This narrative review summarizes the evidence derived from randomized controlled trials pertaining to the treatment of complex regional pain syndrome (CRPS). SOURCE: Using the MEDLINE (January 1950 to April 2009) and EMBASE (January 1980 to April 2009) databases, the following medical subject headings (MeSH) were searched: "Complex Regional Pain Syndrome", "Reflex Sympathetic Dystrophy", and "causalgia" as well as the key words "algodystrophy", "Sudeck's atrophy", "shoulder hand syndrome", "neurodystrophy", "neuroalgodystrophy", "reflex neuromuscular dystrophy", and "posttraumatic dystrophy". Results were limited to randomized controlled trials (RCTs) conducted on human subjects, written in English, published in peer-reviewed journals, and pertinent to treatment. PRINCIPAL FINDINGS: The search criteria yielded 41 RCTs with a mean of 31.7 subjects per study. Blinded assessment and sample size justification were provided in 70.7% and 19.5% of RCTs, respectively. Only biphosphonates appear to offer clear benefits for patients with CRPS. Improvement has been reported with dimethyl sulfoxide, steroids, epidural clonidine, intrathecal baclofen, spinal cord stimulation, and motor imagery programs, but further trials are required. The available evidence does not support the use of calcitonin, vasodilators, or sympatholytic and neuromodulative intravenous regional blockade. Clear benefits have not been reported with stellate/lumbar sympathetic blocks, mannitol, gabapentin, and physical/occupational therapy. CONCLUSIONS: Published RCTs can only provide limited evidence to formulate recommendations for treatment of CRPS. In this review, no study was excluded based on factors such as sample size justification, statistical power, blinding, definition of intervention allocation, or clinical outcomes. Thus, evidence derived from "weaker" trials may be overemphasized. Further well-designed RCTs are warranted. [Emphasis added.]

PMID: 20054678 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/20054678

The specific discussion of biphosphonates begins at page 151 and picks up again at 156, under the topic heading "Pharmacological therapy," which is summarized at pages 158 - 159:

Interpretation

In all placebo-controlled RCTs [Research Clinical Trials], biphosphonates have been shown to decrease pain and swelling as well as to increase range of motion for patients with CRPS. In most trials pertaining to calcitonin, benefits associated with its administration were not detected. The effect of free radical scavengers may be drug dependent; while mannitol is no better than placebo, DMSO seems to provide a mild improvement in range of motion and vasomotor instability in patients with CRPS. Owing to its costs, NAC [a free radical scavenger, N-acetylcysteine] is best reserved for a subgroup of patients with cold CRPS. A short course of oral steroids (prednisolone or methylprednisolone) may help with pain control, edema, and mobility in CRPS patients with or without cerebral infarcts. In light of the marginal benefits or limited supportive evidence, tadalafil, sarpogrelate, and gabapentin should be used with caution.

And as noted the abstract, this review of all widely used CRPS therapies, that had been subject to randomized controlled trials that were published between January 1950 and the 2nd week of April, 2009, concludes at page 164 with the following:

In summary, only biphosphonates appear to offer clear benefits for patients with CRPS. Improvement has been reported with dimethyl sulfoxide, steroids (in CRPS with or without cerebral infarcts), epidural clonidine, intrathecal baclofen, spinal cord stimulation, and motor imagery programs; further trials are required to confirm these findings. The available evidence does not support the use of calcitonin, vasodilators, or sympatholytic and neuromodulative intravenous regional blockade. Clear benefits have not been reported with stellate/lumbar sympathetic blocks, mannitol, gabapentin, and physical/occupational therapy, and further studies are required . . . . [Emphasis added.]

The emphasis on randomized controlled studies, is however important to bear in mind, where the first randomized, placebo-controlled study of ketamine infusions were not published until October and December of 2009. See, Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1, Sigtermans MJ, van Hilten JJ, Bauer MCR, et al, Pain 2009 Oct;145(3):304-11. Epub 2009 Jul 14 FREE FULL TEXT @ http://www.rsds.org/2/library/articl...rmans_etal.pdf and Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: A double-blind placebo controlled study, Schwartzman RJ, Alexander GM, Grothusen JR, Paylor T, Reichenberger E, Perreault M, Pain 2009 Dec 15;147(1-3):107-15. Epub 2009 Sep 23 FREE FULL TEXT @ http://www.rsds.org/2/library/articl...n_Pain2009.pdf

A copy of the official FDA approved U.S. prescribing information sheet for Zometa is attached.

Final caveat re Zometa: I had my second appointment with a nephrologist (kidney specialist) today, who I had seen after it became clear to me that I had no need to void my bladder unless I had taken a diuretic within the preceding 6 - 8 hours, where over a year and a half I had gone from 20 to 80 mg./day of the diuretic Lasix (frusemide) in order to avoid edema (interstitial fluid buildup) secondary to neurogenic vasodilatation an increase in capillary permeability. (Well documented vasoconstriction in the upper extremities compensated for by vasodilatation in the lowest - most "dependent" - portions of my body: the lower legs, ankles and feet, as well as the site if my initial bilateral tendon issues and onset of RSD.) In any event, while the mechanism of Lasix (a "loop diuretic") are largely over my head, their effect is straightforward. See, Wikipedia: Loop Diuretics http://en.wikipedia.org/wiki/Loop_diuretics

The collective effects of decreased blood volume and vasodilatation decrease blood pressure and ameliorate edema.

For a good and fairly understandable article, see, Treatment of Edema, O'Brien JG, Chennubhotla SA, Chennubhotla RV, Am Fam Physician 2005 Jun 1;71(11):2111-7 FREE FULL TEXT @ http://www.aafp.org/afp/2005/0601/p2111.html

Abstract
Edema is the result of an imbalance in the filtration system between the capillary and interstitial spaces. The kidneys play a key role in regulating extracellular fluid volume by adjusting sodium and water excretion. Major causes of edema include venous obstruction, increased capillary permeability, and increased plasma volume secondary to sodium and water retention. A systematic approach is warranted to determine the underlying diagnosis. Treatment includes sodium restriction, diuretic use, and appropriate management of the underlying disorder. Leg elevation may be helpful in some patients. Loop diuretics often are used alone or in combination. In patients with New York Heart Association class III and IV congestive heart failure, spironolactone has been found to reduce morbidity and mortality rates. In patients with cirrhosis, ascites is treated with paracentesis and spironolactone. Dihydropyridine-induced edema can be treated with an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker. Lymphedema occurs when a protein-rich fluid accumulates in the interstitium. Compression garments and range-of-motion exercises may be helpful in patients with this condition.

PMID: 15952439 [PubMed - indexed for MEDLINE

http://www.ncbi.nlm.nih.gov/pubmed/15952439

And although most side effects of loop diuretics are mild and reversible, ranging from excessive thirst to the 30% increase in serum creatinine I experienced as the dose was raised, or even potentially more serious ototoxicity (toxic damage to the ear, often resulting in tinnitus - which I developed transiently near the end of the drug's use and has now disappeared- but is typically found at 3X the dose I was on: Comparison of loop diuretics in patients with chronic renal insufficiency, Voelker JR, Cartwright-Brown D, Anderson S, et al. Kidney International (Oct. 1987) 32 (4): 572–8 http://en.wikipedia.org/wiki/Ototoxicity ) THERE IS A WELL KNOWN KILLER COMBINATION:

Loop diuretics may also precipitate renal failure in patients concomitantly taking an NSAID and an ACE inhibitor -- the so-called "triple whammy" effect.

Diuretics, ACE inhibitors and NSAIDs--the triple whammy, Thomas MC, Med. J. Aust. (February 2000) 172 (4): 184–5 http://en.wikipedia.org/wiki/Loop_diuretics

What the nephrologist told me this afternoon was that I could substitute a Zometa infusion for "concomitantly taking an NSAID and an ACE inhibitor." In other words, if anyone is on a "loop diuretic," including not only Lasix, but Edecrin (etacrynic acid), Demadex (torasemide), and the very potent Bumex (Bumetanide), he suggests a two-week "drug holiday" around the Zometa infusion, one week before and one week after.

This will come as news to both my internist and pain specialist. And well it should, because this is all the official U.S. prescribing information sheet has to say about loop diuretics:

Caution should also be exercised when Zometa is used in combination with loop diuretics due to an increased risk of hypocalcemia. [Para. 7.2]

And my internist ordered full metabolic panels every six weeks I was on Lasix. At least according to the FDA, that should have been enough. Now, to hear the nephrologist tell it, without a drug holiday around each infusion, I was playing Russian roulette with my kidneys. Who knew?

Sorry for going on so, but hope this is helpful.

Mike