I’m happy to add what I know, but nothing can compare to the potential of the article you have brought to our attention!!!
(See below, folks)
I've been on periodic infusions of Zometa (zoledronic acid)
for a fee years - which I understand to be the state of the art drug in that class because the infusion only takes 15 minutes as opposed to as much as 4 hours - and it’s the only thing that's helped with what is loosely termed "deep bone crushing pain."
There are two groups of patients, however, for whom Zometa (hereafter understood to refer to all such "bisphosphonates") is not an option, at least for the treatment of a non-life-threatening condition. In contrast, if one is using it for its initially intended purpose of preventing the uptake into the bloodstream of lose bone material secondary the multiple myeloma, before accumulated calcium results in renal failure, potential side-effects may be less of a concern.*
First, Zometa is SERIOUSY CONTRAINDICATED
for anyone with kidney disease. As such, before I have to have a metabolic panel run (largely to look at my creatinine levels) within 10 days of getting any infusion.
Secondly, patients who are, at the time of the infusion, need major dental work, root canals on up, are at risk of a particularly nasty complication called "osteonecrosis of the jaw," and it's just what it sounds like, the death of the jaw-bone. So, before I started, my PM asked for and got a clearance letter from my dentist. The issue becomes significant in terms the patient population as whole, if there are a large number of people who take narcotics - which dry up salivary glands - while neglecting appropriate dental hygiene, a point on which few patients appear to receive appropriate guidance from their pain management physicians. Worse off yet, are those - thankfully diminishing in number - patients who came to rely on so-called "Fentanyl lollypops," on account of which a close friend with 30+ years of horrific back pain wound up having her few remaining teeth removed, so that she could be fitted with a proper set of dentures: I have no idea whether such a patient could ever
be a good candidate for Zometa infusions.
And as I was told, the first infusion isn't necessarily expected to do anything, but favorable results are can be anticipated after the second. And once it kicks in, the idea is to wait until there's been some reemergence of whatever had been controlled before, because in significantly larger quantities - as are use on women with osteoporosis - the stuff can have more significant complications.
There are any number of good studies of the effect of bisphosphonates on CRPS that are now freely available online. Here is just a sampling:
Bisphosphonate therapy of reflex sympathetic dystrophy syndrome, Adami S, Fossaluzza V, Gatti D, Fracassi E, Braga V, Ann Rheum Dis. 1997 Mar;56(3):201-4.
An Open-label Pilot Trial of Ibandronate for Complex Regional Pain Syndrome, Breuer B, Pappagallo M, Ongseng, Chen CI, Goldfarb R, Clin J Pain. 2008;24:685-689.
Bisphosphonates for the therapy of complex regional pain syndrome I—Systematic review, Brunner F, Schmid A, Kissling R, Held U, Bachmann LM, Eur J Pain. 2009;13:17-21.
Improvement of pain and regional osteoporotic changes in the foot and ankle by low-dose bisphosphonate therapy for complex regional pain syndrome type I: a case series, Abe Y, Iba K, Takada J, Wada T, Yamashita T, J Med Case Rep. 2011 Aug 4;5:349.
These culminate, in many respects, in a recent review article concluding ONLY BIPHOSPHONATES APPEAR TO OFFER CLEAR BENEFITS FOR PATIENTS WITH CRPS:
Treatment of complex regional pain syndrome: a review of the evidence [Traitement du syndrome de douleur re´gionale complexe: une revue des donne´es probantes], Tran DQH, Duong S, Bertini P, Finlayson RJ, Can J Anesth. 2010;57:149-166, 164 (“In summary, only biphosphonates appear to offer clear benefits for patients with CRPS.”)
Finally, under the heading of "you ain't seen nothing yet," is the abstract of the study to which cja1 refers:
Treatment of complex regional pain syndrome type I with neridronate: a randomized, double-blind, placebo-controlled study,Varenna M, Adami S, Rossini M, Gatti D, Idolazzi L, Zucchi F, Malavolta N, Sinigaglia L, Rheumatology (Oxford). 2012 Nov 30. [Epub ahead of print]
Objective. Complex regional pain syndrome type I (CRPS-I) is a severely disabling pain syndrome for which no definite treatment has been established. The aim of this multi-centre, randomized, double-blind placebo-controlled trial was to test the efficacy of the amino-bisphosphonate neridronate in patients with CRP-I.
Methods. Eighty-two patients with CRP-I at either hand or foot were randomly assigned to i.v. infusion of 100 mg neridronate given four times over 10 days or placebo. After 50 days the former placebo patients were given open label the same regimen of neridronate.
Results. Within the first 20 days, visual analogue scale (VAS) score decreased significantly more in the neridronate group. In the following 20 days, VAS remained unchanged in the placebo group and further decreased in the active group by 46.5 mm (95% CI -52.5, -40.5) vs 22.6 mm (95% CI -28.8, -16.3) for placebo group (P < 0.0001). Significant improvements vs placebo were observed also for a number of other indices of pain and quality of life. During the open-extension phase in the formerly placebo group the results of treatment were superimposable on those seen during the blind phase in the active group. A year later none of the patients was referring symptoms linked to CRPS-I.
Conclusion. In patients with acute CRPS-I, four i.v. infusions of neridronate 100 mg are associated with clinically relevant and persistent benefits. These results provide conclusive evidence that the use of bisphosphonates, at appropriate doses, is the treatment of choice for CRPS-I.Trial registration: EU Clinical Trials Register, https://www.clinicaltrialsregister.eu/ 2007-003372-18.
PMID: 23204550 [PubMed - as supplied by publisher]
Breathtaking is the only word I have for it! Thank you cja1: this one caught me unprepared and flatfooted.
Forgive me if I sound flip, but I already carry the precursor to multiple myeloma, "monoclonal gammopathy of undetermined significance" (MGUS)
. That, and perhaps my closest (current) friend in the world has been battling MM for years - so far with amazing success. What's remarkable though, is that both Thalidomide and the precursors to modern bisphosphonates were anecdotally discovered to benefit RSD (now CRPS) patients who were then using the medications in treatment for multiple myeloma. As someone who was diagnosed with MGUS within four years of the onset of CRPS, I have to wonder if more than coincidence is in play: my internist certainly believes that to be the case.
PS Folks, by way of a reality check, please note the study references the treatment/cure(?) of acute cases of CRPS. This means that those of you with under six months of diseases duration should be beating down the door for bisphosphonate treatment NOW! That said, please note the generality of the conclusion: while the authors like their delivery protocol, they don't appear to be asserting that the particular drug they're using is some sort of special sauce.
And as far as the rest of us goes, the general rule over the last 10 years or so is that that which cures the Newbies tends to significantly improve the quality of life for everyone else. So hahzah!!!