Polymyalgia Rheumatica

Thanks for your experience, MrsO. I had a radiological bone scan during the tests for what I turned out to have (i.e. PMR only). As a youngish male of 56 years, my bones are pretty dense. So I appreciated the caution of my GP and rheumy to protect my bones. But I will be discussing this with my GP quite soon. My general health is robust and the 'ole kidneys are working well within parameters.

Luckily for me, I don't seem to suffer obvious side effects from any medicines I've ever taken, like nausea, stomach aches, dizziness, etc. I also was acutely aware of how the alendronate should be taken in order to avoid stomach irritation.

Fingers will remain firmly crossed for the eventual end to the steroid treatment.

I am really not convinced of the "protective" aspect of AA - and as time goes on increasing numbers of medical people are also beginning to wonder. A lot of the work was done by the company who developed Fosomax so personally I am sceptical for that reason alone - I'm not saying they are lying, merely selective. To cut a long story very short, they dished out basic bone density measuring devices and showed how all these people didn't develop osteoporosis and a generation of medics believed the sales pitch. My husband is a medical physicist (my field is physiology) and his department had looked at these things that measure calcification in the achilles tendon area - and they came to the conclusion that if they show osteoporosis it was already VERY advanced. Only a dexa scan is anywhere near accurate - and there is variation between machines even with them. There are several other wonder devices that are equally inaccurate, not least the tympanic membrane thermometers.

It is one thing to hand out a drug like sweeties that has been used for decades and where the long term side effects are well known. Alendronic acid hasn't been about long enough for us to have any idea what a substance that is never going to be removed from the body can do. It is very firmly fixed as part of the structure of our bones - nothing will remove it. Noone knows what will happen to that in 30 years.

And for your consideration: only some 40% of people on steroids actually develop serious degrees of osteoporosis and that includes the people who are on pred from a very young age. . Not sure what the figure is for the general population though by no means everyone does either. However - I am of the opinion that they are working on old parameters. This current generation has had a better diet and far more weightbearing exercise in later years than previous ones. We also tend to be bigger - not always a good thing but in the context of osteoporosis it is! Things may change in later generations of elderly but that remains to be seen.

Put it this way - I'd rather take pred with its 50 year history than AA

Eileen

My telephone consultation is booked. I will let you know how this goes. I am not going to prejudge but I might just stop the AA unilaterally. On 2 mg pred per day, I should think my steroid induced decalcification is on the very low side.

Does anyone know the half-life of AA binding to bones? It shouldn't be infinity. All chemical reactions have an equilibrium position, even at the extremes. There will be a position for almost zero AA serum concentration with that bonded to bones (mass per unit area). Is the time until equilibrium known, I wonder?

The mhra document on alendronic acid 70mg tablets says:

"CLINICAL PHARMACOLOGY

Since alendronic acid is rapidly taken-up by bone shortly after administration, plasma

levels are below the level of quantification, thereby ruling-out a conventional

bioequivalence study with measurement of plasma levels of the drug. It is also known

that the mean terminal half-life of elimination of alendronic acid from bone was

exceedingly long (estimated to be 10.9 years with a range of 5.4-19 years). This may

potentially rule-out the conduct of crossover-type trials because of the possibility of

significant urinary drug levels from the first dosing period being present when the

subject returns for the second drug period. However, in practice it has been found that

the maximum rates of primary urinary alendronate excretion occur between 1-3 hours

after dosing and that over 90% of drug to be excreted renally is recovered in a 0-72

hour urine sampling period, giving a half-life based on urinary excretion data of 33 +/-19 hours.

Furthermore, it was shown that the release of drug from bone is not a

significant cause of carryover effects, thus permitting the use of crossover designs."

Infinite not - but exceeding long! The bioavailability is quite low and the urinary half life not exceptionally long but tied to bone it's a different matter. Will there be chunks of bone with patches that survive long after the rest has crumbled one wonders? It is absorbed preferentially in areas of bone where there is active osteoclast activity so will those bits be resistent to the effect of time?

The Wiki article on it mentions a few of the cases that have given pause for thought. After 7 years or so a femur can just snap - no need to fall. Just put your weight on the leg. Tell me my bone density is falling and I'll start taking it before it gets to a parlous state - that sort of prevention is acceptable. But not giving it to an otherwise healthy person "just in case"of something that is known to only happen in half of us. I live in northern Italy and here I can have an expensive form of pred with no question since the other offering of methyl prednisolone gave me very unpleasant side effects. I assume being on pred they also tend to hand out caclium/vit D supplements - I continue to get that as I did in the UK. They are, however, horrified at the idea of using AA until there is evidence it is needed. If I had taken it now with no real need the situation may arise later when I do need it, I'm only 60 and have been on pred for 4 years, I trust I won't have to take it for the rest of my life - and I've already used up my recommended allocation.

Eileen

Ok, that more or less helps me make up my mind. The AA stops prety much right away. I should live long enough to see my bone AA levels drop a bit and I may not have saturated them if I stop now after about 2.5 years of treatment. The Italians seem to have a quite different attitude to use of AA as well.

Eileen, what prednisolone analogue do you take, if you don't mind me asking?

I go to the gym quite a lot, training with quite heavy weights, and walk for miles most weeks. Maybe the frequent stress on my bones will help protect them from the risks of AA brittleness.

In my limited experience, British GP's are very resistant to using some of the latest, possibly more advanced drugs, probably due to the higher costs. But it seems their conservatism may store up problems for the future for some people At least my diabetes treatment is more or less up to date with use of the latest insulin analogues, which work very well for me (e.g. Lantus & Humalog).

I take Lodotra. It is a formulation that has a very thick specially developed coating which, when taken within 3 hours of food takes 4 hours to disintegrate, releasing all the pred at one go. You take it at 10pm before bed and it releases the pred at 2am so that the peak blood level is 4am. This is based on trials done with RA patients in hospital for some reason who were being disturbed overnight for monitoring anyway and they gave them their pred at various times to find the optimum time to take the pred to minimise morning stiffness. They established that the best time was 2am. This is in line with the concept that the substances that cause the inflammation, called cytokines, are released about 4.30am. The pred is there, lying in wait and pounces on the cytokines ;-) But noone wants to set their alarm to take their meds at 2am do they?

Lodotra was developed by a German company and approved for use in RA in Europe a few years ago, the USA is possibly going to get it soon (but it doesn't speak 'merican so it's struggling). There is about to be/already is a trial going on in the UK to judge its benefits in PMR and possibly GCA - I can't see any great benefit in GCA, most GCA patients tend not to have PMR morning stiffness and that is the primary advantage of Lodotra. It is anticipated that a lower dose may be possible, I haven't managed yet!

The BIG disadvantage is it is EXPENSIVE compared to common-or-garden pred: a tub of 30 pills costs about 27 euros, £25 thereabouts. That's near enough a euro per pill - and 2mg tabs and 1mg tabs cost the same so my 9mg daily dose costs 3 euros, £75 a month. You can't cut the pills because of the essential nature of the coating. But I like it - and have lost a shedload of weight since I went onto it. The other side effects of the Medrol have disappeared too.

Your exercise regime would probably obviated the need for AA anyway - the impact makes your bones bend a tiny bit and that stimulates bone formation. And all I can say is I know a load of PMR patients who would be bight green with envy! Most of us struggle to walk to the corner and back! Pre-PMR I went to the gym daily and skied 3 or 4 days a week in winter so I wasn't a couch potato either. I have got to the stage of managing 2km almost every day at a decent pace. Still not enough given where we live!

My experience is that many UK GPs simply don't do the reading they need to do - and are stuck at the level that they were taught at medical school. They are also very gullible about what they are told by reps. When they are sent the latest updates from, say, the rheumatologists, I know some just file them in File 13 - I've seen it done. So they are NOT using the latest knowledge. There is an excellent review of PMR diagnosis and treatment from the group in Bristol from last year. Do they want to know about it? Like heck...

Eileen

Wrong diagnosis. PMR is a sel-limited disease, generally lasting no more than two years if untreated. It may be the presentation of giant cell arteritis (sometimes known as temporal arteritis), which is a potentially morte serious condition......and more rarely, rheumatoid arthritis. Regardless, you've been on prednisone too long. Need to taper off it under supervision of a RHEUMATOLOGISTand see what remains. Then you can be diagnosed correctly (if symptoms remain). Good luck.

Hi VOC guy

Yes, you are right in saying that PMR is a self-limiting disease but I'm afraid I have to correct you when you say that someone can be "on prednisone too long" - unfortunately, we have to be on prednisolone for as long as it takes, and for some lucky people that can be just a couple of years but for others it can take much longer. PMR will go into remission when it wants to and not when we want it to - it took 5 1/2 years on steroids for my PMR to go into remission. In fact I actually had PMR for 6 1/2 years but because it remained undiagnosed and therefore untreated during the first year, I was put at high risk of contracting GCA......and unfortunately I succumbed!

MrsO is right. PMR progression varies from person to person. My rheumy said that in severe cases it can, not necessarily will, also lead to a form of anaemia if left untreated. Besides, who wants to suffer all that gelling, planning how to get out of bed, putting on shoes, etc, for two years? I've had PMR for almost exactly 2 years and it seems to be petering out, but it was causing me so much painful restriction that I had to get treatment. Now I have almost no symptoms and my ESR was normal a few months ago. But the steroid can't be reduced too quickly and I don't expect to be off it until e/o 2013. The body needs good chance of re establishing its own endocrine balance as the artificial steroid prop is taken away even if the PMR has gone into full remission.

MrsO: My point is/was that if the "PMR" lasted more than about two years, it wasn't PMR, by definition. GCA can present with PMR symptoms, the usual clues being temporal headache, temporal artery swelling with tenderness, pulse cutoff, and possibly tongue or jaw pain (claudication) with chewing, perhaps more in the way of systemic symptoms (fever, weakness), more tendendency toward anemia. Both have elevated acute phase reactant tests (ESR, quantitative CRP). The primary practical issue , as you know, is that GCA (AKA temporal arteritis....altho GCA can and does involve other vessels) can cause sudden, irresversible but usually unilateral blindness.....due to central retinal artery occlusion. The correct diagnosis depends on an experienced physician (usually a rheumatologist) with a high index of suspicion. PMR by itself almost always occurs with sudden onset, morning predominance of symptoms, in a person 65 years of age or older. ESR should be >60 mm/hr. Regarding prednisone, or any other glucocorticoid, a "normal" person's adrenal gland under normal conditions produces cortisol equivalent to about 3-4 mg of prednisone daily. Prolonged use of an exogenous glucocorticoid in higher dosage eventually suppresses endogenous cortisol production, and the patient becomes somewhat "dependent" (physiologically, and perhaps psychologically) on the drug. Regardless, when it is no longer needed it should be tapered off slowly so that the adrenal glands can again pick up the slack.....so to speak. Regarding treatment of uncomplicated PMR, if the patient's symptoms don't rapidly and almost completely respond to prednisone 15 mg (occasionally 20 mg) daily, then start thinking of another diagnosis.....which could include GCA. I won't prolong the discussion at this point by delving into how and when to obtain a temporal artery biopsy, or the imaging alternatives to this. Again, good luck.

VOCguy - I have no idea who you are or what your qualifications are - but I do know one thing. You have very little idea what you are talking about I'm afraid. There is no "definition" as you put it for PMR. All the literature gives clinical criteria for diagnosis, there are no defined tests or proof and the diagnosis remains a clinical one.

PMR usually is of sudden onset in terms of finally experiencing extreme symptoms which send the patient to the doctor but the majority of patients realise in retrospect that they have had mild problems that fit with PMR for some time. The "65 or over" criterion is at least 10 years out of date and the most recent criteria as published by the British Association of Rheumatologists have revised the age downwards to over 50. Even then, experienced and knowledgeable rheumatologists working on research of the syndromes admit it is possible to find PMR in even younger patients. One in five patients with a clinical dx of PMR do NOT have any abnormal ESR or CRP results.

The normal production of cortisol by the adrenals is equivalent to more like 7 to 10mg/day. Use of an endogenous glucocorticoid suppresses cortisol production quite quickly - simply because the body is told there is enough in the blood and the feedback system ensures no more is made.

About the only thing you have said that makes sense is that use of 15mg/day should result in very speedy relief of symptoms in pure PMR and in fact that would actually also achieve relief of the PMR component in a patient with GCA - but is unlikely to achieve improvement in any GCA-specific symptoms. The group working under Professor John Kirwan published a review paper last year under the auspices of the Royal College of Physicians of Edinburgh which I suggest you read. He defines pure PMR as responding rapidly to 15mg pred and shows results with a couple of other clinical presentations resembling PMR.

I fulfil that part of a definition of PMR - I responded 80% to 15mg pred within 6 hours. I had had symptoms that were undx'd for 5 years previously before they became intolerable almost overnight. On removal of pred after 6 weeks the symptoms returned within 48 hours. Also totally in agreement with Prof Kirwan's description. Four years later I have not managed to reduce below 9mg/day without the symptoms returning.

"I won't prolong the discussion at this point by delving into how and when to obtain a temporal artery biopsy, or the imaging alternatives to this" - unfortunately that is hardly applicable to the UK or most of Europe, you get what your rheumatologist offers. But the alternative imaging is not always recognised as diagnostic, just used in research or only available in large centres. The latest offer is a form of vascular ultrasound, confirmed to be of value but not yet widely available. For various reasons, a TAB is only is use in less than 50% of patients even when done immediately before any treatment with steroids.

Eileen

Hello again VOC guy

Have you actually experienced PMR and/or GCA? I'm inclined to think not! If you had, then you would not have made the statement that "because it lasted more than about two years" what I had "wasn't PMR by definition - I DEFINITELY had PMR (I'd obviously rather not have done!), and so do hundreds of other sufferers who are unable to get off steroids in textbook fashion.

Eileen has replied in detail, giving a more accurate picture of some of the facts surrounding PMR, and she does know what she is talking about!

Well,VOC Guy, I wonder what I do have then? From 56 onwards, I had slowly increasing typical PMR symptoms (increasing morning stiffness, unable to turn in bed, sky high ESR & weight loss). Unfortunately, my GP at the time considered I was too young for PMR. At 58, I suddenly became bedbound & immobile. A different GP diagnosed PMR and 30mg of steroids and I was mobile again in 12 hours - strange that eh? I'm 60 now & guess what? 3 flares later and I still have PMR.

Unfortunately, there are still too many G.P.'s, all of whom must have the read the same book as you. 'Younger' people may experience months or years of pain & immobility or worse, lose their sight, because they are too young for PMR/GCA to be considered. After diagnosis, they will insist on too rapid a reduction of steroids and this is the most common reason for a flare (evidence based). Some G.P.'s will insist on following CRP & ESR results - 'your bloods are good, so you must be'. My ESR and my symptoms go 'hand in glove'. About 20% of people do not have elevated markers.

Perhaps you would care to explain to the family of the 37 year old who died recently that he didn't die from the stroke caused by untreated GCA after all His GCA was diagnosed at post mortem - of course he was too young for GCA.

PMR can be sudden onset, other times not.

PMR is a disease of 'older' people , but there are many people in their 50's and younger with PMR.

Some people do get through PMR in 2 years - sometimes a shorter time. Men generally have a shorter journey than women. After 2 years, there are still a reasonable % of people with active PMR and of course there are some people who have a 2nd and even 3rd bout of PMR, months or years after the 1st. There are a few unlucky people who are still on their first bout of PMR after 5 or 6 years and some who will require a very low life long dose to prevent a relapse.

Eileen has explained points in some detail, but I am sure links could be sent to you which will provide accuarate information for you.

I was unable to reduce to under 13mg and I have since started on Methotrexate and am now on 11.5mg prednisilone. From my own professional knowledge, I would not be taking either of these drugs (along with the other bucket load for side effects), unless I was satisfied with the diagnosis that I have PMR. I can think of far more pleasant ways of turning myself into a baby hippo (and that being the least unpleasant side effect) than taking prednisilone.

Margaret

There is an evidence based paper which looks at the duration of PMR and treatment outcomes. About 25% of patients are off pred within 2 years - but are at a high risk of a relapse subsequently. A further 50% are on pred for between 2 and 6 years and the rest require pred longer term of 11 years or more - albeit it often at a low dose of below 5mg - and in a few cases remain on pred for life.

There are a few experts who wonder if there is a component of adrenal insufficiency involved although to my knowledge noone has looked closely at that. But the treatment for adrenal insufficiency is replacement therapy. With prednisolone and usually lifelong.

So yes - PMR can be limited - in considerably less than a quarter of patients. By my training you can't consider THAT to be a rule or even representative. And most doctors seem to be hell bent on causing flares: the most common cause of a flare is reducing too fast or too far. Who usually forces the pace of reduction? Rarely the patient despite their fear of pred and its perceived awfullness.

Eileen

Hello Eileen. Thanks for the reference to the paper. Could you give the full reference please so that people can pursue it?

thanks

Kate