Fracture risk PMR/ GCA: Interesting study on... - PMRGCAuk


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Fracture risk PMR/ GCA

Interesting study on fracture risk in PMR and GCA. Will leave you to draw your own conclusions!

An incidental finding was that GP’s consistently start patients on a higher dose of prednisolone for PMR than recommended by the evidence based clinical guidelines ( 15 to 25mg ). The authors recommend further study on this.

25 Replies

Thanks Keyes -for the link to this recent article. I thought this an interesting statement:

'Glucocorticoids remain the first-line recommended treatment for GCA and PMR, and are a well-established cause of osteoporosis and fragility fracture [3]. However, in other inflammatory conditions, increased fracture risk was also observed in patients not using glucocorticoids [4–6], which may support a direct association between inflammation and osteoporosis.'

Obviously everything is endlessly complicated whatever we do - so it will be interesting to read comments from our in-house 'experts'

Best wishes

in reply to Rimmy

Hi Rimmy,

Yes I thought that was interesting as well. Worthy of further study.

Polywotsit profile image
PolywotsitPMRGCAuk team member

Thanks for posting this link Keyes! It's a good example of what you can do with 'big data '. This size of population rules out chance effects. A study cited by one of the presenters at our Newcastle research roadshow also found that 65% of PMR patients are started off on doses higher than the recommendations. Incidentally, current guidelines recommend 15mg as a starter. Higher doses for very large people or those who don't respond well enough to the 15mg. This was discussed at length in the ACR/EULAR working group, because some countries tend to start people off on a higher dose of 20-25 (e.g. Germany) . I was started off on 20mg although I only weighed 8 stone at the time. I have often wondered whether I could have managed on less and maybe avoided some of the worst effects, including a stress fracture in my foot!

in reply to Polywotsit

It popped up on my twitter feed Kate, lots of great medical stuff there.

Polywotsit profile image
PolywotsitPMRGCAuk team member in reply to

Yes I follow the Keele team but hadn't picked this one up.

PMRpro profile image
PMRproAmbassador in reply to Polywotsit

Sorry Kate, I know your name is on the paper but it is not 15mg any more. It is

"The panel conditionally recommends using the minimum effective GC dose within a range of 12.5–25 mg prednisone equivalent daily as the initial treatment of PMR. A higher initial prednisone dose within this range may be considered in patients with a high risk of relapse and low risk of adverse events, whereas in patients with relevant comorbidities (eg, diabetes, osteoporosis, glaucoma, etc.) and other risk factors for GC-related side effects, a lower dose may be preferred. The panel discourages conditionally the use of initial doses <7.5 mg/day and strongly recommends against the use of initial doses >30 mg/day."

I was started on 15mg prednisolone - miraculous result in 6 hours. But after 14 years I still have PMR symptoms if I go too low. The best tapering period I had was after a short-term high dose i.v. treatment which came after a hellish 9 months on methylprednisolone which simply didn't work, even at 20mg - back to 15mg prednisone and I got the same miracle as originally and then tapered steadily to under 5mg before a flare.

I have to say though - looking at the bit about the risk being worst in the early stages makes me wonder whether that also reflects the clumsiness that so many patients, especially with PMR, report. In the first 5 years of PMR (no pred) I could trip over nothing! It wasn't until relatively recently that I felt comfortable going down steps again. I have always consciously reduced the fall hazards in the house - proper footwear, no slippy rugs, no pets, no trailing wires, good lighting and so on. Thinking about it - the wobbliness disappearing probably coincided with my vit D level being identified as low and being put right. That is also known to be associated with fracture risk.

However - if there is this high risk of fracture, surely that should be a contributory factor in approving tocilizumab?

Polywotsit profile image
PolywotsitPMRGCAuk team member in reply to PMRpro

Oops! Sorry - I didn't make myself very clear there - that's a problem with doing this on the phone instead of the pooter! What I should have said was that one school of thought in the working group, especially the British and US rheumatologists argued strongly that the starting dose should be 15mg to determine whether that would be effective - but another school of thought was 'well, we routinely start people on 25mg'. So in the end there was a kind of compromise position taken in the report.

PMRpro profile image
PMRproAmbassador in reply to Polywotsit

I had assumed that was what happened.

To be honest - I really do get the impression that PMR is far better managed in non-English-speaking countries. And the horror stories tend to be from the US as often as not! The medical staff here are far more aware - I rarely have to explain what it is and Italy is not meant to have particularly high rates but some of the major players in research have been from here.

I'm glad I'm a dinosaur - my baby pooter is infinitely superior for writing!!! And almost as portable.

yogabonnie profile image
yogabonnie in reply to PMRpro

ALL horror stories tend to be from the US as often as not!

PMRpro profile image
PMRproAmbassador in reply to yogabonnie

They don't have a monopoly though ;-)

Thank you for posting this Keyes. Food for thought indeed. I agree with Rimmy about the statement she quotes and with Kate re starting doses (40mg for PMR in my case though was told to decrease to 20mg Pred daily after a week-I was a size 10)

I have to say I was very “doddery” on my legs for months before and after diagnosis and had lots of trips and little falls compared with my “normal” non clumsy self, fortunately no fractures. Maybe we are just more accident prone than the controls? Or can’t weight bear exercise to build up our bones?

I do hope this study doesn’t lead to GPs becoming more determined to prescribe bisphosonates or wanting us off prednisolone even more swiftly. Maybe more of a case for funding Actemra?

Thanks for this post-I’ll need to read it again after the second cup of coffee.

in reply to Maisie1958

Hopefully it will lead to further study re biphosonates and whether they do cut the risk of fractures.

Maisie1958 profile image
Maisie1958 in reply to

Hidden -definitely-I think that was what I was trying to say👍

I always post negatives instead of positives-sorry people 🤔

“The median duration of steroid use was less than 15 months for both conditions, although 25% of patients with PMR had more than 34 months of treatment. “


Is this reliable? I simply can’t get my head around the start and end this skewing the length of treatment, or am I not understanding? (“The study start date was defined as the date of a patient’s registration with their practice, the date their practice was defined as UTS, the patient’s index date or on January 1, 1990, whichever came latest. The study end date was defined as the earliest of the date of the patient’s death, the date the patient transferred out of the practice, the date of last data collection from that practice, the date of first fracture, or August 31, 2015. Those with less than 12 months UTS data prior to index date and less than 3 years UTS follow-up after the index date were excluded.”)

in reply to Soraya_PMR

It’s reliable in so far as it’s data straight from GP surgery’s.

The authors have listed possible problems/ things to consider when looking at the results and how they may be skewed.

As Kate says this is big data and these types of longitudinal studies are usually very helpful as they highlight long term as well as short term side effects/ harms.

Soraya_PMR profile image
Soraya_PMR in reply to

Thanks Keyes. I’m not explaining myself well.

Hmm.... if the study for a patient ends at the point of fracture, then is that considered the end of their steroids? (Which it wouldn’t be IRL)

I’m sorry, brain is just not digesting what I’m reading, maybe I’ll come back after a break.

PMRpro profile image
PMRproAmbassador in reply to

I'll lay odds though that there were no baseline data for bone density - how many of these patients actually had low BMD even pre-pred? Nor diet or exercise histories. There is an awful lot missing.

in reply to PMRpro

But that would assume that patients with PMR/GCA have lower BMD than the general population?

Surely there is a lot missing because it’s a retrospective, longitudinal look at primary care records and not a set up study? Hopefully it will lead to more research to define the risk of fracture.

PMRpro profile image
PMRproAmbassador in reply to

No, that doesn't assume that. But without that information you are missing an important factor. And yes - the missing items are due to it being a retrospective. But that is one of the weaknesses of such studies and it does limit the strength of the study.

It means you are damned, either if you are on steroid or if you are not on steroid when it comes to osteoporosis. I read somewhere it has a strong genetic influence in these patients. Just look around if any of your family had it. It often runs in a family. My Gran had it, I also think inactivity has a lot to do with it, too, besides Vit D level etc. Thanks to this freezing, damp winter, I was very inactive for the past few months. By this rate, I would be osteoporotic in a few months time, with a strong genetic component and I'm not kidding.

Also, always read these "studies" with a large dose of scepticism, sometimes it depends on who had funded the studies (according to one doctor who told me). Sometimes, it's best not to even bother reading it if you are too anxious or even depressed (not uncommon). It can be a health hazard for those, who worry about what's gonna happen unless you have some sort of "medical" interest.

in reply to

It’s from a group that has a great track record in PMR/GCA Research.

I feel that knowledge is power personally, if you aren’t told of the risks then you can’t do anything to mitigate them.

Polywotsit profile image
PolywotsitPMRGCAuk team member in reply to

This kind of study is really useful because it shows up patterns in large populations of patients as against people who don't have the disease. These big numbers are what health services work from, whereas individuals are interested in the risks they are running personally. If we can demonstrate that there are health costs to steroids than we can argue for alternative treatments.

don't get old, folks. that is the answer!!! (and didn't we just read a recent post study that says there is no difference with side effects for those on or off steroids except for cataracts? Eat drink and be merry....!

PMRpro profile image
PMRproAmbassador in reply to yogabonnie

I do!!!! But actually - I think I'd prefer getting old to the alternative ...

I am someone with fractures due to osteoporosis, starting on Forteo daily injections for 2 years. Apparently the only med that helps to make new bone.

The endocrinologist I have seen, is certain 2 bouts of PMR, 20 years apart, both treated with years of Prednisolone has contributed. Now down to 4 mg so hoping to be off this year.

I keep as active as possible, and only take paracetamol 3 or 4 times a day. And I have and always had a good diet, plenty of dog walking, gardening etc. But I am not in a wheelchair or facing a terminal condition, and have many blessings.

PS, I will never regret taking steroids, they gave me a life without pain, when I needed to keep working etc.

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