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Old 04-17-2007, 10:14 PM #11
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Default methotrexate and fractures

I found these abstracts on pubmed which might apply. There's not a lot on methotrexate low-dose causing fractures, but it seems accepted that it does.

Billye, I'm overwhelmed by this--it so sucks. Hope these help in some way.


: Arch Dermatol. 1996 Feb;132(2):184-7.
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Methotrexate osteopathy in long-term, low-dose methotrexate treatment for psoriasis and rheumatoid arthritis.Zonneveld IM, Bakker WK, Dijkstra PF, Bos JD, van Soesbergen RM, Dinant HJ.
Department of Dermatology, Academic Medical Center, University of Amsterdam, The Netherlands.

BACKGROUND: In dermatology and rheumatology, methotrexate is frequently prescribed in low dosages per week; in oncology, high dosages per week are prescribed. Methotrexate osteopathy was first reported in children with leukemia treated with high doses of methotrexate. In animal studies, low doses of methotrexate proved to have an adverse effect on bone metabolism, especially on osteoblast activity.

OBSERVATIONS: Methotrexate osteopathy is a relatively unknown complication of low-dose methotrexate treatment. We describe three patients treated with low-dose oral methotrexate in whom signs and symptoms were present that were similar to those found in children treated with high doses of methotrexate. All three patients had a triad of severe pain localized in the distal tibiae, osteoporosis, and compression fractures of the distal tibia, which could be identified with radiographs, technetium Tc 99m scanning, and magnetic resonance imaging.

CONCLUSIONS: Methotrexate osteopathy can occur in patients treated with low doses of methotrexate, even over a short period of time. As pain is localized in the distal tibia, it is easily misdiagnosed as psoriatic arthritis of the ankle, but the diagnosis can be correctly made by careful investigation and use of imaging techniques. The only therapy is withdrawal of methotrexate. It is important that more physicians become aware of this side effect of methotrexate therapy, which can occur along with arthritic symptoms.



2: Clin Exp Rheumatol. 1995 Sep-Oct;13 Suppl 12:S21-6. Links
Osteoporosis in rheumatoid arthritis.Dequeker J, Maenaut K, Verwilghen J, Westhovens R.
Arthritis and Metabolic Bone Disease Research Unit, K.U. Leuven, Belgium.

OBJECTIVE: To answer and comment on a number of controversial issues in relation to osteoporosis and rheumatoid arthritis (RA), including: Is osteoporosis an extra-articular manifestation of rheumatoid arthritis? Does periarticular osteoporosis reflect disease activity in early arthritis? Is there a threshold for corticosteroid-induced osteoporosis? Can anti-resorbing drugs prevent rheumatoid arthritis progression? Are stress fractures rare in rheumatoid arthritis Is methotrexate toxic for bone?

METHODS: Confrontation of current literature and our own experience in order to formulate a general opinion.

RESULTS AND CONCLUSIONS: Because most studies agree that osteoporosis in postmenopausal women and in men with RA is more evident at the hip and radius than at the spine, and that the most important determinants of bone loss are disability, local disease activity and cumulative corticosteroid dose, osteoporosis is not a common systemic extra-articular manifestation of RA. In early arthritis, periarticular osteoporosis does indeed reflect disease activity because it is closely related to the acute phase reactants, but once periarticular osteoporosis is established it is no longer a marker of disease activity. The threshold does for corticosteroid-induced osteoporotic fractures is the cumulative rather than the actual dose. Statements based on quantitative computed tomography concerning the acute effects (and their reversal) of corticosteroids on bone have to be interpreted with care because of important body composition changes, in particular in bone marrow fat, during corticosteroid treatment. At present there is no evidence that anti-resorbing drugs can change the progress of RA erosions, probably because erosions are the result of non-osteoclast mediated mechanisms. Stress fractures in RA are underdiagnosed and are often confused with synovitis, and therefore it is likely that they are more frequent than commonly thought, in particular at the lower limbs. Methotrexate osteopathy is known in oncological practice. Whether low dose methotrexate is toxic for bone is not clear, but a number of clinical observations suggest that the occurrence of spontaneous fractures and lower extremity pain is more frequent in methotrexate treated patients than expected. Prospective studies are necessary to confirm these impressions.

PMID: 8846540 [PubMed - indexed for MEDLINE]

J Rheumatol. 1996 Dec;23(12):2156-9. Related Articles, Links


Comment in:
J Rheumatol. 1997 Oct;24(10):2051.

Methotrexate osteopathy, does it exist?

Maenaut K, Westhovens R, Dequeker J.

Department of Internal Medicine, K. U. Leuven, Pellenberg, Belgium.

We describe 2 postmenopausal women with rheumatoid arthritis (RA). They developed fractures during their treatment with weekly low dose methotrexate (MTX). The adverse effect of longterm low dose regimens of MTX on bone metabolism has been described as "methotrexate osteopathy," an analogy of the syndrome known in pediatric oncology. MTX may be an additional risk factor for osteoporosis and fractures in RA. This therapy should be relatively contraindicated in patients with multiple risk factors for osteoporosis.

Publication Types:
Case Reports

PMID: 8970056 [PubMed - indexed for MEDLINE]
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Old 04-18-2007, 07:52 AM #12
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Default Thanks folks

Thanks Liza Jane and Dalek,
LJ, I've printed off the abstracts you found and will take them to the rheumie and the neuro. It really does seem to be a crap shoot with the medications, doesn't it?! I'm not sure what to do next. If my husband were better, I'd probably do another trip to Mayo to see what they say and what treatment they'd recommend. We will see what happens next. I'm waiting on doctor's calls now.

Dalek, no one is recommending IVIG at this point. And I really really hate to start that. I don't like being pinned down by a medication like that. Isn't it a once a month dosing?

The neuro said that she wasn't sure what was going on with the increased reflex response and that maybe it was this spinal fracture causing the nerves to be more hyperactive. I know I'm in a lot more pain and I'm irritable and cranky because of it.

Looks like my treatment is all up in the air again.
Billye
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Old 04-18-2007, 09:11 AM #13
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Default Silverlady

Just wanted to send good thoughts that your pain lets up and most important - that they can find you help that will not injure your bones..... is IVIG a viable alternative? Frequency for treatment with it and affect on the recipient is different for every person - I know you went to Mayo about this and at the time it wasnt suggested - any way your current docs can work with Mayo without you having to make another trip?

Take it easy for now - you were doing so wel - I'm sure more of that is right around the corner
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Old 04-18-2007, 10:10 PM #14
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Default not sure

Kmeb,
not sure but I think my neuro will work with Mayo. And my rheumatologist would probably also. I'm to pick up paperwork tomorrow to have some lab tests (bloodwork) done tomorrow and then the rheumatolgist will see me as soon as I get the paperwork back.

I'm just having to learn to throttle back right now. I did discover the large print books at the library and I can read for about 30 min. in the morning and sometimes about the same time in the afternoon. Dry eyes are the pits. Daytime tv is also the same.

Thanks all. I appreciate the support. And Dalek, thanks for thinking of me when you have so much on your plate. You too Kmeb. to both of you.

Billye
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Old 04-19-2007, 11:15 AM #15
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Red face sorry to be late in here on this thread...

I've been working alot more ( the job found some day shifts for me)..

I don't recall Billye if you are using antidepressants. But some new studies have come up showing SSRIs lead to more bone fractures. (reduced bone mineral density).

I am sorry to learn you have to deal with this new challenge! It is a real bummer!
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Old 04-19-2007, 12:02 PM #16
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Default Nope

Hi Mrs. D,
I thought you were going to quit working so hard.

No I'm not taking any anti-depressants. You are right, it is a bummer.

Thanks for the info tho. I'll pass it on.

Billye
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Old 04-19-2007, 11:55 PM #17
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Default Gee Billye

What next? I am so sorry... Like me, I think you should have sent hubby to medical school...
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Old 04-20-2007, 07:12 AM #18
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Default So, what to do?

Isn't this the question?

For you the meds worked, albiet for a while...IF you find a connection between the bone loss and the meds - report it to the FDA, it's easy. You can report to each med mfr...they are supposed to report it to the FDA but not always. I've found that docs who should report don't. IF no one knows about the fact that med combos could/can cause other problems, nothing happens. There's so much NOT known about long term use. Reporting is the only way s/e's could be known. Once the mfrs. get their approval, they really don't bother looking for s/e's or problems unless forced to. There! I've got that off my chest.

As for having stuff on my plate, looks like I'll be able to 'stuff' it all down the disposal when I see the new doc soon. I HOPE! Maybe surgery, maybe new meds...what the heck! What's one more?

Hugs Billye, may you stop doing this and start doing this! - j
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