RESEARCH - Low-dose MTX does not deplete bone in RA

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Low-dose methotrexate does not deplete bone in RA

Rheumawire

Aug 25 2004

Mann

Pisa, Italy - Low-dose methotrexate (MTX) does not appear to deplete

bone-mineral density (BMD) in women with rheumatoid arthritis (RA),

according to new research in the July 2004 issue of the Journal of

Rheumatology [1].

" In my opinion, at the doses routinely used in RA, MTX is safe with

respect to bone health. Nevertheless, patients with RA are at increased

risk for osteoporosis due to nondisease- and disease-specific factors

such as glucocorticoid use. Rheumatologists should be concerned about

this risk, and recommended measures for prevention and treatment of

osteoporosis should be carefully considered, " lead author Dr Ombretta di

Munno (University of Pisa, Italy) tells rheumawire.

In this multicenter, cross-sectional study of 731 female patients with

RA, participants were divided into 2 groups on the basis of MTX use,

including 485 never-users and 256 patients who took MTX for at least 6

months. Researchers found no negative effect of low-dose MTXranging from

7.5 to 20 mg/weekat either the cortical or trabecular sites.

Di Munno et al collected demographic, disease, and treatment-related

variables for each patient. BMD was measured at lumbar spine and

proximal femur by dual-energy x-ray absorptiometry. In the study,

osteoporosis was defined as BMD <2.5 T-score.

The frequency of osteoporosis was similar among never MTX users (29.1%)

and MTX users (28.3%, p=NS) at the lumbar spine. The frequency of

osteoporosis at the femoral neck was also similar: 34.8% vs 37.8%

(p=NS). Mean T-score values at lumbar spine and femoral neck were

comparable in the 2 groups, even after adjusting for age, menopausal

status, body mass index (BMI), Health Assessment Questionnaire (HAQ)

score, and steroid use, the study showed.

" On the basis of this cross-sectional study carried out in female RA

patients giving low-dose MTX (range 7.5-20 mg/week), MTX use was not

associated with bone loss. Our data are in keeping with other

cross-sectional and longitudinal studies using comparable dosages that

are commonly recommended in RA. However, because 'in vitro studies' have

documented that the effects of MTX on bone are dose-related, higher

dosages used to treat diseases such as polymyalgia rheumatica,

refractory RA, or psoriatic arthritis may be associated with negative

changes on bone mass and bone turnover, " di Munno says. The

investigators emphasize that these results should not be extrapolated to

patients treated with higher doses of MTX, which are increasingly being

used in RA.

MTX use was not an independent predictor of BMD; however, age,

menopause, BMI, HAQ score, and steroid use were significant independent

predictors of BMD at lumbar or femoral level, the researchers report. A

logistic procedure showed that only age, HAQ score, and BMI were

significantly associated with the risk of osteoporosis.

Patients were classified as never MTX users or current MTX users.

Current MTX users were further divided into 3 subgroups depending on the

duration of treatment. Subgroups included RA patients taking MTX for

less than 6 months, 6 months to 2 years, or more than 2 years. Only data

from patients treated with MTX for more than 6 months were included in

the new analysis. Among MTX users, 124 had been treated for 6 months to

2 years and 122 had been treated for more than 2 years.

Steroid use was evaluated, and patients were also interviewed about past

or current use of drugs affecting bone metabolism, including estrogens,

bisphosphonates, calcium, vitamin D, calcitonin, anabolic steroids,

fluoride, and thiazides. At the time of recruitment, 50.3% of

postmenopausal patients were treated with drugs affecting bone

metabolism. Researchers also performed statistical analysis after

excluding 98 patients taking bisphosphonates and 13 taking hormone

replacement therapy (HRT) and still found that MTX use did not deplete

bone.

Compared with never MTX users, MTX users had longer disease duration and

higher erythrocyte sedimentation rate (ESR), HAQ score, and number of

swollen joints and a higher frequency of erosive disease. More MTX users

were in a Steinbrocker functional class 3 or 4 and were taking steroids

(80.5% vs 55.7%).

Di Munno applies several caveats to the study conclusions, including the

warning that the investigators had no information about the duration of

current or past MTX therapy or the cumulative MTX doses in these

patients. Another limitation is that no information about folinic acid

supplementation was available. Di Munno points out that folinic acid,

given to prevent MTX-related toxicity, affects osteoblast cells and may

prevent osteoporosis.

Source

Di Munno O, Mazzantini M, Sinigaglia L, et al. Effect

of low dose methotrexate on bone density on women with rheumatoid

arthritis: Results from a Multicenter Cross sectional study. J

Rheumatol 2004; 31:1305-1309.

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