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We read with interest the comments by Rozin and by Quinn and colleagues about our recent publication on low dose methotrexate (MTX) osteopathy in a patient with polyarticular juvenile idiopathic arthritis. Our report was not intended to suggest that MTX osteopathy may be more common than expected, and we agree that reported cases of low dose MTX osteopathy are exceedingly rare compared with the number of patients treated with MTX. Certainly, at a first glance it might not be very surprising that this patient developed serial insufficiency bone fractures after 25 years of prednisone treatment. However, the temporal association with the introduction of MTX and the multiplicity of fractures was striking.
We acknowledge that we did not provide further information about other possible factors that might have influenced the risk fracture in this patient. This 35 year old woman was not menopausal, did not smoke, and had a normal diet, and her physical activity was markedly restricted as her polyarticular joint involvement was severe. Unfortunately, family history of osteoporosis and bone mineral density were not assessed.
We disagree with Rozin about his interpretation of the technetium-99m diphosphonate bone survey. The multiple areas of increased uptake are asymmetric, which would be unlikely for a flare of polyarticular juvenile idiopathic arthritis. Moreover, the enhanced uptake which was localised to the femoral condyles and right calcaneum is not compatible with joint involvement. The increased uptake is certainly too marked and too diffuse to be related to multiple enthesopathies, which would also be very unusual clinical features in this type of inflammatory rheumatism. In a scintigraphic study of the cruciate deficiency model of knee arthritis in dog, the uptake ratio (unstable knee/contralateral knee) did not exceed 2.0 (controls value: 1.0 to 0.10).1 Conversely, in a semiquantitative (“scintimetric”) 99mTc diphosphonate scintigraphic follow up study of patients with peripheral fractures, the uptake ratio (fracture/normal reference site) was much higher (5.0 to 8.0).2 In our patient the uptake ratio was 5.5 and 3.7 for the left knee/right knee and right calcaneum/left calcaneum, respectively, which is further evidence for the diagnosis of multiple fractures.
Data for the in vitro effect of MTX on osteoblasts are conflicting, but we agree with Rozin and Quinn and colleagues that the in vivo effect assessed on bone mineral density is reassuring in most studies.3–6 Moreover, better control of the inflammatory arthritis should allow an increase of physical activity, which in turn may improve osteoporosis. The hypothesis of bone hypersensitivity or idiosyncrasy to MTX that is discussed by Rozin is only speculative, but appealing. Finally, we obviously concur with both comments and agree that such an exceptional observation of MTX osteopathy should certainly not deter from the use of MTX in idiopathic juvenile arthritis or other inflammatory arthritides when it is indicated.
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