Atypical fractures of the lower extremities in two patients with rheumatoid arthritis: clinical presentations of presumed methotrexate osteopathy

We present two patients who developed multiple lower limb stress fractures. Potential causes, such as osteoporosis, malignancies and disturbances in calcium metabolism were investigated. This led the physicians to consider whether methotrexate (MTX) exposure posed a risk of atypical fractures.The association between MTX and lower limb fractures has been described in at least 80 cases in the literature. Stress fractures associated with MTX treatment are atypical of osteoporosis and located in the lower extremities, most often the tibia. The limited data suggest that discontinuation of MTX may improve symptoms and chances of fracture healing, while antiresorptive or osteoanabolic therapies have not proven clinically efficient. It seems evident, however, that the benefits of MTX treatment in rheumatological disease clearly outweigh the risk of MTX osteopathy and related fractures.