The Effect of Low Dose Methotrexate on Fracture Healing

Introduction Low dose methotrexate treatment (10-25 mg./week) is today considered the first choice disease-modifying agent (DMARD) for adult and juvenile rheumatoid arthritis. Methotrexate (MTX) has proven to be a safe and effective drug with relatively few side effects. Being a folate antagonist, MTX was originally designed for use in the treatment of malignancy. From the oncological practice, where MTX is used in high doses (500-1500 mg. repeatedly), there have been reports on an increased risk of spontaneous fractures and osteopathy. From this reason, ongoing anti-rheumatic MTX treatment is often discarded preand postoperatively when orthopedic surgery is performed in the patients with rheumatoid arthritis (RA). Many times this will cause a flare up in the disease activity, leading to increased pain, joint stiffness and thus problems during the rehabilitation period. However, when used as a DMARD in RA, the impact of MTX on bone metabolism, fracture healing and prosthesis in growth is not well understood. The aim of the present study therefore was to assess the early process of fracture healing during low dose MTX treatment, in an experimental fracture model. The evaluation included histomorphometrical analysis of new bone formation and an assessment of the local inflammatory reaction, using immunostaining of tissue macrophages.