Effect of methotrexate and sulphasalazine on UMR 106 rat osteosarcoma cells

Methotrexate is commonly used in the treatment of rheumatoid arthritis. Anosteopathy has been described in children treated with methotrexate forleukaemia, consisting of bone pain, osteoporosis and fractures. Animalsgiven short-term high-dose and long-term low-dose methotrexate have bothreduced bone formation and increased resorption on histomorphometry. Aspatients with rheumatic diseases have numerous risk factors forosteoporosis, possible additional risk from low-dose methotrexate is ofrelevance to the rheumatologist. To investigate further the mechanism ofosteoporosis in animals and man, in vitro studies were carried out on anosteoblast cell line, using concentrations found in patients with rheumaticdisease. UMR 106 rat osteoblast-like osteosarcoma cells were incubated withmethotrexate, and also with sulphasalazine, an anti-rheumatic drug with noknown effect on bone, for comparison. A dose-dependent toxic effect ofmethotrexate on the cell line was observed using concentrations found inpatients with rheumatic disease. This was not observed with sulphasalazine.The reduced bone formation observed in animals and man may be due to adirect effect of methotrexate on the osteoblast.