TY - JOUR T1 - Fractures of the Proximal Tibia Associated with Longterm Use of Methotrexate: 3 Case Reports and a Review of Literature JF - The Journal of Rheumatology JO - J Rheumatol SP - 2434 LP - 2438 DO - 10.3899/jrheum.100385 VL - 37 IS - 11 AU - LOUISE MEIER AU - ANNE-MOON van TUYLL van SERSOOSKERKEN AU - ELLEN LIBERTON AU - LUCAS KLEIJN AU - TOON WESTGEEST AU - MARTIN POLAK AU - RON de NIJS Y1 - 2010/11/01 UR - http://www.jrheum.org/content/37/11/2434.abstract N2 - To the Editor:There are several therapeutic options for which methotrexate (MTX) represents an excellent choice as systemic therapy for mild to severe psoriasis, psoriatic arthritis, and rheumatoid arthritis (RA). MTX is a folic acid antagonist, inhibiting dihydrofolate reductase, an enzyme that converts dihydrofolate to tetrahydrofolate. Impedance of this reaction interferes with purine synthesis and DNA biosynthesis, resulting in dysfunction of DNA replication, followed by cell death1. MTX is commonly used in high doses for the treatment of malignancies, and in lower doses (up to 30 mg once weekly) for autoimmune diseases such as RA and psoriasis2.MTX osteopathy was first described in children with leukemia who were treated with high doses of MTX and was characterized by bone pain, localized osteopenia, and sometimes even microfractures1,3. Some studies suggest also that longterm use of low-dose MTX can aggravate the development of osteopenia and stress fractures1,4,5.Here we describe 3 patients with proximal tibia fractures treated with a low to intermediate dose of MTX. A 51-year-old white woman presented with increasing pain in both knees. Her medical history included a left ankle fracture, a right meniscectomy, and enthesopathy based on psoriasis. Her body weight was 80 kg with a height of 165 cm. She denied any severe trauma preceding her complaints. Her family history was negative for rheumatism and associated symptoms and she has been treated for psoriasis with MTX (maximum dosage 15 mg once weekly) for 12 years. Further medication included pantoprazole (20 mg once daily) and mianserin (30 mg once daily). Folic acid was not prescribed, nor was preventive medication for osteoporosis such as calcium or biphosphonates. On physical examination there were no signs of arthritis. Both knees had crepitus with flexion and extension. The … Address correspondence to L. Meier, Department of Rheumatology, Máxima Medical Center Eindhoven, Postbox 90052, 5600PD Eindhoven, The Netherlands. E-mail: L.Meier{at}mmc.nl ER -