METHOFRACT, a methotrexate osteopathy multicentre cohort study

Abstract

Methotrexate-induced osteopathy (MTX-IO) is a rare condition typically involving the lower limbs, especially tibia or foot fractures, among patients with well-controlled rheumatoid arthritis (RA) or psoriatic arthritis (PsA). This study aimed to identify the affected population, describe fracture characteristics and identify risk factors for poor clinical outcome. A multicentre retrospective study included patients with MTX-IO diagnosed by bone specialists or identified through French pharmacovigilance. The data collected included clinical presentation, imaging features, bone mineral density and biochemical markers. Between 2012 and 2024, 92 patients were included, predominantly postmenopausal women with seropositive RA. A history of major fractures was noted for 22% of the patients, and 56% presented osteoporosis at diagnosis. Fractures were most common in the tibial metaphysis (distal and proximal) (88%) and the foot bones (49%), with multiple fractures often present at diagnosis (76%), and frequently repeated fractures in the patients' recent histories (63%). Diagnosis was conducted using MRI of the painful sites (84%), but bone scintigraphy was also used (41 patients, 45%). Management involved methotrexate discontinuation in 79% of the cases. Fracture healing and pain relief were achieved in 77% of the cases, with a significant difference in outcomes between those who discontinued methotrexate (91%) versus those who continued (29%) (p<0.001). MTX-IO is a rare but significant condition, especially among postmenopausal women with RA or PsA. Early diagnoses via MRI or bone scintigraphy and the discontinuation of methotrexate are critical, as stopping the drug significantly improves outcomes and prevents further fractures.

Keywords: Methotrexate; Osteoporosis; Pain.

Figure 1. Standard fracture aspect and location in methotrexate osteopathy. (A) Transversal fracture of the femoral distal metaphysis (T1 on the right and T2 weighted MRI on the left); (B) fracture of the lateral cuneiform (T1 on the right and T2 weighted MRI on the left); (C) association of bilateral transversal fracture of the proximal and distal tibial metaphysis (T1 on the right and T2 weighted MRI on the left), (D) bone scintigraphy aspect with fracture of distal and proximal tibial metaphysis.

Figure 2. Comparison of evolution according to MTX management. Poor evolution was defined as persistent pain, recurrent fractures or delayed healing. MTX, methotrexate.