Background/Purpose: Methotrexate-induced osteopathy is a rare condition. The clinical presentation is often typical, associating lower limb involvement with metaphyseal bone fractures/cracks, mainly of the tibia or foot bones. The main aim of this study was to identify the affected population and to better describe patients and fracture characteristics and possible risk factors leading to poor clinical evolution.

Methods: We conducted a multicenter retrospective study including all patients identified by a GRIO (osteoporosis research and information group, group of osteoporosis and bone disease specialists) member as a MTX-induced osteopathy. Were included all patients with suggestive clinical and/or imaging presentation, confirmed by a bone expert. Patients not already included and identified by national pharmacovigilance as being suggestive of methotrexate-induced osteopathy were also included, after analysis of the medical file by the principal investigator. The data collected included imaging features (characteristic, location and evolution of the bone lesions), clinical (search for classic causes and risk factors for bone fragility, treatment methods after diagnosis), results of bone mineral density (BMD) at diagnosis and during follow-up if available, biochemical (mainly phosphocalcic metabolism, kidney function).

Results: Between 2012 and 2024, we included a total of 92 patients, identified as affected by MTX-induced osteopathy. Population affected was mainly post-menopausal women (86/92, 93%) with seropositive RA (68/92, 74%), with previous history of major fracture in 22% of patients, and BMD osteoporosis at diagnosis in 56% of patients. The underlying rheumatism was classically considered as inactive or with low disease activity (93%). Prednisone was used in only 34 patients (37%) at diagnosis, with a mean dose of 8 mg (± 7) per day. Site of fracture was mainly on tibial metaphyseal region (88%) or foot bones (49%), with frequent multiple sites at diagnosis (76%) and with frequently repeated fractures in the patient’s recent history (63%). Diagnosis was mainly done using MRI of painful site (84%), but bone scintigraphy was also used (41 patients, 45%) for general skeletal mapping. Management was the discontinuation of methotrexate (79%) with the addition of a complementary treatment in 51 patients (55%). In global population, evolution of fracture (decrease pain and fracture healing) was good in 77% of cases. The critical information was that evolution was good in 91% in case of MTX discontinuation against only 29% in case of MTX continuation (p< 0.001). If we compared patients with good evolution of fracture (n=57) and without good evolution (n=16), only main significant difference between group was MTX continuation (p< 0,001).

Conclusion: Methotrexate-induced osteopathy remains a rare condition but has to be known and searched, especially in cases of pain in the lower limbs of postmenopausal women, not explained by inflammatory activity of the underlying rheumatism. MRI of painful sites or bone scintigraphy appear to be the best choice for diagnosis. In the majority of cases, stopping methotrexate leads to rapid improvement of symptoms and above all avoids the risk of further fractures.

Comparison of evolution according MTX management. n=number

Comparison between good and poor evolution of fracture. N&#3f number, SD = standard deviation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/methofract-a-methotrexate-osteopathy-multicentric-binational-cohort-study/