TOPLINE:

Methotrexate-induced osteopathy is a rare but significant condition, predominantly affecting postmenopausal women with rheumatoid arthritis or psoriatic arthritis. In patients using methotrexate who presented with stress fractures of the lower limbs, early confirmation with MRI or bone scintigraphy could aid diagnosis and discontinuation of methotrexate should be considered.

METHODOLOGY:

• Researchers conducted a multicenter retrospective study involving 92 patients with methotrexate‑induced osteopathy to characterize the affected population, describe fracture patterns, and identify risk factors for poor outcomes.
• Methotrexate-induced osteopathy was diagnosed when pain in the lower limbs occurred together with concordant findings on radiography, MRI, or bone scintigraphy — most commonly atraumatic stress fractures of the metaphyses or fractures of the foot — in patients receiving methotrexate at the time of diagnosis.
• Demographic and clinical data of participants were collected at baseline; treatment data on weekly and cumulative doses of methotrexate, route of administration, treatment duration, and corticosteroid use and dose at diagnosis were also collected.
• The location of fracture sites at diagnosis and any prior fractures, imaging modalities used for diagnosis (radiography, bone scintigraphy, PET, and MRI), and measurements of bone mineral density were recorded.

TAKEAWAY:

• Patients were mostly postmenopausal women with rheumatoid arthritis or psoriatic arthritis; they received standard rheumatologic doses of methotrexate with a mean dose of 18.3 mg/wk, mean treatment duration of 123 months, and mean cumulative dose of 8.5 g.
• Majority of the patients (88%) had tibial involvement, and 49% had foot fractures; 76% had multiple fractures at diagnosis, with 63% experiencing recurrent fractures over time.
• Initial diagnostic imaging was predominantly radiography (93%); more precise assessment was obtained with MRI in 84% of patients and with bone scintigraphy in 46%.
• Methotrexate discontinuation was a therapeutic option in 77% of patients; favorable evolution occurred in 91% of patients who discontinued methotrexate compared with 29% of those who continued it (P < .001).

IN PRACTICE:

“Clinicians should bear in mind that the benefits of using MTX [methotrexate] far outweigh the risk of developing this osteopathy in most cases,” the authors wrote.

SOURCE:

The study was led by François Robin, MD, PhD, Rennes University Hospital in Rennes, France. It was published online on September 25, 2025, in RMD Open.

LIMITATIONS:

The retrospective nature of this study with potential bias is a major limitation. Due to the study design, the researchers could not make conclusions on the efficacy of associated specific bone therapy on fracture evolution. Additionally, the patients presented multiple risk factors for bone fragility, including prolonged corticosteroid therapy, which could influence bone phenotypes. 

DISCLOSURES:

The study did not receive any funding. The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.