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<p>Low-dose methotrexate (MTX; 5–25 mg/week) is widely used as first-line therapy for autoimmune diseases such as rheumatoid arthritis (RA). In addition to its well-established anti-inflammatory effects, rare skeletal toxicities have been described. Methotrexate-induced osteopathy (MTX osteopathy) is characterized by insufficiency fractures, predominantly affecting weight-bearing bones of the lower extremities. The pathophysiology is multifactorial and incompletely understood, involving impaired bone formation and increased osteoclastic activity. While large cohort studies reported no significant bone mineral density loss under low-dose MTX, an increasing number of case series have described clinically relevant fractures. Magnetic resonance imaging (MRI) is superior to conventional radiographs for diagnosis, revealing early bone marrow edema and band-shaped insufficiency fractures in the metaphyseal regions. Therapeutic strategies include MTX discontinuation, mechanical offloading, sufficient vitamin&#xa0;D supplementation, and—depending on individual risk profiles—anabolic or antiresorptive bone-targeted therapies. Novel agents such as romosozumab might offer additional benefits, although controlled trials are lacking. Due to nonspecific clinical symptoms and low radiographic sensitivity, MTX osteopathy is often underrecognized. Rheumatologists should consider MTX osteopathy in patients receiving long-term MTX therapy who develop chronic, load-dependent pain of the lower limbs.</p>

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MTX-Osteopathie in der rheumatologischen Praxis

  • 期刊论文

  • 发表日期：

    2025年7月25日

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  • Anton Sokhan,
  • Judith Haschka,
  • Zora Messner,
  • Roland Kocijan

摘要

Low-dose methotrexate (MTX; 5–25 mg/week) is widely used as first-line therapy for autoimmune diseases such as rheumatoid arthritis (RA). In addition to its well-established anti-inflammatory effects, rare skeletal toxicities have been described. Methotrexate-induced osteopathy (MTX osteopathy) is characterized by insufficiency fractures, predominantly affecting weight-bearing bones of the lower extremities. The pathophysiology is multifactorial and incompletely understood, involving impaired bone formation and increased osteoclastic activity. While large cohort studies reported no significant bone mineral density loss under low-dose MTX, an increasing number of case series have described clinically relevant fractures. Magnetic resonance imaging (MRI) is superior to conventional radiographs for diagnosis, revealing early bone marrow edema and band-shaped insufficiency fractures in the metaphyseal regions. Therapeutic strategies include MTX discontinuation, mechanical offloading, sufficient vitamin D supplementation, and—depending on individual risk profiles—anabolic or antiresorptive bone-targeted therapies. Novel agents such as romosozumab might offer additional benefits, although controlled trials are lacking. Due to nonspecific clinical symptoms and low radiographic sensitivity, MTX osteopathy is often underrecognized. Rheumatologists should consider MTX osteopathy in patients receiving long-term MTX therapy who develop chronic, load-dependent pain of the lower limbs.