Methotrexate osteopathy: five cases and systematic literature review

Area of Science:

• Rheumatology
• Bone Metabolism
• Pharmacology

Background:

• Methotrexate (MTX)-related osteopathy is a rare condition.
• It is defined by pain, osteoporosis, and atypical fractures.
• Initially observed in children with acute leukemia, it also affects patients with inflammatory diseases on low-dose MTX.

Purpose of the Study:

• To report the largest cohort of MTX-related osteopathy cases outside of oncology.
• To analyze clinical data and investigate pathophysiological mechanisms.
• To raise awareness among rheumatologists regarding this rare condition.

Main Methods:

• Systematic review of cases from Rennes University Hospital's Rheumatology Department.
• Data collection included demographics, MTX/corticosteroid doses, fracture details, and bone densitometry.
• A comprehensive literature review was performed to understand MTX osteopathy's pathophysiology.

Main Results:

• Five new cases of MTX osteopathy were identified, forming the largest reported cohort (excluding oncology).
• Fractures were atypical; all patients improved after MTX withdrawal, with some requiring antiresorptive treatment.
• Cellular studies indicated MTX toxicity affects osteoblasts, osteocytes, chondrocytes, and osteoclasts, potentially altering bone cell mechano-transduction.

Conclusions:

• MTX osteopathy, though rare, requires rheumatologist awareness, particularly in patients with inflammatory conditions.
• The exact mechanisms remain unclear, but a dose-dependent effect of MTX on bone-forming cells is suspected.
• This study presents the largest case series, contributing to understanding MTX's impact on bone health.