Methotrexate continuation increases fracture risk in patients who sustained lower limb insufficiency fractures

Hauser, B; Merriman, A; Foley, J; Golla, J; McRorie, E; Ralston, SH

doi:10.1016/j.ard.2025.01.047

Osteoporosis & bone health

Methotrexate continuation increases fracture risk in patients who sustained lower limb insufficiency fractures

Ann Rheum DisPublished 22 Feb 2025Retrospective cohort study

Main finding · Further fracture after initial insufficiency fractureResultχ2 13.4

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Authors' conclusion

In patients with MTXO insufficiency fractures, continuation of MTX is associated with a high risk of further fracture.

Study context

Population: Patients with characteristic methotrexate (MTX) osteopathy (methotrexate osteopathy (MTXO)) lower limb insufficiency fractures; mean MTX dose 20 ± 5.9 mg weekly, treatment duration 10.7 ± 6.2 years32 analysed
Participants: 33 patients

Exposure: MTX continuation vs discontinuation after an initial MTXO insufficiency fracture
Continued MTXn = 21
Stopped MTXn = 11reference
Outcome: Occurrence of subsequent fractures after the initial insufficiency fracture

Methodological detailssingle-centre, case note review

Single-centre
Case note review

Main finding

As reported in the abstract

Further fracture after initial insufficiency fracture

χ2

13.4

P < 0.001

Events by group

Continued MTX95.2%

Stopped MTX27.3%3 of 11

Among those continuing MTX: further insufficiency fractures: 67%
Among those continuing MTX: major osteoporotic fractures: 33%

Observational data: associations, not effects.

Further findings

Clinical improvement in pain during fracture healing · Discontinuation of MTX vs continuation

P = 0.036

Continued MTX36.4%

Stopped MTX77.8%

Clinical improvement in weight-bearing capacity during fracture healing · Discontinuation of MTX vs continuation

P = 0.030

Continued MTX22.7%

Stopped MTX71.4%

Further fracture over time (Kaplan-Meier analysis): P = 0.042

Further fracture over time (Kaplan-Meier analysis): significantly increased number of patients who continued MTX sustained a further fracture over time

Clinical improvement in pain during fracture healing

Discontinuation of MTX associated with greater clinical improvement in pain (77.8% vs 36.4%)

Clinical improvement in weight-bearing capacity during fracture healing

Discontinuation of MTX associated with greater improvement in weight-bearing capacity (71.4% vs 22.7%)

Original publication

Methotrexate continuation increases fracture risk in patients who sustained lower limb insufficiency fractures. Ann Rheum Dis. Published 22 February 2025. doi:10.1016/j.ard.2025.01.047

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