Clinical and Radiological Characterization of Patients with Immobilizing and Progressive Stress Fractures in Methotrexat
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ORIGINAL RESEARCH
Clinical and Radiological Characterization of Patients with Immobilizing and Progressive Stress Fractures in Methotrexate Osteopathy Tim Rolvien1,2 · Nico Maximilian Jandl1,2 · Julian Stürznickel1 · Frank Timo Beil2 · Ina Kötter3 · Ralf Oheim1 · Ansgar W. Lohse4 · Florian Barvencik1 · Michael Amling1 Received: 17 August 2020 / Accepted: 29 September 2020 © The Author(s) 2020
Abstract Methotrexate (MTX) is one of the most commonly prescribed drugs for autoimmune rheumatic diseases. As there is no consensus on its negative effects on bone, the purpose of this investigation was to determine the clinical spectrum of patients with stress fractures due to long-term MTX treatment (i.e., MTX osteopathy). We have retrospectively analyzed data from 34 patients with MTX treatment, severe lower extremity pain and immobilization. MRI scans, bone turnover markers, bone mineral density (DXA) and bone microarchitecture (HR-pQCT) were evaluated. Stress fractures were also imaged with cone beam CT. While the time between clinical onset and diagnosis was prolonged (17.4 ± 8.6 months), the stress fractures had a pathognomonic appearance (i.e., band-/meander-shaped, along the growth plate) and were diagnosed in the distal tibia (53%), the calcaneus (53%), around the knee (62%) and at multiple sites (68%). Skeletal deterioration was expressed by osteoporosis (62%) along with dissociation of low bone formation and increased bone resorption. MTX treatment was discontinued in 27/34 patients, and a combined denosumab–teriparatide treatment initiated. Ten patients re-evaluated at follow-up (2.6 ± 1.5 years) had improved clinically in terms of successful remobilization. Taken together, our findings provide the first in-depth skeletal characterization of patients with pathognomonic stress fractures after long-term MTX treatment. Keywords Methotrexate · Stress fracture · MTX osteopathy · Cone beam CT · Denosumab · Teriparatide
Introduction Tim Rolvien and Nico Maximilian Jandl contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00223-020-00765-5) contains supplementary material, which is available to authorized users. * Michael Amling [email protected]‑hamburg.de 1
Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Lottestraße 59, 22529 Hamburg, Germany
2
Department of Orthopedics, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
3
3rd Department of Medicine (Rheumatology), University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
4
1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
Methotrexate (MTX) is a folate antagonist that is used in low doses (5–25 mg/week) in the first-line treatment of rheumatoid arthritis (RA), as well as in other inflammatory diseases such as systemic lupus erythematosus (SLE). It acts by inhibiting dihydrofolate reductase, which is an
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