Dimethyl fumarate–associated transient bone marrow oedema syndrome

James Triplett, Srimathy Vijayan, Richard Prince, Allan Kermode

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Dimethyl fumarate (DMF) is a commonly used and effective treatment for relapsing and remitting multiple sclerosis. Its use results in impairment of the transcription factor nuclear factor erythroid-derived 2 (E2)-related factor (Nrf2), which is involved in both immunomodulation and bone health. DMF has not previously been reported to cause bone marrow complications, though other fumarates including tenofovir have. The mechanism of fumarate-associated bone toxicity remains unclear with altered osteoblastic gene expression and function suggested. Methods: We present a case of a 54-year-old female with relapsing remitting multiple sclerosis (RRMS) treated for 30 months with DMF who developed relapsing atraumatic lower limb bone pain. Results: Serial imaging revealed multifocal areas of bone marrow oedema and trabecular fractures. The patient was diagnosed with transient bone marrow oedema syndrome. Management consisted of cessation of therapy and treatment with the pro-osteobalstic agent denosumab. Conclusion: In this instance of DMF-associated bone marrow oedema, cessation of DMF and treatment with denosumab resulted in symptomatic improvement. DMF therapy may potentially result in bone marrow oedema due to inhibition of common upstream signalling pathways, including the Nrf2 signalling pathway.

Original languageEnglish
Pages (from-to)876-879
JournalMultiple Sclerosis Journal
Volume25
Issue number6
DOIs
Publication statusPublished - May 2019

Fingerprint

Edema
Bone Marrow
Relapsing-Remitting Multiple Sclerosis
Fumarates
Tenofovir
Bone and Bones
NF-E2 Transcription Factor
Withholding Treatment
Immunomodulation
Therapeutics
Dimethyl Fumarate
Lower Extremity
Gene Expression
Pain
Health
Denosumab

Cite this

@article{7908b335a4bc4f66a1df2267649795b9,
title = "Dimethyl fumarate–associated transient bone marrow oedema syndrome",
abstract = "Background: Dimethyl fumarate (DMF) is a commonly used and effective treatment for relapsing and remitting multiple sclerosis. Its use results in impairment of the transcription factor nuclear factor erythroid-derived 2 (E2)-related factor (Nrf2), which is involved in both immunomodulation and bone health. DMF has not previously been reported to cause bone marrow complications, though other fumarates including tenofovir have. The mechanism of fumarate-associated bone toxicity remains unclear with altered osteoblastic gene expression and function suggested. Methods: We present a case of a 54-year-old female with relapsing remitting multiple sclerosis (RRMS) treated for 30 months with DMF who developed relapsing atraumatic lower limb bone pain. Results: Serial imaging revealed multifocal areas of bone marrow oedema and trabecular fractures. The patient was diagnosed with transient bone marrow oedema syndrome. Management consisted of cessation of therapy and treatment with the pro-osteobalstic agent denosumab. Conclusion: In this instance of DMF-associated bone marrow oedema, cessation of DMF and treatment with denosumab resulted in symptomatic improvement. DMF therapy may potentially result in bone marrow oedema due to inhibition of common upstream signalling pathways, including the Nrf2 signalling pathway.",
keywords = "bone marrow oedema, Dimethyl fumarate, multiple sclerosis",
author = "James Triplett and Srimathy Vijayan and Richard Prince and Allan Kermode",
year = "2019",
month = "5",
doi = "10.1177/1352458518791132",
language = "English",
volume = "25",
pages = "876--879",
journal = "Multiple Sclerosis",
issn = "1352-4585",
publisher = "SAGE Publications Ltd",
number = "6",

}

Dimethyl fumarate–associated transient bone marrow oedema syndrome. / Triplett, James; Vijayan, Srimathy; Prince, Richard; Kermode, Allan.

In: Multiple Sclerosis Journal, Vol. 25, No. 6, 05.2019, p. 876-879.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Dimethyl fumarate–associated transient bone marrow oedema syndrome

AU - Triplett, James

AU - Vijayan, Srimathy

AU - Prince, Richard

AU - Kermode, Allan

PY - 2019/5

Y1 - 2019/5

N2 - Background: Dimethyl fumarate (DMF) is a commonly used and effective treatment for relapsing and remitting multiple sclerosis. Its use results in impairment of the transcription factor nuclear factor erythroid-derived 2 (E2)-related factor (Nrf2), which is involved in both immunomodulation and bone health. DMF has not previously been reported to cause bone marrow complications, though other fumarates including tenofovir have. The mechanism of fumarate-associated bone toxicity remains unclear with altered osteoblastic gene expression and function suggested. Methods: We present a case of a 54-year-old female with relapsing remitting multiple sclerosis (RRMS) treated for 30 months with DMF who developed relapsing atraumatic lower limb bone pain. Results: Serial imaging revealed multifocal areas of bone marrow oedema and trabecular fractures. The patient was diagnosed with transient bone marrow oedema syndrome. Management consisted of cessation of therapy and treatment with the pro-osteobalstic agent denosumab. Conclusion: In this instance of DMF-associated bone marrow oedema, cessation of DMF and treatment with denosumab resulted in symptomatic improvement. DMF therapy may potentially result in bone marrow oedema due to inhibition of common upstream signalling pathways, including the Nrf2 signalling pathway.

AB - Background: Dimethyl fumarate (DMF) is a commonly used and effective treatment for relapsing and remitting multiple sclerosis. Its use results in impairment of the transcription factor nuclear factor erythroid-derived 2 (E2)-related factor (Nrf2), which is involved in both immunomodulation and bone health. DMF has not previously been reported to cause bone marrow complications, though other fumarates including tenofovir have. The mechanism of fumarate-associated bone toxicity remains unclear with altered osteoblastic gene expression and function suggested. Methods: We present a case of a 54-year-old female with relapsing remitting multiple sclerosis (RRMS) treated for 30 months with DMF who developed relapsing atraumatic lower limb bone pain. Results: Serial imaging revealed multifocal areas of bone marrow oedema and trabecular fractures. The patient was diagnosed with transient bone marrow oedema syndrome. Management consisted of cessation of therapy and treatment with the pro-osteobalstic agent denosumab. Conclusion: In this instance of DMF-associated bone marrow oedema, cessation of DMF and treatment with denosumab resulted in symptomatic improvement. DMF therapy may potentially result in bone marrow oedema due to inhibition of common upstream signalling pathways, including the Nrf2 signalling pathway.

KW - bone marrow oedema

KW - Dimethyl fumarate

KW - multiple sclerosis

UR - http://www.scopus.com/inward/record.url?scp=85052224435&partnerID=8YFLogxK

U2 - 10.1177/1352458518791132

DO - 10.1177/1352458518791132

M3 - Article

VL - 25

SP - 876

EP - 879

JO - Multiple Sclerosis

JF - Multiple Sclerosis

SN - 1352-4585

IS - 6

ER -