The Natural History of Flare-Ups in Fibrodysplasia Ossificans Progressiva (FOP): A Comprehensive Global Assessment

Robert J. Pignolo, Christopher Bedford-Gay, Moira Liljesthröm, Blythe P. Durbin-Johnson, Eileen M. Shore, David M Rocke, Frederick S. Kaplan

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Fibrodysplasia ossificans progressiva (FOP) leads to disabling heterotopic ossification (HO) from episodic flare-ups. However, the natural history of FOP flare-ups is poorly understood. A 78-question survey on FOP flare-ups, translated into 15 languages, was sent to 685 classically-affected patients in 45 countries (six continents). Five hundred patients or knowledgeable informants responded (73%; 44% males, 56% females; ages: 1 to 71 years; median: 23 years). The most common presenting symptoms of flare-ups were swelling (93%), pain (86%), or decreased mobility (79%). Seventy-one percent experienced a flare-up within the preceding 12 months (52% spontaneous; 48% trauma-related). Twenty-five percent of those who had received an intramuscular injection reported an immediate flare-up at the injection site, 84% of whom developed HO. Axial flare-ups most frequently involved the back (41.6%), neck (26.4%), or jaw (19.4%). Flare-ups occurred more frequently in the upper limbs before 8 years of age, but more frequently in the lower limbs thereafter. Appendicular flare-ups occurred more frequently at proximal than at distal sites without preferential sidedness. Seventy percent of patients reported functional loss from a flare-up. Thirty-two percent reported complete resolution of at least one flare-up and 12% without any functional loss (mostly in the head or back). The most disabling flare-ups occurred at the shoulders or hips. Surprisingly, 47% reported progression of FOP without obvious flare-ups. Worldwide, 198 treatments were reported; anti-inflammatory agents were most common. Seventy-five percent used short-term glucocorticoids as a treatment for flare-ups at appendicular sites. Fifty-five percent reported that glucocorticoids improved symptoms occasionally whereas 31% reported that they always did. Only 12% reported complete resolution of a flare-up with glucocorticoids. Forty-three percent reported rebound symptoms within 1 to 7 days after completing a course of glucocorticoids. This study is the first comprehensive global assessment of FOP flare-ups and establishes a critical foundation for the design and evaluation of future clinical trials.

Original languageEnglish (US)
Pages (from-to)650-656
Number of pages7
JournalJournal of Bone and Mineral Research
Volume31
Issue number3
DOIs
StatePublished - Mar 1 2016

Fingerprint

Myositis Ossificans
Natural History
Glucocorticoids
Heterotopic Ossification
Intramuscular Injections
Jaw
Upper Extremity
Hip
Lower Extremity
Anti-Inflammatory Agents
Neck
Language
Head
Clinical Trials
Pain
Injections
Wounds and Injuries
Therapeutics

Keywords

  • CLINICAL TRIALS
  • EPIDEMIOLOGY
  • FIBRODYSPLASIA OSSIFICANS PROGRESSIVA
  • FOP

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Pignolo, R. J., Bedford-Gay, C., Liljesthröm, M., Durbin-Johnson, B. P., Shore, E. M., Rocke, D. M., & Kaplan, F. S. (2016). The Natural History of Flare-Ups in Fibrodysplasia Ossificans Progressiva (FOP): A Comprehensive Global Assessment. Journal of Bone and Mineral Research, 31(3), 650-656. https://doi.org/10.1002/jbmr.2728

The Natural History of Flare-Ups in Fibrodysplasia Ossificans Progressiva (FOP) : A Comprehensive Global Assessment. / Pignolo, Robert J.; Bedford-Gay, Christopher; Liljesthröm, Moira; Durbin-Johnson, Blythe P.; Shore, Eileen M.; Rocke, David M; Kaplan, Frederick S.

In: Journal of Bone and Mineral Research, Vol. 31, No. 3, 01.03.2016, p. 650-656.

Research output: Contribution to journalArticle

Pignolo, RJ, Bedford-Gay, C, Liljesthröm, M, Durbin-Johnson, BP, Shore, EM, Rocke, DM & Kaplan, FS 2016, 'The Natural History of Flare-Ups in Fibrodysplasia Ossificans Progressiva (FOP): A Comprehensive Global Assessment', Journal of Bone and Mineral Research, vol. 31, no. 3, pp. 650-656. https://doi.org/10.1002/jbmr.2728
Pignolo, Robert J. ; Bedford-Gay, Christopher ; Liljesthröm, Moira ; Durbin-Johnson, Blythe P. ; Shore, Eileen M. ; Rocke, David M ; Kaplan, Frederick S. / The Natural History of Flare-Ups in Fibrodysplasia Ossificans Progressiva (FOP) : A Comprehensive Global Assessment. In: Journal of Bone and Mineral Research. 2016 ; Vol. 31, No. 3. pp. 650-656.
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