Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Sep 19;9(11):ziaf150.
doi: 10.1093/jbmrpl/ziaf150. eCollection 2025 Nov.

Medical guidelines for fibrodysplasia ossificans progressiva

Frederick S Kaplan  1 , Mona Al Mukaddam  2 , Genevieve Baujat  3 , Alberto Hidalgo Bravo  4 , Matthew Brown  5 , Amanda Cali  6 , Tae-Joon Cho  7 , Corrie Crowe  8 , Carmen L De Cunto  9 , Patricia L R Delai  10 , Robert J Diecidue  11 , Elisabeth Marelise W Eekhoff  12 , Lisa Friedlander  13 , Clive S Friedman  14 , Zvi Grunwald  15 , Nobuhiko Haga  16 , Edward C Hsiao  17 , Richard Keen  18 , Joseph A Kitterman  19 , Charles Levy  20 , Vrisha Madhuri  21 , Rolf Morhart  22 , J Coen Netelenbos  23 , Christiaan Scott  24 , Eileen M Shore  25 , Michael Zasloff  26 , Keqin Zhang  27 , Robert J Pignolo  28
Affiliations

Medical guidelines for fibrodysplasia ossificans progressiva

Frederick S Kaplan et al. JBMR Plus. .

Abstract

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic condition characterized by congenital malformations of the great toes and progressive heterotopic ossification (HO) in specific anatomic patterns. Present management summarized here is focused on early diagnosis, assiduous avoidance of injury and iatrogenic harm, symptomatic amelioration of painful flare-ups, and optimization of residual function. Twenty-one members of the International Clinical Council on FOP (ICC) and seven consultants from 15 countries, chosen for their clinical expertise in FOP, developed this summary statement. Further advances in therapeutics will be based on rigorous clinical trials to assess novel and emerging treatment and prevention strategies. A detailed and updated exploration of the topics outlined in this brief perspective can be found in "The Medical Management of Fibrodysplasia Ossificans Progressiva: Current Treatment Considerations" which can be found on the International Clinical Council on FOP (ICC) website (www.iccfop.org).

Keywords: ACVR1; BMP signaling pathway; fibrodysplasia ossificans progressiva; guidelines; heterotopic ossification.

PubMed Disclaimer

Conflict of interest statement

F.S.K. is a clinical trial investigator for Ashibio, Incyte, Ipsen, and Regeneron and serves in an unpaid capacity on the Medical Registry Advisory Board of the International Fibrodysplasia Ossificans Progressiva Association, the International Clinical Council on FOP, and Tin Soldiers. M.A.M. is a clinical trial investigator for Ashibio, Incyte, Ipsen, and Regeneron, and serves in an unpaid capacity on the Medical Registry Advisory Board of the International Fibrodysplasia Ossificans Progressiva Association, the International Clinical Council on FOP, and Tin Soldiers. G.B. has research grants and conference support from FOP France and Ipsen, is a clinical trial investigator for Incyte, Ipsen, and Regeneron, is a member of the Medical Registry Advisory Board of the IFOPA, of the European Reference Network on rare bone diseases (BOND), of the scientific committee of FOP France, and a representative to the European FOP consortium. A.H.B. is a clinical trial investigator for Incyte, Ipsen, and Regeneron. M.B. is a clinical trial investigator for Incyte, Ipsen, and Regeneron. A.C. is a trustee of The Radiant Hope Foundation. T-J.C. is a clinical trial investigator for Incyte and Ipsen. C.C.: None declared. C.L.D.C. is a clinical trial investigator for Incyte and Ipsen and a member of the Medical Registry Advisory Board of the IFOPA. P.D. is a consultant for Ipsen, a clinical trial investigator for Incyte, Ipsen, and Regeneron, and a member of the Board of Directors of Tin Soldiers Global and the Noi Ci Siamo Association in Switzerland. R.J.D.: None declared. E.M.W.E. is a clinical trial investigator for STOPFOP, Regeneron, Ipsen, and Incyte, a member of the Medical Registry Advisory Board of the IFOPA, the steering committee of the Amsterdam Bone Center, the European Reference Network on rare bone diseases, a representative to the European FOP consortium, Chair of the NVE BoNe, and Chair of the Rare Bone Disease Center Amsterdam UMC. L.F.: None declared. C.F. is a consultant for Ipsen, Clinical Director for The Special Olympics, a member of the Board of Directors of Tin Soldiers Global, and has received an honorarium from Springer for a presentation. Z.G. is a consultant for the Axdev Group. N.H. was a clinical investigator for Ipsen. E.C.H. serves in an unpaid capacity on the Medical Registry Advisory Board of the International Fibrodysplasia Ossificans Progressiva Association; the Fibrous Dysplasia Foundation Medical and Scientific Advisory Boards; and the International Clinical Council on FOP. ECH receives support for clinical trials through his institution from Clementia Pharmaceuticals, an Ipsen Company; Ipsen Pharmaceuticals; Ascendis; and āshibio. R.K. is a consultant for Ipsen, Alexion, Kyowa Kirin, UCB, Amgen, and Richter, a member of the Advisory Board of Alexion, Kyowa Kirin, Theramex, a clinical investigator for Alexion, Kyowa Kirin, Incyte, Ipsen, and Regeneron, and a member of the Advisory Board of The Brittle Bone Society and the National Health Service (NHS) of England. J.K.: None declared. C.E.L.: None declared. V.M.: None declared. R.M. is a consultant for Ipsen. J.C.N.: None declared. C.S. is a consultant for Ipsen and was a previous clinical trial investigator for Ipsen and Regeneron. E.M.S.: None declared. M.A.Z. was a member of the Clementia/Ipsen Data Safety Monitoring Board (DSMB) during the Palovarotene clinical trials and is currently on the Incyte DSMB. K.Z. is a clinical trial investigator for Incyte, Ipsen, and Regeneron. R.J.P. is a clinical trial investigator for Ashibio, Incyte, Ipsen, and Regeneron, a member of the Medical Registry Advisory Board of the IFOPA, and a consultant for Incyte, Ipsen, and Regeneron. RJP is a co-inventor for the use of Andecaliximab in conditions of heterotopic ossification.

Figures

Figure 1
Figure 1
Targets and potential therapies for fibrodysplasia ossificans progressiva.
See this image and copyright information in PMC

References

    1. Pignolo RJ, Shore EM, Kaplan FS. Fibrodysplasia ossificans progressiva: diagnosis, management, and therapeutic horizons. Pediatr Endocrinol Rev. 2013;10 Suppl 2(02):437–448. - PMC - PubMed
    1. Hüning I, Gillessen-Kaesbach G. Fibrodysplasia ossificans progressiva: clinical course, genetic mutations and genotype-phenotype correlation. Mol Syndromol. 2014;5(5):201–211. 10.1159/000365770 - DOI - PMC - PubMed
    1. Pignolo RJ, Bedford-Gay C, Liljesthröm M, et al. The natural history of flare-ups in fibrodysplasia ossificans progressiva (FOP): a comprehensive global assessment. J Bone Miner Res. 2016;31(3):650–656. 10.1002/jbmr.2728 - DOI - PMC - PubMed
    1. Pignolo RJ, Baujat G, Brown MA, et al. The natural history of fibrodysplasia ossificans progressiva: a prospective, global 36-month study. Genet Med. 2022;24(12):2422–2433. 10.1016/j.gim.2022.08.013 - DOI - PubMed
    1. Al Mukaddam M, Toder KS, Davis M, et al. The impact of fibrodysplasia ossificans progressiva (FOP) on patients and their family members: results from an international burden of illness survey. Expert Rev Pharmacoecon Outcomes Res. 2022;22(8):1199–1213. 10.1080/14737167.2022.2115360 - DOI - PubMed

LinkOut - more resources