{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:24:58Z","timestamp":1791415498640,"version":"4.3.3"},"reference-count":84,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2019,11,13]],"date-time":"2019-11-13T00:00:00Z","timestamp":1573603200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2019,11,13]],"date-time":"2019-11-13T00:00:00Z","timestamp":1573603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Curr Osteoporos Rep"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1007\/s11914-019-00541-x","type":"journal-article","created":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T16:54:09Z","timestamp":1576515249000},"page":"387-394","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Inflammation in Fibrodysplasia Ossificans Progressiva and Other Forms of Heterotopic Ossification"],"prefix":"10.1007","volume":"17","author":[{"given":"Koji","family":"Matsuo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert Dalton","family":"Chavez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Barruet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward C.","family":"Hsiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,13]]},"reference":[{"issue":"1","key":"541_CR1","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/nrm3254","volume":"13","author":"F Long","year":"2011","unstructured":"Long F. Building strong bones: molecular regulation of the osteoblast lineage. Nat Rev Mol Cell Biol. 2011;13(1):27\u201338. https:\/\/doi.org\/10.1038\/nrm3254.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"6","key":"541_CR2","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1007\/s00774-003-0439-1","volume":"21","author":"N Udagawa","year":"2003","unstructured":"Udagawa N. The mechanism of osteoclast differentiation from macrophages: possible roles of T lymphocytes in osteoclastogenesis. J Bone Miner Metab. 2003;21(6):337\u201343. https:\/\/doi.org\/10.1007\/s00774-003-0439-1.","journal-title":"J Bone Miner Metab"},{"issue":"2","key":"541_CR3","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1006\/bbrc.1998.9788","volume":"253","author":"N Nakagawa","year":"1998","unstructured":"Nakagawa N, Kinosaki M, Yamaguchi K, Shima N, Yasuda H, Yano K, et al. RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis. Biochem Biophys Res Commun. 1998;253(2):395\u2013400. https:\/\/doi.org\/10.1006\/bbrc.1998.9788.","journal-title":"Biochem Biophys Res Commun"},{"issue":"7","key":"541_CR4","doi-asserted-by":"publisher","first-page":"3597","DOI":"10.1073\/pnas.95.7.3597","volume":"95","author":"H Yasuda","year":"1998","unstructured":"Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin\/osteoclastogenesis-inhibitory factor and is identical to TRANCE\/RANKL. Proc Natl Acad Sci U S A. 1998;95(7):3597\u2013602. https:\/\/doi.org\/10.1073\/pnas.95.7.3597.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"541_CR5","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1002\/jbmr.2422","volume":"30","author":"L Vi","year":"2015","unstructured":"Vi L, Baht GS, Whetstone H, Ng A, Wei Q, Poon R, et al. Macrophages promote osteoblastic differentiation in-vivo: implications in fracture repair and bone homeostasis. J Bone Miner Res. 2015;30(6):1090\u2013102. https:\/\/doi.org\/10.1002\/jbmr.2422.","journal-title":"J Bone Miner Res"},{"issue":"12","key":"541_CR6","doi-asserted-by":"publisher","first-page":"3192","DOI":"10.1016\/j.ajpath.2014.08.017","volume":"184","author":"LJ Raggatt","year":"2014","unstructured":"Raggatt LJ, Wullschleger ME, Alexander KA, Wu AC, Millard SM, Kaur S, et al. Fracture healing via periosteal callus formation requires macrophages for both initiation and progression of early endochondral ossification. Am J Pathol. 2014;184(12):3192\u2013204. https:\/\/doi.org\/10.1016\/j.ajpath.2014.08.017.","journal-title":"Am J Pathol"},{"key":"541_CR7","doi-asserted-by":"publisher","first-page":"6637","DOI":"10.1038\/ncomms7637","volume":"6","author":"T Negishi-Koga","year":"2015","unstructured":"Negishi-Koga T, Gober HJ, Sumiya E, Komatsu N, Okamoto K, Sawa S, et al. Immune complexes regulate bone metabolism through FcRgamma signalling. Nat Commun. 2015;6:6637. https:\/\/doi.org\/10.1038\/ncomms7637.","journal-title":"Nat Commun"},{"issue":"12","key":"541_CR8","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1111\/j.1365-2362.2011.02545.x","volume":"41","author":"G Schett","year":"2011","unstructured":"Schett G. Effects of inflammatory and anti-inflammatory cytokines on the bone. Eur J Clin Investig. 2011;41(12):1361\u20136. https:\/\/doi.org\/10.1111\/j.1365-2362.2011.02545.x.","journal-title":"Eur J Clin Investig"},{"issue":"6","key":"541_CR9","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1242\/dmm.010280","volume":"5","author":"FS Kaplan","year":"2012","unstructured":"Kaplan FS, Chakkalakal SA, Shore EM. Fibrodysplasia ossificans progressiva: mechanisms and models of skeletal metamorphosis. Dis Model Mech. 2012;5(6):756\u201362. https:\/\/doi.org\/10.1242\/dmm.010280.","journal-title":"Dis Model Mech"},{"issue":"10","key":"541_CR10","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1007\/s00256-005-0958-z","volume":"34","author":"EF McCarthy","year":"2005","unstructured":"McCarthy EF, Sundaram M. Heterotopic ossification: a review. Skelet Radiol. 2005;34(10):609\u201319. https:\/\/doi.org\/10.1007\/s00256-005-0958-z.","journal-title":"Skelet Radiol"},{"issue":"1","key":"541_CR11","doi-asserted-by":"publisher","first-page":"16","DOI":"10.3928\/01477447-20091124-13","volume":"33","author":"M Kocic","year":"2010","unstructured":"Kocic M, Lazovic M, Mitkovic M, Djokic B. Clinical significance of the heterotopic ossification after total hip arthroplasty. Orthopedics. 2010;33(1):16. https:\/\/doi.org\/10.3928\/01477447-20091124-13.","journal-title":"Orthopedics"},{"issue":"4","key":"541_CR12","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1093\/neurosurgery\/57.4.759","volume":"57","author":"C Leung","year":"2005","unstructured":"Leung C, Casey AT, Goffin J, Kehr P, Liebig K, Lind B, et al. Clinical significance of heterotopic ossification in cervical disc replacement: a prospective multicenter clinical trial. Neurosurgery. 2005;57(4):759\u201363; discussion -63. https:\/\/doi.org\/10.1093\/neurosurgery\/57.4.759.","journal-title":"Neurosurgery"},{"issue":"5","key":"541_CR13","first-page":"459","volume":"73","author":"EA Hurvitz","year":"1992","unstructured":"Hurvitz EA, Mandac BR, Davidoff G, Johnson JH, Nelson VS. Risk factors for heterotopic ossification in children and adolescents with severe traumatic brain injury. Arch Phys Med Rehabil. 1992;73(5):459\u201362.","journal-title":"Arch Phys Med Rehabil"},{"issue":"3","key":"541_CR14","doi-asserted-by":"publisher","first-page":"476","DOI":"10.2106\/JBJS.F.00412","volume":"89","author":"BK Potter","year":"2007","unstructured":"Potter BK, Burns TC, Lacap AP, Granville RR, Gajewski DA. Heterotopic ossification following traumatic and combat-related amputations. Prevalence, risk factors, and preliminary results of excision. J Bone Joint Surg Am. 2007;89(3):476\u201386. https:\/\/doi.org\/10.2106\/JBJS.F.00412.","journal-title":"J Bone Joint Surg Am"},{"issue":"24","key":"541_CR15","doi-asserted-by":"publisher","first-page":"2032","DOI":"10.2106\/JBJS.N.01156","volume":"97","author":"JT Beckmann","year":"2015","unstructured":"Beckmann JT, Wylie JD, Potter MQ, Maak TG, Greene TH, Aoki SK. Effect of naproxen prophylaxis on heterotopic ossification following hip arthroscopy: a double-blind randomized placebo-controlled trial. J Bone Joint Surg Am. 2015;97(24):2032\u20137. https:\/\/doi.org\/10.2106\/JBJS.N.01156.","journal-title":"J Bone Joint Surg Am"},{"issue":"11","key":"541_CR16","doi-asserted-by":"publisher","first-page":"e204","DOI":"10.1097\/BOT.0b013e31825d60a5","volume":"26","author":"KN Evans","year":"2012","unstructured":"Evans KN, Forsberg JA, Potter BK, Hawksworth JS, Brown TS, Andersen R, et al. Inflammatory cytokine and chemokine expression is associated with heterotopic ossification in high-energy penetrating war injuries. J Orthop Trauma. 2012;26(11):e204\u201313. https:\/\/doi.org\/10.1097\/BOT.0b013e31825d60a5.","journal-title":"J Orthop Trauma"},{"issue":"9","key":"541_CR17","doi-asserted-by":"publisher","first-page":"2845","DOI":"10.1007\/s11999-014-3694-7","volume":"472","author":"JA Forsberg","year":"2014","unstructured":"Forsberg JA, Potter BK, Polfer EM, Safford SD, Elster EA. Do inflammatory markers portend heterotopic ossification and wound failure in combat wounds? Clin Orthop Relat Res. 2014;472(9):2845\u201354. https:\/\/doi.org\/10.1007\/s11999-014-3694-7.","journal-title":"Clin Orthop Relat Res"},{"issue":"3","key":"541_CR18","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1016\/j.ijrobp.2003.11.015","volume":"60","author":"EE Pakos","year":"2004","unstructured":"Pakos EE, Ioannidis JP. Radiotherapy vs. nonsteroidal anti-inflammatory drugs for the prevention of heterotopic ossification after major hip procedures: a meta-analysis of randomized trials. Int J Radiat Oncol Biol Phys. 2004;60(3):888\u201395. https:\/\/doi.org\/10.1016\/j.ijrobp.2003.11.015.","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"541_CR19","doi-asserted-by":"publisher","unstructured":"\u2022 Barruet E, Morales BM, Cain CJ, Ton AN, Wentworth KL, Chan TV, et al. NF-kappaB\/MAPK activation underlies ACVR1-mediated inflammation in human heterotopic ossification. JCI Insight. 2018;3(22). https:\/\/doi.org\/10.1172\/jci.insight.122958Analysis of FOP patient-derived sera and monocytes strongly indicates the contribution of myeloid cells in ACVR1-mediated inflammation.","DOI":"10.1172\/jci.insight.122958"},{"key":"541_CR20","unstructured":"The International Clinical Consortium on FOP The medical management of fibrodysplasia ossificans progressiva: current treatment considerations. Clin Proc Intl Clin Consort FOP 2011:4:1-100."},{"issue":"1","key":"541_CR21","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1186\/s13023-017-0674-5","volume":"12","author":"G Baujat","year":"2017","unstructured":"Baujat G, Choquet R, Bouee S, Jeanbat V, Courouve L, Ruel A, et al. Prevalence of fibrodysplasia ossificans progressiva (FOP) in France: an estimate based on a record linkage of two national databases. Orphanet J Rare Dis. 2017;12(1):123. https:\/\/doi.org\/10.1186\/s13023-017-0674-5.","journal-title":"Orphanet J Rare Dis"},{"issue":"5","key":"541_CR22","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/ng1783","volume":"38","author":"EM Shore","year":"2006","unstructured":"Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho TJ, Choi IH, et al. A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet. 2006;38(5):525\u20137. https:\/\/doi.org\/10.1038\/ng1783.","journal-title":"Nat Genet"},{"issue":"50","key":"541_CR23","doi-asserted-by":"publisher","first-page":"15438","DOI":"10.1073\/pnas.1510540112","volume":"112","author":"K Hino","year":"2015","unstructured":"\u2022 Hino K, Ikeya M, Horigome K, Matsumoto Y, Ebise H, Nishio M, et al. Neofunction of ACVR1 in fibrodysplasia ossificans progressiva. Proc Natl Acad Sci U S A. 2015;112(50):15438\u201343. https:\/\/doi.org\/10.1073\/pnas.1510540112This report reveals a novel mechaism of BMP signaling through mutated ACVR1 in FOP.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"303","key":"541_CR24","doi-asserted-by":"publisher","first-page":"303ra137","DOI":"10.1126\/scitranslmed.aac4358","volume":"7","author":"SJ Hatsell","year":"2015","unstructured":"\u2022 Hatsell SJ, Idone V, Wolken DM, Huang L, Kim HJ, Wang L, et al. ACVR1R206H receptor mutation causes fibrodysplasia ossificans progressiva by imparting responsiveness to activin A. Sci Transl Med. 2015;7(303):303ra137. https:\/\/doi.org\/10.1126\/scitranslmed.aac4358Activin A, a cytokine produced by many cell types including immune cells, appears to be a key driver of heterotopic ossification in FOP.","journal-title":"Sci Transl Med"},{"issue":"20","key":"541_CR25","doi-asserted-by":"publisher","first-page":"10792","DOI":"10.1074\/jbc.M115.713487","volume":"291","author":"S Aykul","year":"2016","unstructured":"Aykul S, Martinez-Hackert E. Transforming growth factor-beta family ligands can function as antagonists by competing for Type II receptor binding. J Biol Chem. 2016;291(20):10792\u2013804. https:\/\/doi.org\/10.1074\/jbc.M115.713487.","journal-title":"J Biol Chem"},{"key":"541_CR26","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s12964-015-0104-z","volume":"13","author":"OE Olsen","year":"2015","unstructured":"Olsen OE, Wader KF, Hella H, Mylin AK, Turesson I, Nesthus I, et al. Activin A inhibits BMP-signaling by binding ACVR2A and ACVR2B. Cell Commun Signal. 2015;13:27. https:\/\/doi.org\/10.1186\/s12964-015-0104-z.","journal-title":"Cell Commun Signal"},{"issue":"8","key":"541_CR27","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1056\/NEJM199608223350804","volume":"335","author":"AB Shafritz","year":"1996","unstructured":"Shafritz AB, Shore EM, Gannon FH, Zasloff MA, Taub R, Muenke M, et al. Overexpression of an osteogenic morphogen in fibrodysplasia ossificans progressiva. N Engl J Med. 1996;335(8):555\u201361. https:\/\/doi.org\/10.1056\/NEJM199608223350804.","journal-title":"N Engl J Med"},{"issue":"2","key":"541_CR28","doi-asserted-by":"publisher","first-page":"347","DOI":"10.2106\/JBJS.F.00472","volume":"89","author":"FS Kaplan","year":"2007","unstructured":"Kaplan FS, Glaser DL, Shore EM, Pignolo RJ, Xu M, Zhang Y, et al. Hematopoietic stem-cell contribution to ectopic skeletogenesis. J Bone Joint Surg Am. 2007;89(2):347\u201357. https:\/\/doi.org\/10.2106\/JBJS.F.00472.","journal-title":"J Bone Joint Surg Am"},{"issue":"3","key":"541_CR29","doi-asserted-by":"publisher","first-page":"652","DOI":"10.2106\/JBJS.H.01177","volume":"91","author":"VY Lounev","year":"2009","unstructured":"Lounev VY, Ramachandran R, Wosczyna MN, Yamamoto M, Maidment AD, Shore EM, et al. Identification of progenitor cells that contribute to heterotopic skeletogenesis. J Bone Joint Surg Am. 2009;91(3):652\u201363. https:\/\/doi.org\/10.2106\/JBJS.H.01177.","journal-title":"J Bone Joint Surg Am"},{"issue":"8","key":"541_CR30","doi-asserted-by":"publisher","first-page":"1746","DOI":"10.1002\/jbmr.1637","volume":"27","author":"SA Chakkalakal","year":"2012","unstructured":"Chakkalakal SA, Zhang D, Culbert AL, Convente MR, Caron RJ, Wright AC, et al. An Acvr1 R206H knock-in mouse has fibrodysplasia ossificans progressiva. J Bone Miner Res. 2012;27(8):1746\u201356. https:\/\/doi.org\/10.1002\/jbmr.1637.","journal-title":"J Bone Miner Res"},{"issue":"1","key":"541_CR31","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1038\/s41467-018-02988-5","volume":"9","author":"X Wang","year":"2018","unstructured":"\u2022 Wang X, Li F, Xie L, Crane J, Zhen G, Mishina Y, et al. Inhibition of overactive TGF-beta attenuates progression of heterotopic ossification in mice. Nat Commun. 2018;9(1):551. https:\/\/doi.org\/10.1038\/s41467-018-02988-5This paper suggests the importance of TGF-beta signaling in FOP, indicating TGF-beta is a potential therapeutic target.","journal-title":"Nat Commun"},{"issue":"1","key":"541_CR32","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/S8756-3282(01)00638-X","volume":"30","author":"CM Champagne","year":"2002","unstructured":"Champagne CM, Takebe J, Offenbacher S, Cooper LF. Macrophage cell lines produce osteoinductive signals that include bone morphogenetic protein-2. Bone. 2002;30(1):26\u201331.","journal-title":"Bone"},{"issue":"4","key":"541_CR33","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1002\/cyto.b.21594","volume":"94","author":"G Del Zotto","year":"2018","unstructured":"Del Zotto G, Antonini F, Azzari I, Ortolani C, Tripodi G, Giacopelli F, et al. Peripheral blood mononuclear cell immunophenotyping in fibrodysplasia ossificans progressiva patients: evidence for monocyte DNAM1 up-regulation. Cytometry B Clin Cytom. 2018;94(4):613\u201322. https:\/\/doi.org\/10.1002\/cyto.b.21594.","journal-title":"Cytometry B Clin Cytom"},{"key":"541_CR34","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1097\/00003086-199801000-00005","volume":"346","author":"FH Gannon","year":"1998","unstructured":"Gannon FH, Valentine BA, Shore EM, Zasloff MA, Kaplan FS. Acute lymphocytic infiltration in an extremely early lesion of fibrodysplasia ossificans progressiva. Clin Orthop Relat Res. 1998;346:19\u201325.","journal-title":"Clin Orthop Relat Res"},{"issue":"4","key":"541_CR35","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1016\/S0002-9440(10)63372-X","volume":"165","author":"L Kan","year":"2004","unstructured":"Kan L, Hu M, Gomes WA, Kessler JA. Transgenic mice overexpressing BMP4 develop a fibrodysplasia ossificans progressiva (FOP)-like phenotype. Am J Pathol. 2004;165(4):1107\u201315. https:\/\/doi.org\/10.1016\/S0002-9440(10)63372-X.","journal-title":"Am J Pathol"},{"issue":"1","key":"541_CR36","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1634\/stemcells.2008-0576","volume":"27","author":"L Kan","year":"2009","unstructured":"Kan L, Liu Y, McGuire TL, Berger DM, Awatramani RB, Dymecki SM, et al. Dysregulation of local stem\/progenitor cells as a common cellular mechanism for heterotopic ossification. Stem Cells. 2009;27(1):150\u20136. https:\/\/doi.org\/10.1634\/stemcells.2008-0576.","journal-title":"Stem Cells"},{"issue":"1","key":"541_CR37","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.jss.2016.04.040","volume":"206","author":"K Ranganathan","year":"2016","unstructured":"Ranganathan K, Agarwal S, Cholok D, Loder S, Li J, Sung Hsieh HH, et al. The role of the adaptive immune system in burn-induced heterotopic ossification and mesenchymal cell osteogenic differentiation. J Surg Res. 2016;206(1):53\u201361. https:\/\/doi.org\/10.1016\/j.jss.2016.04.040.","journal-title":"J Surg Res"},{"issue":"9","key":"541_CR38","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.1002\/jbmr.2848","volume":"31","author":"H Wang","year":"2016","unstructured":"Wang H, Lindborg C, Lounev V, Kim JH, McCarrick-Walmsley R, Xu M, et al. Cellular hypoxia promotes heterotopic ossification by amplifying BMP signaling. J Bone Miner Res. 2016;31(9):1652\u201365. https:\/\/doi.org\/10.1002\/jbmr.2848.","journal-title":"J Bone Miner Res"},{"issue":"8","key":"541_CR39","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1053\/hupa.2001.26464","volume":"32","author":"FH Gannon","year":"2001","unstructured":"Gannon FH, Glaser D, Caron R, Thompson LD, Shore EM, Kaplan FS. Mast cell involvement in fibrodysplasia ossificans progressiva. Hum Pathol. 2001;32(8):842\u20138. https:\/\/doi.org\/10.1053\/hupa.2001.26464.","journal-title":"Hum Pathol"},{"issue":"2","key":"541_CR40","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1002\/jbmr.3304","volume":"33","author":"MR Convente","year":"2018","unstructured":"Convente MR, Chakkalakal SA, Yang E, Caron RJ, Zhang D, Kambayashi T, et al. Depletion of mast cells and macrophages impairs heterotopic ossification in an Acvr1(R206H) mouse model of fibrodysplasia ossificans progressiva. J Bone Miner Res. 2018;33(2):269\u201382. https:\/\/doi.org\/10.1002\/jbmr.3304.","journal-title":"J Bone Miner Res"},{"issue":"3","key":"541_CR41","doi-asserted-by":"publisher","first-page":"E338","DOI":"10.1073\/pnas.1515397113","volume":"113","author":"S Agarwal","year":"2016","unstructured":"Agarwal S, Loder S, Brownley C, Cholok D, Mangiavini L, Li J, et al. Inhibition of Hif1alpha prevents both trauma-induced and genetic heterotopic ossification. Proc Natl Acad Sci U S A. 2016;113(3):E338\u201347. https:\/\/doi.org\/10.1073\/pnas.1515397113.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"541_CR42","doi-asserted-by":"publisher","first-page":"e10172","DOI":"10.1002\/jbm4.10172","volume":"3","author":"C Meyers","year":"2019","unstructured":"Meyers C, Lisiecki J, Miller S, Levin A, Fayad L, Ding C, et al. Heterotopic ossification: a comprehensive review. JBMR Plus. 2019;3(4):e10172. https:\/\/doi.org\/10.1002\/jbm4.10172.","journal-title":"JBMR Plus"},{"issue":"3","key":"541_CR43","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1302\/2046-3758.23.2000152","volume":"2","author":"MP Sullivan","year":"2013","unstructured":"Sullivan MP, Torres SJ, Mehta S, Ahn J. Heterotopic ossification after central nervous system trauma: a current review. Bone Joint Res. 2013;2(3):51\u20137. https:\/\/doi.org\/10.1302\/2046-3758.23.2000152.","journal-title":"Bone Joint Res"},{"issue":"9","key":"541_CR44","doi-asserted-by":"publisher","first-page":"2831","DOI":"10.1007\/s11999-015-4240-y","volume":"473","author":"AT Qureshi","year":"2015","unstructured":"Qureshi AT, Crump EK, Pavey GJ, Hope DN, Forsberg JA, Davis TA. Early Characterization of blast-related heterotopic ossification in a rat model. Clin Orthop Relat Res. 2015;473(9):2831\u20139. https:\/\/doi.org\/10.1007\/s11999-015-4240-y.","journal-title":"Clin Orthop Relat Res"},{"key":"541_CR45","doi-asserted-by":"publisher","first-page":"74","DOI":"10.3389\/fendo.2017.00074","volume":"8","author":"HH Sung Hsieh","year":"2017","unstructured":"Sung Hsieh HH, Chung MT, Allen RM, Ranganathan K, Habbouche J, Cholok D, et al. Evaluation of salivary cytokines for diagnosis of both trauma-induced and genetic heterotopic ossification. Front Endocrinol. 2017;8:74. https:\/\/doi.org\/10.3389\/fendo.2017.00074.","journal-title":"Front Endocrinol"},{"key":"541_CR46","doi-asserted-by":"publisher","first-page":"377","DOI":"10.3389\/fimmu.2019.00377","volume":"10","author":"KA Alexander","year":"2019","unstructured":"Alexander KA, Tseng HW, Fleming W, Jose B, Salga M, Kulina I, et al. Inhibition of JAK1\/2 tyrosine kinases reduces neurogenic heterotopic ossification after spinal cord injury. Front Immunol. 2019;10:377. https:\/\/doi.org\/10.3389\/fimmu.2019.00377.","journal-title":"Front Immunol"},{"issue":"2","key":"541_CR47","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1002\/path.4519","volume":"236","author":"F Genet","year":"2015","unstructured":"Genet F, Kulina I, Vaquette C, Torossian F, Millard S, Pettit AR, et al. Neurological heterotopic ossification following spinal cord injury is triggered by macrophage-mediated inflammation in muscle. J Pathol. 2015;236(2):229\u201340. https:\/\/doi.org\/10.1002\/path.4519.","journal-title":"J Pathol"},{"key":"541_CR48","doi-asserted-by":"publisher","unstructured":"Torossian F, Guerton B, Anginot A, Alexander KA, Desterke C, Soave S, et al. Macrophage-derived oncostatin M contributes to human and mouse neurogenic heterotopic ossifications. JCI insight. 2017;2(21). https:\/\/doi.org\/10.1172\/jci.insight.96034.","DOI":"10.1172\/jci.insight.96034"},{"issue":"6","key":"541_CR49","doi-asserted-by":"publisher","first-page":"704","DOI":"10.3171\/2019.1.PEDS18680","volume":"23","author":"Christopher E. Louie","year":"2019","unstructured":"Louie CE, Hong J, Bauer DF. Heterotopic ossification following suboccipital craniectomy decompression surgery for Chiari malformation type I: case report. J Neurosurg Pediatr. 2019:1\u20134. https:\/\/doi.org\/10.3171\/2019.1.PEDS18680.","journal-title":"Journal of Neurosurgery: Pediatrics"},{"issue":"9","key":"541_CR50","doi-asserted-by":"publisher","first-page":"1967","DOI":"10.1007\/s00264-015-3048-4","volume":"40","author":"EA Newman","year":"2016","unstructured":"Newman EA, Holst DC, Bracey DN, Russell GB, Lang JE. Incidence of heterotopic ossification in direct anterior vs posterior approach to total hip arthroplasty: a retrospective radiographic review. Int Orthop. 2016;40(9):1967\u201373. https:\/\/doi.org\/10.1007\/s00264-015-3048-4.","journal-title":"Int Orthop"},{"key":"541_CR51","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.bone.2017.12.028","volume":"109","author":"KP Egan","year":"2018","unstructured":"Egan KP, Duque G, Keenan MA, Pignolo RJ. Circulating osteogentic precursor cells in non-hereditary heterotopic ossification. Bone. 2018;109:61\u20134. https:\/\/doi.org\/10.1016\/j.bone.2017.12.028.","journal-title":"Bone"},{"issue":"1","key":"541_CR52","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.bone.2013.03.020","volume":"55","author":"P Hoff","year":"2013","unstructured":"Hoff P, Rakow A, Gaber T, Hahne M, Senturk U, Strehl C, et al. Preoperative irradiation for the prevention of heterotopic ossification induces local inflammation in humans. Bone. 2013;55(1):93\u2013101. https:\/\/doi.org\/10.1016\/j.bone.2013.03.020.","journal-title":"Bone"},{"issue":"2","key":"541_CR53","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1002\/jor.22212","volume":"31","author":"AS Dighe","year":"2013","unstructured":"Dighe AS, Yang S, Madhu V, Balian G, Cui Q. Interferon gamma and T cells inhibit osteogenesis induced by allogeneic mesenchymal stromal cells. J Orthop Res. 2013;31(2):227\u201334. https:\/\/doi.org\/10.1002\/jor.22212.","journal-title":"J Orthop Res"},{"issue":"4","key":"541_CR54","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1080\/03009740902776919","volume":"38","author":"VG Botzoris","year":"2009","unstructured":"Botzoris VG, Argyropoulou MI, Voulgari PV, Zikou AK, Drosos AA. Heterotopic ossification in systemic sclerosis. Scand J Rheumatol. 2009;38(4):317\u20139. https:\/\/doi.org\/10.1080\/03009740902776919.","journal-title":"Scand J Rheumatol"},{"issue":"5","key":"541_CR55","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1002\/1097-0142(19810901)48:5<1256::aid-cncr2820480534>3.0.co;2-4","volume":"48","author":"JJ Eckardt","year":"1981","unstructured":"Eckardt JJ, Ivins JC, Perry HO, Unni KK. Osteosarcoma arising in heterotopic ossification of dermatomyositis: case report and review of the literature. Cancer. 1981;48(5):1256\u201361. https:\/\/doi.org\/10.1002\/1097-0142(19810901)48:5<1256::aid-cncr2820480534>3.0.co;2-4.","journal-title":"Cancer"},{"issue":"1","key":"541_CR56","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s40478-016-0308-5","volume":"4","author":"C Preusse","year":"2016","unstructured":"Preusse C, Allenbach Y, Hoffmann O, Goebel HH, Pehl D, Radke J, et al. Differential roles of hypoxia and innate immunity in juvenile and adult dermatomyositis. Acta Neuropathol Commun. 2016;4(1):45. https:\/\/doi.org\/10.1186\/s40478-016-0308-5.","journal-title":"Acta Neuropathol Commun"},{"issue":"6","key":"541_CR57","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1007\/s004280050289","volume":"433","author":"M Jeziorska","year":"1998","unstructured":"Jeziorska M, McCollum C, Wooley DE. Observations on bone formation and remodelling in advanced atherosclerotic lesions of human carotid arteries. Virchows Arch. 1998;433(6):559\u201365.","journal-title":"Virchows Arch"},{"issue":"6","key":"541_CR58","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1007\/s00428-007-0430-7","volume":"450","author":"I Steiner","year":"2007","unstructured":"Steiner I, Kasparova P, Kohout A, Dominik J. Bone formation in cardiac valves: a histopathological study of 128 cases. Virchows Arch. 2007;450(6):653\u20137. https:\/\/doi.org\/10.1007\/s00428-007-0430-7.","journal-title":"Virchows Arch"},{"issue":"5","key":"541_CR59","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1002\/art.1780230510","volume":"23","author":"AT Masi","year":"1980","unstructured":"Masi AT, Rodnan GP, Medsger TA, Altman RD, D'Angelo WA, Fries JF, et al. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum. 1980;23(5):581\u201390.","journal-title":"Arthritis Rheum"},{"issue":"9388","key":"541_CR60","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/S0140-6736(03)14368-1","volume":"362","author":"MC Dalakas","year":"2003","unstructured":"Dalakas MC, Hohlfeld R. Polymyositis and dermatomyositis. Lancet. 2003;362(9388):971\u201382. https:\/\/doi.org\/10.1016\/S0140-6736(03)14368-1.","journal-title":"Lancet"},{"issue":"5","key":"541_CR61","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1161\/01.STR.0000013741.41309.67","volume":"33","author":"JL Hunt","year":"2002","unstructured":"Hunt JL, Fairman R, Mitchell ME, Carpenter JP, Golden M, Khalapyan T, et al. Bone formation in carotid plaques: a clinicopathological study. Stroke. 2002;33(5):1214\u20139.","journal-title":"Stroke"},{"issue":"11","key":"541_CR62","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1161\/01.cir.103.11.1522","volume":"103","author":"ER Mohler 3rd","year":"2001","unstructured":"Mohler ER 3rd, Gannon F, Reynolds C, Zimmerman R, Keane MG, Kaplan FS. Bone formation and inflammation in cardiac valves. Circulation. 2001;103(11):1522\u20138. https:\/\/doi.org\/10.1161\/01.cir.103.11.1522.","journal-title":"Circulation"},{"issue":"4","key":"541_CR63","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1080\/00313020802036764","volume":"40","author":"GS Soor","year":"2008","unstructured":"Soor GS, Vukin I, Leong SW, Oreopoulos G, Butany J. Peripheral vascular disease: who gets it and why? A histomorphological analysis of 261 arterial segments from 58 cases. Pathology. 2008;40(4):385\u201391. https:\/\/doi.org\/10.1080\/00313020802036764.","journal-title":"Pathology"},{"issue":"Suppl 2","key":"541_CR64","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1007\/s003920070100","volume":"89","author":"GR Campbell","year":"2000","unstructured":"Campbell GR, Campbell JH. Vascular smooth muscle and arterial calcification. Z Kardiol. 2000;89(Suppl 2):54\u201362.","journal-title":"Z Kardiol"},{"issue":"46","key":"541_CR65","doi-asserted-by":"publisher","first-page":"45969","DOI":"10.1074\/jbc.M306972200","volume":"278","author":"SL Cheng","year":"2003","unstructured":"Cheng SL, Shao JS, Charlton-Kachigian N, Loewy AP, Towler DA. MSX2 promotes osteogenesis and suppresses adipogenic differentiation of multipotent mesenchymal progenitors. J Biol Chem. 2003;278(46):45969\u201377. https:\/\/doi.org\/10.1074\/jbc.M306972200.","journal-title":"J Biol Chem"},{"issue":"1-2","key":"541_CR66","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/s11010-015-2432-0","volume":"406","author":"T Liu","year":"2015","unstructured":"Liu T, Lin J, Ju T, Chu L, Zhang L. Vascular smooth muscle cell differentiation to an osteogenic phenotype involves matrix metalloproteinase-2 modulation by homocysteine. Mol Cell Biochem. 2015;406(1-2):139\u201349. https:\/\/doi.org\/10.1007\/s11010-015-2432-0.","journal-title":"Mol Cell Biochem"},{"issue":"20","key":"541_CR67","doi-asserted-by":"publisher","first-page":"2505","DOI":"10.1161\/01.CIR.0000096485.64373.C5","volume":"108","author":"Y Tintut","year":"2003","unstructured":"Tintut Y, Alfonso Z, Saini T, Radcliff K, Watson K, Bostrom K, et al. Multilineage potential of cells from the artery wall. Circulation. 2003;108(20):2505\u201310. https:\/\/doi.org\/10.1161\/01.CIR.0000096485.64373.C5.","journal-title":"Circulation"},{"issue":"12","key":"541_CR68","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1038\/nm.2252","volume":"16","author":"D Medici","year":"2010","unstructured":"Medici D, Shore EM, Lounev VY, Kaplan FS, Kalluri R, Olsen BR. Conversion of vascular endothelial cells into multipotent stem-like cells. Nat Med. 2010;16(12):1400\u20136. https:\/\/doi.org\/10.1038\/nm.2252.","journal-title":"Nat Med"},{"issue":"5","key":"541_CR69","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1359\/jbmr.1998.13.5.828","volume":"13","author":"MJ Doherty","year":"1998","unstructured":"Doherty MJ, Ashton BA, Walsh S, Beresford JN, Grant ME, Canfield AE. Vascular pericytes express osteogenic potential in vitro and in vivo. J Bone Miner Res. 1998;13(5):828\u201338. https:\/\/doi.org\/10.1359\/jbmr.1998.13.5.828.","journal-title":"J Bone Miner Res"},{"issue":"5","key":"541_CR70","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1189\/jlb.0403170","volume":"74","author":"M Kuwana","year":"2003","unstructured":"Kuwana M, Okazaki Y, Kodama H, Izumi K, Yasuoka H, Ogawa Y, et al. Human circulating CD14+ monocytes as a source of progenitors that exhibit mesenchymal cell differentiation. J Leukoc Biol. 2003;74(5):833\u201345. https:\/\/doi.org\/10.1189\/jlb.0403170.","journal-title":"J Leukoc Biol"},{"issue":"4","key":"541_CR71","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1083\/jcb.148.4.679","volume":"148","author":"AD Weston","year":"2000","unstructured":"Weston AD, Rosen V, Chandraratna RA, Underhill TM. Regulation of skeletal progenitor differentiation by the BMP and retinoid signaling pathways. J Cell Biol. 2000;148(4):679\u201390. https:\/\/doi.org\/10.1083\/jcb.148.4.679.","journal-title":"J Cell Biol"},{"issue":"2","key":"541_CR72","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/0014-4827(80)90517-0","volume":"129","author":"M Pacifici","year":"1980","unstructured":"Pacifici M, Cossu G, Molinaro M, Tato F. Vitamin A inhibits chondrogenesis but not myogenesis. Exp Cell Res. 1980;129(2):469\u201374. https:\/\/doi.org\/10.1016\/0014-4827(80)90517-0.","journal-title":"Exp Cell Res"},{"issue":"9","key":"541_CR73","doi-asserted-by":"publisher","first-page":"1666","DOI":"10.1002\/jbmr.2820","volume":"31","author":"SA Chakkalakal","year":"2016","unstructured":"\u2022 Chakkalakal SA, Uchibe K, Convente MR, Zhang D, Economides AN, Kaplan FS, et al. Palovarotene inhibits heterotopic ossification and maintains limb mobility and growth in mice with the human ACVR1(R206H) fibrodysplasia ossificans progressiva (FOP) mutation. J Bone Miner Res. 2016;31(9):1666\u201375. https:\/\/doi.org\/10.1002\/jbmr.2820Palovalone is a potential therapeutic agent which is currently being tested in clinical trials in FOP patients. It may function by both blocking chondrocyte mineralization as well as immune cell function.","journal-title":"J Bone Miner Res"},{"key":"541_CR74","doi-asserted-by":"publisher","unstructured":"Lees-Shepard JB, Nicholas SE, Stoessel SJ, Devarakonda PM, Schneider MJ, Yamamoto M, et al. Palovarotene reduces heterotopic ossification in juvenile FOP mice but exhibits pronounced skeletal toxicity. eLife. 2018;7. https:\/\/doi.org\/10.7554\/eLife.40814.","DOI":"10.7554\/eLife.40814"},{"issue":"4","key":"541_CR75","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1002\/jor.23747","volume":"36","author":"BM Wheatley","year":"2018","unstructured":"Wheatley BM, Cilwa KE, Dey D, Qureshi AT, Seavey JG, Tomasino AM, et al. Palovarotene inhibits connective tissue progenitor cell proliferation in a rat model of combat-related heterotopic ossification. J Orthop Res. 2018;36(4):1135\u201344. https:\/\/doi.org\/10.1002\/jor.23747.","journal-title":"J Orthop Res"},{"issue":"2","key":"541_CR76","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.cell.2012.03.017","volume":"149","author":"M Laplante","year":"2012","unstructured":"Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell. 2012;149(2):274\u201393. https:\/\/doi.org\/10.1016\/j.cell.2012.03.017.","journal-title":"Cell"},{"issue":"11","key":"541_CR77","doi-asserted-by":"publisher","first-page":"2536","DOI":"10.1016\/j.ajpath.2017.07.010","volume":"187","author":"AT Qureshi","year":"2017","unstructured":"Qureshi AT, Dey D, Sanders EM, Seavey JG, Tomasino AM, Moss K, et al. Inhibition of mammalian target of rapamycin signaling with rapamycin prevents trauma-induced heterotopic ossification. Am J Pathol. 2017;187(11):2536\u201345. https:\/\/doi.org\/10.1016\/j.ajpath.2017.07.010.","journal-title":"Am J Pathol"},{"issue":"5","key":"541_CR78","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1016\/j.stemcr.2018.10.007","volume":"11","author":"K Hino","year":"2018","unstructured":"Hino K, Zhao C, Horigome K, Nishio M, Okanishi Y, Nagata S, et al. An mTOR signaling modulator suppressed heterotopic ossification of fibrodysplasia ossificans progressiva. Stem Cell Reports. 2018;11(5):1106\u201319. https:\/\/doi.org\/10.1016\/j.stemcr.2018.10.007.","journal-title":"Stem Cell Reports"},{"key":"541_CR79","unstructured":"IFOPA. Rapamycin Clinical Trial for FOP 2019. Available from: https:\/\/www.ifopa.org\/rapamycin. Accessed 1 July 2019"},{"key":"541_CR80","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.bone.2017.12.011","volume":"109","author":"FS Kaplan","year":"2018","unstructured":"Kaplan FS, Zeitlin L, Dunn SP, Benor S, Hagin D, Al Mukaddam M, et al. Acute and chronic rapamycin use in patients with fibrodysplasia ossificans progressiva: a report of two cases. Bone. 2018;109:281\u20134. https:\/\/doi.org\/10.1016\/j.bone.2017.12.011.","journal-title":"Bone"},{"issue":"255","key":"541_CR81","doi-asserted-by":"publisher","first-page":"255ra132","DOI":"10.1126\/scitranslmed.3008810","volume":"6","author":"JR Peterson","year":"2014","unstructured":"Peterson JR, De La Rosa S, Eboda O, Cilwa KE, Agarwal S, Buchman SR, et al. Treatment of heterotopic ossification through remote ATP hydrolysis. Sci Transl Med. 2014;6(255):255ra132. https:\/\/doi.org\/10.1126\/scitranslmed.3008810.","journal-title":"Sci Transl Med"},{"issue":"2","key":"541_CR82","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/s00590-012-0944-9","volume":"23","author":"Kairui Zhang","year":"2012","unstructured":"Zhang K, Wang L, Zhang S, Yu B, Liu F, Cui Z, et al. Celecoxib inhibits the heterotopic ossification in the rat model with Achilles tenotomy. Eur J Orthop Surg Traumatol 2013;23(2):145\u2013148. https:\/\/doi.org\/10.1007\/s00590-012-0944-9.","journal-title":"European Journal of Orthopaedic Surgery & Traumatology"},{"issue":"2","key":"541_CR83","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1016\/j.arth.2013.06.039","volume":"29","author":"CJ Lavernia","year":"2014","unstructured":"Lavernia CJ, Contreras JS, Villa JM, Rossi MD. Celecoxib and heterotopic bone formation after total hip arthroplasty. J Arthroplast. 2014;29(2):390\u20132. https:\/\/doi.org\/10.1016\/j.arth.2013.06.039.","journal-title":"J Arthroplast"},{"issue":"3","key":"541_CR84","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1097\/CORR.0000000000000594","volume":"477","author":"AD Robertson","year":"2019","unstructured":"Robertson AD, Chiaramonti AM, Nguyen TP, Jaffe DE, Holmes RE, Hanna EL, et al. Failure of indomethacin and radiation to prevent blast-induced heterotopic ossification in a Sprague-Dawley rat model. Clin Orthop Relat Res. 2019;477(3):644\u201354. https:\/\/doi.org\/10.1097\/CORR.0000000000000594.","journal-title":"Clin Orthop Relat Res"}],"container-title":["Current Osteoporosis Reports"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11914-019-00541-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s11914-019-00541-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11914-019-00541-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T00:51:08Z","timestamp":1605142268000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s11914-019-00541-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,13]]},"references-count":84,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["541"],"URL":"https:\/\/doi.org\/10.1007\/s11914-019-00541-x","relation":{},"ISSN":["1544-1873","1544-2241"],"issn-type":[{"value":"1544-1873","type":"print"},{"value":"1544-2241","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,13]]},"assertion":[{"value":"13 November 2019","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"Edward Hsiao serves on the registry advisory board of the International Fibrodysplasia Ossificans Progressiva Association, is on the International Clinical Council on FOP, and is on the Fibrous Dysplasia Foundation Medical Advisory Board. ECH receives clinical trials research support through his institution from Clementia Pharmaceuticals Inc. to support clinical trials of palovarotene in FOP. ECH previously received clinical trials support through his institution from Regeneron Pharmaceuticals, Inc. These pose no conflicts for this study.Koji Matsuo, Robert Dalton Chavez, and Emilie Barruet declare that they have no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"This article does not contain any studies with human or animal subjects performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human and Animal Rights and Informed Consent"}}]}}