Fibrodysplasia Ossificans Progressiva: What Have We Achieved and Where Are We Now? Follow-up to the 2015 Lorentz Workshop

Ruiter, Ruben D. de; Smilde, Bernard J.; Pals, Gerard; Bravenboer, Nathalie; Knaus, Petra; Schoenmaker, Ton; Botman, Esmée; Sánchez‐Duffhues, Gonzalo; Pacifici, Maurizio; Pignolo, Robert J.; Shore, Eileen M.; Egmond, Marjolein van; Oosterwyck, Hans Van; Kaplan, Frederick S.; Hsiao, Edward C.; Yu, Paul B.; Bocciardi, Renata; Cunto, Carmen L. De; Delai, Patricia; Vries, Teun J. de; Hilderbrandt, Susanne; Jaspers, Richard T.; Keen, Richard; Koolwijk, Peter; Morhart, Rolf; Netelenbos, J.C.; Rustemeyer, Thomas; Scott, Christiaan; Stockklausner, Clemens; Dijke, Peter ten; Triffit, James; Ventura, Francesc; Ravazzolo, Roberto; Micha, Dimitra; Eekhoff, Elisabeth M. W.

doi:10.3389/fendo.2021.732728

Cited by 21 publications

(29 citation statements)

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“…This process is aggravated through an only partially understood process of inflammation and hypoxia, which involves HIF, mast cells and several inflammatory factors ( Figure 3 ). 22 …”

Section: Pathophysiologymentioning

confidence: 99%

Monitoring and Management of Fibrodysplasia Ossificans Progressiva: Current Perspectives

Smilde¹,

Botman²,

Ruiter³

et al. 2022

ORR

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Fibrodysplasia ossificans progressiva (FOP), sometimes known as myositis ossificans progressiva, is an ultra-rare disease in which bone is formed in muscular tissue, tendons and ligaments. This is known as heterotopic ossification (HO). FOP is caused by a heterozygous mutation in the highly conserved ACVR1/ALK2 gene which affects about 1 in 1.5–2 million individuals. At birth, patients with the predominant R206H mutation only exhibit a bilateral hallux valgus. During childhood, heterotopic bone formation develops in a typical pattern, affecting the axial muscles first before appendicular body parts are involved. HO can start spontaneously but is often elicited by soft tissue trauma or medical procedures. After soft tissue injury, an inflammatory process called a flare-up can start, followed by the formation of HO. HO leads to a limited range of motion, culminating in complete ankylosis of nearly all joints. As a result of HO surrounding the thorax, patients often suffer from thoracic insufficiency syndrome (TIS). TIS is the most common cause of a limited life expectancy for FOP patients, with a median life expectancy of 56 years. Management is focused on preventing soft-tissue injury that can provoke flare-ups. This includes prevention of iatrogenic damage by biopsies, intramuscular injections and surgery. Anti-inflammatory medication is often started when a flare-up occurs but has a poor basis of evidence. Several forms of potential treatment for FOP are being researched in clinical trials. Progression of the disease is monitored using CT and 18F-NaF PET/CT combined with functional assessments. Patients are regularly evaluated for frequently occurring complications such as restrictive lung disease. Here, we review the current management, monitoring and treatment of FOP.

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“…This process is aggravated through an only partially understood process of inflammation and hypoxia, which involves HIF, mast cells and several inflammatory factors ( Figure 3 ). 22 …”

Section: Pathophysiologymentioning

confidence: 99%

Monitoring and Management of Fibrodysplasia Ossificans Progressiva: Current Perspectives

Smilde¹,

Botman²,

Ruiter³

et al. 2022

ORR

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“…Additionally, sporadic cases of MO have been linked to genetic mutations. Fibrodysplasia ossificans progressiva is an extremely rare condition, presenting as painful flares with bone formation in muscles, tendons and ligaments as well as congenital deformity of bones, caused by a mutation of the ACVR1 gene [18] , [19] , [20] . This condition carries a dark prognosis due to increasing immobility as a consequence of the uncontrolled heterotopic bone formation [21] .…”

Section: Discussionmentioning

confidence: 99%

Aggressive atraumatic myositis ossificans in a toddler

Silveri¹,

Stoppiello²,

Gaiero³

et al. 2022

Radiology Case Reports

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“…The observation followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations ( 25 ). Blood samples, clinical and safety data were collected at four study visits: Visit 0 (screening) – verification of the FOP diagnosis, indication of vaccination, vaccination according to ICC on FOP; Visit 1 (baseline) – patient’s recruitment (evaluation of the inclusion/exclusion criteria) and disease activity assessment (clinical evaluation) ( 26 ); Visit 2 (follow-up, month 1) – disease activity assessment, safety data collection (patient clinical questionnaire, PCQ) and blood sample collection (total blood count with differential, biochemical and immunological parameters including inflammatory markers, humoral and T cell post-vaccination response assessment); and Visit 3 (follow-up, month 3) - disease activity assessment (clinical evaluation, deltoid muscle ultrasonography), blood sample collection (humoral post-vaccination response). The study design is summarized in Figure 1 .…”

Section: Methodsmentioning

confidence: 99%

SARS-CoV-2-specific humoral and cellular immune responses to BNT162b2 vaccine in Fibrodysplasia ossificans progressiva patients

et al. 2022

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IntroductionFibrodysplasia ossificans progressiva (FOP) is characterized by progressive heterotopic ossification triggered by various conditions, such as trauma, infection, including COVID-19 infection, and vaccination. Although SARS-CoV-2 vaccinations prevent poor outcomes in the general population, there is limited evidence on safety, immunogenicity, and efficacy of SARS-CoV-2 vaccines for inpatients with FOP.MethodsA case series of two patients with FOP focused on humoral, cellular post-vaccination response, and the incidence of adverse events after administration of the BNT162b2 vaccine (Comirnaty).ResultsInjection site reactions, fever, myalgia, and fatigue were the most common adverse events (AE). Neither severe AE (SAE), nor disease flare-ups were observed. No differences between patients with FOP and healthy controls were observed in humoral and cellular responses.ConclusionsThe BNT162b2 vaccine induced high humoral and cellular response levels in patients with FOP. Vaccination was not associated with SAE or disease relapse. The AEs spectrum was comparable to that of the general population.

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Fibrodysplasia Ossificans Progressiva: What Have We Achieved and Where Are We Now? Follow-up to the 2015 Lorentz Workshop

Cited by 21 publications

References 73 publications

Monitoring and Management of Fibrodysplasia Ossificans Progressiva: Current Perspectives

Monitoring and Management of Fibrodysplasia Ossificans Progressiva: Current Perspectives

Aggressive atraumatic myositis ossificans in a toddler

SARS-CoV-2-specific humoral and cellular immune responses to BNT162b2 vaccine in Fibrodysplasia ossificans progressiva patients

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