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Evolving Management Of Fibrodysplasia Ossificans Progressiva

Leo Migdal
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evolving management of fibrodysplasia ossificans progressiva

Correspondence: E Marelise W Eekhoff, Department of Internal Medicine section Endocrinology, Amsterdam UMC location Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, the Netherlands, Tel +31 204440588, Email emw.eekhoff@amsterdamumc.nl Received 2022 Jan 29; Accepted 2022 Apr 2; Collection date 2022. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). 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.

Keywords: fibrodysplasia ossificans progressiva, heterotopic ossification, activin A receptor type 1, treatment strategies Introduction: Heterotopic ossification (HO), acquired or hereditary, is a diverse pathological condition defined by the production of extraskeletal bone in muscles, soft tissues, and connective tissues. Acquired HO is relatively prevalent and develops mostly in response to trauma, although its etiology is unknown. Genetic forms provide insight into the pathobiological mechanisms of this disorder. Fibrodysplasia ossificans progressiva (FOP) is a rare hereditary form of HO that can have a significant impact on affected individuals. FOP steadily weakens affected subjects and increases their risk of death.

Areas covered: The U.S. Food and Drug Administration has recently approved the retinoid palovarotene as the first compound to treat heterotopic ossification in patients with FOP. This review provides a comprehensive overview of current and potential future pharmacotherapeutic options and their modes of action. The online databases PubMed, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched using the terms 'heterotopic ossification' and 'fibrodysplasia ossificans progressiva' or synonyms, with a special focus over the last 5 years of... Expert opinion: Approval of palovarotene, as the first retinoid indicated for reduction in the volume of new HO, may revolutionize the therapeutic landscape. However, long-term safety and efficacy data for palovarotene are currently lacking.

Keywords: ACVR1/ALK2 gene; Extraskeletal bone formation; fibrodysplasia ossificans progressiva; heterotopic ossification; palovarotene.

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