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Medical Guidelines And Treatment Strategies For Fibrodysplasia

Leo Migdal
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medical guidelines and treatment strategies for fibrodysplasia

Received 2024 Nov 12; Accepted 2025 May 6; Collection date 2025. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed... Fibrous dysplasia (FD) is a rare, benign skeletal disorder characterized by expansile, fibrotic bone lesions that replace normal bone, resulting in decreased bone strength, pain, and fractures. The clinical presentation of FD can vary widely, complicating the diagnosis. FD can manifest as monostotic (single bone) or polyostotic (multiple bones) disease and can occur independently or as part of McCune–Albright Syndrome (MAS), a genetic condition that includes café-au-lait skin hyperpigmentation and endocrine abnormalities. FD/MAS arises from activating mutations in the GNAS gene, leading to constitutive activation of the Gsα protein and elevated cAMP levels.

Despite understanding the genetic cause of FD, effective treatments remain limited. Current management strategies focus primarily on symptom control following the most recent comprehensive guidelines published in 2019. This review highlights emerging pharmacologic treatments, including denosumab, a monoclonal antibody that has shown promise in reducing lesion size and pain in FD patients, and burosumab, a monoclonal antibody targeting FGF23, which reduces renal... In addition, we review updates in advanced genetic testing techniques, such as cell-free DNA and direct lesion sampling for next-generation sequencing, which are promising methods for improving the diagnostic accuracy of FD. Finally, multimodal approaches for pain management in FD, including nonsteroidal anti-inflammatory drugs, bisphosphonates, and novel agents like cannabinoids, are being used alongside the traditional approaches with physical therapy and psychological support. Ongoing research aims to enhance our understanding of FD pathogenesis and develop targeted therapies that could potentially reverse disease progression.

This review underscores the importance of implementing a multidisciplinary approach in the management of FD/MAS and finding new therapeutic approaches that will help address the diverse manifestations and improve the quality of life for... Keywords: bisphosphonates, fibrous dysplasia, McCune-Albright syndrome, metabolic bone disease, pain management Fibrous dysplasia (FD) of the bone is a genetic skeletal dysplasia characterized by the abnormal formation of fibrous tissue in place of normal bone, leading to decreased bone strength, expansile bone lesions, and fractures. 1 FD accounts for 2.5% of all bone lesions and 7% of benign skeletal dysplasias, 2 with craniofacial and long bones being major sites. 3 Although the genetic mutations that lead to FD are known and are located at the GNAS locus, medical treatments for this disfiguring disorder are sorely lacking. 4 FD most commonly occurs in isolation as monostotic disease, but can also affect multiple bones (polyostotic FD) or be part of McCune–Albright Syndrome (MAS), a somatic mosaic genetic condition characterized by polyostotic FD,...

FOP is an autosomal dominant genetic disorder marked by congenital malformations of the great toes and progressive HO in specific anatomic patterns. Early diagnosis is critical, as the disease manifests with episodic, painful inflammatory soft tissue swellings called flare-ups, which often lead to irreversible heterotopic bone formation through endochondral ossification. Minor trauma—including intramuscular injections, dental procedures, muscle fatigue, and viral illnesses—can precipitate flare-ups, underscoring the need for careful medical management to avoid iatrogenic harm (Pignolo et al., 2025)[1]. Clinically, the diagnosis of FOP is suggested by the presence of malformed great toes and progressive HO. Confirmatory diagnosis requires genetic testing revealing pathogenic gain-of-function variants in the ACVR1 gene, encoding a bone morphogenetic protein (BMP) type I receptor. Approximately 97% of individuals with classic FOP harbor the recurrent ACVR1R206H variant, while others possess different ACVR1 mutations with variable phenotypes (Kaplan et al., 2025)[1].

The discovery of ACVR1 mutations has propelled the development of targeted therapies aimed at inhibiting aberrant BMP signaling, a central pathogenic mechanism in FOP (Shore et al., 2006). Clinical management emphasizes early diagnosis, avoidance of trauma and invasive procedures, symptomatic treatment of flare-ups, and preservation of function. Most patients experience progressive disability, wheelchair dependence by the third decade, and a median life expectancy of approximately 56 years due to complications such as thoracic insufficiency syndrome (Kaplan et al., 2010)[1]. Flare-ups in FOP are inflammatory episodes that often precede heterotopic bone formation. Prompt identification and treatment are essential to mitigate progression. Corticosteroids, particularly prednisone at 2 mg/kg/day for 4 days initiated within 24 hours of flare-up onset, are recommended for flare-ups involving major joints, limbs, jaw, and submandibular regions.

For axial flare-ups (chest/back), corticosteroids are less effective; NSAIDs or COX-2 inhibitors may be used cautiously for symptomatic relief while avoiding narcotics (Kaplan et al., 2025)[1]. Prophylactic corticosteroids are advised following significant soft tissue trauma and invasive procedures such as dental surgeries to prevent flare-ups. Prednisone dosing for prophylaxis is 1-2 mg/kg/day for 3-4 days post-trauma or procedure. Minor bumps or bruises do not warrant corticosteroid use. Local application of cool packs and NSAIDs assist with inflammation and pain management (Pignolo et al., 2025)[1]. Frederick S.

Kaplan Mona Al Mukaddam Genevieve Baujat Alberto Hidalgo Bravo Matthew Brown Amanda Cali Tae-Joon Cho Corrie Crowe Carmen L. De Cunto Patricia L. R. Delai Robert J. Diecidue, Thomas Jefferson UniversityFollow Elisabeth Marelise W Eekhoff Lisa Friedlander Clive S. Friedman Zvi Grunwald, Thomas Jefferson UniversityFollow Nobuhiko Haga Edward C.

Hsiao Richard Keen Joseph A. Kitterman Charles Levy Vrisha Madhuri Rolf Morhart J. Coen Netelenbos Christiaan Scott Eileen M. Shore Michael Zasloff Keqin Zhang Robert J. Pignolo This article is the author’s final published version in JBMR Plus, Volume 9, Issue 11, 2025, Article number ziaf150.

The published version is available at https://doi.org/10.1093/jbmrpl/ziaf150. Copyright © The Author(s) 2025. 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... Kaplan, Frederick S.; Al Mukaddam, Mona; Baujat, Genevieve; Hidalgo Bravo, Alberto; Brown, Matthew; Cali, Amanda; Cho, Tae-Joon; Crowe, Corrie; De Cunto, Carmen L.; Delai, Patricia L. R.; Diecidue, Robert J.; Eekhoff, Elisabeth Marelise W; Friedlander, Lisa; Friedman, Clive S.; Grunwald, Zvi; Haga, Nobuhiko; Hsiao, Edward C.; Keen, Richard; Kitterman, Joseph A.; Levy, Charles; Madhuri, Vrisha; Morhart, Rolf; Netelenbos, J. Coen; Scott, Christiaan; Shore, Eileen M.; Zasloff, Michael; Zhang, Keqin; and Pignolo, Robert J., "Medical Guidelines for Fibrodysplasia Ossificans Progressiva" (2025). Department of Oral and Maxillofacial Surgery Faculty Papers. Paper 8.https://jdc.jefferson.edu/omsfp/8

Home Disease Information Treatment Guidelines: A Clinical Pathway for FD/MAS Care In the June of 2019 the International Consortium of FD/MAS Researchers published Best practice management guidelines for fibrous dysplasia/McCune-Albright syndrome: a consensus statement from the FD/MAS international consortium in Orphanet Journal of Rare Diseases. FDF has been involved with this publication from the very first draft, ensuring that patient perspectives were taken in to account. The result is an updated and improved guide for patients, caregivers and clinicians managing the fibrous dysplasia and McCune-Albright syndrome (FD/MAS). Previous Treatment Guidelines used research to create a checklist of sorts for patient care. This updated version combines the research and checklist formats in to one document: This links to the Clinical Pathway in full.

Additional files included at the end of the full article provide flowcharts for patients and clinicians to follow: We deliver important information about treatment, research, resources and other initiatives. Received 2019 Feb 7; Accepted 2019 May 21; Collection date 2019. Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the... The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Fibrous Dysplasia / McCune Albright syndrome (FD/MAS) represents a wide spectrum of diseases due to somatic gain-of-function mutations of the GNAS gene.

The mutation leads to overactivity in the target tissues and to a wide phenotype of clinical features that vary in severity and age of onset. The rarity of the disease and its variable presentation to multiple specialities often leads to misdiagnosis and inappropriate variability in investigations and treatments. To address this, our international consortium of clinicians, researchers, and patients’ advocates has developed pragmatic clinical guidelines for best clinical practice for the definition, diagnosis, staging, treatment and monitoring for FD/MAS to empower patients... With the lack of strong evidence to inform care, the guidelines were developed based on review of published literature, long-standing extensive experience of authors, input from other healthcare professionals involved in the care of... This has led to the formulation of a set of statements to inform healthcare professionals, patients, their families, carers and patient groups of the best practice of care. It is anticipated the implementation of these recommendations will lead to improvement in the care of patients with FD/MAS internationally.

The online version of this article (10.1186/s13023-019-1102-9) contains supplementary material, which is available to authorized users. Keywords: Fibrous dysplasia, McCune Albright syndrome, Guidelines, Diagnosis, Management

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