Fibrous Dysplasia: An Epidemiological and Correlational Evaluation of Multimodal Data (FIBR DYSPLASIA)

Fibrous Dysplasia: An Epidemiological and Correlational Study of Anthropometric, Clinical, Treatment, and Genetic Data

Fibrous dysplasia is a benign, pseudotumoral, genetic but non-hereditary condition characterized by the presence of one or more areas of abnormal bone development in which the normal structure is replaced by fibrous tissue. It is an extremely heterogeneous condition, as it can be monostotic, polyostotic, or panostotic, or it may occur within the context of more complex syndromes such as McCune-Albright syndrome (in which polyostotic fibrous dysplasia is associated with café-au-lait spots and precocious puberty) or Mazabraud syndrome (in which intramuscular myxomas are present).

This condition is caused by post-zygotic missense mutations, so it is never hereditary, and the affected individual will constitute a so-called "genetic mosaic," a fact that explains the wide variability in the localization of the pathological areas. The mutations in question occur in a gene (GNAS) located on chromosome 20 (20q13.2-13.3); this gene encodes a G protein with GTPase activity, the function of which is consequently impaired.

The aim of this study is to evaluate in detail the characteristics of the patients, their hospitalizations, and related interventions. Given the rarity of the condition, such investigations are often conducted on very limited datasets. The present study is expected to include over 200 patients, providing a comprehensive picture.

An additional aim is to assess the impact of somatic mutations in the GNAS gene and their impact in terms of clinical manifestations.

Study Overview

• Status: Recruiting
• Conditions: Fibrous Dysplasia of Bone; Fibrous Dysplasia; Fibrous Dysplasia/McCune-Albright Syndrome; Mazabraud Syndrome

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Luca Sangiorgi, MD, PhD, MSc; Phone Number: +390516366342; Email: luca.sangiorgi@ior.it

Study Locations

• Italy
  • BO
    • Bologna, BO, Italy, 40136
      • Recruiting
      • Irccs Istituto Ortopedico Rizzoli
      • Contact: Luca Sangiorgi; Phone Number: 0516366342; Email: luca.sangiorgi@ior.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All consecutive patients affected by Fibrous Dysplasia, McCune-Albright syndrome and Mazabraud syndrome

Description

Inclusion Criteria:

• All patients affected by Fibrous Dysplasia, McCune-Albright syndrome and Mazabraud syndrome (retrospectively included from 2009)
• Availability of clinical and radiological data collected during their recovery at the IOR
• Availability of tumor tissue in the biobank in sufficient quantity and quality

Exclusion Criteria:

• Patients who do not meet the inclusion criteria

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
All patients affected by Fibrous Dysplasia, McCune-Albright syndorme and Mazabraud syndrome; All patients affected by Fibrous Dysplasia, McCune-Albright syndorme and Mazabraud syndrome with available clinical, radiological and surgical data
Fibrous Dysplasia, McCune-Albright syndrome patients with available tissue sample; All patients affected by Fibrous Dysplasia, McCune-Albright syndorme and Mazabraud syndrome with an available tissue biospecimens for molecular investigation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Description of surgical procedures	Analyze the correlation between the reason for hospitalization (e.g. pain, fractures, etc.), the resulting type of procedure (categorized surgical procedures), and the patients' characteristics considering age (years), sex (male or female), lesion dimension (in cm).	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genotype-phenotype correlation	Identification of somatic pathogenic variants (described using HGMD) and genotype-phenotype correlation of molecular data with available clinical information	4 years
Description of clinical features of Fibrous Dysplasia patients	Describe natural history of patients affected by Fibrous Dysplasia, McCune-Albright syndorme and Mazabraud syndrome	4 years
Number and types of post-interventions complications and pain	To analyze the number and types of complications following surgeries (e.g. additional surgery, functional limitations) for fibrous dysplasia and to assess the impact of surgery on long bones in terms of pain (presence/absence)	4 years

Collaborators and Investigators

• Sponsor: Istituto Ortopedico Rizzoli

Publications and helpful links

General Publications

• Javaid MK, Boyce A, Appelman-Dijkstra N, Ong J, Defabianis P, Offiah A, Arundel P, Shaw N, Pos VD, Underhil A, Portero D, Heral L, Heegaard AM, Masi L, Monsell F, Stanton R, Dijkstra PDS, Brandi ML, Chapurlat R, Hamdy NAT, Collins MT. Best practice management guidelines for fibrous dysplasia/McCune-Albright syndrome: a consensus statement from the FD/MAS international consortium. Orphanet J Rare Dis. 2019 Jun 13;14(1):139. doi: 10.1186/s13023-019-1102-9.
• Stanton RP, Ippolito E, Springfield D, Lindaman L, Wientroub S, Leet A. The surgical management of fibrous dysplasia of bone. Orphanet J Rare Dis. 2012 May 24;7 Suppl 1(Suppl 1):S1. doi: 10.1186/1750-1172-7-S1-S1. Epub 2012 May 24.
• Majoor BCJ, Traunmueller E, Maurer-Ertl W, Appelman-Dijkstra NM, Fink A, Liegl B, Hamdy NAT, Sander Dijkstra PD, Leithner A. Pain in fibrous dysplasia: relationship with anatomical and clinical features. Acta Orthop. 2019 Aug;90(4):401-405. doi: 10.1080/17453674.2019.1608117. Epub 2019 Apr 30.
• Cohen MM Jr, Howell RE. Etiology of fibrous dysplasia and McCune-Albright syndrome. Int J Oral Maxillofac Surg. 1999 Oct;28(5):366-71.
• Weinstein LS, Chen M, Liu J. Gs(alpha) mutations and imprinting defects in human disease. Ann N Y Acad Sci. 2002 Jun;968:173-97. doi: 10.1111/j.1749-6632.2002.tb04335.x.
• Riminucci M, Saggio I, Robey PG, Bianco P. Fibrous dysplasia as a stem cell disease. J Bone Miner Res. 2006 Dec;21 Suppl 2:P125-31. doi: 10.1359/jbmr.06s224.

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: April 21, 2026
• First Submitted That Met QC Criteria: April 29, 2026
• First Posted (Actual): May 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Pain; McCune-Albright Syndrome; Surgical procedures; Fibrous Dysplasia; GNAS; Mazabraud Syndrome
• Additional Relevant MeSH Terms: Neurologic Manifestations; Bone Diseases; Musculoskeletal Diseases; Osteochondrodysplasias; Bone Diseases, Developmental; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain; Fibrous Dysplasia of Bone; Fibrous Dysplasia, Polyostotic
• Other Study ID Numbers: 294/2022/Sper/IOR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data are not publicly available due to privacy and/or ethical restrictions

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No