Screening og naturhistorie af patienter med polyostotisk fibrøs dysplasi og McCune-Albright syndrom

Polyostotic fibrous dysplasia (PFD) is a sporadic disorder which affects multiple sites in the skeleton. The bone at these sites is rapidly resorbed and replaced by abnormal fibrous tissue or mechanically abnormal bone. PFD may occur alone or as part of the McCune-Albright Syndrome (MAS), a syndrome originally defined by the triad of PFD, cafe-au-lait pigmentation of the skin, and precocious puberty. The bony lesions are frequently disfiguring, disabling and painful, and depending on the location of the lesion, can cause significant morbidity. Lesions in weight-bearing bones can lead to disabling fractures, while lesions in the skull can lead to compression of vital structures such as cranial nerves.

The natural history of this disease is poorly described and there are no clearly defined systemic therapies for the bone disease. This is a data collection and specimen acquisition protocol. The purpose of the study is to define the natural history of the disease by following PFD/MAS subjects over time and by using in vitro experimentation with samples/tissue from subjects with the disease.

Study Objectives

1. Primary Objective

   Define the natural history of disease by gaining clinical and basic information about PFD/MAS by following subjects clinically and using in vitro experimentation with tissue from subjects with the disease.

2. Secondary Objective

Refer eligible subjects for enrollment into other appropriate research protocols, if any are currently active.

Study Population

The study population will include:

1. Subjects with known or suspected Polyostotic Fibrous Dysplasia (PFD) or in combination with McCune-Albright Syndrome (MAS)
2. Subjects who meet eligibility criteria will be accepted regardless of gender, race, or ethnicity

Design

This study is an observational/natural history study of PFD/MAS.

Outcome Measures

Primary

1. Successfully enroll subjects with PFD or MAS for the collection, evaluation and analysis of data obtained from clinical visits.

2. Obtain onsite and offsite research tissue (waste tissue) from patients with PFD/MAS that are enrolled onto this study or from individuals with PFD/MAS that are offsite and willing to donate waste tissue to NIH. Research tissue will be used with existing primary cell culture technology (ongoing in our laboratories) to:

   • understand the basic bone biology of the pathologic cell (or cells) involved in the lesions of PFD/MAS
   • determine the presence or absence of mutated cells at "uninvolved sites" to formulate better strategies of predicting the initiation of new lesions, the natural history of lesion progression and/or response to therapy
   • understand osteogenic differentiation, in particular, the role of G(s)alpha in these lesions, which will be transferable to our understanding of bone biology in general
   • understand the pathophysiology of FD and/or endocrine lesions
   • develop better methods of identifying and expanding unaffected bone cells from patients with PFD in an effort to create better grafting material(s)

3. Identify and predict clinical and biological behavior of fibrous dysplastic bone lesions based on:

   • stability, rate of growth, rate of change, progression and regression, and development of new lesions
   • differences between cranial, axial and appendicular lesions

4. Define the natural history of the multiple endocrinopathies associated with MAS and the response to standard of care medications

5. Define clinical and biological aspects of the disease not previously identified

6. Generate future research studies related to PFD alone or in combination with MAS

Secondary

1) Successfully enroll eligible subjects into active research protocols applicable to the FD/MAS population.