Onset, progression, and plateau of skeletal lesions in fibrous dysplasia and the relationship to functional outcome.
Most lesions in FD and their attendant functional disability occur within the first decade; 90% of lesions are present by 15 years, and the median age when assistive devices are needed is 7 years. These findings have implications for prognosis and determining the timing and type of therapy.


BACKGROUND
Fibrous dysplasia of bone (FD) is an uncommon skeletal disorder in which normal bone is replaced by abnormal fibro-osseous tissue. Variable amounts of skeletal involvement and disability occur. The age at which lesions are established, the pace at which the disease progresses, if (or when) the disease plateaus, and how these parameters relate to the onset of disability are unknown. To answer these questions, we performed a retrospective analysis of a group of subjects with FD.


METHODS
One hundred nine subjects with a spectrum of FD were studied for up to 32 years. Disease progression was assessed in serial (99)Tc-MDP bone scans by determining the location and extent of FD lesions using a validated bone scan scoring tool. Physical function and the need for ambulatory aids were assessed.


RESULTS
Ninety percent of the total body disease skeletal burden was established by age 15. Disease was established in a region-specific pattern; in the craniofacial region, 90% of the lesions were present by 3.4 yr, in the extremities, 90% were present by 13.7 yr, and in the axial skeleton, 90% were present by 15.5 yr. Twenty-five of 103 subjects eventually needed ambulatory aids. The median age at which assistance was needed was 7 yr (range, 1-43 yr). The median bone scan score for subjects needing assistance was 64.3 (range, 18.6-75) compared with 23.1 (range, 0.5-63.5) in the unassisted subjects (p < 0.0001). Among subjects needing assistance with ambulation, 92% showed this need by 17 yr.


CONCLUSIONS
The majority of skeletal lesions and the associated functional disability occur within the first decade of life. The implication is that the window of time for preventative therapies is narrow. Likewise, therapeutic interventions must be tailored to where the patient is in the natural history of the disease (i.e., progressive disease [young] versus established disease [older subjects]). These findings have implications for prognosis, the timing and type of therapy, and the development of trials of new therapies and their interpretation.
Hart
Elizabeth S
ES
Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institute of Health, Bethesda, Maryland 20892-4320, USA.
Kelly
Marilyn H
MH
Brillante
Beth
B
Chen
Clara C
CC
Ziran
Navid
N
Lee
Janice S
JS
Feuillan
Penelope
P
Leet
Arabella I
AI
Kushner
Harvey
H
Robey
Pamela G
PG
Collins
Michael T
MT
D001842:Bone and Bones / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005357:Fibrous Dysplasia of Bone / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008297:Male; D016138:Walking