Fracture incidence in polyostotic fibrous dysplasia and the McCune-Albright syndrome.
In patients with polyostotic fibrous dysplasia of bone, the peak incidence of fractures is during the first decade of life, followed by a decrease thereafter. Phosphaturia is associated with an earlier incidence and increased frequency of fractures.


BACKGROUND
Fibrous dysplasia (FD) is a disorder involving either one (monostotic) or several bones (polyostotic FD [PFD] and sometimes is associated with cafe-au-lait hyperpigmentation of the skin and one or more hyperfunctioning endocrinopathies (McCune-Albright syndrome [MAS]). Both PFD and MAS are often associated with phosphaturia. Although fractures occur frequently in PFD/MAS, fracture incidence and the effect of age and co-existing metabolic abnormalities (endocrinopathy and/or phosphaturia) on fractures are ill defined.


METHODS
We reviewed the medical records and examined the endocrine and phosphorus metabolism of 35 patients with PFD/MAS. We report on the age at which extremity fractures occurred and their location and treatment. The results of endocrine and phosphorus metabolism testing and associations between age of first fractures, number of fractures, fracture rate, and metabolic abnormalities were noted.


RESULTS
The average follow-up was 14.2 years (range, 2-39 years), during which 172 fractures occurred. The number and sites of fractures were 103 femoral, 25 tibial, 33 humeral, and 11 forearm. Twenty-seven patients had PFD with one or more endocrinopathies and/or phosphaturia, and eight had PFD alone. The endocrinopathies included precocious puberty (n = 19), hyperthyroidism (n = 9), growth hormone excess (n = 6), and one patient each with Cushing syndrome and primary hyperparathyroidism. Twelve patients had phosphaturia. The peak rate of fractures occurred between 6 and 10 years of age and decreased thereafter. Patients with metabolic abnormalities sustained their first fracture at an earlier age (6.9 versus 16.6 years, p < 0.005) and had a higher lifetime rate of fractures (0.29 versus 0.08 fractures/year), relative to patients with PFD alone. Phosphaturia was the single metabolic dysfunction associated with both an earlier age of first fracture (5.1 versus 16.6 years, p < 0.05) and a greater lifetime fracture rate (0.35 versus 0.08 fractures/year, p < 0.05).


CONCLUSIONS
The occurrence of extremity fractures in FD peaks between 6 and 10 years of age and declines thereafter. Fractures occur earlier and more frequently in the presence of phosphaturia. These data have implications for long-term prognosis, clinical management, and interpretation of therapeutic interventions.
Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892-4320, USA.
Arabella I
AI
Leet
Caroline
C
Chebli
Harvey
H
Kushner
Clara C
CC
Chen
Marilyn H
MH
Kelly
Beth A
BA
Brillante
Pamela G
PG
Robey
Paolo
P
Bianco
Shlomo
S
Wientroub
Michael T
MT
Collins
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D019080:Cafe-au-Lait Spots / Q000097:blood / Q000150:complications; D002118:Calcium / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005358:Fibrous Dysplasia, Monostotic / Q000097:blood* / Q000150:complications* / Q000453:epidemiology; D005359:Fibrous Dysplasia, Polyostotic / Q000097:blood* / Q000150:complications* / Q000453:epidemiology; D050723:Fractures, Bone / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D006728:Hormones / Q000097:blood*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010758:Phosphorus / Q000097:blood / Q000652:urine; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors
D006728:Hormones; D010758:Phosphorus; D002118:Calcium