title: An instrument to measure skeletal burden and predict functional outcome in fibrous dysplasia of bone.
abstract: An instrument to measure skeletal burden in fibrous dysplasia was developed. Biological and clinical relevance was shown by correlating skeletal burden scores with bone markers, quality of life, and ambulatory status. Childhood scores predict adult ambulatory status, and scores were unaffected when bone markers decreased with bisphosphonate treatment or aging.
  
  
  BACKGROUND
  Fibrous dysplasia (FD) is a skeletal disease with a broad clinical expression. There is no objective method to assess the extent of skeletal involvement or predict outcome. We developed an instrument to measure skeletal burden that correlates with physical function, health-related quality of life (HRQL), and ambulatory status.
  
  
  METHODS
  Seventy-nine patients with FD underwent bone scintigraphy. The skeletal burden score was derived from a weighted score based on the regional measurement using bone scintigraphy to estimate the amount of FD in anatomical segments. Six readers scored 20 scans twice to determine the inter- and intrareader agreement. To assess biological significance, scores were correlated with bone markers. To assess functional outcome, scores on the SF-36 (adults) or CHQ-PF50 (children) were correlated with skeletal burden scores. In a group of patients who had bone scans as children and adults (n = 6), the ability to predict ambulatory status was tested. Skeletal burden scores were assessed in patients before and after treatment with pamidronate (n = 5).
  
  
  RESULTS
  The inter- and intrareader agreement of burden scores were r = 0.96, and 0.98, respectively (p < 0.001 for both). The scores correlated with markers of bone metabolism and HRQL (Spearman rho, 0.54-0.67 p < 0.001 and -0.43, p = 0.001, respectively). The mean score of patients who ambulated unassisted was significantly lower than those requiring assistance (p < 0.001 unassisted versus crutch and/or wheelchair). In unassisted ambulators, younger patients had higher scores, suggesting high childhood scores may predict adulthood impairment. In six patients with childhood and adulthood scans, childhood scores >30 predicted assisted ambulation in adulthood. There was a negative correlation between bone markers and age (Spearman rho, -0.42 to -0.70; p < 0.001), but not age and skeletal burden score. Pamidronate treatment decreased serum alkaline phosphatase but had no effect on the skeletal burden score.
  
  
  CONCLUSIONS
  This is a validated and reliable instrument for the measurement of skeletal burden of FD and is able to predict functional outcome.
authors.affiliation: Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-4320, USA. mc247k@nih.gov
authors.forename: Michael T
authors.initials: MT
authors.lastname: Collins
authors.forename: Harvey
authors.initials: H
authors.lastname: Kushner
authors.forename: James C
authors.initials: JC
authors.lastname: Reynolds
authors.forename: Caroline
authors.initials: C
authors.lastname: Chebli
authors.forename: Marilyn H
authors.initials: MH
authors.lastname: Kelly
authors.forename: Anurag
authors.initials: A
authors.lastname: Gupta
authors.forename: Beth
authors.initials: B
authors.lastname: Brillante
authors.forename: Arabella I
authors.initials: AI
authors.lastname: Leet
authors.forename: Mara
authors.initials: M
authors.lastname: Riminucci
authors.forename: Pamela Gehron
authors.initials: PG
authors.lastname: Robey
authors.forename: Paolo
authors.initials: P
authors.lastname: Bianco
authors.forename: Shlomo
authors.initials: S
authors.lastname: Wientroub
authors.forename: Clara C
authors.initials: CC
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000469:Alkaline Phosphatase / Q000378:metabolism; D015415:Biomarkers; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D002648:Child; D004164:Diphosphonates / Q000494:pharmacology; D005260:Female; D005357:Fibrous Dysplasia of Bone / Q000175:diagnosis* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D011788:Quality of Life; D011877:Radionuclide Imaging; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D004164:Diphosphonates; D000469:Alkaline Phosphatase