ESPE Yearbook of Paediatric Endocrinology

J Bone Miner Res. 2022 Feb;37(2):236-243.Abstract: https://pubmed-ncbi-nlm-nih-gov.proxy.kib.ki.se/34668234/

In Brief: This study characterized a large cohort of patients with fibrous dysplasia/McCune Albright syndrome in order to assess the fracture prevalence and identify risk factors for future factures.

Commentary: Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is due to mosaic, activating mutations in GNAS, causing aberrant Gαs activation and cAMP production disrupting normal differentiation of bone cell progenitors, resulting in fibrotic leasions in the affected parts of the skeleton. Skeletal disease is typically recognised during childhood, with the final disease burden established during late adolescence or early adulthood. The disease spectrum ranges from minimal disease with small leasions affecting one or a few bones, to severe disease affecting a large proportion of the skeleton leading to fractures, pain, and disability. Due to the rarity and large variability of the condition, the lifetime risk and predictive risk factors have not been well-established.

In the study, two large prospective cohorts were combined (total n = 419 patients) evaluated as part of a natural history study at the Natonal Institutes of Health (Bethesda, MD, USA) (n = 186) or retrospective chart review of the clinical cohort at Leiden University Medical Center (Leiden, the Netherlands) (n = 233). In the combined cohort 59% had MAS (FD + endocrinopathies) with histories of precocious puberty (30%), hyperthyroidism (17%), GH excess (11%), neonatal Cushing syndrome (4%), and hypophosphatemia (28%).

Out of 419 indivduals, 248 (59%) patients suffered one or more fracture (median 1, range 0–70, IQR 4). The median age at first fracture was 8 years (range 1–76, IQR 10) and fracture rates peaked between 6 and 10 years of age and decreased thereafter. Lifetime fracture risk was associated with the fibrous dysplasia burden score ( p < 0.01) and MAS hyperthyroidism (p = 0.01). Both skeletal burden score >25 and age at first fracture ≤7 years were associated with a higher total number of lifetime fractures (p < 0.01).

The study presents the largest cohort of FD/MAS so far and spans the full lifespan and therefore provides new information on the fracture burden and risk factors for fractures in the FD/MAS population thereby helping clinicians to identify FD/MAS patients at risk for fractures and may be candidates for early therapeutic interventions.