Unraveling fibrous dysplasia/McCune-Albright syndrome

Abstract

Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a chronic and possibly debilitating disorder, for which treatment may be challenging due to the heterogenic patient presentation, rarity of the disease, and variable treatment response. This thesis aimed to address several knowledge gaps in the pathophysiology, natural progression and treatment of FD/MAS. The thesis includes a proof-of-concept study on cell viability and activity in a 7-day ex-vivo bone tissue culture model, a study evaluating the expression of RANKL in breast cancer tissues of patients with FD/MAS, and research on potential biomarkers and other parameters of disease expression. Moreover, this thesis shed light on the incidence and prevalence of FD/MAS in a Danish registry, provided data on the effect of treatment in a multidisciplinary care pathway on pain and quality of life, and assessed risk factors for development and progression of the coxa vara deformity. Lastly, the safety of withdrawal from denosumab therapy was evaluated. The studies included in this thesis contribute to an improved understanding of the aetiology and characteristics of FD/MAS and may advance future development of new therapeutic options and personalized treatment.