Fibrous dysplasia is a rare bone disease due to a postzygotic mutation of the GNAS gene which leads to development of fibrous skeletal lesions. Fibrous dysplasia(FD) lesions may involve one bone (monostotic fibrous dysplasia-MFD) or multiple bones (polyostotic fibrous dysplasia-PFD). Association of fibrous dysplasia with endocrinopathies is called McCune-Albright syndrome(MAS). Patients with FD may have an impaired quality of life due to pain, deformities, impaired mobility and fractures. 

There is no cure for FD/MAS and while several treatments attempt to alleviate pain and improve mobility, current systemic therapies failed to demonstrate sustained effects on pain or on disease progression measured by functional parameters or imaging aspects. Denosumab, acting as a RANKL-inhibitor may be a potential treatment, with promising results in mouse models and in observational studies with off label use in patients.

In order to further analyze the effects of Denosumab, a randomized,double-blind,controlled trial  comparing Denosumab treatment with placebo in symptomatic adult patients with FD/MAS has recently started. Study objectives are to investigate whether 3 monthly Denosumab will improve the clinical(pain, mobility, quality of life scores),radiological and biochemical manifestations of FD bone lesions, with maximal pain score difference after 6 months as a main endpoint.

Eligible patients(pain score≥4) will be randomized to treatment with either a subcutaneous Denosumab 120 mg injection or placebo at baseline and at 3 months in a double-blinded setting. At 6 months,after 2 injections,patients with pain score<4 will exit the study and proceed in usual care, while patients with pain score≥4 or lesional growth will be offered Denosumab120 mg at 6 and 9 months in an open-label design. 

This study is expected to confirm and extend earlier findings of successful response to Denosumab and will address patient-specific outcomes such as pain and mobility, combined with quantification of disease activity and lesion size evolution measured by laboratory assesment and imaging.