Treatment of fibrous dysplasia: focus on denosumab

ABSTRACT

Introduction

Fibrous dysplasia (FD) is a rare bone disease that is associated with various endocrine conditions, such as McCune Albright syndrome. It manifests as abnormal osteolysis, multiple fractures, or deformities that are reported during disease course. The receptor activator of nuclear factor-kappa B (RANK)/RANK ligand (RANKL) pathway is upregulated in FD and can be targeted with denosumab, a blocking monoclonal antibody.

Areas covered

Preclinical and clinical data on the scientific rationale for using denosumab in FD and on the efficacy and safety of this therapy for this condition have been reviewed, in addition to other therapies.

Expert opinion

Denosumab is a potential therapeutic agent against FD. A combined synergic approach involving theranostics might increase its therapeutic potential.

KEYWORDS:

• Bone
• craniofacial
• denosumab
• fibrous dysplasia
• McCune albright
• oxidative stress
• RANK/RANKL

Article highlights

• Fibrous dysplasia (FD) is a rare disease caused by mutations in Gs protein, primarily affecting the bone and secondarily the endocrine system (this association being named as McCune Albright syndrome, MAS) and the skin

• Bone impairment in FD is due to an abnormally increased osteoclast activity with bone demineralization and increased risk of fractures

• RANKL/RANK/OPG pathway plays a physiologic role in modulating bone synthesis and remodeling but in FD/MAS this is impaired due to OPG downregulation and RANK/RANKL signaling upregulation

• Denosumab is an inhibitor of RANK/RANKL which was previously evaluated in osteoporosis and which was found to decrease osteoclast activity and to stimulate bone formation

• In FD/MAS denosumab was found to be effective in pediatric as well as in adult population with immediate effects on osteoclast activity and with sustained bone formation

• Given the fact that various pathogenic pathways were identified so far in FD/MAS and that no single therapy is universally efficacious, other targeting therapies should be considered alone or in association. Denosumab for example could be associated with PDE4 inhibitors provided the latter class is clinically proved to be efficacious in this condition

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.