Pharmacological Interventions Targeting Pain in Fibrous Dysplasia/McCune-Albright Syndrome

• Published in: International journal of molecular sciences 2023-01, Vol.24 (3), p.2550
• Main Authors: Tucker-Bartley, Anthony, Selen, Daryl J, Golden, Emma, van Gool, Raquel, Ebb, David, Mannstadt, Michael, Upadhyay, Jaymin
• Format: Article
• Language: English
• Subjects: Analgesics; Bisphosphonates; Bone and Bones - pathology; Bone density; Bone diseases; Bone dysplasia; Case reports; Clinical trials; Collagen; Diphosphonates - pharmacology; Diphosphonates - therapeutic use; Disease control; Endocrine disorders; Endocrine System Diseases - genetics; FDA approval; Fibrous dysplasia; Fibrous Dysplasia, Polyostotic - complications; Fibrous Dysplasia, Polyostotic - drug therapy; Fibrous Dysplasia, Polyostotic - genetics; Fractures; Humans; Hyperpigmentation; Hypocalcemia; Ligands; Missense mutation; Monoclonal antibodies; Musculoskeletal Pain - complications; Mutation; Nucleotides; Osteoporosis; Pain; Pain management; Pharmacology; Phenotypes; Polypeptides; Puberty; Rare diseases; Review; Tomography
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24032550

Fibrous dysplasia (FD) is a rare, non-inherited bone disease occurring following a somatic gain-of-function R201 missense mutation of the ( gene. The spectrum of the disease ranges from a single FD lesion to a combination with extraskeletal features; an amalgamation with café-au-lait skin hyperpigmentation, precocious puberty, and other endocrinopathies defines McCune-Albright Syndrome (MAS). Pain in FD/MAS represents one of the most prominent aspects of the disease and one of the most challenging to treat-an outcome driven by (i) the heterogeneous nature of FD/MAS, (ii) the variable presentation of pain phenotypes (i.e., craniofacial vs. musculoskeletal pain), (iii) a lack of studies probing pain mechanisms, and (iv) a lack of rigorously validated analgesic strategies in FD/MAS. At present, a range of pharmacotherapies are prescribed to patients with FD/MAS to mitigate skeletal disease activity, as well as pain. We analyze evidence guiding the current use of bisphosphonates, denosumab, and other therapies in FD/MAS, and also discuss the potential underlying pharmacological mechanisms by which pain relief may be achieved. Furthermore, we highlight the range of presentation of pain in individual cases of FD/MAS to further describe the difficulties associated with employing effective pain treatment in FD/MAS. Potential next steps toward identifying and validating effective pain treatments in FD/MAS are discussed, such as employing randomized control trials and probing new pain pathways in this rare bone disease.