Characterizing Pain in Polyostotic Fibrous Dysplasia/McCune-Albright Syndrome Patients: A Pilot Study

Abstract Fibrous dysplasia (FD)/McCune-Albright Syndrome (MAS) is a rare skeletal disorder associated with significant pain and symptom burden. Pain in FD/MAS has been predominantly attributed to bone fracturing or fibrous tissue changes within the skeletal system. However, recent evidence indicates that factors beyond skeletal disease burden may contribute to pain in FD/MAS, including central nervous system alterations. Further, the type of pain patients experience (e.g., constant, flare, radiating, local) has yet to be fully characterized, limiting the development of individualized treatment approaches. In this pilot study, we examined the associations between bone lesions detected using sodium fluoride F18 [18F-NaF] positron emission tomographic (PET)/computed tomographic (CT) scans and self-reported pain in 14 patients with FD/MAS. All participants completed body pain maps and questionnaires regarding pain and symptom burden. Bone turnover markers (e.g., osteocalcin, alkaline phosphatase, and N-terminal telopeptidase [NTx]) were also evaluated in relation to pain. Contrary to the previously described characterization of FD/MAS pain as persistent background pain with occasional flares, only 38% of the current sample described pain as “persistent pain with pain attacks”. Patients also described pain as “persistent with slight fluctuations” (31%), “pain attacks with pain between them” (23%), and “pain attacks without pain between them” (8%). Patients reported pain across multiple body sites. Neither background pain nor flare pain were reliably associated with skeletal burden scores or bone lesions in our sample. The presence of bone lesions in FD/MAS may not provide sufficient evidence to predict pain. Other factors, including the size or number of bone lesions, as well as other skeletal abnormalities, may also contribute to the pain experience. Future phenotyping efforts in FD/MAS are needed to better understand peripheral and central nervous system contributions that may lead to improved therapeutic strategies.