Addressing the unmet challenge of pain in rare bone diseases: new insights from the RUDY UK registry

Journal article

Background: Pain is a common symptom in many rare bone disorders, often linked to depression and a substantial decline in quality of life. However, there is little information on the quality of the pain which may provide insights into pain mechanisms. This study aimed to describe and compare the frequency and characteristics of self-reported pain in adults with Fibrous Dysplasia of Bone/McCune-Albright Syndrome (FD/MAS), Osteogenesis Imperfecta (OI), and X-linked Hypophosphatemia (XLH). Methods: A cross-sectional study was conducted using the online UK RUDY registry. Adults with self -reported FD/MAS, OI, and XLH who completed the painDETECT questionnaire (PD-Q) were included. Pain prevalence and phenotypes were assessed using baseline PD-Q responses which were also mapped to a modified widespread pain index as a measure of generalized pain. Descriptive analyses were performed using R®. Results: A total of 281 adults completed the baseline PD-Q (94 FD/MAS, 94 OI, and 93 XLH). Among these, 86% of patients currently experienced pain and 47% reported severe strongest pain in the past four weeks, with no significant differences between conditions. Pain prevalence and phenotype were similar across diseases, though pain sites differed. Neuropathic-like pain and female sex were significantly associated with poorer pain outcomes, including higher pain prevalence and intensity (p < 0.05). Generalized pain (18%) was significantly associated with moderate to severe anxiety (p = 0.03), depression (p < 0.001) and sleep impairment (p < 0.001). Conclusion: Despite distinct pathophysiological mechanisms, pain distribution appears similar across these bone diseases, suggesting a major role for non-skeletal factors. Generalized pain was frequent and associated with anxiety, depression, and sleep disturbances, suggesting nociplastic features maybe a significant driver of pain in adults with rare bone diseases.

Authors: Legrand, MA; Clemeno, FA; Chapurlat, R; Irani, A; Javaid, MK

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: BioMed Central
• Journal: Orphanet Journal of Rare Diseases
• Volume: 21
• Issue: 1
• Pages: 33
• Article number: 33
• Publication date: 2026-01-29
• Acceptance date: 2025-11-26
• DOI: 10.1186/s13023-025-04167-4
• EISSN: 1750-1172
• ISSN: 1750-1172
• Language: English
• Keywords: Fibrous Dysplasia/McCune-Albright; Bone pain; Rare bone disease; Osteogenesis imperfecta; X-linked hypophosphatemia; Pain phenotype