Rare musculoskeletal diseases in adults: a research priority setting partnership with the James Lind Alliance

Abstract

Background Osteogenesis imperfecta, fibrous dysplasia/McCune-Albright syndrome and X-linked hypophosphatemia are three rare musculoskeletal diseases characterised by bone deformities, frequent fractures and pain. Little high-quality research exists on appropriate treatment and long-term management of these conditions in adults. This is further worsened by limited research funding in rare diseases and a general mismatch between the existing research priorities and those of the patients. This partnership adopted the James Lind Alliance approach to identify the top 10 research priorities for rare musculoskeletal diseases in adults through joint patient, carer and healthcare professional collaboration. Results The initial survey for question collection recruited 198 respondents, submitting a total of 988 questions. 77% of the respondents were patients with a rare musculoskeletal disease. Following out-of-scope question exclusion, repeating query grouping and scientific literature check for answers, 39 questions on treatment and long-term management remained. In the second public survey, 220 respondents, of whom 85% were patients with a rare musculoskeletal disease, their carers, relatives or friends, prioritised these uncertainties, which allowed selection of the top 25. In the last stage, patients, carers and healthcare professionals gathered for a priority setting workshop to reach a consensus on the final top 10 research priorities. These focus on the uncertainties surrounding appropriate treatment and holistic long-term disease management, highlighting several aspects indirect to abnormal bone metabolism, such as extra-skeletal symptoms, psychological care of both patients and their families and disease course through ageing. Conclusions This James Lind Alliance priority setting partnership is the first to investigate rare bone diseases. The priorities identified here were developed jointly by patients, carers and healthcare professionals. We encourage researchers, funding bodies and other stakeholders to use these priorities in guiding future research for those affected by rare musculoskeletal disorders.

Patient-Reported Complications, Symptoms, and Experiences of Living With X-Linked Hypophosphatemia Across the Life-Course

“…Our findings concur with a recent expert consensus exercise to identify research priorities for rare musculoskeletal diseases, which cited the need for more research into the psychological impacts and support needs of patients and their families, the role of fatigue, as well as disease progression in aging [ 37 ]. There is also a need for direct research with children and young people with XLH, rather than via proxy, in order to fully illustrate their experiences.…”

Consensus Recommendations for the Diagnosis and Management of X-Linked Hypophosphatemia in Belgium

“…Several key questions regarding XLH and other rare metabolic bone diseases remain unanswered ( 186 ): What are the best way to manage fatigue? What is the mechanism of pain?…”

Potential influences on optimizing long-term musculoskeletal health in children and adolescents with X-linked hypophosphatemia (XLH)

“…Limited treatment options are available for rare genetic musculoskeletal disorders such as XLH, and gaps of knowledge persist in natural disease history, long-term risks, disease management, and quality of life in those affected [ 91 ]. The limited awareness among healthcare professionals regarding these disorders is compounded by natural variability in clinical presentation and disease burden.…”

“…These issues are worsened by limited research funding in rare diseases. The James Lind Alliance (JLA), hosted by the National Institute for Health Research, is a non-profit initiative providing a transparent approach, supervised by an impartial JLA adviser, that brings patients, carers and healthcare professionals together for a research priority setting partnership (PSP) [ 91 ]. One of these partnerships applied the JLA method to a group of rare musculoskeletal disorders in adults, including XLH, to identify the most important research directions in diagnosis, treatment, and long-term management.…”

“…One of these partnerships applied the JLA method to a group of rare musculoskeletal disorders in adults, including XLH, to identify the most important research directions in diagnosis, treatment, and long-term management. They reported that one of the main overarching knowledge gaps appears to be the need for better understanding of rare metabolic bone disease progression in adulthood [ 91 ]. This recommendation, together with the absence of data on long-term outcomes of XLH, led to several workshops with the authors to provide their expert opinion on optimizing musculoskeletal health and in identifying key areas that may affect the long-term prognosis of XLH, based on current research, knowledge of the pathophysiology of the disease, and current treatment options.…”