Dataset Information

A multidisciplinary care pathway improves quality of life and reduces pain in patients with fibrous dysplasia/McCune-Albright syndrome: a multicenter prospective observational study.

ABSTRACT:

Background

Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) may cause pain, impaired ambulation and decreased quality of life (QoL). International guidelines advocate management of FD/MAS in a tertiary multidisciplinary care pathway, but no longitudinal data are available to support this recommendation. This multicenter prospective observational study aimed to evaluate effects of 1 year of treatment in the FD/MAS care pathway in 2 tertiary clinics on QoL and pain, assessed by change in Short Form 36 and Brief Pain Inventory between baseline and follow-up. Patients completing baseline questionnaires < 1 year after intake were classified as new referrals, others as under chronic care.

Results

92 patients were included, 61 females (66%). 22 patients (24%) had monostotic disease, 16 (17%) isolated craniofacial FD, 27 (40%) polyostotic FD and 17 (19%) MAS. 26 were new referrals (28%) and 66 chronic patients (72%). Median age at baseline was 47 years (Q1-Q3 36-56). Skeletal burden correlated with baseline Physical Function (r_s = - 0.281, p = 0.007). QoL was in all domains lower compared to the general population. New referrals reported clinically important differences (CID) over time in domains Physical Function (mean 67 ± SD24 to 74 ± 21, effect size (ES) 0.31, p = 0.020), Role Physical (39 ± 41 to 53 ± 43, ES 0.35, p = 0.066), Social Functioning (64 ± 24 to 76 ± 23, ES 0.49, p = 0.054), and Health Change (39 ± 19 to 53 ± 24, ES 0.76, p = 0.016), chronic patients in Physical Function (52 ± 46 to 66 ± 43, ES 0.31, p = 0.023) and Emotional Wellbeing (54 ± 27 to 70 ± 15, ES 0.59, p < 0.001). New referrals reported a CID of 1 point in maximum pain, average pain and pain interference, chronic patients reported stable scores. Change in pain interference and Role Physical were correlated (r_s = - 0.472, p < 0.001). Patients with limited disease extent improved more than patients with severe disease. Patients receiving FD-related therapy had lower baseline scores than patients not receiving therapy and reported improvements in QoL after 1 year. Yet also patients without FD-related therapy improved in Physical Function.

Conclusions

All FD-subtypes may induce pain and reduced QoL. A multidisciplinary care pathway for FD/MAS may improve pain and QoL, mainly in new referrals without MAS comorbidities with low baseline scores. Therefore, we recommend referral of patients with all subtypes of FD/MAS to specialized academic centers.

SUBMITTER: Meier ME

PROVIDER: S-EPMC9758844 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

A multidisciplinary care pathway improves quality of life and reduces pain in patients with fibrous dysplasia/McCune-Albright syndrome: a multicenter prospective observational study.

Meier Maartje E ME Hagelstein-Rotman Marlous M van de Ven Annenienke C AC Van der Geest Ingrid C M ICM Donker Olav O Pichardo Sarina E C SEC Hissink Muller Petra C E PCE van der Meeren Stijn W SW Dorleijn Desirée M J DMJ Winter Elizabeth M EM van de Sande Michiel A J MAJ Appelman-Dijkstra Natasha M NM

Orphanet journal of rare diseases 20221217 1

<h4>Background</h4>Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) may cause pain, impaired ambulation and decreased quality of life (QoL). International guidelines advocate management of FD/MAS in a tertiary multidisciplinary care pathway, but no longitudinal data are available to support this recommendation. This multicenter prospective observational study aimed to evaluate effects of 1 year of treatment in the FD/MAS care pathway in 2 tertiary clinics on QoL and pain, assessed by change i ...[more]

PMID: 36528764

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Project description:BackgroundReducing delayed diagnosis is a significant healthcare priority for individuals with rare diseases. Fibrous Dysplasia/ McCune Albright Syndrome (FD/MAS) is a rare bone disease caused by somatic activation mutations of NASA. FD/MAS has a broad clinical phenotype reflecting variable involvement of bone, endocrine and other tissues, distribution and severity. The variable phenotype is likely to prolong the diagnostic journey for patients further.AimTo describe the time from symptom onset to final diagnosis in individuals living with FDMAS.MethodsWe used the UK-based RUDY research database ( www.rudystudy.org ), where patients self-report their diagnosis of FD/MAS. Participants are invited to complete the diagnostic journey based on the EPIRARE criteria.Results51 individuals diagnosed with FD/MAS were included in this analysis. Among them, 70% were female, and the median age was 51.0 years (IQR 34.5-57.5]. 12 (35%) individuals reported McCune Albright Syndrome, 11 (21.6%) craniofacial and 11(21.6%) for each of poly- and mono-ostotic FD and 6 (11.8%) did not know their type of FD/MAS. Pain was the commonest first symptom (58.8%), and 47.1% received another diagnosis before the diagnosis of FD/MAS. The median time to final diagnosis from the first symptom was two years with a wide IQR (1,18) and range (0-59 years). Only 12 (23.5%) of individuals were diagnosed within 12 months of their first symptoms. The type of FD/MAS was not associated with the reported time to diagnosis. Significant independent predictors of longer time to final diagnosis included older current age, younger age at first symptom and diagnosis after 2010.ConclusionIndividuals with FDMAS have a variable time to diagnosis that can span decades. This study highlights the need for further research on how to improve diagnostic pathways within Orthopaedic and Ear, Nose and Throat (ENT)/Maxillofacial services. Our data provides a baseline to assess the impact of novel NHS diagnostic networks on reducing the diagnostic odyssey.

Project description:Denosumab (Dmab) treatment can benefit patients with fibrous dysplasia/McCune-Albright syndrome (FD/MAS) by suppressing the receptor activator of nuclear factor κB ligand (RANKL)-mediated increased bone resorption. However, limited data of two pediatric cases indicate that a rebound phenomenon may occur after withdrawal. Therefore we studied the safety of Dmab discontinuation in FD/MAS. Thirty-seven patients using Dmab, mostly after unsuccessful bisphosphonate (BP) treatment, were included. Health records were screened for pain scores, side effects, and bone turnover markers (BTMs) (calcium, alkaline phosphatase [ALP], procollagen 1 N-terminal propeptide [P1NP], and β-crosslaps [B-CTX, also termed β-C-terminal telopeptide]) during treatment, and for BTMs and clinical rebound effects after withdrawal. BTM levels after withdrawal were compared to pretreatment values. Data were calculated as median (interquartile range [IQR]). BTMs normalized in two-thirds of patients and pain scores decreased significantly during treatment (p = 0.002). One patient (2.7%) developed osteonecrosis of the jaw. Sixteen patients discontinued Dmab treatment after a median of 1.6 years (IQR 1.0 years) because of insufficient effect on pain (n = 10, 63%), side effects (n = 4, 25%), or other reasons (n = 4, 25%). Follow-up posttreatment was 3.2 (2.8) years, wherein no fractures, pain flares, or lesion progression occurred. Calcium remained normal in all but one patient, who had a mild asymptomatic hypercalcemia (2.73 mmol/L) 5 months after discontinuation. ALP passed pretreatment levels in five of 11 patients (46%), increased most after 6 months by 18 (43) U/L, and returned to baseline levels thereafter. P1NP exceeded pretreatment levels in four of nine patients (44%), CTX in eight of nine patients (89%). P1NP rose most after 3 months and stabilized thereafter. CTX showed the highest relative elevation. Patients with high pretreatment levels responding well to Dmab seemed to have the highest rebound. These results suggest beneficial effects of Dmab on pain and BTMs, and show a biochemical but asymptomatic rebound phenomenon after withdrawal in adults with FD/MAS, mainly in case of high pretreatment levels, good response, and multiple injections. Further studies on the safety of Dmab and withdrawal are needed and ongoing. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Project description:Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare bone and endocrine disorder arising along a broad spectrum. Long-bone fractures are a common, painful, and potentially disabling complication. However, fracture prevalence and risk factors have not been well-established, making it difficult to predict which patients are at risk for a severe course. Clinical and imaging data were reviewed from two large, well-phenotyped cohorts (National Institutes of Health [NIH] in the United States and the Leiden University Medical Center [LUMC] in the Netherlands) to identify long-bone fractures at FD sites. Skeletal burden score was quantified using bone scintigraphy. Multiple linear regressions were performed to identify clinical associations with fractures. A total of 419 patients were included (186 NIH, 233 LUMC); 194 (46%) had MAS endocrinopathies. Median age at last follow-up was 30.2 years (range 3.2-84.6, interquartile range [IQR] 25.5), and median skeletal burden score was 16.6 (range 0-75, IQR 33). A total of 48 (59%) patients suffered one or more lifetime fracture (median 1, range 0-70, IQR 4). Median age at first fracture was 8 years (range 1-76, IQR 10). Fracture rates peaked between 6 and 10 years of age and decreased thereafter. Lifetime fracture rate was associated with skeletal burden score (β = 0.40, p < 0.01) and MAS hyperthyroidism (β = 0.22, p = 0.01). Younger age at first fracture was associated with skeletal burden score (β = -0.26, p = 0.01) and male sex (β = -0.23, p = 0.01). Both skeletal burden score >25 and age at first fracture ≤7 years were associated with a higher total number of lifetime fractures (median 4, range 1-70, IQR 5 versus median 1, range 1-13, IQR 1) (p < 0.01). In conclusion, higher skeletal burden score and MAS hyperthyroidism are associated with long-bone fractures in FD/MAS. Both skeletal burden score ≥25 and age at first fracture ≤7 years are associated with a higher lifetime long-bone fracture risk and may predict a more severe clinical course. These results may allow clinicians to identify FD/MAS patients at risk for severe disease who may be candidates for early therapeutic interventions. © 2021 American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Dataset Information

A multidisciplinary care pathway improves quality of life and reduces pain in patients with fibrous dysplasia/McCune-Albright syndrome: a multicenter prospective observational study.

Background

Results

Conclusions

Publications

A multidisciplinary care pathway improves quality of life and reduces pain in patients with fibrous dysplasia/McCune-Albright syndrome: a multicenter prospective observational study.

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