This study aimed to examine the effect of a coordinated care pathway, with information provision, counseling, and a multidisciplinary care as described in the guidelines, on QoL and pain in patients with FD/MAS. At baseline patients with FD/MAS reported significant and clinically relevant impairments in all domains of QoL and the majority reported moderate-severe pain. After referral to our tertiary FD clinics, patients reported a clinically important difference in SF-36 domains Physical Function, Role Limitations due to Physical Problems, Social Functioning and Health Change as well as a clinically relevant decrease of 1 point in maximum pain, average pain and pain interference. The baseline scores in our study reflect the accomplished level of QoL and pain in the referring secondary care facility. Therefore these data suggest that treatment in our tertiary FD care pathway for FD/MAS may benefit QoL and pain compared to usual care in other hospitals. Remarkably the SF-36 domain Pain did not reflect the improvements observed in the BPI. This SF-36 domain consists of 2 questions on pain intensity in 6 response categories and pain interference in 5. This scale may not have been sufficiently responsive to change to capture the 1-point change demonstrated by the BPI. Yet the improvements in the domains interference of pain with general activity and in Role Limitations due to Physical Problems appeared to be larger than in pain and Physical Function, which implies that the FD/MAS care pathway mainly improves negative consequences of pain and impaired mobility rather than the item itself. The moderate correlation between change in pain inference and in Role Physical domain underlines this observation. Another striking finding is the discrepancy between stable scores for General Health and clinically relevant increases in Health Change. The General Health domain consists of items on self-perceived health status, tendency to become ill compared to others and expectations on future health whereas the Health Change domain consists of 1 item on health status compared to 1 year ago. Possibly health state is perceived as better than 1 year ago, but still considerably worse compared to others. Nevertheless this rise in Health Change is in line with the reported improvements in other domains and these data highlight that symptomatic patients with FD/MAS may benefit from referral to a specialized tertiary center with multidisciplinary care.
New referrals generally reported worse scores for QoL and pain at baseline compared to chronic patients. Yet also in chronic patients clinically relevant improvements were observed, specifically in Role Physical and Emotional Wellbeing. Similarly in several other SF-36 domains and in pain interference smaller improvements were observed, which were neither significant nor clinically relevant, but we cannot rule out that a larger difference may be accomplished during a longer trajectory in the FD/MAS care pathway. The amelioration in chronic patients, although to a lesser extent, suggests that the improvements in new referrals could not merely be attributed to low baseline performance with large room for improvement or to regression to the mean, but confirms that the care pathway benefits QoL and pain, even in long-term care.
The COVID-19 pandemic might have influenced our results, as half of the patients (n=49, 53%) completed the first questionnaire before and the second after the national social distancing measures in March 2020, whereas 22 patients (24%) completed both questionnaires before and 21 (23%) both during the pandemic. The major increase in Social Functioning, which we had not expected, may be explained by the fact that patients with low baseline scores for Social Functioning, mainly new referrals, experienced less difficulties in social life during the pandemic because of the absence of social gatherings.
A previous cross-sectional study on QoL and pain in FD/MAS has been conducted in our center by Majoor et al26 and showed better scores for QoL and pain compared to the present study. Accordingly our cohort demonstrated impairments in all domains of QoL in comparison to the general Dutch population, whereas Majoor et al. did not detect this for domains Role Emotional and Mental Health. Since QoL and pain are affected by FD subtype, skeletal burden, lesion location and age14, 25, 38, variable study populations will result in a diversity of QoL and pain scores. Our study consisted of more patients with PFD and MAS, less with MFD and included an extra subgroup of patients with CFD. Secondly our study included new referrals, who may have a less extensive treatment history compared to patients under chronic care. Lastly mainly patients with MFD reported impairments in our study compared to the previous study, which may all account for the difference between both studies.
Indeed of all FD subtypes in our cohort, patients with MFD demonstrated most impairments in domains Physical Function, Pain and Role Physical and most interference of pain with general activities. Both QoL and pain responded well to academic care and improved during follow-up. The largest reduction in pain interference with general activity was observed in patients with isolated craniofacial FD. On the contrary patients with MAS experienced least improvement over time in both SF-36 and BPI scores. A hypothesis for the least severe FD subtypes benefiting most from therapy is that selection bias occurred when MFD or CFD patients with minor complaints were treated in non-academic centers and those with severe complaints were referred and treated in academic centers, selecting the patients who are more likely to benefit from treatment. Nevertheless this highlights that even patients with low skeletal burden may experience substantial negative FD-related consequences and may benefit from referral to a specialized center.
A secondary aim was to assess illness perceptions. The observed increase in QoL in our cohort could not be supported by a change in Illness Perceptions. The counselling, providing information and treatment in the LUMC care pathway surprisingly did not effectuate better perceived coherence of the disease or a higher perceived control over disease related complaints. The correlation between temporal change in SF-36 domain Role Physical and in pain interference is in line with the finding that QoL in our cohort was not influenced by altered illness perceptions but rather by improved pain management.
However QoL may even improve without change in pain scores. This was demonstrated by patients who had not received FD-related therapy during follow-up but still experienced a major improvement in Role Physical with an ES of 0.47 after 1 year, despite constant pain severity or interference. We hypothesize that the rise in QoL in our cohort may not only be explained by the effect of antiresorptive therapy or pain management but also by other factors, possibly multidisciplinary care, recognition of FD-related complaints, lifestyle advice or disease acceptance.
The COVID-19 pandemic could comprise a limitation of our study, as several negative consequences of the pandemic have been established in the general population including stress or worry39, less physical activity40, depressive symptoms, listlessness and decreased quality of life41. We were not able to assess the influence of several lockdowns on our study, but it might have exerted negative effects on Role Limitations due to Physical Problems, Emotional Wellbeing, Energy/Fatigue, pain and pain interference. If so, this would result in an underestimation of the effect of the care pathway. Contrarily less physical activity could also benefit pain severity and interference. Another limitation is the discrepancy in sample sizes between referral groups, as the smaller sample of new referrals delivers results with more variance and more vulnerable to outliers. In addition the baseline scores of new referrals were used as proxy for the level of QoL and pain accomplished during secondary care before referral to our facility, but the true scores remain unknown. Finally our study comprised a heterogenous population of patients with FD/MAS with several subtypes, variable treatment history and various treatments started during follow-up. Ideally to assess the added value of the care pathway a randomized controlled trial should be conducted, where patients are randomized into treatment in the care pathway or in usual care, but limited resources hindered this design. Alternatively the approach in this study could be regarded as a strength, as it reflects the clinical heterogeneity present in every tertiary referral center and maintains external validity. This validity is further supported by the limited non-response bias, demonstrated by comparable characteristics of complete cases and non-responders. For these reasons results of this study may be generalized to patients with FD/MAS in other academic hospitals. Another strength of this study is the insight into questionnaires valuable for patients with FD/MAS, to screen for impairments not routinely addressed during standard medical consultations. Results were discussed with the Dutch Patient Association Fibrous Dysplasia to allow for improved and simplified questionnaire logistics in our FD/MAS care pathway. Lastly our study is the first to generate a longitudinal follow-up of PROMs in academic care and the first to combine outcomes such as QoL, mobility, pain and illness perceptions in patients with FD/MAS.