Patients With Isolated Craniofacial Dysplasia Report Better Quality of Life Compared With Those With Craniofacial Dysplasia and Extracranial Involvement.

PURPOSE: Craniofacial fibrous dysplasia (CFD) is a subtype of fibrous dysplasia/McCune-Albright syndrome (FD/MAS) characterized by FD lesions in one or more of the skull bones. The orbit is often involved, with facial pain, facial deformity, and increased risk of compressive optic neuropathy as associated clinical manifestations possibly leading to altered illness perceptions and impairments in quality of life(QoL). The aim of this study was to evaluate illness perceptions and QoL in patients with CFD among our FD/MAS cohort. METHODS: One hundred ninety-one patients were included. Illness perceptions and QoL were assessed by using validated questionnaires, that is, the Illness Perceptions Questionnaire-Revised and the Short-Form 36. Patients were first grouped as CFD versus non-CFD, a second selection was based on the presence of "Isolated CFD" versus "CFD+PFD/MAS." Non-CFD patients were grouped as monostotic fibrous dysplasia "MFD" versus polyostotic "PFD/MAS." RESULTS: Patients with isolated CFD attributed less symptoms to their disease compared with patients with CFD+PFD/MAS (p < 0.05). Furthermore, patients with isolated CFD reported better QoL on all domains (except role emotional and mental health) compared with patients with CFD+PFD/MAS (p < 0.05). Patients with isolated CFD also reported better QoL compared with non-CFD groups (on 3 out of 8 subscales) (p < 0.05). CONCLUSIONS: Patients with isolated CFD attribute less symptoms to their disease and report better QoL compared with patients with CFD with extracranial involvement or FD without cranial involvement. These findings indicate that craniofacial involvement alone is not sufficient to cause negative illness perceptions and impairments in QoL. Therefore, it can be postulated that isolated CFD should be considered a unique patient subtype within the spectrum of FD/MAS patients.

Denosumab in Patients With Fibrous Dysplasia Previously Treated With Bisphosphonates.

CONTEXT: Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare bone disorder commonly treated with bisphosphonates, but clinical and biochemical responses may be incomplete. OBJECTIVE: To evaluate the efficacy and tolerability of the receptor activator of nuclear factor-κB ligand inhibitor denosumab in the treatment of patients with FD/MAS refractory to bisphosphonate therapy. DESIGN: Case series. SETTING: Academic center of expertise for rare bone diseases. PATIENTS: Data were collected from 12 consecutive patients with FD/MAS with persistent pain and increased biochemical markers of bone turnover (BTMs) after long-term treatment with bisphosphonates (median, 8.8 years) and were treated with subcutaneous denosumab 60 mg at 3- or 6-month intervals with a follow-up for at least 12 months. MAIN OUTCOME(S): Sustained reduction of BTMs and bone pain. RESULTS: A 60 mg dose of denosumab once every 3 months, but not once every 6 months, induced a sustained reduction of BTMs. After a median treatment period of 15.5 months (range, 12 to 19) serum alkaline phosphatase activity and propeptide of type 1 procollagen levels were respectively reduced from 212 ± 39.4 IU/L to 79 ± 6.0 IU/L (P = 0.004) and from 346.2 ± 111.1 ng/mL to 55.7 ± 16.6 ng/mL (P = 0.023) and normalized in 70% and 75% of patients, respectively. Although not quantitavely measured, 10 patients reported a reduction in bone pain of whom 6 reported complete elimination of pain. Treatment with denosumab was well tolerated. CONCLUSION: Our results indicate that 60 mg of denosumab every 3 months is a promising, well-tolerated treatment of most patients with FD/MAS refractory to bisphosphonate therapy. These results together with those of previously published case reports provide the necessary background for the design of a larger, controlled study.

Pain in fibrous dysplasia: relationship with anatomical and clinical features.

Background and purpose - Fibrous dysplasia (FD) is a rare bone disorder associated with pain, deformities, and pathological fractures. The pathophysiological mechanism of FD-related pain remains ill-understood. We evaluated the degree of pain and the potential contributory factors in 2 patient cohorts from Austria and the Netherlands. Patients and methods - 197 patients (16-85 years) with FD (Graz n = 105, Leiden n = 92) completed a survey concerning the presence and severity of pain at their FD site. Sex, age, type of FD, and localization of FD lesions were examined for a relationship with the presence and severity of pain. Results - Of 197 patients from the combined cohort (61% female, mean age 49 (SD 16) years, 76% monostotic) who completed the questionnaires, 91 (46%) reported pain at sites of FD lesions. Severity of pain was higher in patients with lesions of the lower extremities and ribs compared with upper extremity or craniofacial lesions. Severe subtypes of FD (polyostotic/McCune-Albright syndrome) were more often associated with pain, often severe. Interpretation - Our data suggest that almost 50% of patients with FD report pain at FD sites, thus representing a major clinical manifestation of the disorder, importantly also in patients with monostotic lesions. Lesions in lower extremities and ribs were more painful.

Prevalence and Clinical Features of Mazabraud Syndrome: A Multicenter European Study.

BACKGROUND: Mazabraud syndrome is a rare disorder, characterized by the presence of fibrous dysplasia (FD) with associated intramuscular myxomas. Data are scarce on the prevalence, clinical features, and natural history of this disorder and outcomes. In this multicenter study, we evaluated a series of patients from 6 European centers. METHODS: All centers affiliated with the European Musculo-Skeletal Oncology Society (EMSOS) were invited to include data on all patients with Mazabraud syndrome who were seen between 1980 and 2015. The study investigated the prevalence of Mazabraud syndrome, the type, severity, and localization of FD lesions in relation to myxomas, the histopathology of myxomas, and results of GNAS-mutation analysis, when available. RESULTS: Thirty-two patients (22 female) from 6 centers were included. The prevalence of Mazabraud syndrome was 2.2% in the combined cohort of 1,446 patients with FD, and the syndrome was diagnosed at a mean of 10.1 years after diagnosis of FD. The myxomas were predominantly localized in the upper leg. Excision was performed in 20 patients, recurrence occurred in 6 of these patients (30%) at a median of 8.5 years (range, 1.9 to 16.0 years), and revision surgery was necessary in 5 (25%). High cellularity of myxomas was associated with recurrence (p < 0.05). A GNAS mutation was identified in the myxoma tissue of 5 (83%) of 6 patients with GNAS-mutation analysis. CONCLUSIONS: This study is the first, to our knowledge, to provide data on the prevalence of Mazabraud syndrome in a relatively large cohort. Although the outcomes of surgical resection were good, a quarter of the patients required revision surgery despite clear resection margins. High cellularity of myxomas was associated with recurrence. GNAS mutations were identified in 83% (5 of 6), emphasizing the shared origin of FD and myxomas. Our data show that patients with FD who have disproportionate complaints, irrespective of FD type, extent, or severity, should be investigated for the possible presence of myxomas. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Individualized approach to the surgical management of fibrous dysplasia of the proximal femur.

BACKGROUND: Fibrous dysplasia of the proximal femur presents with heterogeneous clinical manifestations dictating different surgical approaches. However, to date there are no clear recommendations to guide the choice of surgical approach and no general guidelines for the optimal orthopedic management of these lesions. The objective of this study was to evaluate treatment outcomes of angled blade plates and intramedullary nails, using as outcome indicators revision-free survival, pain, function and femoral neck-shaft-angle. Based on a review of published literature and our study findings, we propose a treatment algorithm, taking into account different factors, which may play a role in the selection of one surgical approach over another. METHODS: Data were evaluated in thirty-two patients (18 male) from a combined cohort from the Netherlands and Austria, who had a surgical intervention using an angled blade plate (n = 27) or an intramedullary nail (n = 5) between 1985 and 2015, and who had a minimal follow-up of one year. The primary outcome was success of the procedure according to the revised Henderson classification. Secondary outcomes, which were assessed at one year and at the end of follow-up included: function (as measured by walking ability), pain and change in femoral neck-shaft angle over time. RESULTS: Analysis of data showed that revision-free survival was 72% after a median follow-up of 4.1 years. Revision was necessary in two patients for structural failure due to a fracture distal to an angled blade plate and in 7 patients due to angled blade plate-induced iliotibial tract pain. At the end of follow-up 91% of all patients had good walking ability and 91% were pain free. There was no significant postoperative change in femoral neck shaft angle. CONCLUSION: Our data show that fibrous dysplasia of the proximal femur can be adequately and safely treated with angled blade plates or intramedullary nails, providing these are used according to specific characteristics of the individual patient. Based on published literature and our own experience, we propose an individualized, patient-tailored approach for the surgical management of fibrous dysplasia of the proximal femur.

Determinants of impaired quality of life in patients with fibrous dysplasia.

BACKGROUND: Fibrous dysplasia is a rare bone disorder, commonly associated with pain, deformity and fractures, which may significantly impact on quality of life. In this study we evaluate quality of life in patients with fibrous dysplasia using the Short Form-36 and the Brief Pain Inventory questionnaires. Data were compared with those of the general Dutch population. RESULTS: Out of 138 patients from a cohort of 255 patients with fibrous dysplasia that were sent questionnaires assessing quality of life and pain, the response rate was 70.3%, with 97 patients, predominantly female (65%), completing the questionnaires. Monostotic fibrous dysplasia was predominant (n = 62, 64%). Fibrous dysplasia patients had significantly lower quality of life outcome scores than the general Dutch population for all tested domains of the Short Form-36 except for the "Mental health" and the "Role emotional" domains. More severe forms of fibrous dysplasia, had the more severe Short-Form-36 quality of life outcomes, but there was no significant difference in Brief Pain Inventory domains between different subtypes of fibrous dysplasia. Quality of life was lower in patients with higher disease burden, as reflected by high skeletal burden scores (p = 0.003) and high levels of P1NP (p = 0.002). CONCLUSION: We demonstrate impairments in all domains of quality of life, except for 'Mental health' and 'Role emotional' domains, across the wide spectrum of fibrous dysplasia including its milder forms. We identified high skeletal burden scores, reflecting disease severity, as the most consistent predictor of impaired quality of life. Our findings hold significant clinical implications as they draw attention to the clinically unmet need to address quality of life issues in the management of patients with all subtypes of fibrous dysplasia, including its milder forms.