Improvement of Fibrous Dysplasia After Burosumab Therapy in a Pediatric Patient with McCune-Albright Syndrome: A Case Report.

CASE: Burosumab is a novel drug developed to treat hereditary fibroblast growth factor 23 (FGF23)-related disorders. We report the case of an 11-year-old girl with McCune-Albright syndrome (MAS) who sustained hypophosphatemia due to excess FGF23 and multiple bone lesions of fibrous dysplasia (FD). Burosumab therapy markedly improved not only the biochemical parameters but also the radiographic appearance of the FD lesions and clinical symptoms. CONCLUSION: This is the first report to demonstrate that burosumab is effective in improving FD lesions in a patient with MAS.

[Osteosarcoma Secondary to Polyostotoic Fibrous Dysplasia of the Ribs].

Sarcomatous transformation of fibrous dysplasia is extremely rare. We present the case of a 54-yearold man with multiple rib masses, multiple enlarged lymph nodes throughout the body, and multiple osteolytic lesions on computed tomography( CT). A positron emission tomography( PET) scan showed abnormal enhancement in each. A needle biopsy of the right supraclavicular fossa lymph node revealed sarcoidosis. Considering the possibility of malignancy associated with sarcoidosis, a rib tumor resection and mediastinal lymph node biopsy were performed to confirm the diagnosis of the rib lesion. The pathology results showed that the rib mass was a low-grade central osteosarcoma and the mediastinal lymph node was sarcoidosis. The distribution of the lesions was consistent with osteosarcoma secondary to multiple fibrous bone dysplasia. As the osteosarcoma was low grade, the patient was followed up. Three years after surgery, there was no increase in residual disease.

RANK-L inhibitor as a promising agent for refractory extensive craniofacial fibrous dysplasia: A case report.

BACKGROUND: McCune-Albright syndrome is a rare disorder characterized by polyostotic fibrous dysplasia (FD), café-au-lait skin pigmentation, and endocrine dysfunction. Extensive FD in the craniofacial region can present significant challenges in terms of disease control and carries a high risk of permanent visual impairment. METHODS: We present a case of medically and surgically resistant FD that required nine optic nerve decompressions. RESULTS: The condition was ultimately controlled with the use of the denosumab agent. CONCLUSION: The case highlights the importance and potential efficacy of denosumab in resistant FD management, particularly in cases involving sensitive organs.

Fibrous Dysplasia With Atypical Bilateral Upper Extremity Pattern.

ABSTRACT: Fibrous dysplasia (FD) typically presents unilaterally in the lower limbs, or in the skull, mandible, or pelvis. Bilateral presentation is rarely reported. Most cases are diagnosed in the teens with 75% of patients diagnosed before the age of 30 years. In this case, a 63-year-old woman with suspected diagnosis of malignancy was referred to 99mTc-MDP scan and found to have polyostotic FD in bilateral upper extremities. Nuclear medicine can play an important role in diagnosing FD cases with atypical presentation and help risk stratification for more aggressive transformation.

Lesion Expansion in Gnathic Fibrous Dysplasia: Natural History, Indicators of Progression, and Response to Bisphosphonates.

Fibrous dysplasia (FD) is characterized by expansile fibro-osseous lesions that may occur in association with endocrinopathies as part of McCune-Albright syndrome (MAS). Craniofacial FD is a significant source of morbidity and most commonly involves the gnathic bones. There is a critical need to understand the natural history and risk factors for gnathic FD progression to develop preventative trials and identify candidates for intervention. The purpose of this study was to characterize gnathic FD lesion expansion and to identify risk factors associated with lesion growth. Patients with gnathic FD and serial CT imaging were evaluated. Volumetric analyses of CT scans were performed using MIM Encore software. Generalized mixed model analysis was used to account for intra-subject correlation, with FD lesion volume as the dependent variable. In addition to age, effects of MAS-associated endocrinopathies, sex, disease severity, and bisphosphonate treatment were evaluated. A total of 104 total lesions in 52 patients were characterized longitudinally. Median age at initial scan was 8.8 years (range 3.4-18.8), and median age at final scan was 16.8 years (range 6.9-33.4 years). The median number of scans per subject was 4 (range 2-14). FD lesion volume increased with age (2.50 cm3 /yr, 95% confidence interval [CI] 1.95-3.04, p < 0.001). However, lesion expansion rate decreased over time (-0.05 cm3 /yr, 95% CI -0.07 to 0.04, p < 0.001). Mandibular lesions tended to expand at a greater rate than maxillary lesions (p < 0.001). Growth hormone excess was associated with accelerated expansion rate (p = 0.002). Other MAS-associated endocrinopathies, pubertal status, sex, weight, lesion density, disease severity, and bisphosphonate treatment were not associated with lesion volume or expansion. Gnathic FD lesion expansion is most rapid in younger children and declines as patients approach adulthood. The availability of quantitative natural history data will guide clinicians in identifying patients who are candidates for medical and surgical interventions and clinical trials for preventative therapies. Published 2023. This article is a U.S. Government work and is in the public domain in the USA.

Case Report Of Rib Polyostotic Fibrous Dysplasia.

Polyostotic fibrous dysplasia is a rare benign asymptomatic tumour of the ribs not requiring surgery on most occasions. We present here a case with left 10th and 11th rib fibrous dysplasia which was causing a hinderance to the Urologist for renalstone extraction. Therefore the 10th and 11th ribs were excised followed by chest wall reconstruction.

Coxa Vara Deformity in Fibrous Dysplasia/McCune-Albright Syndrome: Prevalence, Natural History and Risk Factors: A Two-Center Study.

This study aimed to evaluate the prevalence of and risk factors for coxa vara deformity in patients with fibrous dysplasia/McCune-Albright syndrome (FD/MAS). This study was conducted at the National Institutes of Health and Leiden University Medical Center. All patients with any subtype of FD/MAS, FD involving the proximal femur, one or more X-rays available and age <30 years were included. X-rays were scored for the neck-shaft angle (NSA). Varus deformity was defined as NSA <110 degrees or >10 degrees below age-specific values. Risk factors for deformity were assessed by nested case-control analysis, comparing patients and femurs with and without deformity, and by linear mixed effects model, modeling temporal NSA decrease (the natural course of the NSA) in non-operated femurs with two or more X-rays. Assessed variables included growth hormone excess, hyperthyroidism, hypophosphatemia, >25% of the femur affected, calcar destruction, radiolucency, and bilateral involvement. In total 180 patients were studied, 57% female. Mean ± SD baseline age was 13.6 ± 7.5 years; median follow-up 5.4 (interquartile range [IQR], 11.1) years. Sixty-three percent (63%) were diagnosed with MAS. A total of 94 patients were affected bilaterally; 274 FD femurs were analyzed; 99 femurs had a varus deformity (36%). In the nested case-control analysis, risk factors were as follows: presence of MAS (p < 0.001), hyperthyroidism (p < 0.001), hypophosphatemia (p < 0.001), high percentage of femur affected (p < 0.001), and calcar destruction (p < 0.001). The linear mixed effects model included 114 femurs, identified risk factors were: growth hormone excess (ß = 7.2, p = 0.013), hyperthyroidism (ß = 11.3, p < 0.001), >25% of the femur affected (ß = 13.2, p = 0.046), calcar destruction (ß = 8.3, p = 0.004), radiolucency (ß = 3.9, p = 0.009), and bilateral involvement (ß = 9.8, p = 0.010). Visual inspection of the graph of the model demonstrated most progression of deformity if NSA <120 degrees with age < 15 years. In conclusion, in tertiary care centers, the prevalence of FD/MAS coxa vara deformity was 36%. Risk factors included presence of MAS, high percentage of femur affected, calcar destruction, radiolucency, NSA <120 degrees and age < 15 years. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Severe craniofacial fibrous dysplasia associated with decreased visual acuity: a case report.

Fibrous dysplasia is a developmental abnormality characterized by the replacement of normal bone tissue by fibrous connective tissue with poorly organized bone trabeculae. This disorder rarely occurs in the craniofacial region, but in such cases it causes facial asymmetries and has severe clinical implications for the patient. This case report describes the treatment of an 18-year-old man who presented with complaints of facial deformity and decreased visual acuity. Cone beam computed tomography revealed a diffuse bone lesion affecting the region of the maxillary, frontal, and nasal bones on the left side of the face. After microscopic examination, the diagnosis of craniofacial fibrous dysplasia was made. The patient underwent a bilateral temporal craniotomy to perform decompression of the orbital apices and correct the loss of visual acuity. In addition, surgical cosmetic contouring of the facial bones was performed. The patient has been followed up by a multidisciplinary team; at his most recent examination, 18 months after the last surgical intervention, his clinical condition remained stable.

A Novel Bone Contouring Technique Using Multiple Tangential Shaving for Conservative Management of Craniofacial Fibrous Dysplasia.

This study aimed to propose a novel surgical technique, named multiple tangential shaving of bone contour, for the conservative management of craniofacial fibrous dysplasia. We retrospectively reviewed 17 patients who underwent conservative management of craniofacial fibrous dysplasia using multiple tangential shaving technique between July 2005 and December 2020. Demographics, tumor characteristics, and surgery-related factors were investigated. All patients underwent preoperative (T0) and postoperative computed tomography scans taken at least twice within 1 month for immediate assessment (T1) and at least 12 months postoperatively for long-term assessment (T2). Clinical outcomes, including tumor recurrence, perioperative complications, and physician measure of esthetic outcomes (Whitaker score), were investigated. This technique was applied for contouring of the zygomatic-maxillary and calvarial bone for patients aged between 16 and 60 years (mean age: 26 y). The mean±SD tumor volume reduction was 15.5±8.95 cm 3 , and the postoperative mean±SD tumor growth rate was 5.52±6.26% per year. Satisfactory outcome was obtained in terms of esthetics with a mean±SD Whitaker score of 1.41±0.62. Patients required a mean operation time of 1.67±0.43 hours and a mean number of shaving operations of 1.35±0.61 during the follow-up period. Five of 17 patients required reoperation because of the tumor recurrence (N=4) and to correct new-onset diplopia after surgery (N=1). In conclusion, the multiple tangential shaving technique allows an easy approach for conservative management of craniofacial fibrous dysplasia. An acceptable rate of tumor recurrence and esthetic outcomes can be obtained by selecting the appropriate candidate for a conservative approach.

Caracterización clínica de pacientes chilenos con displasia fibrosa/síndrome de McCune-Albright / Clinical features of Chilean patients with Fibrous Dysplasia/McCune-Albright Syndrome

BACKGROUND: Fibrous Dysplasia/McCune-Albright Syndrome (FD/MAS) is characterized by a spectrum of manifestations that may include fibrous dysplasia of bone and multiple endocrinopathies. AIM: To describe the clinical spectrum, the study and follow-up of patients with FD/MAS cared at our institution. MATERIAL AND METHODS: Review of medical records of 12 pediatric and adult patients (11 women) who met the clinical and genetic diagnostic criteria for FD/ MAS. RESULTS: The patients' mean age at diagnosis was 4.9 ± 5.5 years. The most common initial clinical manifestation was peripheral precocious puberty (PPP) in 67% of patients and 75% had café-au-lait spots. Fibrous dysplasia was present in 75% of patients and the mean age at diagnosis was 7.9 ± 4.7 years. Ten patients had a bone scintigraphy, with an age at the first examination that varied between 2 and 38 years of age. The most frequent location of dysplasia was craniofacial and appendicular. No patient had a recorded history of cholestasis, hepatitis, or pancreatitis. In four patients, a genetic study was performed that was positive for the pathogenic variant of guanine nucleotide binding protein, alpha stimulating (GNAS). CONCLUSIONS: These patients demonstrate the variable nature of the clinical presentation and study of FD/MAS. It is essential to increase the index of diagnostic suspicion and adherence to international recommendations.

Long-term imaging course of Chiari malformation type I due to fibrous dysplasia/McCune-Albright syndrome.

INTRODUCTION: McCune-Albright syndrome (MAS) and fibrous dysplasia (FD) have been reported to cause Chiari type I malformation (CM1) and skull base invagination (BI). CASE: A 6-year-old girl was diagnosed with MAS and FD. She was diagnosed with CM1 at age 8 years, and the syringomyelia had gradually increased by age 20 years. We performed foramen magnum decompression and C1 laminectomy, and the syringomyelia stopped spreading after surgery. DISCUSSION: This patient underwent long-term radiological observation and morphological evaluations, which revealed that the skull thickening was progressing, while the posterior cranial fossa volume (PCFV) remained unchanged for 14 years. Therefore, although PCFV did not decrease, it was considered to be relatively inadequate due to the increase in brain volume with growth, resulting in posterior fossa overcrowding, causing CM1. CONCLUSION: In patients with FD/MAS, long-term evaluation of bone thickening, odontoid position, and PCFV is necessary.

[Clinical features of Chilean patients with Fibrous Dysplasia/McCune-Albright Syndrome]. / Caracterización clínica de pacientes chilenos con displasia fibrosa/síndrome de McCune-Albright.

BACKGROUND: Fibrous Dysplasia/McCune-Albright Syndrome (FD/MAS) is characterized by a spectrum of manifestations that may include fibrous dysplasia of bone and multiple endocrinopathies. AIM: To describe the clinical spectrum, the study and follow-up of patients with FD/MAS cared at our institution. MATERIAL AND METHODS: Review of medical records of 12 pediatric and adult patients (11 women) who met the clinical and genetic diagnostic criteria for FD/ MAS. RESULTS: The patients' mean age at diagnosis was 4.9 ± 5.5 years. The most common initial clinical manifestation was peripheral precocious puberty (PPP) in 67% of patients and 75% had café-au-lait spots. Fibrous dysplasia was present in 75% of patients and the mean age at diagnosis was 7.9 ± 4.7 years. Ten patients had a bone scintigraphy, with an age at the first examination that varied between 2 and 38 years of age. The most frequent location of dysplasia was craniofacial and appendicular. No patient had a recorded history of cholestasis, hepatitis, or pancreatitis. In four patients, a genetic study was performed that was positive for the pathogenic variant of guanine nucleotide binding protein, alpha stimulating (GNAS). CONCLUSIONS: These patients demonstrate the variable nature of the clinical presentation and study of FD/MAS. It is essential to increase the index of diagnostic suspicion and adherence to international recommendations.

Long Bone Fractures in Fibrous Dysplasia/McCune-Albright Syndrome: Prevalence, Natural History, and Risk Factors.

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 (ß = 0.40, p < 0.01) and MAS hyperthyroidism (ß = 0.22, p = 0.01). Younger age at first fracture was associated with skeletal burden score (ß = -0.26, p = 0.01) and male sex (ß = -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.

McCune-Albright syndrome onset with vaginal bleeding.

McCune-Albright syndrome (MAS), a rare genetic disorder, affects multiple organs and classically presents with the triad of polyostotic fibrous dysplasia (FD), skin hyperpigmentation (café-au-lait spots) and precocious puberty. Diagnosis occurs when patients manifest at least two of these three symptoms. We describe a 4-year-old girl who was admitted to our hospital due to recurrent vaginal bleeding, initially diagnosed as precocious puberty. On brain MRI, abnormalities in the maxillary and occipital bones were compatible with FD. Clinical examination after craniofacial bone lesions and clinical signs indicated MAS revealed abnormally pigmented macules on the neck and back, which were initially overlooked. No abnormal hormone tests were observed. Precocious puberty is the most common MAS-associated symptom that results in the admission to the hospital, whereas the clinical manifestation of FD in the first years of life is usually equivocal and probably has not been discovered by parents. Thus, comprehensive medical examinations are necessary to obtain a prompt and proper diagnosis.

Jaffe Lichtenstein Type of Polyostotic Skeletal Fibrous Dysplasia With the Involvement of Cranial Bones.

ABSTRACT: Fibrous dysplasia (FD), a benign fibro-osseous bone tumor commonly involving the craniofacial region, presents a wide spectrum of radiographic patterns. When FD lesions are suspected, various imaging modalities and histopathologic analyses may be required to reach a firm diagnosis. Here, the authors report the case of a 10-year-old male patient presenting with polyostotic type of FD with follow-up data for the next 9 years. The patient showed involvement of cranial bones and bilateral femurs, with skin pigmentation and no endocrine disease, consistent with the diagnosis of Jaffe Lichtenstein disease. The craniofacial radiographic features obtained with computed tomography and cone-beam computerized tomography are documented in this article.

Denosumab Reduces Lesional Fluoride Skeletal Burden on Na[18F]F PET-CT in Patients With Fibrous Dysplasia/McCune-Albright Syndrome.

CONTEXT: The correlation between fibrous dysplasia/McCune-Albright syndrome (FD/MAS) skeletal disease burden on Na[18F]F positron emission tomography-computed tomography (PET-CT) and serum bone turnover markers (BTMs) was recently described. The effect of treatment on lesional fluoride burden in FD/MAS is unknown. OBJECTIVE: To investigate treatment response measurements in patients with FD/MAS who underwent Na[18F]F-PET-CT and treatment with antiresorptives. METHODS: Observational case series at an academic center of expertise for rare bone diseases. Fifteen consecutive patients were observed with FD/MAS with baseline and follow-up Na[18F]F-PET-CT parameters of healthy bone and FD lesions, BTMs, and pain scores at start of denosumab (n = 8) treatment and non-denosumab patients (n = 7). On Na[18F]F-PET-CT the volumetric measures of FD burden (fluoride tumor volume [FTV]) and "fraction affected skeleton" (FAS) represented the portion of the skeleton affected. This was correlated with BTMs and pain. RESULTS: Disease activity decreased significantly, with FTV 361 cm3 to 97 cm3 (P = .018) in denosumab-treated patients, but not in non-denosumab patients (P = .249). Serum P1NP and alkaline phosphatase (ALP) decreased significantly: 82 ng/mL vs 55 ng/mL (P = .023) and 119 IU/L vs 84 IU/L (P = .020), respectively. In denosumab-treated patients pain scores improved leading to pain medication reduction. This correlated with lesional uptake, but healthy bone activity did not change. BTMs and FTV correlated positively (P1NP r = 0.730, P < .001; and ALP r = 0.406, P = .006), as did change in BTMs and FTV: P1NP (P = 0.032) and ALP (P = 0.024). FAS strongly correlated with treatment-induced decrease in ALP (P = .027) and P1NP (P = .009). CONCLUSION: Na[18F]F-PET-CT captured treatment-induced lesional changes which correlated with BTMs and pain reduction. Therefore Na[18F]F-PET-CT can be used as an objective local parameter of response to denosumab treatment in FD/MAS.