Polyostotic Fibrous Dysplasia Research Articles

Fibrous dysplasia of the head and neck in Southern Finland: a retrospective study on clinical characteristics, diagnostics, and treatment.

Fibrous dysplasia (FD) is a rare genetic disease with benign bone tumors. FD can affect one (monostotic FD) or multiple bones (polyostotic FD), with craniofacial lesions being common. Because of its rarity, there are only few clinical reports on FD in the head and neck region and its clinical characteristics remain incompletely defined. This study aimed to determine patient demographics, symptoms, diagnostics, and given treatment in patients with FD of the head and neck in a Finnish population. A retrospective review on all patients diagnosed with or treated for FD of the head and neck at the Helsinki University Hospital during 2005-2020. In total 74 patients were identified; 54% were male and the mean age 45years. Overall 95% had monostotic FD. Mandibula and maxilla were the most common anatomic sites. Majority of patients had symptoms, most commonly pain and lesion growth, and 49% had extra-skeletal symptoms. For all, diagnosis was primarily based on imaging findings, biopsies were obtained from 41%. Altogether 54 patients (73%) were managed by observation only, 20 patients (27%) received treatment; ten bisphosphonates, six surgery and four both. Although highly variable in its clinical manifestations, head and neck FD lesions are often symptomatic and impose risk for extra-skeletal complications. Treatment is often conservative but should be individually tailored. Future studies are encouraged to better define the disease characteristics and hopefully offer new treatment possibilities.

Decreased calcium permeability caused by biallelic TRPV5 mutation leads to autosomal recessive renal calcium-wasting hypercalciuria.

Hypercalciuria is the most common metabolic risk factor in people with kidney stone disease. Its etiology is mostly multifactorial, although monogenetic causes of hypercalciuria have also been described. Despite the increased availability of genetic diagnostic tests, the vast majority of individuals with familial hypercalciuria remain unsolved. In this study, we investigated a consanguineous pedigree with idiopathic hypercalciuria. The proband additionally exhibited severe skeletal deformities and hyperparathyroidism. Whole-exome sequencing of the proband revealed a homozygous ultra-rare variant in TRPV5 (NM_019841.7:c.1792G>A; p.(Val598Met)), which encodes for a renal Ca2+-selective ion channel. The variant segregates with the three individuals with hypercalciuria. The skeletal phenotype unique to the proband was due to an additional pathogenic somatic mutation in GNAS (NM_000516.7:c.601C>T; p.(Arg201Cys)), which leads to polyostotic fibrous dysplasia. The variant in TRPV5 is located in the TRP helix, a characteristic amphipathic helix that is indispensable for the gating movements of TRP channels. Biochemical characterization of the TRPV5 p.(Val598Met) channel revealed a complete loss of Ca2+ transport capability. This defect is caused by reduced expression of the mutant channel, due to misfolding and preferential targeting to the proteasome for degradation. Based on these findings, we conclude that biallelic loss of TRPV5 function causes a novel form of monogenic autosomal recessive hypercalciuria, which we name renal Ca2+-wasting hypercalciuria (RCWH). The recessive inheritance pattern explains the rarity of RCWH and underscores the potential prevalence of RCWH in highly consanguineous populations, emphasizing the importance of exploration of this disorder within such communities.

Successful surgical management of polyostotic costal fibrous dysplasia—a case report

Successful surgical management of polyostotic costal fibrous dysplasia—a case report

A rare case of fibrous dysplasia in the mandible: a case report

Background: Fibrous dysplasia (FD) is a benign fibro-osseous lesion of the bone which can be monostotic FD and the polyostotic form. Polyostotic FD with café-au-lait spots of the skin and hormonal imbalances is called McCune–Albright syndrome. Besides, Mazabraud syndrome is characterized by polyostotic FD and intramuscular myxomas. FD has its onset during childhood or early adolescence and usually occurs within the first or second decade of life.
 The mode of presentation of the FD of the jaw ranges from asymptomatic to dental anomalies, pain, and facial asymmetry. Given the clinical history and radiological assessment, cystic lesions have some important differential diagnoses which range from cystic ameloblastoma, fibrous dysplasia, aneurysmal bone cyst, and odontogenic keratocyst.
 Case report: This presents a 19-year-old female who presented to the maxillofacial surgeons’ clinic with a referral from a peripheral hospital. Her major complaint was right-sided facial swelling which was noticed 4 years before the presentation. A plain radiograph revealed an expansile lesion of the mid-right mandible appearing as a well-outlined, fairly oval multiloculated cystic radiolucent mass with multiple internal septations. A preliminary diagnosis of a complex cystic right jaw mass with benign features was made with possible differential diagnoses such as ameloblastoma, fibrous dysplasia, aneurysmal bone cyst, and odontogenic keratocyst were suggested as possible differential diagnoses. Finally, she had an excision biopsy with a histological diagnosis of fibrous dysplasia. The outcome of the surgery was satisfactory at one year review.
 

Incidence and Prevalence of Fibrous Dysplasia/McCune-Albright Syndrome: A Nationwide Registry-Based Study in Denmark.

Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare genetic disorder. Incidence and prevalence are not well-studied. Epidemiological research is complicated by the rarity of FD/MAS, absence of registries, heterogeneous presentation, and possibly asymptomatic phenotype. FD/MAS may present with FGF23-mediated hypophosphatemia, of which the epidemiology is also unclear. Evaluate incidence and prevalence of FD/MAS and FD/MAS-related hypophosphatemia. This cohort study based on the nationwide Danish National Patient Registry from 1995-2018, included patients identified by ICD-10 codes M85.0 (monostotic FD [MFD]) and Q78.1 (polyostotic FD [PFD]/MAS). Incidence rates and prevalence were calculated and stratified by sex, age, calendar period, and diagnosis code. Cases were screened for FD-associated hypophosphatemia by diagnosis code E.83 (disorder of mineral metabolism) and dispatched vitamin D analogues. A total of 408 patients were identified, 269 with MFD (66%), 139 with PFD/MAS (34%), comparable between sexes. Incidence of FD/MAS demonstrated increasing secular trend with a rate of 3.6 per 1 000 000 person-years (95% CI: 2.9, 4.5) in 2015-2018. Incidence peaked between age 11 and 20. Prevalence of FD/MAS increased over time to 61.0 (95% CI: 54.6, 67.4) per 1 000 000 persons in 2018. The incidence rate of MFD was 1.5-fold that of PFD/MAS in the first decade, rising to 2.5-fold in the last decade. No FD/MAS cases were registered with diagnosis code or treatment for hypophosphatemia. FD/MAS is rare, diagnosis peaks during adolescence without sex predominance, and MFD is most prevalent. Hypophosphatemia may be underdiagnosed and undertreated, or it may be underregistered, comparing this study to literature.

Aloarthroplasty of the Hip After Pathological Fracture of the Right Femoral Neck and Right Femoral Dyaphysis and Osteosynthesis after Fracture of the Left Femoral Dyaphysis in 41-Year-Old Female Patient with Polyostotic Fibrous Dysplasia? Case Report

A 41-year- old female patient with pathological basicervical right femoral neck fracture and fractures of both femoral bones 15-20 cm distally from the small trochanter is presented. Skeletal scintigraphy was performed and multiple pathological accumulations of radioactive substances were found in almost the entire locomotor system. First, we implanted a partial biarticular hip prosthesis with long stem in right femur, and one year later osteosynthesis of the left femoral diaphysis was done. Pathohistological examination did not find tumor cells and polyostotic fibrous dysplasia also was not clear. Our patient had not problems with bones earlier and she was never treated for this disease, except surgery of femoral fractures. Today, 11 years later the patient is in good general state, she has no pain in her legs and fractures of femur bones healed completely. We did not find a case in literature that a two fractures of proximal right femur bone (femoral neck and proximal diaphysis) and fracture of the left femoral diaphysis were solved with long stem prosthesis, and osteosynthesis of another femoral bone in patient who, we believe, has fibrous dysplasia and was never treated for this disease.

The Facial Osteoplasty for Polyostotic Fibrous Dysplasia in a Patient With McCune-Albright Syndrome: A Case Report

The Facial Osteoplasty for Polyostotic Fibrous Dysplasia in a Patient With McCune-Albright Syndrome: A Case Report

THU452 Polyostotic Fibrous Dysplasia Complicated By Aneurysmal Bone Cyst In A Patient With McCune-Albright Syndrome

Abstract Disclosure: E. Milazzo: None. K.L. Hermayer: None. Introduction: McCune-Albright Syndrome (MAS) is a rare mosaic disorder with GNAS mutations, encoding the alpha-subunit of the Gs G-coupled protein receptor, activating it, and inappropriately producing cAMP. The hyperfunctioning endocrinopathies associated with MAS are due to signaling through the TSH, LH, FSH, GHRH, and ACTH receptors. MAS clinical presentation occurs with café-au-lait skin macules, precocious puberty, and fibrous dysplasia (FD) of the bone. FD is a benign tumor that leads to increased rates of bone fractures and if it causes facial deformities, can be complicated with orbital neuropathies. An aneurysmal bone cyst (ABC) is a blood-filled cyst that can be a primary or secondary lesion due to co-existing lesions. ABC is a rare complication of FD. We report a rare case of ABC in a MAS patient who presented with acute visual disturbance and enlargement of the forehead and was successfully treated with surgery. Clinical Case: A 20-year-old female diagnosed with MAS at the age of 2 who had precocious puberty by the 3rd year of life and developed polyostotic FD in the right arm, left femur, cranial, and skull bones with multiple long bone fractures by the age of 5-6 and required numerous orthopedic surgeries. She presented with the characteristic café-au-lait skin macules on the back and right arm. In 2018, a slow decline of left eye vision required left cranial decompression of the optic nerve, with pathology showing fibrous tissue compatible with FD. In 2021, she complained of acute right forehead enlargement, compressing her right eye with blurry vision. An MRI showed FD involving the facial and skull bones with a new expansible lesion in the right frontal bone with internal layering fluid, exerting a mild mass effect on the frontal lobe and extending superiorly to the orbit with inferior displacement of the globe. These findings were consistent with an ABC. Right frontal craniectomy and cranioplasty were performed in 12/2021, with pathology showing a fibrous pseudocyst wall with associated lymphoplasmacytic inflammation and evidence of prior hemorrhage with Ki-67 in the cyst wall at 15%. Lab work showed chronic alkaline phosphatase elevation at 567IU/L (42-106IU/L), normal calcium at 9.2mg/dl (8.4-10.3mg/dl), phosphate at 3.3mg/dl (3.3-5.1mg/dl), and PTH at 26pg/ml (15-65mg/dl), with Vitamin D insufficiency at 25.1ng/ml (30-100ng/ml). Endocrinology workup was negative for thyroid, adrenal, gonadotrophic, and GH dysfunction. 5 months post-surgery, the patient demonstrated complete recovery, and MRI showed no recurrence of the ABC. Conclusion: ABC is a benign solitary tumor generally arising from the metaphysis of long bones and rarely involves the cranium. ABC associated with FD has only been reported in a few cases. The treatment is surgical excision, with radiation and cryotherapy used in nonorbital cases. Presentation: Thursday, June 15, 2023

Lower-limb intramedullary nailing in patients with polyostotic fibrous dysplasia who had a previous unsuccessful treatment. A report of 48 cases

BackgroundIntramedullary nailing (IN) seems to be the best primary surgical treatment for patients with either polyostotic fibrous dysplasia or McCune–Albright syndrome (PFD/MAS) when the femur and tibia are totally affected by fibrous dysplasia (FD) and pain, fracture and deformity are likely to occur. However, other management protocols have been applied in these cases, often leading to disabling sequelae. This study sought to evaluate if IN could also have been effective as a salvage procedure to provide patients with satisfactory results, regardless of the poor results due to the improper treatment previously performed.Materials and methodsTwenty-four retrospectively registered PFD/MAS patients with 34 femurs and 14 tibias totally affected by fibrous dysplasia had received various treatments with unsatisfactory results in other institutions. Before the IN performed in our hospital, 3 patients were wheelchair bound; 4 were fractured; 17 limped; and many used an aid for walking. Salvage IN was performed in our hospital at a mean patient age of 23.66 ± 6.06 years (range, 15–37 years). The patients were evaluated before—except for the four fractured ones—and after IN using the validated Jung scoring system, and the data were statistically analyzed.ResultsThe mean length of follow-up after IN was 9.12 ± 3.68 years (range, 4–17 years). The patients’ mean Jung score significantly improved from 2.52 ± 1.74 points before IN to 6.78 ± 2.23 at follow-up (p < 0.05). Ambulation was improved in ambulatory patients and restored in wheelchair users. The complication rate was 21%.ConclusionsRegardless of the high rate of complications, IN may be considered a reliable surgical procedure to salvage a failed treatment in PFD/MAS, with long-lasting satisfactory results achieved in most patients.Trial registration statement: Not applicable.Level of evidence: IV.

Polyostotic Fibrous Dysplasia in a Six-year-Old Boy.

Fibrous dysplasia (FD) is a rare congenital benign bone disease that manifests as a defect in the bone remodeling process, affecting the function, differentiation, and maturation of osteoblasts. This process is located in the bone marrow, where the normal marrow tissue is replaced with immature bone islands and fibrous stroma. The etiology is unclear so far, but it is known to be connected with a point mutation of the gene that encodes Gs α protein at the time of embryogenesis, and because of that, all of the affected somatic cells become dysplastic. It is important to determine whether the mutation occurred earlier in the process of embryogenesis so that there will be more mutant cells and the disease will appear in a more severe form. The clinical presentation of FD is variable, so there are plenty of potential differential diagnoses. The most common include Paget disease, non-ossifying fibroma, osteofibrous dysplasia, aneurysmal bone cyst, adamantinoma, giant cell tumor, fracture callus, and low-grade central osteosarcoma.

Menière's Syndrome Associated With Fibrous Dysplasia of the Temporal Bone.

Menière's Syndrome Associated With Fibrous Dysplasia of the Temporal Bone.

The 'Eye Mask Sign' in Fibrous Dysplasia on 99mTc-MDP Skeletal Scintigraphy and SPECT/CT.

Fibrous dysplasia (FD) is a fibro-osseous disorder that manifests with distinct or overlapping clinical patterns. FD may be monostotic or polyostotic and commonly associated with syndromes such as McCune-Albright syndrome and Mazabraud syndrome. We report a case of polyostotic FD with bilateral involvement of craniofacial bones in a distinct pattern and propose this characteristic appearance as the 'eye mask sign' on 99mTc-Methylene Diphosphonate (MDP) skeletal scintigraphy and SPECT/CT. Other unusual skeletal scintigraphic features noted in this case are also described (Figs. 1, 2, and 3).

Autonomous growth hormone secretion due to McCune Albright syndrome in paediatric age group: an ominous triad.

The current study aimed to report cases of McCune Albright syndrome (MAS) with growth hormone (GH) hyper secretion along with a systematic review of literature to elucidate challenges and intricacies in its diagnosis and management. It was a single centre study carried out in individuals with MAS and autonomous GH secretion (AGHS). In addition, a systematic search of literature across three databases (PubMed, Scopus and EMBASE) was performed from inception until May 31, 2021 to identify cases of MAS with AGHS in the pediatric age group (<18 years). Three cases from authors centre and 42 cases identified from systematic literature review were analysed. Precocious puberty was the most common presenting endocrinopathy seen in 56.8% (25/44) cases, followed by hyperthyroidism (10/45), hypophosphatemia (4/45), and hypercortisolism (2/45). Cranio-facial fibrous dysplasia (CFFD) was seen in all while polyostotic fibrous dysplasia and Café au lait macule was seen in 40/45 (88.9%) and 35/45 (77.8%), respectively. Pituitary adenoma (58.3% microadenoma) was localized in 53.3% (24/45) cases on pituitary imaging. Biochemical and clinical remission of AGHS was achieved in 61.5% (24/45) cases with medical therapy. Diagnosing AGHS in MAS is challenging because of concomitant presence of CFFD, non-GH endocrinopathies associated height spurt and elevated serum IGF-1. GH-GTT should be performed in presence of elevated growth velocity and serum IGF-1 (>1 X ULN) despite adequate control of non-GH endocrinopathies. Medical management can lead to disease control in substantial number of cases and often entails use of multiple agents.

A Rare Case of Polyostotic Fibrous Dysplasia

This case repost discusses clinical and biochemical features of polyostotic fibrous dysplasia, a rare entity which leads to significant morbidity and multisystem manifestation in children.The diagnosis ,differentials, treatment and complications are discussed. The role of FGF 23 in the pathogenesis of the disease is briefly discussed. This case description would improve the understanding of the clinical presentation as well as the diagnosis and treatment of fibrous dysplasia. Keywords: polyostotic fibrous dysplasia, FGF 23, hypophosphatemia

McCune-Albright Syndrome: A-rare-case report

McCune-Albright syndrome (MAS) is a rare genetic disordered originally recognized by the triad of polyostotic fibrous dysplasia, precocious puberty, and cafe-au-late spots. We report a case of 2 years-11-month-old girl who came with complaints of menstruation 5 days ago. Breasts appear enlarged. On physical examination, it appears that the café au lait region of the abdomen and left femur resembles the "coast of Maine". There was an increase in the levels of FT4, estradiol, and alkaline phosphatase, and low TSHs, LH, and FSH levels. The radiological examination of the bones of the left hand corresponded to the bone age of 6 years. Bone survey photo showing multiple lytic and blastic lesions in the proximal 1/3 of the left femur. We are monitoring this patient, and planning to administer Tamoxifen and Zoledronic acid. Tamoxifen (an estrogen agonist/antagonist) or Letrozole (an aromatase inhibitor) have been used for the management of precocious puberty and rapid bone maturation. Despite differing in presentation, all patients with precocious puberty were successfully treated with Tamoxifen and/or Letrozole, to emphasize the significant progress of bone age. A systematic approach to diagnosis and management is essential to optimize outcomes for patients with MAS, especially with fibrous dysplasia. No medical therapy is able to change the course of the disease in fibrous dysplasia. However, screening and treatment for endocrinopathy can reduce some bone morbidities.

Case Study: A rare case report of 39 years old Female with Polyostotic Fibrous Dysplasia

Fibrous dysplasia (FD) is a rare bone disorder in which the affected bone is replaced by abnormal scar-like(fibrous) connective tissue. This abnormal fibrous tissue makes the bone weak, abnormally fragile and proneto fracture. Pain may occur in the affected areas. This condition was first described in 1942 by Lichtenstein andJaffe, is also referred as Lichtenstein-Jaffe disease. Anyone can have FD and it can be diagnosed at any age. FDcan affect one bone (known as monostotic FD), multiple bones (known as polyostotic FD) or the entire skeleton(known as panostotic FD). The treatment of FD depends on diagnostic testing, number of bones affected andlocation of affected bones. In some cases, polyostotic fibrous dysplasia can be treated with a class of drugs calledbisphosphonates, which prevent bone loss and can reduce pain. Here presenting a case study of 39yrs femalewith Polyostotic Fibrous Dysplasia.

Surgical correction of valgus deformities of the knee in Polyostotic Fibrous Dysplasia.

Coxa vara and shepherd's crook deformity represent the most common femoral deformities in patients affected by polyostotic fibrous dysplasia (PFD) and McCune Albright syndrome (MAS). The tibia is also commonly affected, with antero-medial bowing and valgus deformity. Surgical treatment of these deformities are technically demanding and, in most cases, intramedullary nails are the preferred method to stabilize corrective osteotomies. Genu valgus may also be present, as a residual defect after the surgical correction of the aforementioned deformities. The aim of our study was to report the outcomes obtained in five patients with PFD or MAS operated on for complex deformities of the lower limbs with an associated residual genu valgum greater than 15°. It was surgically treated by distal femoral or proximal tibial osteotomy stabilized with a screw plate. The osteotomy was performed distal to the intramedullary nail in femurs, while it was performed after removing the intramedullary nail in the proximal metaphysis of the tibia. In latter cases, the intramedullary device was reinserted at least 6 months after surgery. At follow-up, the femoro-tibial angle was corrected in all cases and the patients were satisfied with the final result. Two patients showed mild limping, unrelated to the alignment of the knee. In our opinion, residual valgus deformities of the lower limb greater than 15 degrees should be corrected to improve function and cosmetic appearance of these patients. The osteotomy of the distal femur or of the proximal tibia stabilized by a screw-plate represent the treatment of choice for the correction of these deformities.

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

BackgroundFibrous 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.Results92 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 (rs = − 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 (rs = − 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.ConclusionsAll 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.

A Case Report of Polyostotic form of Fibrous Dysplasia: Imaging Features in Radiograph, Computed Tomography and Magnetic Resonance Imaging

Fibrous dysplasia is a disease that causes aberrant development of osteoblasts, which results in fibrous stroma replacing normal bone. Lichtenstein first described it in 1938. It is a sporadic disorder caused due to a postzygotic mutation in the GNAS1 gene. It can affect a single bone (monostotic) or several bones (polyostotic). The most common locations are the skull &amp; ribs. It is typically an incidental finding and asymptomatic. When a pathologic fracture or malignant alteration complicates it, symptoms could develop. As polyostotic FD is a rare disorder that only occasionally occurs in 20–25% of patients, therefore the aim of this article is to report such a rare case of polyostotic FD in a 30-year-old female patient showing the characteristic changes. Keywords: Polyostotic fibrous dysplasia, GNAS1 gene mutation, Sporadic disorder

Cross-sectional evaluation of FGD-avid polyostotic fibrous dysplasia: MRI, CT and PET/MRI findings

A 42-year-old male with left hip pain was diagnosed of several right femoral and tibial bone tumours. All lesions were osteolytic with sclerotic margins. The symptomatic lesion in the proximal femur also showed bone expansion and focal cortical thinning. Whole-body [18F]-fluorodeoxyglucose (FDG) PET/CT and segmental PET/MRI of the left hip and femur were performed for metabolic characterization of the lesions and for biopsy guidance. The lesions showed a heterogenous degree of FDG uptake corresponding to different metabolic stages of the disease. A biopsy of the tumour portion showing the highest FDG uptake revealed a fibrous dysplasia (FD). In conclusion, although generally affecting paediatric and adolescent subjects, polyostotic FD may be detected in the adulthood. Despite the benign nature of the disease, increased glucose metabolism can be seen in some lesions. Hybrid imaging combining morphological and functional information may help guide biopsy and better define the treatment strategy.