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Case 2, clinical and dental images. A, Technetium-99 bone scan highlighting areas of increased radiotracer uptake in bone (arrowheads) affected by fibrous dysplasia in the skull and bilateral femurs, humeri, and fibulas. (Fig 3 continued on next page.) Metwally et al. Fibrous Dysplasia and MRONJ. J Oral Maxillofac Surg 2016.
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Purpose:
Osteonecrosis of the jaw (ONJ) is an established side effect of intravenous bisphosphonates and other antiresorptive medications. Although bisphosphonates are frequently prescribed for patients with the skeletal disorder fibrous dysplasia (FD), there are no reports of ONJ in this population. This has led some to conclude that patients wit...
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The aim of this study was to assess the imaging and histological features of experimental periapical lesions, including the adjacent alveolar bone, in rats under zoledronic acid treatment. The study used 40 male Wistar rats distributed into 8 groups of 5 animals each: G1: induction of periapical lesion (PL) and weekly intraperitoneal administration...
An 83-year-old woman underwent mastectomy for breast cancer of the right breast in 2008. In addition to hormone therapy and irradiation, zoledronate was started for bone metastasis 6 months postoperatively. Five years after the operation, the patient developed osteonecrosis of the jaw, and underwent sequestrectomy because of uncontrollable pain in...
MRONJ (Medication-Related Osteonecrosis of the Jaw) is a condition observed in a subset of cancer patients who have undergone treatment with zoledronic acid in order to either prevent or treat bone metastases. The primary aim of this research was to establish the importance of risk factors in the development of medication-related osteonecrosis of t...
Citations
... Early reports on intravenous pamidronate showed beneficial effects on bone pain, but inconsistent effects on the radiographic appearance of FD [31][32][33]. Concerningly, recent evidence has established that patients with FD are at risk for osteonecrosis of the jaw as a consequence of bisphosphonate therapy [34]. Therefore, intravenous bisphos- phonates are a treatment option for FD-related bone pain, but caution is needed for long-term treatment with potent intravenous formulations [34]. ...
... Concerningly, recent evidence has established that patients with FD are at risk for osteonecrosis of the jaw as a consequence of bisphosphonate therapy [34]. Therefore, intravenous bisphos- phonates are a treatment option for FD-related bone pain, but caution is needed for long-term treatment with potent intravenous formulations [34]. The proposed protocols of intravenous pamidronate or zoledronate differ from those published in articles. ...
Fibrous dysplasia is an uncommon genetic disorder in which bone is replaced by immature bone and fibrous tissue, manifesting as slowgrowing lesions. Sporadic post-zygotic activating mutations in GNAS gene result in dysregulated GαS-protein signaling and elevation of cyclic adenosine monophosphate in affected tissues. This condition has a broad clinical spectrum, ranging from insignificant solitary lesions to severe disease. The craniofacial area is the most common site of fibrous dysplasia, and nine out of 10 patients with fibrous dysplasia affecting the craniofacial bones present before the age of 5. Surgery is the mainstay of treatment, but the technique varies according to the location and severity of the lesion and associated symptoms. The timing and indications of surgery should be carefully chosen with multidisciplinary consultations and a patient-specific approach.
... Intravenous bisphosphonates may be helpful for treatment of FD-related bone pain, although their efficacy in treating craniofacial pain is less clear [10]. Osteonecrosis of the jaw has been reported in patients with craniofacial FD treated with bisphosphonates [47]; risk factors appear to be similar to the general population, including high dose, long-term intravenous treatment, preceding invasive oral procedures, and poor dental hygiene [48]. ...
Purpose of Review
This study aims to review diagnosis, potential complications, and clinical management in craniofacial fibrous dysplasia.
Recent Findings
Fibrous dysplasia (FD) is a rare mosaic disorder in which normal bone and marrow are replaced with expansile fibro-osseous lesions. Disease presents along a broad spectrum and may be associated with extraskeletal features as part of McCune-Albright syndrome (MAS). The craniofacial skeleton is one of the most commonly impacted areas in FD, and its functional and anatomical complexities create unique challenges for diagnosis and management.
Summary
This review summarizes current approaches to diagnosis and management in FD/MAS, with emphasis on the clinical and therapeutic implications for the craniofacial skeleton.
... In patients with osteoporosis, it occurs in approximately 18% of cases after the first infusion; however, the incidence rate decreases in subsequent infusions (26). In our cohort, most patients (five out of seven) experienced acute phase reactions following the first ZA infusion, but no serious side effects have been reported to date, including osteonecrosis of the jaw, which seems to be more common among patients with FD (5.4%) than in patients with osteoporosis treated with bisphosphonates (27). ...
Objective:
Fibrous dysplasia (FD) is a rare bone disorder that can involve any part of the skeleton, leading to bone pain, deformities, and fractures. Treatment with intravenous bisphosphonates has been used with variable results. Therefore, we aimed to evaluate the effects of zoledronic acid (ZA) therapy in patients with monostotic or polyostotic FD.
Methods:
The medical records of thirteen patients with FD evaluated between 2015 and 2020 were retrospectively analyzed. In the subgroup of patients treated with ZA (n = 7), data on pain relief, changes in bone turnover markers (BTMs), and adverse events following ZA infusions were retrieved. Moreover, radiological changes in response to treatment were recorded in patients who underwent radiological follow-up.
Results:
Of the patients, 5 (38%) presented with monostotic whereas 8 (62%) had polyostotic FD. Bone pain was a common finding (69%), and most patients (62%) exhibited elevated baseline BTMs. Partial or complete pain relief was reported in 6 of 7 patients treated with ZA. BTMs, especially C-telopeptide of type I collagen (CTX), significantly decreased after therapy (change rate: -61.8% [IQR -71, -60%]), and median CTX levels were significantly lower than at baseline (0.296 ng/mL [0.216, 0.298] vs. 0.742 ng/mL [0.549, 0.907], respectively; P = 0.04). No radiological improvement was observed in cases with radiological follow-up (n = 3). No serious adverse effects of ZA were reported.
Conclusion:
ZA treatment was well tolerated and provided beneficial effects in relieving bone pain and reducing BTMs, especially CTX. Our data reinforce the role of ZA in the treatment of FD-related bone pain.
... Par exemple, dans une cohorte australienne, 52,5 % des ONM prises en charge étaient consécutives à un traitement par IRO hors oncologie avec 44,2 % pour une ostéoporose, 4,6 % pour une polyarthrite rhumatoïde et 3,3 % pour une maladie de Paget [24]. Des cas associés au traitement d'une dysplasie fibreuse sont également retrouvés dans la littérature, majoritairement au niveau des localisations maxillomandibulaires de la maladie [22,25]. Enfin, la présentation clinique est identique que l'ONM se déclare dans un contexte oncologique ou non. ...
Résumé
Comme pour tout traitement, la prescription d’inhibiteurs de la résorption osseuse (IRO) implique de mettre en balance les bénéfices et les risques attendus du traitement. Peu fréquente mais invalidante, l’ostéonécrose des mâchoires d’origine médicamenteuse (ONM) n’en reste pas moins l’effet indésirable le plus redouté des patients(e)s comme de certains professionnels de santé, possiblement en rapport avec une méconnaissance des éléments constituant cette balance bénéfices/risques. Une approche multidisciplinaire concertée, la prévention primaire via la réalisation systématique d’un bilan bucco-dentaire préthérapeutique dès lors que la situation clinique le permet, mais aussi l’instauration d’un suivi oral régulier permettent de considérablement limiter le risque d’ONM associé aux IRO, de faciliter l’adhérence au traitement et d’améliorer la qualité des soins.
... Lala et al. state that the use of bisphosphonates improves the clinical situation in children and adults [17]. To note, osteonecrosis of the jaws is a major complication of bisphosphonate treatment [18,19]. Thus, caution should be considered when prescribing bisphosphonates for a long period in patients suffering from FD [19]. ...
... To note, osteonecrosis of the jaws is a major complication of bisphosphonate treatment [18,19]. Thus, caution should be considered when prescribing bisphosphonates for a long period in patients suffering from FD [19]. ...
Fibrous dysplasia is a developmental disorder of the bone that originates from a genetic defect disturbing the osteogenesis leading to the replacement of normal bone with the excess proliferation of fibrous tissue. It can be associated with hyperpigmentation of the skin and endocrine disorders. Fibrous dysplasia can manifest in a monostotic form affecting one bone or in a polyostotic form involving several bones. Approximately 30% of monostotic forms are observed in the maxilla and the mandible. It frequently appears in the posterior region and is usually unilateral. It is found in teenagers and could become static after adulthood. Patients can present with swelling, facial asymmetry, pain, or numbness on the affected side. Treatment modalities vary between conservative surgical treatment, radical surgical approach, and medical treatment based on bisphosphonates. Here, we present a case of a monostotic form of fibrous dysplasia affecting the posterior left region of the mandible in a 9-year-old male complaining of gradually increased swelling on the left mandibular side of one-year duration. The diagnosis of fibrous dysplasia is established based on clinical, radiographical, and histopathological features. Conservative surgery is implemented with surgical shaving and reencountering of the bone excess to reduce the facial asymmetry. Recurrence is reported 10 years later and is also treated with a localized osteoplasty and remodeling of the bone contours. Five years later, the lesion remains stable. In conclusion, a conservative approach should be adopted as the first line of treatment for young patients suffering from monostotic fibrous dysplasia.
... High-dose denosumab treatment is associated with a 1-5% risk of ONJ, which has been confirmed in studies of GCT [15, 22••, 23, 24]. Clinicians should be aware that the prevalence of ONJ may vary across disease states; for example, ONJ has been reported in 5% of one large cohort of FD patients treated with bisphosphonates, suggesting this population may be at higher risk [25]. ...
Purpose of Review
This review summarizes current understanding of the role of denosumab, an inhibitor of receptor activator of nuclear kappa-B ligand (RANKL), in the management of 3 skeletal neoplasms: giant cell tumors, aneurysmal bone cysts, and fibrous dysplasia.
Recent Findings
A growing body of literature supports denosumab use in giant cell tumors, a neoplasm in which RANKL plays a clear pathogenic role. Comparatively less data is available in aneurysmal bone cysts and fibrous dysplasia; however, the pathogenic similarity of these disorders to giant cell tumors, as well as encouraging preliminary data, suggests denosumab may be useful. Denosumab’s inhibitory effects on bone turnover are fully reversible after drug discontinuation. This raises important unanswered questions for clinical management, including potential risks of tumor recurrence and bone turnover rebound.
Summary
Denosumab is a promising potential treatment for skeletal neoplasms. However, its clinical use is impacted by ongoing safety concerns related to postdiscontinuation rebound, particularly in children. There is a critical need to understand denosumab treatment and discontinuation effects on tumor recurrence and to develop strategies for long-term treatment in patients who cannot be managed surgically.
... Radiológiai képe a két elváltozásnak megegyezik, a fogak ritkán resorbeálódnak, habos vagy tejüvegszerű csontképet látni. Lehet kisméretű éles, és lehet multilocularis is az elváltozás [13,23,24]. Tekintve a fent említett egyes kórképek radiológiai jeleit biztos diagnózist csak hisztológiai mintavétel és diagnózis után lehet megállapítani. ...
A tanszékünkön megjelent 69 éves nőbeteg anamnézisének felvétele és stomato-onkológiai szűrése után panoráma(OP)felvétel készült, amelyen multiplex szklerotikus, cystosus felritkulások láthatók a mandibulán. A tapasztalt elváltozások alap-
ján további képalkotó modalitások alkalmazása vált indokolttá, így posteroanterior (PA) és oldalirányú (LAT) koponya-, illetve
cone beam CT (CBCT) felvételeket készítettünk. A PA és LAT koponyafelvételeken kóros eltérés a mandibulán kívül egyéb területen nem ábrázolódott. Minthogy a páciens ötéven belül nem jelent meg tüdőszűrő vizsgálaton, ezért nem rendelkezünk PA-mellkasfelvétellel. A páciens képanyaga alapján megerősítettük a fibrosus dysplasia radiológiai diagnózisát.
... As a result of adding the resection, the healing has been uneventful without recurrence although residual FD bone exists. Metwally et al. [6] reported the first cases of BRONJ associated with FD, in which only a Stage 2 case presented continual infection despite the combination of local debridement and antibiotic therapy. These findings suggest that surgical resection may be more useful than local debridement for advanced BRONJ associated with FD. ...
... Our patient who had been taking an oral BP for years developed BRONJ after tooth extractions within FD bone. FD patients have been reported to develop BRONJ after tooth extractions within FD bone despite the long-term discontinuation of intravenous BPs [6]. These findings indicate that tooth extraction within FD bone may be a higher risk factor for BRONJ regardless of the presence/absence of the discontinuation of BPs. ...
... The number of patients with FD complicated by BRONJ could increase, since FD patients can receive BP therapy for FD-related bone pain [6][7][8]. Our case supports aggressive treatment such as surgical resection for advanced BRONJ associated with FD. ...
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is an adverse drug reaction represented by destruction and/or death of bone. Fibrous dysplasia (FD) is a rare bony disorder characterised by abnormal fibro-osseous tissue that has lowered resistance to infection. Effective treatments for BRONJ that follows FD are unclear. Here, we report that advanced BRONJ associated with FD was successfully treated by surgical resection. A 69-year-old woman, whose left maxillary bone showed a ground glass appearance on computed tomography (CT) images, was taking alendronate. At 1 year after teeth within the abnormal bone were extracted, exposed bone was observed in the extraction sites and CT images revealed separated sequestrums. Under the clinical diagnosis of Stage 2 BRONJ with FD, we performed not only sequestrectomy but also a partial resection of the FD. Thereafter, the healing was uneventful without recurrence. In conclusion, our case suggests that surgical resection is useful for advanced BRONJ associated with FD.
... A randomized, placebocontrolled trial of the oral bisphosphonate alendronate detected increased FD lesion density in children (but not adults) with FD, and did not improve pain, fracture, or other clinically-relevant outcome measures (57). Concerningly, osteonecrosis of the jaw was reported in 5% of bisphosphonate-treated patients in one large retrospective series, suggesting FD may potentially carry an increased risk for this complication (58). The current evidence therefore supports that bisphosphonate use in FD should be limited to treatment of bone pain, using the lowest effective dose and interval. ...
Fibrous Dysplasia/McCune-Albright Syndrome (FD/MAS), arising from gain-of-function mutations in Gαs, and Cutaneous Skeletal Hypophosphatemia Syndrome (CSHS), arising from gain-of-function mutations in the Ras/MAPK pathway, are strikingly complex, mosaic diseases with overlapping phenotypes. Both disorders are defined by mosaic skin and bone involvement, and both are complicated by increased FGF23 production. These similarities have frequently led to mis-diagnoses, primarily in patients with CSHS who are often assumed to have FD/MAS. The intriguing similarities in skeletal involvement in these genetically distinct disorders has led to novel insights into FGF23 physiology, making an understanding of FD/MAS and CSHS relevant to both clinicians and researchers interested in bone and endocrine disorders. This review will give an overview of FD/MAS and CSHS, focusing on the roles of mosaicism and FGF23 in the pathogenesis and clinical presentation of these disorders.
... Despite their likely analgesic effects, bisphosphonates have not been demonstrated to improve bone quality or prevent FD lesion expansion [45][46][47]. Concerningly, osteonecrosis of the jaw has been reported in association with bisphosphonate treatment in FD [48]; therefore, it is recommended that bisphosphonates be limited to treatment of FD-related pain, using the lowest effective dose and interval [34]. ...
McCune-Albright syndrome (MAS) is a rare, mosaic disorder presenting along a broad clinical spectrum. Disease arises from somatic-activating GNAS mutations, leading to constitutive Gαs activation and ligand-independent signaling of the Gαs-coupled protein receptor. The phenotype is largely determined by location and extent of tissues in which the GNAS mutation is expressed, as well as the pathophysiologic effects of Gαs activation within these tissues. Patients pre-sent clinically with a variable combination of fibrous dysplasia of bone (FD), café-au-lait skin macules, and hyperfunctioning endocrinopathies. In bone, Gαs leads to impaired differentiation of skeletal stem cells and formation of discrete, expansile FD lesions, resulting in fractures, pain, and functional impairment. A systematic approach to diagnosis and management is critically important to optimize outcomes for patients with FD/MAS. There are no medical therapies capable of altering the disease course in FD; however, screening and treatment for endocrinopathies can mitigate some skeletal morbidities. This review summarizes current understanding of MAS pathophysiology, describes the spectrum of clinical features, and includes a detailed discussion of the recommended approach to diagnosis and management.
