Nuevos avances en el conocimiento de la historia natural de la displasia fibrosa / News advances in the knowledge of natural history of the fibrous dysplasia

La displasia fibrosa (DF) es una enfermedad infrecuente del hueso, no hereditaria, producida por una mutación activadora del gen GNAS, responsable de codificar la unidad a-estimuladora de la proteína G (Gsa). La presentación clínica de la enfermedad es muy variada, pues adopta desde formas asintomáticas hasta otras marcadamente sintomáticas. En los últimos años, el análisis exhaustivo de bases de datos de pacientes con DF ha permitido conocer más sobre su historia natural. En este artículo se revisa la información actualmente disponible sobre algunos aspectos que ayudarán al mejor enfoque clínico del paciente, como son: la utilidad clínica de los marcadores óseos, los factores pronósticos para el desarrollo de fracturas, la DF como condición predisponente para el desarrollo de tumores específicos, nuevas perspectivas sobre la fisiopatología del dolor óseo y nuevas estrategias terapéuticas. Un mayor conocimiento sobre la historia natural de esta enfermedad finalmente redundará en la mejor calidad de vida de los pacientes con DF. (AU)

Fibrous dysplasia (FD) is an infrequent, non-hereditary bone disease caused by a somatic mutation of the GNAS gene, responsible for encoding the a-subunit of the G-protein (Gsa). The clinical presentation of the disease varies greatly, with some patients being asymptomatic and others markedly symptomatic. The exhaustive analysis of the database from patients with FD has allowed to learn more about the natural history of this disease. This article reviews the current information available on the clinical utility of bone markers, the prognostic factors for the occurrence of fractures, the evidence supporting as a predisposing condition for the development of specific tumors, new perspectives on the pathophysiology of bone pain, and emerging therapeutic strategies. A greater understanding of the natural history of this disease will allow to make better medical decisions, which will ultimately contribute to improve FD patients' quality of life. (AU)

18 F-NaF PET/CT IMAGING IN FIBROUS DYSPLASIA OF BONE.

Fibrous dysplasia (FD) is a mosaic skeletal disorder resulting in fractures, deformity, and functional impairment. Clinical evaluation has been limited by a lack of surrogate endpoints capable of quantitating disease activity. The purpose of this study was to investigate the utility of 18 F-NaF PET/CT imaging in quantifying disease activity in patients with FD. Fifteen consecutively evaluated subjects underwent whole-body 18 F-NaF PET/CT scans, and FD burden was assessed by quantifying FD-related 18 F-NaF activity. 18 F-NaF PET/CT parameters obtained included (i) SUVmax (standardized uptake value [SUV] of the FD lesion with the highest uptake); (ii) SUVmean (average SUV of all 18 F-NaF-positive FD lesions); (iii) total volume of all 18 F-NaF-positive FD lesions (TV); and (iv) total FD lesion activity determined as the product of TV multiplied by SUVmean (TA = TV × SUVmean ) (TA). Skeletal outcomes, functional outcomes, and bone turnover markers were correlated with 18 F-NaF PET/CT parameters. TV and TA of extracranial FD lesions correlated strongly with skeletal outcomes including fractures and surgeries (p values ≤ 0.003). Subjects with impaired ambulation and scoliosis had significantly higher TV and TA values (P < 0.05), obtained from extracranial and spinal lesions, respectively. Craniofacial surgeries correlated with TV and TA of skull FD lesions (P < 0.001). Bone turnover markers, including alkaline phosphatase, N-telopeptides, and osteocalcin, were strongly correlated with TV and TA (P < 0.05) extracted from FD lesions in the entire skeleton. No associations were identified with SUVmax or SUVmean . Bone pain and age did not correlate with 18 F-NaF PET/CT parameters. FD burden evaluated by 18 F-NaF-PET/CT facilitates accurate assessment of FD activity, and correlates quantitatively with clinically-relevant skeletal outcomes. © 2019 American Society for Bone and Mineral Research.

Clinical and translational pharmacological aspects of the management of fibrous dysplasia of bone.

Fibrous dysplasia (FD) is a genetic, noninheritable rare bone disease caused by a postzygotic activating mutation of the α subunit of the stimulatory G-protein causing increased abnormal bone formation leading to pain, deformity and fractures. To date, no cure has been identified for FD/McCune-Albright syndrome (MAS) and treatment is symptomatic and aimed at decreasing pain and/or local bone turnover. Various drugs have been used to achieve clinical improvement in FD/MAS patients including bisphosphonates and denosumab, however further translational studies are also warranted to address unresolved pathophysiological issues and explore novel pharmacological targets for the management of FD/MAS. In this article, we review literature on the medical treatment of FD/MAS, discuss the unresolved pathophysiological issues and explore novel pharmacological targets for the management of FD/MAS.

A retrospective clinico-pathologic analysis of cemento-osseous dysplasia in a South African patient population.

BACKGROUND: Cemento-osseous dysplasia (COD) is a fibro-osseous jaw bone lesion. The affected bone in COD progressively becomes sclerotic, poorly vascularized and susceptible to secondary osteomyelitis. OBJECTIVE: To provide a clinico-pathologic appraisal of COD in a South African patient population. METHODS: Archived records of 133 patients diagnosed with COD were reviewed for patient demographics, COD location, COD type, osteomyelitis or simple bone cyst secondary to COD. RESULTS: The mean age was 53.4 ± 13.5 years with a 94.7% female predilection. COD mainly affected the mandible (57.1%), followed by involvement of both jaws (38.3%) and maxilla (4.5%). Florid COD was the most prevalent (69.9%), followed by focal COD (18%) and periapical COD (12%). Florid COD showed a clear trend of increasing with age, peaking in the sixth decade and decreasing thereafter. Osteomyelitis and simple bone cyst presented as complications of COD in 74.4% and 5.3% of cases respectively, while 21.8% of all cases of jaw osteomyelitis during the study period were secondary to COD. CONCLUSION: A higher frequency of jaw osteomyelitis secondary to COD was found compared to previous studies. No significant association was shown between any of the COD types and secondary osteomyelitis.

Florid cemento-osseous dysplasia: a contraindication to orthodontic treatment in compromised areas.

Florid cemento-osseous dysplasia is a sclerosing disease that affects the mandible, especially the alveolar process, and that is, in most cases, bilateral; however, in some cases it affects up to three or even four quadrants. During the disease, normal bone is replaced with a thinly formed, irregularly distributed tissue peppered with radiolucent areas of soft tissue. Newly formed bone does not seem to invade periodontal space, but, in several images, it is confused with the roots, without, however, compromising pulp vitality or tooth position in the dental arch. There is no replacement resorption, not even when the images suggest dentoalveolar ankylosis. Orthodontists should make an accurate diagnosis when planning treatments, as this disease, when fully established, is one of the extremely rare situations in which orthodontic treatment is contraindicated. This contraindication is due to: (a) procedures such as the installment of mini-implants and mini-plaques, surgical maneuvers to apply traction to unerupted teeth and extractions should be avoided to prevent contamination of the affected bone with bacteria from the oral microbiota; and (b) tooth movement in the areas affected is practically impossible because of bone disorganization in the alveolar process, characterized by high bone density and the resulting cotton-wool appearance. Densely mineralized and disorganized bone is unable to remodel or develop in an organized way in the periodontal ligaments and the alveolar process. Organized bone remodeling is a fundamental phenomenon for tooth movement.

Significado clínico del aumento de los valores séricos de FGF-23 en la displasia fibrosa / Clinical significance of increased serum levels of FGF-23 in fibrous dysplasia

Introducción y objetivo: La displasia fibrosa (DF) puede asociarse al desarrollo de osteomalacia hipofosfatémica por la producción de FGF-23 en el tejido óseo displásico. En este estudio se analizan los valores de FGF-23 en pacientes con DF y su relación con la actividad de la enfermedad y con los valores de fosfato sérico. Pacientes y métodos: Se incluyó a 12 pacientes adultos con DF. Se revisaron las características clínicas, los parámetros analíticos y los tratamientos realizados y su relación con los valores de FGF-23. Resultados: Seis de 12 pacientes (50%) tenían un aumento del FGF-23; estos pacientes tenían una edad, una extensión y una actividad de la enfermedad similares a aquellos con FGF-23 normal. No se observaron diferencias entre los valores de fosfato sérico entre ambos grupos (FGF-23 alto: 3,9±0,9mg/dl vs. FGF-23 normal: 3,5±0,6mg/dl). Ningún paciente con aumento de FGF-23 tenía valores de fosfato sérico bajos. Conclusión: Los pacientes adultos con DF presentan con frecuencia un aumento del FGF-23 sin repercusión en los niveles séricos de fosfato, lo que indica una alteración en el procesamiento de esta proteína en el tejido óseo displásico en esta patología

Introduction and objective: Fibrous dysplasia (FD) can be associated with the development of hypophosphatemic osteomalacia, caused by the production of FGF-23 by dysplastic bone tissue. This study analysed FGF-23 levels in patients with FD, and their association with disease activity and serum phosphate values. Patients and methods: Twelve adult patients with FD were included in the study. Clinical history, disease extension and activity and treatments received were reviewed, and the relationship of those values with FGF-23 and serum P levels was analysed. Results: FGF-23 was elevated in 6/12 patients (50%). Patients with high FGF-23 levels had similar age and disease activity and extension than those who did not. No differences were observed in serum phosphate values between both groups (increased FGF-23: 3.9±0.9 mg/dl vs. decreased FGF-23: 3.5±0.6 mg/dl). In fact, none of the patients with increased FGF-23 had low serum phosphate values. Conclusion: Adult FD patients frequently present elevated FGF-23 values with no serum phosphate level repercussion, suggesting an alteration in the processing of this protein in the dysplastic bone tissue for this pathology

Florid cemento-osseous dysplasia: a contraindication to orthodontic treatment in compromised areas

ABSTRACT Florid cemento-osseous dysplasia is a sclerosing disease that affects the mandible, especially the alveolar process, and that is, in most cases, bilateral; however, in some cases it affects up to three or even four quadrants. During the disease, normal bone is replaced with a thinly formed, irregularly distributed tissue peppered with radiolucent areas of soft tissue. Newly formed bone does not seem to invade periodontal space, but, in several images, it is confused with the roots, without, however, compromising pulp vitality or tooth position in the dental arch. There is no replacement resorption, not even when the images suggest dentoalveolar ankylosis. Orthodontists should make an accurate diagnosis when planning treatments, as this disease, when fully established, is one of the extremely rare situations in which orthodontic treatment is contraindicated. This contraindication is due to: (a) procedures such as the installment of mini-implants and mini-plaques, surgical maneuvers to apply traction to unerupted teeth and extractions should be avoided to prevent contamination of the affected bone with bacteria from the oral microbiota; and (b) tooth movement in the areas affected is practically impossible because of bone disorganization in the alveolar process, characterized by high bone density and the resulting cotton-wool appearance. Densely mineralized and disorganized bone is unable to remodel or develop in an organized way in the periodontal ligaments and the alveolar process. Organized bone remodeling is a fundamental phenomenon for tooth movement.

RESUMO A displasia cemento-óssea florida é uma doença óssea esclerosante exclusiva dos maxilares, relacionada ao osso do processo alveolar e, na maioria dos casos, envolvendo bilateralmente a mandíbula; mas há casos em que envolve três ou até os quatro quadrantes. Nesse processo, troca-se o osso normal por um tecido densamente formado, irregularmente distribuído e salpicado por áreas radiolúcidas com tecido mole. O osso neoformado parece não invadir o espaço periodontal, mas, em muitas imagens, confunde-se com as raízes, sem comprometer a vitalidade pulpar e a posição dentária na arcada. Não há reabsorção dentária por substituição, mesmo quando as imagens sugerem anquilose alveolodentária. Um diagnóstico preciso por parte do ortodontista deve ser feito em seus planejamentos, visto que essa doença, quando se encontra plenamente instalada, representa uma das raríssimas situações em que o tratamento ortodôntico está contraindicado. Nesses casos, o tratamento ortodôntico está contraindicado porque: a) alguns procedimentos, como a aplicação de mini-implantes e miniplacas, manobras cirúrgicas para tracionamento de dentes não irrompidos e exodontias, devem ser evitados, para se impedir a entrada de bactérias da microbiota bucal no osso comprometido; e b) a possibilidade de movimentação dos dentes nas áreas comprometidas praticamente inexiste, pela desorganização óssea no processo alveolar, caracterizada por elevada densidade óssea, que gera as imagens tipo flocos de algodão. O osso densamente mineralizado e desorganizado não é capaz de se remodelar e desenvolver organizadamente, nos ligamentos periodontais e no osso do processo alveolar. A remodelação óssea organizada é fundamental como um dos fenômenos necessários para o deslocamento dos dentes.

Dental Manifestations of Pediatric Bone Disorders.

PURPOSE OF REVIEW: Several bone disorders affecting the skeleton often are manifest in the maxillofacial region. This review presents the most common bone disorders in children and their dental-oral manifestations: fibrous dysplasia, Paget's disease, osteogenesis imperfecta, renal osteodystrophy, hypophosphatasia, and osteoporosis. The specific intraoral characteristics will reviewed in detail. RECENT FINDINGS: Recent studies confirmed the close relationship between the mandible and the maxilla with the most prevalent systemic bone disorders in children. This review will help practitioners to integrate the oral health into the systemic health and improve the multidisciplinary approach of pediatric patients between medicine and dentistry.

The Status of Affected Infraorbital Nerve and Inferior Alveolar Nerve in Patients With Jaw Fibrous Dysplasia: A Clinical and Radiographic Evaluation.

The affected infraorbital nerve (IFBN) and inferior alveolar nerve (IFAN) status in patients with jaw fibrous dysplasia has not been definitely depicted. In this study, the authors try to explore the status of affected IFBN and IFAN in patients with jaw fibrous dysplasia. Ten patients with jaw fibrous dysplasia were included in this study. The complaints of numbness in the IFBA and IFAN innervated area were asked and recorded, and careful clinical examination was performed to evaluate the touch sense, pain sense, pressure sense, and temperature sense in the IFBA and IFAN innervated areas. Computed tomography scans also were performed to evaluate the imaging characteristics of affected IFBA and IFAN. The results showed that 1 patient with maxillary lesion showed complaints of slight numbness, and clinical examination showed that the patient exhibited slight insensitive in pain sense. In addition, 1 patient with mandibular lesion showed relative obvious complaints of numbness, and clinical examination showed that the patient exhibited slight insensitive in pain sense and temperature sense, but not serious. All other patients exhibited no numbness in the IFBA and IFAN innervated area. Although the position and morphology changed in some patients, all neural canal of affected IFBA or IFAN existed and showed no invasion of lesion. Taking these findings together, it further confirmed that evaluation of the function of IFBAN and IFAN is necessary for patients with jaw fibrous dysplasia, and the affected IFBAN and IFAN may should be reserved in most patients with jaw fibrous dysplasia when resecting or recontouring the lesion.

The natural history of focal fibrocartilaginous dysplasia in the young child with tibia vara.

BACKGROUND: Focal fibrocartilaginous dysplasia is an uncommon disorder that affects young children causing unilateral deformity of the tibia. The lesion is seen in other similar conditions but this anomaly shows peculiar clinical characteristic. METHODS: Eleven young patients have been seen between the years 2002-2010 and followed up clinically and radiographically from 3 to 9 years. Family history, previous episode of trauma, infections, and bone disease in the children were not recountered. RESULTS: All cases were treated conservatively and self-corrected by the last follow-up. One case (9.09%) displayed a 4° of varus, and one case (9.09%) displayed a 5° of varus and one (9.09%) a slight leg length discrepancy. CONCLUSION: According to our results and those reported in the literature, focal fibrocartilaginous dysplasia is a benign affection that does not need treatment with a Levine and Drennan angle of <30°.

Rapid biochemical response to denosumab in fibrous dysplasia of bone: report of two cases.

We report on the clinical and biochemical outcomes in two adult patients with active polyostotic fibrous dysplasia (FD) treated with the RANK-L inhibitor, denosumab, following unsatisfactory responses to prior long-term bisphosphonate therapy. A 44-year-old female (case 1) who had received a cumulative dose of 20 mg zoledronic acid over 2.5 years and a 48-year-old male (case 2) who had received a cumulative dose of 45 mg zoledronic acid over 8 years both experienced minimal reductions in pain scores and markers of bone turnover. Following initiation of denosumab 60 mg sc, changes in bone pain, bone turnover [assessed by serum amino-terminal propeptide of type I collagen (PINP) and urinary deoxypyridinoline] were monitored over a period of 20 and 8 months, respectively. Following administration of denosumab, both patients demonstrated a rapid and pronounced biochemical response: Within 4-7 weeks, bone turnover markers fell to levels within the respective reference range, and one patient reported a reduction in pain. Treatment with denosumab was well tolerated. However, transient asymptomatic hypocalcaemia and/or hypophosphatemia associated with a transient two to threefold increase in serum PTH levels was observed in both patients. Dosing intervals for denosumab varied significantly between the two patients, depending on disease activity at baseline. Denosumab appears to be effective in reducing bone turnover in adult patients with active FD. However, caution should be exercised, and patients should be monitored carefully as significant fluctuations in biochemical and hormonal indices can occur.

Fibrous dysplasia of the mobile spine: report of 8 cases and review of the literature.

STUDY DESIGN: Eight cases of fibrous dysplasia (FD) of the mobile spine treated surgically at the same center were retrospectively reviewed. OBJECTIVE: The study focuses on the issues concerning the diagnosis of FD and the outcome of conventional surgical techniques (resection or curettage) and vertebroplasty in the treatment of spinal FD lesions. SUMMARY OF BACKGROUND DATA: Surgical excision or curettage is considered the standard treatment of spinal FD, whereas vertebroplasty is also performed occasionally. METHODS: Between January 2005 and October 2010, 8 consecutive patients with spinal FD underwent conventional surgery (6 cases) or combined with vertebroplasty (2 cases). Before surgery, 4 patients underwent percutaneous computed tomography-guided biopsy, whereas 3 had incorrect histopathological diagnosis. In each of the 8 cases, the final pathological diagnosis was established after their open surgery. RESULTS: Pain relief was observed postoperatively in all patients. Three patients with neurological impairment became symptom-free after surgery. No cement extravasation was observed. Screw loosening and allograft resorption were observed in 1 case each. Signs of radiological improvement (filling of lytic lesions or thickening of the bone cortex surrounding the lesions) were not detected in any case. CONCLUSION: The radiological features of spinal FD may be atypical. The rate of correct preoperative pathological diagnosis by computed tomography-guided biopsy was low for patients with suspected spinal FD. Vertebroplasty is probably a valuable therapeutic option for spinal FD with pathological fractures. Limited decompression and stability with vertebroplasty might be recommended for patients with neurological deficits.

Pathophysiology and medical treatment of pain in fibrous dysplasia of bone.

One of the most common complications of fibrous dysplasia of bone (FD) is bone pain. Usual pain killers are often of inadequate efficacy to control this bone pain. The mechanism of bone pain in FD remains uncertain, but by analogy with bone tumors one may consider that ectopic sprouting and formation of neuroma-like structures by sensory and sympathetic nerve fibers also occur in the dysplastic skeleton. Bone pain has been reported in up to 81% of adults and 49% of children. It affects predominantly the lower limbs and the spine. The degree of pain is highly variable and adults reports more pain than children. Bisphosphonates have been shown to reduce bone pain in uncontrolled studies. Their influence on bone strength remains unknown. In a randomized trial testing alendronate, bone pain was not significantly improved. Another trial assessing the effect of risedronate is ongoing. Possible future therapies include tocilizumab, denosumab and drugs targeting nerve growth factor and its receptor TrkA.

Surgery versus watchful waiting in patients with craniofacial fibrous dysplasia--a meta-analysis.

BACKGROUND: Fibrous dysplasia (FD) is a benign bone tumor which most commonly involves the craniofacial skeleton. The most devastating consequence of craniofacial FD (CFD) is loss of vision due to optic nerve compression (ONC). Radiological evidence of ONC is common, however the management of this condition is not well established. Our objective was to compare the long-term outcome of patients with optic nerve compression (ONC) due to craniofacial fibrous dysplasia (CFD) who either underwent surgery or were managed expectantly. METHODOLOGY/PRINCIPAL FINDINGS: We performed a meta-analysis of 27 studies along with analysis of the records of a cohort of patients enrolled in National Institutes of Health (NIH) protocol 98-D-0145, entitled Screening and Natural History of Fibrous Dysplasia, with a diagnosis of CFD. The study group consisted of 241 patients; 122 were enrolled in the NIH study and 119 were extracted from cases published in the literature. The median follow-up period was 54 months (range, 6-228 months). A total of 368 optic nerves were investigated. All clinically impaired optic nerves (n = 86, 23.3%) underwent therapeutic decompression. Of the 282 clinically intact nerves, 41 (15%) were surgically decompressed and 241 (85%) were followed expectantly. Improvement in visual function was reported in fifty-eight (67.4%) of the clinically impaired nerves after surgery. In the intact nerves group, long-term stable vision was achieved in 31/45 (75.6%) of the operated nerves, compared to 229/241 (95.1%) of the non-operated ones (p = 0.0003). Surgery in asymptomatic patients was associated with visual deterioration (RR 4.89; 95% CI 2.26-10.59). CONCLUSIONS: Most patients with CFD will remain asymptomatic during long-term follow-up. Expectant management is recommended in asymptomatic patients even in the presence of radiological evidence of ONC.

Fibrous dysplasia of the sphenoid and skull base.

This article reviews the current literature and level-1 evidence of the natural history and the medical and surgical treatment of skull base fibrous dysplasia. The high rate of optic nerve (ON) involvement and the potential risk of visual impairment as a result of nerve compression have led many surgeons to suggest prophylactic decompression of the ON in asymptomatic patients. However, review of the cases reported in the literature reveals that ON decompression surgery is indicated only for patients with visual deficits, whereas asymptomatic patients with radiologic evidence of ON compression are better managed conservatively.

Transfer, analysis, and reversion of the fibrous dysplasia cellular phenotype in human skeletal progenitors.

Human skeletal progenitors were engineered to stably express R201C mutated, constitutively active Gs alpha using lentiviral vectors. Long-term transduced skeletal progenitors were characterized by an enhanced production of cAMP, indicating the transfer of the fundamental cellular phenotype caused by activating mutations of Gs alpha. Like skeletal progenitors isolated from natural fibrous dysplasia (FD) lesions, transduced cells could generate bone but not adipocytes or the hematopoietic microenvironment on in vivo transplantation. In vitro osteogenic differentiation was noted for the lack of mineral deposition, a blunted upregulation of osteocalcin, and enhanced upregulation of other osteogenic markers such as alkaline phosphatase (ALP) and bone sialoprotein (BSP) compared with controls. A very potent upregulation of RANKL expression was observed, which correlates with the pronounced osteoclastogenesis observed in FD lesions in vivo. Stable transduction resulted in a marked upregulation of selected phosphodiesterase (PDE) isoform mRNAs and a prominent increase in total PDE activity. This predicts an adaptive response in skeletal progenitors transduced with constitutively active, mutated Gs alpha. Indeed, like measurable cAMP levels, the differentiative responses of transduced skeletal progenitors were profoundly affected by inhibition of PDEs or lack thereof. Finally, using lentiviral vectors encoding short hairpin (sh) RNA interfering sequences, we demonstrated that selective silencing of the mutated allele is both feasible and effective in reverting the aberrant cAMP production brought about by the constitutively active Gs alpha and some of its effects on in vitro differentiation of skeletal progenitors.

Fibrous dysplasia of bone and McCune-Albright syndrome.

Fibrous dysplasia of bone is a genetic, non-inheritable disease, characterized by bone pain, bone deformities and fracture, involving one or several bones. It is caused by mis-sense mutations occurring post-zygotically in the gene coding for the alpha-subunit of the stimulatory G-protein, Gs, in the guanine nucleotide binding, alpha stimulating (GNAS) complex locus in chromosome 20q13. This mutation results in osteoblastic differentiation defects, and bone resorption is often increased. The bone lesions may be associated with endocrine dysfunctions and café-au-lait spots; this is known as McCune-Albright syndrome. Patients with polyostotic fibrous dysplasia often have renal phosphate wasting. The disease, however, has a wide clinical spectrum, so many patients are asymptomatic. Diagnosis relies on radiographs and pathology. Bisphosphonates have been used in the treatment of fibrous dysplasia to relieve bone pain and improve lytic lesions, but they are still under clinical evaluation. Calcium, vitamin D and phosphorus supplements may be useful in some patients. Surgery is also helpful to prevent and treat fracture and deformities.

[Fibrous dysplasia]. / Fibröse Dysplasie.

Fibrous dysplasia is a tumorlike, benign lesion, caused by sporadic mutation during early embryogenesis. The skeletal involvement becomes increasingly visible during growth. The number and extent of dysplastic lesions increase until the age of 15. The polyostotic form is often associated with endocrine dysfunction, which should be diagnosed and treated early. Malignant transformation of fibrous dysplastic lesions is less than 1%; therefore, treatment or resection of the lesion itself is not necessary. The progress of the lesions during growth can lead to pain, fractures, and deformities. Bisphosphonates are effective for pain relief, but have no assured effect on the natural history of the disease. Fracture healing is not compromised by the disease. Conservative treatment with casts is therefore effective, especially for the upper limbs. The surgical approach with deformity correction and stabilization remains challenging particularly with regard to the proximal femur. Intramedullary devices should be preferred to plates, if possible.