McCune-Albright syndrome (MAS) was first defined as a triad of polyostotic fibrous dyskinesia, café au lait milk spots, and precocious puberty. Other endocrine disorders, including hyperthyroidism, hypersecretion of growth hormone, excessive renal phosphate loss with or without rickets or osteomalacia, and Cushing’s syndrome, were later thought to be associated with the original MAS. MAS can sometimes be associated with scoliosis and may be progressive scoliosis. A review of studies on McCune-Albright syndrome combined with scoliosis is presented below. The etiology of McCune-Albright syndrome was first reported by Bianco et al. to be a disorder of fibrous dysplasia (FD) arising from a disorder of bone marrow stromal cell differentiation. A portion of the bone marrow stromal cells are multipotent stem cells that may differentiate into osteoblasts, osteocytes, chondrocytes, and myeloid adipocytes. The molecular mechanism of the disorder is the activating mutation of the GNAS gene, which encodes the alpha subunit of the signaling G protein, Gsα. gsα plays a major role in cellular signaling pathways by increasing cAMP production and activating mutations that trigger ligand-dependent cAMP/protein kinase signaling. cAMP is involved in a variety of cell surface receptor signaling, including parathyroid hormone, follicle stimulating hormone, luteinizing hormone and thyrotropin producing hormone. Recently, mutations at the Q227 locus have also been found to be associated with FD. If bone marrow stromal cells are defective in Gsα, these cells appear to have poor fibrous structure of bone or skeletal manifestations similar to those triggered by hyperparathyroidism in response to parathyroid hormone regulation. Milk coffee spots on the skin may result from impaired regulation of melanotropic hormones in melanocytes in the skin, precocious puberty from the effects of ovarian follicle stimulating hormone signaling, hyperthyroidism from impaired thyroid stimulating hormone signaling, etc. The endocrine disorder most frequently associated with scoliosis is excessive renal phosphate loss, suggesting that increased bone plasticity following osteochondrosis is one of the mechanisms by which scoliosis occurs. This disease lacks progeny inheritance characteristics and is currently agreed to be a post heterozygous mutation, the result of somatic disseminated mutations. II. The natural history of McCune-Albright syndrome with scoliosis The natural history of McCune-Albright syndrome with scoliosis has not been reported very often. This may be due to its low incidence. Fibroarchitectural dysplasia appears early when it involves the skeleton, with 90% of generalized skeletal lesions usually appearing around age 15. Hart et al. found that craniofacial fibrous dysplasia appeared earliest, with 90% of lesions appearing at a mean age of 3.4 years. In the extremity skeletal fibrous dysplasia lesions, 90% appeared at 13.7 years of age, while in the medial skeleton, 90% of the lesions appeared at 15.5 years of age. In a study of 172 patients with fibrous dysplasia with pathological fractures, aged 6-53 years, the peak age of fracture was between 5 and 10 years, then decreased in adolescence (10-15 years), and the chance of fracture decreased further in adulthood. It is not clear whether scoliosis progresses rapidly in adolescence or persists into adulthood, since it has been established that scoliosis in combination with fibrous dysplasia may be a deformity due to the patient’s inherent bone weakness. It is suspected that scoliosis will continue to progress into adulthood because pulmonary complications have been identified in patients with fibrous dysplasia combined with scoliosis after childhood and after growth plate closure.Guille and Bowen [20] reported three patients with polyostotic fibrous dysplasia with scoliosis.One was a 7-year-old male diagnosed with polyostotic fibrous dysplasia.At 12.8 years of age, T4- T9 right thoracic curvature with a Cobb angle of 25° and T12-L3 thoracolumbar kyphosis of 15°. 4 years later, the right thoracic curvature (T2-T9) progressed to 80° and the left thoracolumbar curvature (T10-L4) progressed to 73°. Another patient was a 5-year-old boy who had a history of multiple pathological fractures of the lower extremities and orthopedic osteotomies. The patient had a rapid onset and progression of scoliosis over a 6-month period. He was shorter than his peers at the onset of the disease. The third patient was a 10-year-old girl diagnosed with McCune-Albright syndrome. at age 13, the thoracolumbar curve was 40 degrees (T3-L3). at age 15, the Cobb angle was not significantly altered. However, a wedge-shaped compression fracture of the L1 vertebrae with mild kyphosis was present. At the age of 21 years, the rib arch was sunken and compressed on the superior border of the left iliac bone. It was ineffective after traction treatment. All three patients showed progression of scoliosis over time. 24 patients with MAS were reported by Mancini et al. Two of these patients had long-term follow-up and were 10 and 4 years old, respectively, at the time of diagnosis of MAS. The maximum Cobb angles for scoliosis in these two patients were T4-T10 55°/T11-L5 80° and T4-T10 100°/T11-L5 100°. There was no trend of progression after their skeletal growth and growth arrest.Collins studied 104 patients with FD. Follow-up ranged from 1-25 years, with a mean of 6 years. 81% of patients had MAS. 63% of FD involved the spine, and 40% of patients developed scoliosis. If scoliosis is left untreated, it can lead to decreased lung function or death. In this study, spinal stability was maintained for as many as 26 years after internal fixation. Malignant lesions of poor fibrous structure may be associated with MAS. Its incidence is less than 1% in patients diagnosed with fibrous dysplasia and MAS. The epidemiology of McCune-Albright syndrome combined with scoliosis The incidence of fibrous dysplasia of bone is not well understood, but the literature reports that its incidence is about 5% of benign skeletal disorders and that monostotic fibrous dysplasia is about 8-10 times more common than polyostotic fibrous dysplasia. Skeletal disorders and extraosseous diseases may have various combinations of clinical manifestations, such as fibrous dysplasia combined with skin lesions without endocrine dysfunction, fibrous dysplasia combined with endocrine dysfunction without skin lesions, and typical skin lesions with endocrine dysfunction but without fibrous dysplasia. In a study of 62 cases of polyostotic fibrous dysplasia by Leet et al. using whole-body bone scanning, 63% of patients were found to have fibrous dysplasia of the vertebral body, of which scoliosis was found in 40-52% of patients. There was a significant correlation between the involved vertebrae and the segment in which scoliosis occurred, suggesting that fibrous dysplasia may be a causal factor in scoliosis. Precocious puberty was significantly correlated with scoliosis. Because precocious puberty is capable of accelerating growth, this may contribute to scoliosis. Harris et al. reported a 7% and 14% incidence of cervical and lumbar involvement, respectively, in patients with polyostotic dysplasia. Mancini et al. reported 56 patients with dysplasia involving the spine, 24 of whom were diagnosed with McCune-Albright syndrome, of whom 42% had scoliosis. 6 had spinal involvement and 5 had lesions located within the scoliosis segment. Collins studied 104 patients with FD. 81% of the patients had MAS and 40% had scoliosis. The clinical presentation and diagnosis of scoliosis in McCune-Albright syndrome is based on the clinical presentation and the typical imaging findings to diagnose MAS with scoliosis. Genetic diagnosis is mainly based on the detection of mutations in GNAS. There are several different methods to detect mutations. Clinical evaluation includes gait, limb and spine examination. A full spine standing frontal and lateral radiograph or a whole body bone scan can diagnose or detect scoliosis early. If ECT shows scoliosis, then a complete evaluation of scoliosis should be performed. In addition to radiographs, CT and MRI may better clarify the severity of scoliosis and the size of the spinal canal involvement. Skin examination is also very important and is a good basis for diagnosing McCune-Albright syndrome. Bone scans can be used to score the bones involved throughout the body and help predict future motor function and quality of life. Endocrine system disorders can be evaluated, diagnosed and treated in detail in a specialist clinic. V. Progress in the treatment of scoliosis in McCune-Albright syndrome The treatment of patients with McCune-Albright syndrome with scoliosis includes a definitive diagnosis and close follow-up. The effectiveness of bracing is not well understood and may require an individualized treatment plan.Leet et al. showed that posterior spinal fusion for severe scoliosis resulted in no loss of fixation or osseous discontinuity during 22 years of follow-up. Patients with scoliosis combined with fibrous dysplasia diagnosed in childhood and adolescence need to be monitored into adulthood to avoid excessive progression of scoliosis.Guille and Bowen reported three patients with polyostotic fibrous dysplasia with scoliosis, two of whom underwent posterior fusion. In one case, a posterior articular osteotomy, cortical removal of the posterior portion of the spine, and allograft bone grafting were performed with postoperative cast immobilization, and at 5 years follow-up, the spine was strongly fused. In another case, a 5-year-old male patient with rapidly progressing scoliosis within 6 months (45° right thoracic bend at T5-T12 and 49° left lumbar bend at T12-L5) had good in situ spinal fusion with no bone resorption or pseudoarticular formation after a simple posterior osteotomy. Janus et al. reported a patient with polyostotic fibrous dysplasia with scoliosis who underwent posterior fusion with good results. In the study by Leet et al. 4 patients underwent posterior spinal endoprosthetic fusion with no loss of fixation or pseudoarthrosis. Mancini et al. reported posterior spinal orthopedic endoprosthetic fusion in 1 of 11 patients with scoliosis in combination with spinal fibrous dysplasia. Ten patients with untreated MAS with scoliosis had minimal deformity changes. The follow-up period ranged from 1-25 years. Scoliosis with FD is considered to progress after growth arrest. Internal spinal fixation may be necessary for long-term spinal stability. Other than surgery, the only effective treatment for FD is currently bisphosphonates. Although FD is an osteoblastic disease, bisphosphonates inhibit osteoclasts, and their use is justified for two reasons. First, the expansion of the lesion may result from the resorption of nearby normal bone by osteoclasts, and bisphosphonates inhibit their resorption, thus preventing the expansion of the lesion. Second, FD is a “hypermetabolic” bone disease, sometimes with a marked increase in bone metabolites and occasionally an increase in the number of osteoclasts in the area of the lesion, and inhibiting the function and number of osteoclasts may control disease progression. Bisphosphonates, although helpful in reducing pain and improving bone mass, may have no effect on the natural history of scoliosis. In conclusion, the most common triad of McCune-Albright syndrome is polyostotic fibrous dysplasia, cutaneous coffee-milk spots, and precocious puberty. McCune-Albright syndrome is often complicated by scoliosis. McCune-Albright syndrome is associated with scoliosis, and early orthopedic fixation and fusion may facilitate a better prognosis. Because of its rare onset, treatment options for its scoliosis should be individualized.