RARE DISEASE
McCune-Albright syndrome
McCune-Albright syndrome
McCune-Albright syndrome
Synonyms: Gonadotropin-independent female-limited sexual precocity
Synonyms: Gonadotropin-independent female-limited sexual precocity
Synonyms: Gonadotropin-independent female-limited sexual precocity
Drug discovery
309
papers
On emerging therapies
Overview
McCune-Albright syndrome (MAS) is a rare genetic mosaic disorder caused by somatic activating GNAS mutations, leading to constitutive G-protein activation. It classically presents with the triad of polyostotic fibrous dysplasia (bone lesions), café-au-lait skin macules, and endocrine hyperfunction (e.g., precocious puberty, hyperthyroidism, growth hormone excess). Management is multidisciplinary, focusing on symptom-specific interventions due to the absence of curative therapies [1][2][5][7].
Burden
High morbidity: Recurrent fractures, chronic pain, skeletal deformities, and endocrine dysfunction [1][2][7].
Complications include vision/hearing loss (craniofacial lesions), mobility impairment, and psychosocial challenges from early puberty [1][6][11].
Lifespan is typically normal, but requires lifelong multispecialty care [5][8][11].
Therapies
Bone: Bisphosphonates (e.g., pamidronate) for pain/fracture risk; surgical stabilization for deformities [1][3][14].
Endocrine: Aromatase inhibitors (e.g., letrozole) or tamoxifen for precocious puberty; antithyroid drugs/thionamides for hyperthyroidism; somatostatin analogs for growth hormone excess [3][4][9][14].
Supportive: Physical therapy, vitamin D/phosphorus supplementation for hypophosphatemia, and regular monitoring for malignant transformation (<1% risk) [1][3][14].
Categories: rare bone diseases, rare developmental anomalies during embryogenesis, rare endocrine diseases, rare genetic diseases, rare gynecological and obstetric diseases, rare neoplastic diseases, rare skin diseases
Research Papers
309 drug discovery papers about McCune-Albright syndrome. Recent publications:
309 drug discovery papers about McCune-Albright syndrome. Recent publications:
categories:
Small molecules
small molecules
2026-09-09 | Letrozole in Paediatric Females for Peripheral Precocious Puberty: A Systematic Review of Efficacy and Safety.
Letrozole, a third-generation aromatase inhibitor, has been increasingly investigated as an off-label treatment to improve growth outcomes in paediatric boys, whereas its use in girls has remained limited because of concerns regarding safety and efficacy, given the critical role of oestrogens in female physiology. This gender gap has delayed research on letrozole in girls. To systematically evaluate the clinical efficacy, growth outcomes, and safety profile of letrozole in girls with peripheral precocious puberty (PPP). PubMed/MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to May 2026, following PRISMA 2020 guidelines (PROSPERO: CRD420261423918). Eligible studies evaluated letrozole monotherapy in girls aged ≤18 years. Risk of bias was assessed using JBI checklists and Murad tool. Data were synthesised narratively according to the SWiM guideline. Twenty-two observational studies encompassing 151 female patients were included. Twenty-one studies evaluated letrozole for PPP, predominantly McCune-Albright syndrome, where treatment effectively slowed pubertal progression, reduced bone age advancement, and improved predicted adult height. One exploratory study evaluated girls with short stature without pubertal disorders. Transition to central precocious puberty occurred during follow-up in 41.3% of patients. Safety was favourable (adverse events: 3.3%), with no clinically significant hyperandrogenism or hepatotoxicity. Letrozole demonstrates meaningful clinical benefits in girls with PPP, particularly regarding pubertal control and predicted adult height, accompanied by a favourable safety profile. Well-designed prospective studies are needed to establish optimal dosing, long-term safety, and final adult height outcomes in the female paediatric population.
2026-08-09 | The Efficacy of Bisphosphonates in the Treatment of Mcune Albright Syndrome
Review title: The Efficacy of Bisphosphonates in the Treatment of Mcune Albright Syndrome Type and method of review: Systematic review, with meta-analysis where appropriate Stage of review at time of this submission: Review ongoing — the protocol has been finalised and the peer-reviewed search prepared; formal screening not yet started. Review question: In Patients of any age with McCune-Albright syndrome or polyostotic fibrous dysplasia of bone, what is the effect of Bisphosphonate therapy (intravenous or oral) — pamidronate, zoledronic acid, alendronate, risedronate, neridronate compared with Placebo, no antiresorptive therapy, pre-treatment baseline, or an alternative bisphosphonate on Bone pain and change in bone turnover markers (primary); bone mineral density, radiological lesion response, fracture incidence, skeletal disease burden, function, adverse events (secondary)? Searches: The following sources will be searched: Europe PMC (PubMed, MEDLINE & preprints), PubMed / MEDLINE, Embase, Cochrane CENTRAL, Scopus, Google Scholar. Additional records may be imported from other databases. No date or language restrictions are applied unless otherwise stated. The search strategy underwent peer review (PRESS) before execution. Condition or domain being studied: Patients of any age with McCune-Albright syndrome or polyostotic fibrous dysplasia of bone Participants / population: Patients of any age with McCune-Albright syndrome or polyostotic fibrous dysplasia of bone Intervention(s), exposure(s): Bisphosphonate therapy (intravenous or oral) — pamidronate, zoledronic acid, alendronate, risedronate, neridronate Comparator(s) / control: Placebo, no antiresorptive therapy, pre-treatment baseline, or an alternative bisphosphonate Main outcome(s): Bone pain and change in bone turnover markers (primary); bone mineral density, radiological lesion response, fracture incidence, skeletal disease burden, function, adverse events (secondary) Data extraction (selection and coding): Two reviewers will independently screen titles/abstracts and full texts, blinded to each other’s decisions, and extract data in duplicate using a standardised, piloted form. Disagreements will be resolved by discussion or a third reviewer. Risk of bias (quality) assessment: The risk of bias of each included study will be assessed independently by two reviewers using a study-design-appropriate tool. Disagreements will be resolved by consensus. Risk of bias in the review itself will be appraised with ROBIS. Strategy for data synthesis: Results will be synthesised narratively. Where studies are sufficiently homogeneous, effect estimates will be pooled in a meta-analysis using a fixed- or random-effects model as indicated by heterogeneity (I²). The certainty of the evidence will be rated using GRADE.
2026-08-01 | EP314 - ECE_3852 - Unveiling McCune-Albright syndrome: polyostotic fibrous dysplasia and hyperfunctioning endocrinopathies
Abstract Introduction Fibrous Dysplasia (FD) is a disorder characterized by the replacement of bone tissue by fibrous tissue and irregularly distributed bone trabeculae, increasing the risk of pathological fractures. It may impact either a solitary bone (monostotic) or multiple bones (polyostotic; PFD). The proximal femur, ribs, and skull base are the most often affected bones. PFD accompanied by café-au-lait skin pigmentation and hyperfunctioning endocrinopathies is identified as McCune-Albright syndrome (MAS). Case report We report a case of a 22-year-old male patient presenting with severe headaches, left eye ptosis, and visual field deficits. He was initially assessed at the neurology clinic. MRI scans showed a pituitary macroadenoma with suprasellar and parasellar extension and abnormally expanded bones of the skull and face. The medical history included pathological fractures of both femurs at age of 12 and several corrective surgeries for subsequent bone bowing. Skeletal radiographs showed multiple lytic lesions in the femur and tibia. A 99mTc-MDP full-body scan demonstrated radiotracer uptake in the appendicular and axial bones. The patient was treated with intravenous bisphosphonates since he was 17 years old; however, confirmatory testing for bone disease was not done. The skeletal investigations were indicative of PFD. The presence of café-au-lait skin pigmentation implied MAS. Hormonal analysis confirmed acromegaly and hypopituitarism. After transcranial surgical decompression treatment with Sandostatin LAR was initiated, however, due to an insufficient therapeutic response, a decision was made to switch to Pasireotide every 28 days. Patient remains under our care for regular follow-ups and monitoring. Conclusions MAS is a diagnostic challenge and a delayed diagnosis might result in significant consequences. Screening and early detection of endocrinopathies can improve the quality of life of patients with PFD.
2026-07-18 | Abstract A010: Dual estrogen receptor and PKCβ signaling modulation by (Z)-Endoxifen: A mechanism-driven therapeutic strategy for estrogen-driven pathology in McCune–Albright Syndrome
Abstract Purpose: McCune–Albright syndrome (MAS) is a rare mosaic disorder caused by activating GNAS mutations that drive autonomous estrogen production and chronic estrogen receptor (ER) activation. Although current management suppresses estrogen synthesis, persistent ER-dependent and proliferative signaling contribute to morbidity, including precocious puberty, uterine bleeding, ovarian cysts, and long-term endometrial risk. Therapies directly targeting downstream ER and noncanonical proliferative pathways are limited. We evaluated (Z)-endoxifen as a mechanism-driven strategy to modulate both ER signaling and kinase-mediated proliferative pathways in MAS. Methods: Weighted gene expression signatures for estrogen, tamoxifen, and (Z)-endoxifen were generated in ER+ MCF7 cells. Intersection and stratified analyses defined shared and compound-specific gene sets. Gene Set Enrichment Analysis (GSEA) using MSigDB Hallmark and Reactome pathways identified enriched signaling networks. Published phosphoproteomic and RNA-seq datasets were integrated to assess kinase modulation, focusing on PKCβ and AKT signaling. Results: Intersection analysis identified 1,605 genes modulated across treatments, representing a core estrogen-responsive network enriched for MYC Targets, Estrogen Response, E2F Targets, and G2M Checkpoint. (Z)-Endoxifen significantly modulated estrogen-response and mTORC1 pathways within this shared set and strongly downregulated cell-cycle programs (E2F Targets, G2M Checkpoint), supporting a dominant antiproliferative transcriptional profile. (Z)-Endoxifen-specific signatures (1,015 upregulated; 872 downregulated) showed selective suppression of mitotic and cell-cycle pathways, including Mitotic Spindle and G2/M Transition. Integrated mechanistic data demonstrate that (Z)-endoxifen directly targets PKCβ1, promoting its dephosphorylation and degradation and inhibiting PKCβ1 and AKT (Ser473) phosphorylation. RNA-seq comparisons show concordant suppression of E2F Targets and G2M genes with PKCβ1 silencing and (Z)-endoxifen treatment, including reduced Cyclin D1, CDK4, phospho-Rb, CHEK1, and E2F1 expression. Conclusions: (Z)-Endoxifen demonstrates a dual mechanism relevant to MAS: blockade of ER-mediated transcription and suppression of PKCβ/AKT-driven proliferative signaling. This multi-pathway modulation addresses a therapeutic gap in MAS and supports clinical evaluation of (Z)-endoxifen as a targeted strategy for estrogen-driven pathology. Citation Format: Sandra S. Hammer, Janet R. Rea, Scott M. Blackburn, Steven C. Quay. Dual estrogen receptor and PKCβ signaling modulation by (Z)-Endoxifen: A mechanism-driven therapeutic strategy for estrogen-driven pathology in McCune–Albright Syndrome [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Breaking Barriers in the Fight against Rare Cancers; 2026 Jul 18-20; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(14_Suppl):Abstract nr A010.
2026-06-29 | Atypical Management of Type 2 Amiodarone-Induced Thyrotoxicosis Without Corticosteroids: A Case Report and Review of Therapeutic Challenges.
Amiodarone-induced thyrotoxicosis (AIT) is a complex endocrine disorder associated with significant morbidity, particularly in patients with underlying cardiac disease. Type 2 AIT, a destructive thyroiditis, is typically managed with corticosteroids. However, treatment becomes challenging when glucocorticoids are contraindicated. We present the case of a 37-year-old male with atrial fibrillation, dilated cardiomyopathy, and McCune-Albright syndrome who developed persistent biochemical thyrotoxicosis while on amiodarone therapy. Despite suppressed thyroid-stimulating hormone and elevated free thyroxine levels, he remained clinically asymptomatic. A thyroid uptake scan demonstrated low uptake consistent with type 2 AIT, although thyroid receptor antibodies were positive, suggesting possible mixed pathology. Management was complicated by coexisting liver lesions, precluding corticosteroid therapy. The patient was managed with low-dose carbimazole, resulting in gradual normalization of thyroid function. This case highlights the complexity of diagnosing and managing AIT and demonstrates that thionamides may be a viable alternative in selected patients in whom corticosteroids are contraindicated, particularly in cases with overlapping features of type 1 and type 2 AIT.
cell therapies
2023-07-19 | Successful ART outcome in a woman with McCune-Albright syndrome: a case report and literature review.
McCune-Albright syndrome (MAS) is a rare genetic disease affecting multiple organs, including endocrine tissues. This endocrinopathy is sometimes responsible for infertility, as it may induce an independent functioning of the ovaries leading to anovulatory cycles. This case report describes the infertility journey of a 22-year-old female who had early puberty and irregular periods with high estrogen and progesterone levels, low FSH and LH (on day 3 of her menstrual cycle), and a multi-cystic right ovary. She received several infertility treatments: initially in vitro oocyte maturation (IVM) followed by cyst transvaginal ultrasound-guided aspiration, all unsuccessful. A right hemi-ovariectomy was performed that eventually restored regular cycles and made it possible to perform ovarian stimulation (OS) and in vitro fertilization (IVF). Live birth was obtained after the first embryo transfer.
2021-12-21 | Fertility in McCune Albright syndrome female: A case study focusing on AMH as a marker of ovarian dysfunction and a literature review.
The molecular basis of McCune Albright syndrome (MAS) is a recurrent GNAS Postzygotic gain of function sporadic mutation, resulting in a mosaic disease. Most of girls present precocious puberty, caused by the development of recurrent ovarian cysts with autonomous Hyperestrogenic stimulation. After menarche, the majority of patients with ovarian GNAS mutation have menstrual disturbances and infertility. We wanted to focus on the fertility of MAS females and propose an appropriate management, by a detailed case report and an exhaustive review of the literature on fertility and pregnancy in MAS females. We present the case of a 29-year-old MAS female, who had previously undergone a unilateral ovariectomy and was managed by in vitro fertilization (IVF). Eight oocytes with many morphological abnormalities were retrieved. The GNAS mutation was found at a low frequency in follicular cells. The ovarian histopathological examination showed developing follicles of all stages, strongly expressing AMH by immunohistochemistry. In addition, AMH was high (45.5 pmol/L) and the AMH / AFC ratio (5.69 pmol/L per follicle) was much higher than in PCOS and control groups (2.16, and 1.34 respectively). Ovarian and endometrial involvement can be responsible for infertility in MAS women. IVF and oophorectomy may be useful in management. The genetic characterization of the different tissues may have a prognostic utility. Moreover, we suggest that the AMH could be a marker of the ovarian activity in MAS. Further studies are needed to clarify the potential oocyte abnormalities and the risk of miscarriages in order to guide genetic counseling.
2021-04-19 | McCune Albright Syndrome: Gastrointestinal Polyps and Platelet Dysfunction over 12 Years.
Gastrointestinal (GI) polyps with unknown malignant potential and a platelet storage pool deficiency that increases the risk of severe intraoperative and other types of bleeding have been identified in McCune-Albright syndrome (MAS). The natural course of these disorders has not been well characterized. The aim of this study was to report the follow-up of GI polyps and platelet dysfunction (PD) in a cohort of 28 patients with MAS. Twenty-eight patients with MAS (15 females) were included. Endoscopic screening for GI polyps was undertaken in 14 subjects and 19 were tested for PD. Six subjects (5 males) were diagnosed with GI polyps at a median age of 23 (range 15-43) years, and were monitored for a median period of 8 (range 4.5-11.5) years. At endoscopic follow-up, the 4 patients with hamartomatous polyps at first endoscopy had either normal findings (n = 2), or duodenal gastric metaplasia (n = 2). Two patients with caecal polyps were identified. Of 8 subjects with a platelet storage pool deficiency, 5 required transfusions during surgery, and subsequent platelet cover in 2 markedly reduced intraoperative blood loss. New polyps with uncertain malignant potential are diagnosed after long term follow-up in MAS. Platelet cover reduces the need for red blood cell transfusion during orthopaedic surgery and may be useful to reduce non-operative bleeding events. We recommend regular upper and lower endoscopy and screening for PD in all MAS patients.
2015-04-09 | Postpubertal Persistent Hyperestrogenemia in McCune-Albright Syndrome: Unilateral Oophorectomy Improved Fertility but Detected an Unexpected Borderline Epithelial Ovarian Tumor
Background McCune–Albright syndrome (MAS), due to a somatic mutation of the GNAS1 gene, begins usually in girls with peripheral precocious puberty. Ovarian autonomy may persist in adulthood with acyclic hyperestrogenemia, infertility, and a potential risk of estrogen-dependent cancer. Case A 22-year-old woman, with MAS, was referred for infertility with left macropolycystic ovary, hyperestrogenemia, and chronic anovulation unsuccessfully treated by controlled hyperstimulation. Once ovarian cyst punctures and cDNA analysis verified that GNAS1 mutation was restricted to the left ovary, unilateral ovariectomy was performed. It improved right ovarian function, allowed an in vitro fertilization–induced pregnancy, but revealed an unexpected borderline epithelial ovarian tumor. Summary and Conclusion Several breast cancers have already been reported in young MAS patients but not a borderline epithelial ovarian tumor. In this context, we would recommend that persistent hyperestrogenemia in an adult be corrected and gynecological follow-up of the breasts, ovaries, and endometrium be implemented.
2008-01-01 | Restoration of ovulation after unilateral ovariectomy in a woman with McCune–Albright syndrome: a case report
McCune-Albright syndrome (MAS) is characterized by peripheral precocious puberty, café-au-lait spots, and polyostotic fibrous dysplasia. This syndrome is due to a post-zygotic mutation of the GNAS1 gene with mosaic distribution and unilateral predominance. Clinical manifestations depend on the tissues carrying the mutation. We describe the ovarian function before and after unilateral ovariectomy in a woman with MAS and bilateral distribution of the GNAS1 gene mutation.A 33-year-old patient, previously diagnosed as having MAS, presented irregular menstrual cycles (30-180 days) and monophasic temperature curves. Transvaginal ultrasound and blood tests were repeated at 3-day intervals over 3 months. Findings included a persistent quiescent left ovary, a persistent polycystic right ovary, constantly high estradiol-17beta (E2) levels, and very low FSH and LH levels. She also presented severe persistent pelvic pain. Because of unilateral ovarian activity, a unilateral right ovariectomy was performed as well as biopsy of the remaining left ovary. A GNAS1 gene mutation was identified in both ovaries. A regular monthly menstrual cycle was immediately restored. On day 3 of the menstrual cycle, E2 level was 30 pg/ml, FSH level was 7.5 mIU/ml, and LH level was 6.4 mIU/ml. On day 17, pelvic ultrasound showed one follicle of 25 mm in the left ovary. On day 21, the progesterone level was 13.1 ng/ml.This is the first report of ovulation being restored following unilateral ovariectomy in an adult patient suffering from severe MAS with GNAS1 gene mutation identified in both ovaries.
antibodies
2026-09-14 | Orthopaedic diagnostic pitfalls in fibroblast growth factor 23-mediated hypophosphatemic rickets/osteomalacia in fibrous dysplasia/McCune-Albright syndrome: Two burosumab-treated cases.
Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) can obscure fibroblast growth factor 23 (FGF23)-mediated hypophosphatemic rickets/osteomalacia. We report two FD/MAS patients with recurrent fractures, hypophosphatemia, elevated FGF23, and serial imaging showing overlooked rachitic changes years before diagnosis. Burosumab improved serum phosphate levels after dose adjustment and was associated with mobility gains in Case 1 and increased growth velocity with physeal normalization in Case 2. Age-appropriate phosphate assessment and FGF23 testing are warranted when orthopaedic findings suggest impaired mineralization.
2026-06-11 | Denosumab in Bisphosphonate-Refractory Polyostotic Fibrous Dysplasia in McCune–Albright Syndrome: A Case Report
McCune–Albright syndrome (MAS) is a rare mosaic disorder characterized by polyostotic fibrous dysplasia (PFD), café-aulait macules, and hyperfunctioning endocrinopathies. Management of skeletal disease remains challenging, particularly in patients with incomplete response to bisphosphonates. We report a 15-year-old male with clinically diagnosed MAS presenting with extensive PFD, craniofacial involvement with optic nerve compression, multiple low-trauma fractures due to bone involvement, and markedly elevated alkaline phosphatase (ALP). Despite two years of intravenous zoledronate therapy, biochemical response was partial, with persistently elevated ALP levels. Following transition to Denosumab, ALP declined from 1284 U/L to 294 U/L within one treatment cycle. Subsequent values showed fluctuation but remained overall lower than pre-denosumab levels. Clinically, the patient reported reduction in bone pain and no new fractures during follow-up. This case highlights denosumab as a potential therapeutic option in bisphosphonate-refractory MAS associated PFD. However, variability in biochemical response and limited long-term safety data warrant cautious use and close monitoring.
2026-05-08 | Burosumab use in fibroblast growth factor-23-mediated hypophosphatemia in McCune-Albright syndrome/fibrous dysplasia.
McCune-Albright syndrome (MAS) is a rare disorder characterized by fibrous dysplasia (FD), café-au-lait spots, and hyperfunctioning endocrinopathies. FD lesions can overproduce fibroblast growth factor-23 (FGF-23), leading to renal phosphate wasting, hypophosphatemia, and impaired bone mineralization. Conventional treatment with oral phosphate and calcitriol is limited by gastrointestinal intolerance. Burosumab, a monoclonal antibody against FGF-23, is approved for X-linked hypophosphatemia and tumor-induced osteomalacia and has shown promise in case reports of pediatric and adult patients with MAS-related FGF-23-mediated hypophosphatemia. We describe a 46-year-old woman with MAS and extensive FD who presented with worsening bone pain and FGF-23-mediated hypophosphatemia. She was started on phosphate and calcitriol with improvement in pain. Due to failure to achieve treatment targets, she was transitioned to burosumab 0.50 mg/kg injections every 4 weeks with normalization of serum phosphorus but persistent elevation of alkaline phosphatase. This case represents the second reported adult and oldest patient treated with burosumab for MAS-related FGF-23-mediated hypophosphatemia after failure of conventional therapy. Although its use in MAS remains off-label, burosumab may provide a more targeted and better-tolerated therapeutic option.
2026-03-20 | Efficacy of Denosumab for Treatment of Pain in Fibrous Dysplasia and McCune-Albright Syndrome: A Systematic Review.
Fibrous dysplasia (FD) skeletal lesions have a range of clinical manifestations including pain, which is a major contributor to reduced quality of life in patients with FD/MAS. Denosumab has been shown to reduce skeletal lesion activity and improve radiographic bone density; however, there is mixed evidence regarding its effect on pain. The primary objective was to evaluate the efficacy of denosumab for the treatment of bone pain in FD/MAS. A systematic review was conducted according to PRISMA guidelines utilising electronic databases including PubMed, Cochrane Library, Embase, Web of Science, and ClinicalTrials.gov. Included studies were those that described patients with a diagnosis of FD, with or without MAS, who were treated with denosumab. The primary outcomes were change in pain score using quantitative pain scales (Visual Analogue Scale, Brief Pain Index, and patient-reported numerical rating scale), proportion of pain responders (≥ 2-point reduction in pain or an overall subjective improvement in pain), and change in analgesic requirement. The secondary outcome was adverse on-treatment and post-treatment events related to denosumab. There were 16 studies included (88 total patients, 86 treated with denosumab). Mean pain score decreased by 3.51 points on a 10-point scale. 81.8% of patients were pain responders, demonstrating a clinically meaningful improvement in pain. Reduction or cessation of analgesic use was reported in 51.7% of patients. Adverse events occurred in 55.8% of patients, most commonly hypocalcemia (11.6%) and hypophosphatemia (8.1%). Rebound hypercalcemia following denosumab discontinuation occurred in 8 patients (9.3%), 4 of which were severe. In patients with FD/MAS undergoing treatment with denosumab, pain improved in 81.8% of patients, and analgesic requirement decreased in greater than half of patients. Careful monitoring is required surrounding treatment due the potential for severe adverse events, particularly rebound hypercalcemia following treatment discontinuation.
2026-03-06 | Denosumab in pediatric patients with fibrous dysplasia/McCune-Albright syndrome: a single-center, open-labeled study.
Fibrous Dysplasia/McCune-Albright Syndrome (FD/MAS) is a rare skeletal disorder frequently manifesting in childhood, often leading to progressive bone lesions, pain and functional impairment. Denosumab as a monoclonal antibody targeting RANKL has emerged as a potential therapeutic option, while its safety and efficacy in pediatric population remains poorly defined. Investigate the efficacy and safety of denosumab in pediatric FD/MAS population. 12-month single-arm study. Single center study at Peking Union Medical College Hospital. FD/MAS patients under 18. Denosumab 1mg/kg with a maximum dosage of 60mg every 3 months for 12-month follow-up. FD-related bone pain, bone turnover markers, 99mTc-MDP bone scintigraphy, bone mineral density. In 5 pediatric FD/MAS patients treated with denosumab, significant clinical improvements were observed, including alleviation of FD-associated bone pain, reductions in bone turnover markers, and regression of FD lesions. Alkaline phosphatase levels dropped to an average of 41.8% of baseline, accompanied by concurrent reductions in C-terminal telopeptide and type 1 N-terminal pro-peptide levels. Adverse events particularly hypercalcemia following treatment cessation occurred in 2 of the 5 patients, indicating a relatively high incidence of rebound hypercalcemia and highlighting the need for careful monitoring and cautious use of denosumab in pediatric patients. Denosumab appears to be effective in pediatric FD/MAS patients, however safety concerns remain. Comprehensive pre-treatment evaluation and close monitoring throughout the treatment course are essential. Further prospective studies and randomized controlled trials are needed to determine optimal dosing strategies and establish long-term safety in this population.
small molecules
2026-09-09 | Letrozole in Paediatric Females for Peripheral Precocious Puberty: A Systematic Review of Efficacy and Safety.
Letrozole, a third-generation aromatase inhibitor, has been increasingly investigated as an off-label treatment to improve growth outcomes in paediatric boys, whereas its use in girls has remained limited because of concerns regarding safety and efficacy, given the critical role of oestrogens in female physiology. This gender gap has delayed research on letrozole in girls. To systematically evaluate the clinical efficacy, growth outcomes, and safety profile of letrozole in girls with peripheral precocious puberty (PPP). PubMed/MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to May 2026, following PRISMA 2020 guidelines (PROSPERO: CRD420261423918). Eligible studies evaluated letrozole monotherapy in girls aged ≤18 years. Risk of bias was assessed using JBI checklists and Murad tool. Data were synthesised narratively according to the SWiM guideline. Twenty-two observational studies encompassing 151 female patients were included. Twenty-one studies evaluated letrozole for PPP, predominantly McCune-Albright syndrome, where treatment effectively slowed pubertal progression, reduced bone age advancement, and improved predicted adult height. One exploratory study evaluated girls with short stature without pubertal disorders. Transition to central precocious puberty occurred during follow-up in 41.3% of patients. Safety was favourable (adverse events: 3.3%), with no clinically significant hyperandrogenism or hepatotoxicity. Letrozole demonstrates meaningful clinical benefits in girls with PPP, particularly regarding pubertal control and predicted adult height, accompanied by a favourable safety profile. Well-designed prospective studies are needed to establish optimal dosing, long-term safety, and final adult height outcomes in the female paediatric population.
2026-08-09 | The Efficacy of Bisphosphonates in the Treatment of Mcune Albright Syndrome
Review title: The Efficacy of Bisphosphonates in the Treatment of Mcune Albright Syndrome Type and method of review: Systematic review, with meta-analysis where appropriate Stage of review at time of this submission: Review ongoing — the protocol has been finalised and the peer-reviewed search prepared; formal screening not yet started. Review question: In Patients of any age with McCune-Albright syndrome or polyostotic fibrous dysplasia of bone, what is the effect of Bisphosphonate therapy (intravenous or oral) — pamidronate, zoledronic acid, alendronate, risedronate, neridronate compared with Placebo, no antiresorptive therapy, pre-treatment baseline, or an alternative bisphosphonate on Bone pain and change in bone turnover markers (primary); bone mineral density, radiological lesion response, fracture incidence, skeletal disease burden, function, adverse events (secondary)? Searches: The following sources will be searched: Europe PMC (PubMed, MEDLINE & preprints), PubMed / MEDLINE, Embase, Cochrane CENTRAL, Scopus, Google Scholar. Additional records may be imported from other databases. No date or language restrictions are applied unless otherwise stated. The search strategy underwent peer review (PRESS) before execution. Condition or domain being studied: Patients of any age with McCune-Albright syndrome or polyostotic fibrous dysplasia of bone Participants / population: Patients of any age with McCune-Albright syndrome or polyostotic fibrous dysplasia of bone Intervention(s), exposure(s): Bisphosphonate therapy (intravenous or oral) — pamidronate, zoledronic acid, alendronate, risedronate, neridronate Comparator(s) / control: Placebo, no antiresorptive therapy, pre-treatment baseline, or an alternative bisphosphonate Main outcome(s): Bone pain and change in bone turnover markers (primary); bone mineral density, radiological lesion response, fracture incidence, skeletal disease burden, function, adverse events (secondary) Data extraction (selection and coding): Two reviewers will independently screen titles/abstracts and full texts, blinded to each other’s decisions, and extract data in duplicate using a standardised, piloted form. Disagreements will be resolved by discussion or a third reviewer. Risk of bias (quality) assessment: The risk of bias of each included study will be assessed independently by two reviewers using a study-design-appropriate tool. Disagreements will be resolved by consensus. Risk of bias in the review itself will be appraised with ROBIS. Strategy for data synthesis: Results will be synthesised narratively. Where studies are sufficiently homogeneous, effect estimates will be pooled in a meta-analysis using a fixed- or random-effects model as indicated by heterogeneity (I²). The certainty of the evidence will be rated using GRADE.
2026-08-01 | EP314 - ECE_3852 - Unveiling McCune-Albright syndrome: polyostotic fibrous dysplasia and hyperfunctioning endocrinopathies
Abstract Introduction Fibrous Dysplasia (FD) is a disorder characterized by the replacement of bone tissue by fibrous tissue and irregularly distributed bone trabeculae, increasing the risk of pathological fractures. It may impact either a solitary bone (monostotic) or multiple bones (polyostotic; PFD). The proximal femur, ribs, and skull base are the most often affected bones. PFD accompanied by café-au-lait skin pigmentation and hyperfunctioning endocrinopathies is identified as McCune-Albright syndrome (MAS). Case report We report a case of a 22-year-old male patient presenting with severe headaches, left eye ptosis, and visual field deficits. He was initially assessed at the neurology clinic. MRI scans showed a pituitary macroadenoma with suprasellar and parasellar extension and abnormally expanded bones of the skull and face. The medical history included pathological fractures of both femurs at age of 12 and several corrective surgeries for subsequent bone bowing. Skeletal radiographs showed multiple lytic lesions in the femur and tibia. A 99mTc-MDP full-body scan demonstrated radiotracer uptake in the appendicular and axial bones. The patient was treated with intravenous bisphosphonates since he was 17 years old; however, confirmatory testing for bone disease was not done. The skeletal investigations were indicative of PFD. The presence of café-au-lait skin pigmentation implied MAS. Hormonal analysis confirmed acromegaly and hypopituitarism. After transcranial surgical decompression treatment with Sandostatin LAR was initiated, however, due to an insufficient therapeutic response, a decision was made to switch to Pasireotide every 28 days. Patient remains under our care for regular follow-ups and monitoring. Conclusions MAS is a diagnostic challenge and a delayed diagnosis might result in significant consequences. Screening and early detection of endocrinopathies can improve the quality of life of patients with PFD.
2026-07-18 | Abstract A010: Dual estrogen receptor and PKCβ signaling modulation by (Z)-Endoxifen: A mechanism-driven therapeutic strategy for estrogen-driven pathology in McCune–Albright Syndrome
Abstract Purpose: McCune–Albright syndrome (MAS) is a rare mosaic disorder caused by activating GNAS mutations that drive autonomous estrogen production and chronic estrogen receptor (ER) activation. Although current management suppresses estrogen synthesis, persistent ER-dependent and proliferative signaling contribute to morbidity, including precocious puberty, uterine bleeding, ovarian cysts, and long-term endometrial risk. Therapies directly targeting downstream ER and noncanonical proliferative pathways are limited. We evaluated (Z)-endoxifen as a mechanism-driven strategy to modulate both ER signaling and kinase-mediated proliferative pathways in MAS. Methods: Weighted gene expression signatures for estrogen, tamoxifen, and (Z)-endoxifen were generated in ER+ MCF7 cells. Intersection and stratified analyses defined shared and compound-specific gene sets. Gene Set Enrichment Analysis (GSEA) using MSigDB Hallmark and Reactome pathways identified enriched signaling networks. Published phosphoproteomic and RNA-seq datasets were integrated to assess kinase modulation, focusing on PKCβ and AKT signaling. Results: Intersection analysis identified 1,605 genes modulated across treatments, representing a core estrogen-responsive network enriched for MYC Targets, Estrogen Response, E2F Targets, and G2M Checkpoint. (Z)-Endoxifen significantly modulated estrogen-response and mTORC1 pathways within this shared set and strongly downregulated cell-cycle programs (E2F Targets, G2M Checkpoint), supporting a dominant antiproliferative transcriptional profile. (Z)-Endoxifen-specific signatures (1,015 upregulated; 872 downregulated) showed selective suppression of mitotic and cell-cycle pathways, including Mitotic Spindle and G2/M Transition. Integrated mechanistic data demonstrate that (Z)-endoxifen directly targets PKCβ1, promoting its dephosphorylation and degradation and inhibiting PKCβ1 and AKT (Ser473) phosphorylation. RNA-seq comparisons show concordant suppression of E2F Targets and G2M genes with PKCβ1 silencing and (Z)-endoxifen treatment, including reduced Cyclin D1, CDK4, phospho-Rb, CHEK1, and E2F1 expression. Conclusions: (Z)-Endoxifen demonstrates a dual mechanism relevant to MAS: blockade of ER-mediated transcription and suppression of PKCβ/AKT-driven proliferative signaling. This multi-pathway modulation addresses a therapeutic gap in MAS and supports clinical evaluation of (Z)-endoxifen as a targeted strategy for estrogen-driven pathology. Citation Format: Sandra S. Hammer, Janet R. Rea, Scott M. Blackburn, Steven C. Quay. Dual estrogen receptor and PKCβ signaling modulation by (Z)-Endoxifen: A mechanism-driven therapeutic strategy for estrogen-driven pathology in McCune–Albright Syndrome [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Breaking Barriers in the Fight against Rare Cancers; 2026 Jul 18-20; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(14_Suppl):Abstract nr A010.
2026-06-29 | Atypical Management of Type 2 Amiodarone-Induced Thyrotoxicosis Without Corticosteroids: A Case Report and Review of Therapeutic Challenges.
Amiodarone-induced thyrotoxicosis (AIT) is a complex endocrine disorder associated with significant morbidity, particularly in patients with underlying cardiac disease. Type 2 AIT, a destructive thyroiditis, is typically managed with corticosteroids. However, treatment becomes challenging when glucocorticoids are contraindicated. We present the case of a 37-year-old male with atrial fibrillation, dilated cardiomyopathy, and McCune-Albright syndrome who developed persistent biochemical thyrotoxicosis while on amiodarone therapy. Despite suppressed thyroid-stimulating hormone and elevated free thyroxine levels, he remained clinically asymptomatic. A thyroid uptake scan demonstrated low uptake consistent with type 2 AIT, although thyroid receptor antibodies were positive, suggesting possible mixed pathology. Management was complicated by coexisting liver lesions, precluding corticosteroid therapy. The patient was managed with low-dose carbimazole, resulting in gradual normalization of thyroid function. This case highlights the complexity of diagnosing and managing AIT and demonstrates that thionamides may be a viable alternative in selected patients in whom corticosteroids are contraindicated, particularly in cases with overlapping features of type 1 and type 2 AIT.
cell therapies
2023-07-19 | Successful ART outcome in a woman with McCune-Albright syndrome: a case report and literature review.
McCune-Albright syndrome (MAS) is a rare genetic disease affecting multiple organs, including endocrine tissues. This endocrinopathy is sometimes responsible for infertility, as it may induce an independent functioning of the ovaries leading to anovulatory cycles. This case report describes the infertility journey of a 22-year-old female who had early puberty and irregular periods with high estrogen and progesterone levels, low FSH and LH (on day 3 of her menstrual cycle), and a multi-cystic right ovary. She received several infertility treatments: initially in vitro oocyte maturation (IVM) followed by cyst transvaginal ultrasound-guided aspiration, all unsuccessful. A right hemi-ovariectomy was performed that eventually restored regular cycles and made it possible to perform ovarian stimulation (OS) and in vitro fertilization (IVF). Live birth was obtained after the first embryo transfer.
2021-12-21 | Fertility in McCune Albright syndrome female: A case study focusing on AMH as a marker of ovarian dysfunction and a literature review.
The molecular basis of McCune Albright syndrome (MAS) is a recurrent GNAS Postzygotic gain of function sporadic mutation, resulting in a mosaic disease. Most of girls present precocious puberty, caused by the development of recurrent ovarian cysts with autonomous Hyperestrogenic stimulation. After menarche, the majority of patients with ovarian GNAS mutation have menstrual disturbances and infertility. We wanted to focus on the fertility of MAS females and propose an appropriate management, by a detailed case report and an exhaustive review of the literature on fertility and pregnancy in MAS females. We present the case of a 29-year-old MAS female, who had previously undergone a unilateral ovariectomy and was managed by in vitro fertilization (IVF). Eight oocytes with many morphological abnormalities were retrieved. The GNAS mutation was found at a low frequency in follicular cells. The ovarian histopathological examination showed developing follicles of all stages, strongly expressing AMH by immunohistochemistry. In addition, AMH was high (45.5 pmol/L) and the AMH / AFC ratio (5.69 pmol/L per follicle) was much higher than in PCOS and control groups (2.16, and 1.34 respectively). Ovarian and endometrial involvement can be responsible for infertility in MAS women. IVF and oophorectomy may be useful in management. The genetic characterization of the different tissues may have a prognostic utility. Moreover, we suggest that the AMH could be a marker of the ovarian activity in MAS. Further studies are needed to clarify the potential oocyte abnormalities and the risk of miscarriages in order to guide genetic counseling.
2021-04-19 | McCune Albright Syndrome: Gastrointestinal Polyps and Platelet Dysfunction over 12 Years.
Gastrointestinal (GI) polyps with unknown malignant potential and a platelet storage pool deficiency that increases the risk of severe intraoperative and other types of bleeding have been identified in McCune-Albright syndrome (MAS). The natural course of these disorders has not been well characterized. The aim of this study was to report the follow-up of GI polyps and platelet dysfunction (PD) in a cohort of 28 patients with MAS. Twenty-eight patients with MAS (15 females) were included. Endoscopic screening for GI polyps was undertaken in 14 subjects and 19 were tested for PD. Six subjects (5 males) were diagnosed with GI polyps at a median age of 23 (range 15-43) years, and were monitored for a median period of 8 (range 4.5-11.5) years. At endoscopic follow-up, the 4 patients with hamartomatous polyps at first endoscopy had either normal findings (n = 2), or duodenal gastric metaplasia (n = 2). Two patients with caecal polyps were identified. Of 8 subjects with a platelet storage pool deficiency, 5 required transfusions during surgery, and subsequent platelet cover in 2 markedly reduced intraoperative blood loss. New polyps with uncertain malignant potential are diagnosed after long term follow-up in MAS. Platelet cover reduces the need for red blood cell transfusion during orthopaedic surgery and may be useful to reduce non-operative bleeding events. We recommend regular upper and lower endoscopy and screening for PD in all MAS patients.
2015-04-09 | Postpubertal Persistent Hyperestrogenemia in McCune-Albright Syndrome: Unilateral Oophorectomy Improved Fertility but Detected an Unexpected Borderline Epithelial Ovarian Tumor
Background McCune–Albright syndrome (MAS), due to a somatic mutation of the GNAS1 gene, begins usually in girls with peripheral precocious puberty. Ovarian autonomy may persist in adulthood with acyclic hyperestrogenemia, infertility, and a potential risk of estrogen-dependent cancer. Case A 22-year-old woman, with MAS, was referred for infertility with left macropolycystic ovary, hyperestrogenemia, and chronic anovulation unsuccessfully treated by controlled hyperstimulation. Once ovarian cyst punctures and cDNA analysis verified that GNAS1 mutation was restricted to the left ovary, unilateral ovariectomy was performed. It improved right ovarian function, allowed an in vitro fertilization–induced pregnancy, but revealed an unexpected borderline epithelial ovarian tumor. Summary and Conclusion Several breast cancers have already been reported in young MAS patients but not a borderline epithelial ovarian tumor. In this context, we would recommend that persistent hyperestrogenemia in an adult be corrected and gynecological follow-up of the breasts, ovaries, and endometrium be implemented.
2008-01-01 | Restoration of ovulation after unilateral ovariectomy in a woman with McCune–Albright syndrome: a case report
McCune-Albright syndrome (MAS) is characterized by peripheral precocious puberty, café-au-lait spots, and polyostotic fibrous dysplasia. This syndrome is due to a post-zygotic mutation of the GNAS1 gene with mosaic distribution and unilateral predominance. Clinical manifestations depend on the tissues carrying the mutation. We describe the ovarian function before and after unilateral ovariectomy in a woman with MAS and bilateral distribution of the GNAS1 gene mutation.A 33-year-old patient, previously diagnosed as having MAS, presented irregular menstrual cycles (30-180 days) and monophasic temperature curves. Transvaginal ultrasound and blood tests were repeated at 3-day intervals over 3 months. Findings included a persistent quiescent left ovary, a persistent polycystic right ovary, constantly high estradiol-17beta (E2) levels, and very low FSH and LH levels. She also presented severe persistent pelvic pain. Because of unilateral ovarian activity, a unilateral right ovariectomy was performed as well as biopsy of the remaining left ovary. A GNAS1 gene mutation was identified in both ovaries. A regular monthly menstrual cycle was immediately restored. On day 3 of the menstrual cycle, E2 level was 30 pg/ml, FSH level was 7.5 mIU/ml, and LH level was 6.4 mIU/ml. On day 17, pelvic ultrasound showed one follicle of 25 mm in the left ovary. On day 21, the progesterone level was 13.1 ng/ml.This is the first report of ovulation being restored following unilateral ovariectomy in an adult patient suffering from severe MAS with GNAS1 gene mutation identified in both ovaries.
antibodies
2026-09-14 | Orthopaedic diagnostic pitfalls in fibroblast growth factor 23-mediated hypophosphatemic rickets/osteomalacia in fibrous dysplasia/McCune-Albright syndrome: Two burosumab-treated cases.
Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) can obscure fibroblast growth factor 23 (FGF23)-mediated hypophosphatemic rickets/osteomalacia. We report two FD/MAS patients with recurrent fractures, hypophosphatemia, elevated FGF23, and serial imaging showing overlooked rachitic changes years before diagnosis. Burosumab improved serum phosphate levels after dose adjustment and was associated with mobility gains in Case 1 and increased growth velocity with physeal normalization in Case 2. Age-appropriate phosphate assessment and FGF23 testing are warranted when orthopaedic findings suggest impaired mineralization.
2026-06-11 | Denosumab in Bisphosphonate-Refractory Polyostotic Fibrous Dysplasia in McCune–Albright Syndrome: A Case Report
McCune–Albright syndrome (MAS) is a rare mosaic disorder characterized by polyostotic fibrous dysplasia (PFD), café-aulait macules, and hyperfunctioning endocrinopathies. Management of skeletal disease remains challenging, particularly in patients with incomplete response to bisphosphonates. We report a 15-year-old male with clinically diagnosed MAS presenting with extensive PFD, craniofacial involvement with optic nerve compression, multiple low-trauma fractures due to bone involvement, and markedly elevated alkaline phosphatase (ALP). Despite two years of intravenous zoledronate therapy, biochemical response was partial, with persistently elevated ALP levels. Following transition to Denosumab, ALP declined from 1284 U/L to 294 U/L within one treatment cycle. Subsequent values showed fluctuation but remained overall lower than pre-denosumab levels. Clinically, the patient reported reduction in bone pain and no new fractures during follow-up. This case highlights denosumab as a potential therapeutic option in bisphosphonate-refractory MAS associated PFD. However, variability in biochemical response and limited long-term safety data warrant cautious use and close monitoring.
2026-05-08 | Burosumab use in fibroblast growth factor-23-mediated hypophosphatemia in McCune-Albright syndrome/fibrous dysplasia.
McCune-Albright syndrome (MAS) is a rare disorder characterized by fibrous dysplasia (FD), café-au-lait spots, and hyperfunctioning endocrinopathies. FD lesions can overproduce fibroblast growth factor-23 (FGF-23), leading to renal phosphate wasting, hypophosphatemia, and impaired bone mineralization. Conventional treatment with oral phosphate and calcitriol is limited by gastrointestinal intolerance. Burosumab, a monoclonal antibody against FGF-23, is approved for X-linked hypophosphatemia and tumor-induced osteomalacia and has shown promise in case reports of pediatric and adult patients with MAS-related FGF-23-mediated hypophosphatemia. We describe a 46-year-old woman with MAS and extensive FD who presented with worsening bone pain and FGF-23-mediated hypophosphatemia. She was started on phosphate and calcitriol with improvement in pain. Due to failure to achieve treatment targets, she was transitioned to burosumab 0.50 mg/kg injections every 4 weeks with normalization of serum phosphorus but persistent elevation of alkaline phosphatase. This case represents the second reported adult and oldest patient treated with burosumab for MAS-related FGF-23-mediated hypophosphatemia after failure of conventional therapy. Although its use in MAS remains off-label, burosumab may provide a more targeted and better-tolerated therapeutic option.
2026-03-20 | Efficacy of Denosumab for Treatment of Pain in Fibrous Dysplasia and McCune-Albright Syndrome: A Systematic Review.
Fibrous dysplasia (FD) skeletal lesions have a range of clinical manifestations including pain, which is a major contributor to reduced quality of life in patients with FD/MAS. Denosumab has been shown to reduce skeletal lesion activity and improve radiographic bone density; however, there is mixed evidence regarding its effect on pain. The primary objective was to evaluate the efficacy of denosumab for the treatment of bone pain in FD/MAS. A systematic review was conducted according to PRISMA guidelines utilising electronic databases including PubMed, Cochrane Library, Embase, Web of Science, and ClinicalTrials.gov. Included studies were those that described patients with a diagnosis of FD, with or without MAS, who were treated with denosumab. The primary outcomes were change in pain score using quantitative pain scales (Visual Analogue Scale, Brief Pain Index, and patient-reported numerical rating scale), proportion of pain responders (≥ 2-point reduction in pain or an overall subjective improvement in pain), and change in analgesic requirement. The secondary outcome was adverse on-treatment and post-treatment events related to denosumab. There were 16 studies included (88 total patients, 86 treated with denosumab). Mean pain score decreased by 3.51 points on a 10-point scale. 81.8% of patients were pain responders, demonstrating a clinically meaningful improvement in pain. Reduction or cessation of analgesic use was reported in 51.7% of patients. Adverse events occurred in 55.8% of patients, most commonly hypocalcemia (11.6%) and hypophosphatemia (8.1%). Rebound hypercalcemia following denosumab discontinuation occurred in 8 patients (9.3%), 4 of which were severe. In patients with FD/MAS undergoing treatment with denosumab, pain improved in 81.8% of patients, and analgesic requirement decreased in greater than half of patients. Careful monitoring is required surrounding treatment due the potential for severe adverse events, particularly rebound hypercalcemia following treatment discontinuation.
2026-03-06 | Denosumab in pediatric patients with fibrous dysplasia/McCune-Albright syndrome: a single-center, open-labeled study.
Fibrous Dysplasia/McCune-Albright Syndrome (FD/MAS) is a rare skeletal disorder frequently manifesting in childhood, often leading to progressive bone lesions, pain and functional impairment. Denosumab as a monoclonal antibody targeting RANKL has emerged as a potential therapeutic option, while its safety and efficacy in pediatric population remains poorly defined. Investigate the efficacy and safety of denosumab in pediatric FD/MAS population. 12-month single-arm study. Single center study at Peking Union Medical College Hospital. FD/MAS patients under 18. Denosumab 1mg/kg with a maximum dosage of 60mg every 3 months for 12-month follow-up. FD-related bone pain, bone turnover markers, 99mTc-MDP bone scintigraphy, bone mineral density. In 5 pediatric FD/MAS patients treated with denosumab, significant clinical improvements were observed, including alleviation of FD-associated bone pain, reductions in bone turnover markers, and regression of FD lesions. Alkaline phosphatase levels dropped to an average of 41.8% of baseline, accompanied by concurrent reductions in C-terminal telopeptide and type 1 N-terminal pro-peptide levels. Adverse events particularly hypercalcemia following treatment cessation occurred in 2 of the 5 patients, indicating a relatively high incidence of rebound hypercalcemia and highlighting the need for careful monitoring and cautious use of denosumab in pediatric patients. Denosumab appears to be effective in pediatric FD/MAS patients, however safety concerns remain. Comprehensive pre-treatment evaluation and close monitoring throughout the treatment course are essential. Further prospective studies and randomized controlled trials are needed to determine optimal dosing strategies and establish long-term safety in this population.
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