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Article ; Online: Endocrinopathies in Leukodystrophy.

Szymczuk, Vivian / Merchant, Nadia

Current problems in pediatric and adolescent health care

2022 Volume 53, Issue 1, Page(s) 101351

MeSH term(s)	Humans ; Endocrine System Diseases ; Hereditary Central Nervous System Demyelinating Diseases
Language	English
Publishing date	2022-12-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	2078029-1
ISSN	1538-3199 ; 0045-9380 ; 1538-5442
ISSN (online)	1538-3199
ISSN	0045-9380 ; 1538-5442
DOI	10.1016/j.cppeds.2022.101351
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Article ; Online: Persistent Gynecomastia due to Short-term Low-dose Finasteride for Androgenetic Alopecia.

Farkas, Hal Steven / Jee, Youn Hee / Szymczuk, Vivian / Leschek, Ellen Werber

JCEM case reports

2024 Volume 2, Issue 5, Page(s) luae050

Abstract: We report a case of persistent gynecomastia in a healthy 20-year-old man after 1 month of low-dose finasteride. Finasteride was discontinued after 2 months, and gynecomastia was unchanged 5 months after drug withdrawal. The gynecomastia regressed but did ...

Abstract	We report a case of persistent gynecomastia in a healthy 20-year-old man after 1 month of low-dose finasteride. Finasteride was discontinued after 2 months, and gynecomastia was unchanged 5 months after drug withdrawal. The gynecomastia regressed but did not resolve after 6 months of treatment with raloxifene, a selective estrogen receptor modulator. One year later, bilateral mammoplasty was performed to remove the remaining breast tissue. Finasteride, a 5-alpha-reductase inhibitor, is widely used for the treatment of androgenetic alopecia. Gynecomastia is an expected side effect of this therapy given its mechanism of action. However, only 8 cases of gynecomastia have been reported with low-dose (1 mg daily) finasteride treatment since its approval for androgenetic alopecia in 1997. This raises the concern that gynecomastia resulting from low-dose finasteride is significantly underreported, causing inadequately informed patients. Further, because of the risk of gynecomastia, it is important for prescribing physicians to counsel patients regarding this complication and to consider early intervention when finasteride-induced gynecomastia first arises to prevent fibrosis and thus irreversible gynecomastia.
Language	English
Publishing date	2024-04-24
Publishing country	England
Document type	Journal Article ; Review
ISSN	2755-1520
ISSN (online)	2755-1520
DOI	10.1210/jcemcr/luae050
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Article ; Online: Metaphyseal sclerosis in a child with a giant cell tumour treated with denosumab.

Szymczuk, Vivian / Boyce, Alison / Merchant, Nadia

Lancet (London, England)

2023 Volume 402, Issue 10397, Page(s) e4

MeSH term(s)	Humans ; Child ; Denosumab/therapeutic use ; Sclerosis ; Bone Density Conservation Agents/therapeutic use ; Bone Neoplasms/diagnostic imaging ; Bone Neoplasms/drug therapy ; Giant Cell Tumors ; Giant Cell Tumor of Bone/diagnostic imaging ; Giant Cell Tumor of Bone/drug therapy ; Giant Cell Tumor of Bone/pathology
Chemical Substances	Denosumab (4EQZ6YO2HI) ; Bone Density Conservation Agents
Language	English
Publishing date	2023-07-15
Publishing country	England
Document type	Journal Article
ZDB-ID	3306-6
ISSN	1474-547X ; 0023-7507 ; 0140-6736
ISSN (online)	1474-547X
ISSN	0023-7507 ; 0140-6736
DOI	10.1016/S0140-6736(23)00915-7
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Article ; Online: Craniofacial Fibrous Dysplasia: Clinical and Therapeutic Implications.

Szymczuk, Vivian / Taylor, Jocelyn / Boyce, Alison M

Current osteoporosis reports

2023 Volume 21, Issue 2, Page(s) 147–153

Abstract: Purpose of review: This study aims to review diagnosis, potential complications, and clinical management in craniofacial fibrous dysplasia.: Recent findings: Fibrous dysplasia (FD) is a rare mosaic disorder in which normal bone and marrow are ... ...

Abstract	Purpose of review: This study aims to review diagnosis, potential complications, and clinical management in craniofacial fibrous dysplasia. Recent findings: Fibrous dysplasia (FD) is a rare mosaic disorder in which normal bone and marrow are replaced with expansile fibro-osseous lesions. Disease presents along a broad spectrum and may be associated with extraskeletal features as part of McCune-Albright syndrome (MAS). The craniofacial skeleton is one of the most commonly impacted areas in FD, and its functional and anatomical complexities create unique challenges for diagnosis and management. This review summarizes current approaches to diagnosis and management in FD/MAS, with emphasis on the clinical and therapeutic implications for the craniofacial skeleton.
MeSH term(s)	Humans ; Craniofacial Fibrous Dysplasia/complications ; Fibrous Dysplasia of Bone/diagnostic imaging ; Fibrous Dysplasia of Bone/therapy ; Fibrous Dysplasia of Bone/complications ; Fibrous Dysplasia, Polyostotic/therapy ; Fibrous Dysplasia, Polyostotic/complications ; Fibrous Dysplasia, Polyostotic/diagnosis ; Bone and Bones/pathology
Language	English
Publishing date	2023-02-28
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Intramural
ZDB-ID	2186581-4
ISSN	1544-2241 ; 1544-1873
ISSN (online)	1544-2241
ISSN	1544-1873
DOI	10.1007/s11914-023-00779-6
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Article ; Online: Serum Phosphorus as a Driver of Skeletal Morbidity in Fibrous Dysplasia.

Gun, Zubeyir Hasan / Osamor, Charles / Taylor, Jocelyn / Li, Xiaobai / Szymczuk, Vivian / Boyce, Alison M

The Journal of clinical endocrinology and metabolism

2024 Volume 109, Issue 5, Page(s) 1334–1340

Abstract: Context: Fibrous dysplasia (FD) results in fractures, pain, and deformities. Abnormal osteoprogenitor cells overproduce FGF23, leading to hyperphosphaturia in most patients and frank hypophosphatemia in a subset. Studies suggest hypophosphatemia is ... ...

Abstract	Context: Fibrous dysplasia (FD) results in fractures, pain, and deformities. Abnormal osteoprogenitor cells overproduce FGF23, leading to hyperphosphaturia in most patients and frank hypophosphatemia in a subset. Studies suggest hypophosphatemia is associated with increased FD-related morbidity. However, the relationship between phosphorus and skeletal complications has not been investigated, and the optimal therapeutic target has not been determined. Objective: Characterize the impact of serum phosphorus on FD-related morbidity and identify levels associated with increased skeletal complications. Methods: Natural history study with 240 subjects at a clinical research center who had ≥1 fasting phosphorus level, determined as age- and sex-adjusted Z-scores. Subjects were categorized based on frank hypophosphatemia (Z-score ≤ -2; n = 48); low-normophosphatemia (> -2 to ≤ -1; n = 66); and high-normophosphatemia (> -1 to ≤ 2; n = 125). Main outcomes were fractures, orthopedic surgeries, and scoliosis. Results: Subjects with frank and low-normophosphatemia had increased fracture and surgery rates vs high-normophosphatemia. The prevalence of moderate to severe scoliosis was similarly higher in the frank and low-normophosphatemia groups. In a subanalysis of patients matched for Skeletal Burden Score ≥35, fracture and surgery rates remained higher in the frank hypophosphatemia group, suggesting association between phosphorus and skeletal complications is not explained by differences in FD burden alone. Conclusion: Both frank hypophosphatemia and low-normophosphatemia are associated with increased FD-related complications. This supports FGF23-mediated hypophosphatemia as a driver of skeletal morbidity, which may impact a larger proportion of the FD/McCune-Albright syndrome population than previously recognized. These findings enable clinicians to identify at-risk patients and will inform development of prospective studies to determine optimal therapeutic targets.
MeSH term(s)	Humans ; Phosphorus ; Scoliosis/complications ; Prospective Studies ; Fibrous Dysplasia of Bone/complications ; Fibrous Dysplasia of Bone/epidemiology ; Fibrous Dysplasia, Polyostotic/complications ; Fibrous Dysplasia, Polyostotic/epidemiology ; Hypophosphatemia/epidemiology ; Hypophosphatemia/etiology ; Prevalence ; Fractures, Bone
Chemical Substances	Phosphorus (27YLU75U4W)
Language	English
Publishing date	2024-03-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgad671
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Article ; Online: Lesion Expansion in Gnathic Fibrous Dysplasia: Natural History, Indicators of Progression, and Response to Bisphosphonates.

Pan, Kristen S / Taylor, Jocelyn / Szymczuk, Vivian / Boyce, Alison M

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

2023 Volume 38, Issue 10, Page(s) 1465–1471

Abstract: Fibrous dysplasia (FD) is characterized by expansile fibro-osseous lesions that may occur in association with endocrinopathies as part of McCune-Albright syndrome (MAS). Craniofacial FD is a significant source of morbidity and most commonly involves the ... ...

Abstract	Fibrous dysplasia (FD) is characterized by expansile fibro-osseous lesions that may occur in association with endocrinopathies as part of McCune-Albright syndrome (MAS). Craniofacial FD is a significant source of morbidity and most commonly involves the gnathic bones. There is a critical need to understand the natural history and risk factors for gnathic FD progression to develop preventative trials and identify candidates for intervention. The purpose of this study was to characterize gnathic FD lesion expansion and to identify risk factors associated with lesion growth. Patients with gnathic FD and serial CT imaging were evaluated. Volumetric analyses of CT scans were performed using MIM Encore software. Generalized mixed model analysis was used to account for intra-subject correlation, with FD lesion volume as the dependent variable. In addition to age, effects of MAS-associated endocrinopathies, sex, disease severity, and bisphosphonate treatment were evaluated. A total of 104 total lesions in 52 patients were characterized longitudinally. Median age at initial scan was 8.8 years (range 3.4-18.8), and median age at final scan was 16.8 years (range 6.9-33.4 years). The median number of scans per subject was 4 (range 2-14). FD lesion volume increased with age (2.50 cm
MeSH term(s)	Child ; Humans ; Adult ; Child, Preschool ; Adolescent ; Young Adult ; Diphosphonates/pharmacology ; Diphosphonates/therapeutic use ; Fibrous Dysplasia of Bone/pathology ; Fibrous Dysplasia, Polyostotic/complications ; Fibrous Dysplasia, Polyostotic/diagnostic imaging ; Fibrous Dysplasia, Polyostotic/drug therapy ; Bone and Bones/pathology ; Tomography, X-Ray Computed
Chemical Substances	Diphosphonates
Language	English
Publishing date	2023-07-31
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	632783-7
ISSN	1523-4681 ; 0884-0431
ISSN (online)	1523-4681
ISSN	0884-0431
DOI	10.1002/jbmr.4886
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Article ; Online: Weight loss supplement causing acute heart block in a child.

O'Brien, Daniel R / Szymczuk, Vivian / Albaro, Cecilia A

Cardiology in the young

2020 Volume 30, Issue 1, Page(s) 131–133

Abstract: A 16-year-old male was admitted to the paediatric ICU with acute onset of vomiting, somnolence, and chest pain, and electrocardiogram showing 2nd degree heart block after ingesting an Aleurites moluccana (Candlenut) seed as a herbal weight loss ... ...

Abstract	A 16-year-old male was admitted to the paediatric ICU with acute onset of vomiting, somnolence, and chest pain, and electrocardiogram showing 2nd degree heart block after ingesting an Aleurites moluccana (Candlenut) seed as a herbal weight loss supplement. Electrocardiogram showed progressively worsening heart block with down-sloping of the ST segments, resembling digoxin toxicity. After 2 days of ICU observation, his symptoms began to improve and eventually resolved. The side effects of herbal supplements are often unknown but by analysing cases such as these, physicians can develop a better understanding of these substances to help guide management.
MeSH term(s)	Adolescent ; Aleurites/adverse effects ; Aleurites/chemistry ; Anti-Obesity Agents/adverse effects ; Atrioventricular Block/chemically induced ; Chest Pain/etiology ; Dietary Supplements/adverse effects ; Electrocardiography ; Humans ; Male ; Seeds/adverse effects ; Weight Loss
Chemical Substances	Anti-Obesity Agents
Language	English
Publishing date	2020-01-06
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	1078466-4
ISSN	1467-1107 ; 1047-9511
ISSN (online)	1467-1107
ISSN	1047-9511
DOI	10.1017/S104795111900283X
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Article ; Online: Burosumab treatment for fibrous dysplasia.

Gladding, Anne / Szymczuk, Vivian / Auble, Bethany A / Boyce, Alison M

Bone

2021 Volume 150, Page(s) 116004

Abstract: Background: Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare mosaic disorder of Gα: Case description: A 7-year-old boy with severe FD/MAS presented with persistent hypophosphatemia and skeletal complications despite conventional ... ...

Abstract	Background: Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare mosaic disorder of Gα Case description: A 7-year-old boy with severe FD/MAS presented with persistent hypophosphatemia and skeletal complications despite conventional treatment with oral phosphate and calcitriol. He was started on burosumab and achieved sustained normalization of serum phosphorus and marked improvement in alkaline phosphatase levels. This was accompanied by an encouraging clinical response, including decreased bone pain, improved muscle strength, and improved ambulation. No adverse effects of burosumab therapy were observed. Conclusions: This is the first reported case of burosumab treatment in a patient with FD/MAS. The encouraging biochemical and clinical response in this patient highlights the need for future studies to explore the safety and efficacy of burosumab in the FD/MAS pediatric population.
MeSH term(s)	Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized ; Child ; Familial Hypophosphatemic Rickets ; Fibroblast Growth Factor-23 ; Humans ; Hypophosphatemia ; Male
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; FGF23 protein, human ; Fibroblast Growth Factor-23 (7Q7P4S7RRE) ; burosumab (G9WJT6RD29)
Language	English
Publishing date	2021-05-11
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	632515-4
ISSN	1873-2763 ; 8756-3282
ISSN (online)	1873-2763
ISSN	8756-3282
DOI	10.1016/j.bone.2021.116004
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Article: RANKL inhibition reduces lesional cellularity and Gα

de Castro, Luis F / Whitlock, Jarred M / Michel, Zachary / Pan, Kristen / Taylor, Jocelyn / Szymczuk, Vivian / Boyce, Brendan / Martin, Daniel / Kram, Vardit / Galisteo, Rebeca / Melikov, Kamran / Chernomordik, Leonid V / Collins, Michael T / Boyce, Alison M

Bone research

2024 Volume 12, Issue 1, Page(s) 10

Abstract: Fibrous dysplasia (FD) is a rare, disabling skeletal disease for which there are no established treatments. Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand (RANKL) as a potential treatment ... ...

Abstract	Fibrous dysplasia (FD) is a rare, disabling skeletal disease for which there are no established treatments. Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand (RANKL) as a potential treatment strategy. In this study, we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre- and post-treatment in a phase 2 clinical trial of denosumab (NCT03571191) and in murine in vivo and ex vivo preclinical models. Histological analysis of human and mouse tissue demonstrated increased osteogenic maturation, reduced cellularity, and reduced expression of the pathogenic Gα
MeSH term(s)	Animals ; Humans ; Mice ; Denosumab/pharmacology ; Fibrous Dysplasia of Bone/drug therapy ; Ligands ; Osteoblasts/metabolism ; Osteogenesis/genetics
Chemical Substances	Denosumab (4EQZ6YO2HI) ; Ligands
Language	English
Publishing date	2024-02-20
Publishing country	China
Document type	Clinical Trial, Phase II ; Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2803313-9
ISSN	2095-6231 ; 2095-4700
ISSN (online)	2095-6231
ISSN	2095-4700
DOI	10.1038/s41413-023-00311-7
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Article ; Online: Skeletal Disease Acquisition in Fibrous Dysplasia: Natural History and Indicators of Lesion Progression in Children.

Szymczuk, Vivian / Taylor, Jocelyn / Michel, Zachary / Sinaii, Ninet / Boyce, Alison M

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

2022 Volume 37, Issue 8, Page(s) 1473–1478

Abstract: Fibrous dysplasia (FD) is a rare mosaic disorder resulting in fractures, pain, and disability. Bone lesions appear during childhood and expand during skeletal growth. The rate at which FD lesions progress and the biochemical determinants of FD lesion ... ...

Abstract	Fibrous dysplasia (FD) is a rare mosaic disorder resulting in fractures, pain, and disability. Bone lesions appear during childhood and expand during skeletal growth. The rate at which FD lesions progress and the biochemical determinants of FD lesion formation have not been established, making it difficult to investigate and implement preventative therapies. The purpose of this study was to characterize FD lesion progression in children, and to identify clinical variables associated with progressive disease. Clinical data and imaging from an ongoing natural history study at the National Institutes of Health (NIH) were reviewed. 99m-Technetium methylene diphosphonate (99Tc-MDP) scans were used to determine Skeletal Burden Score (SBS), a validated quantitative scoring system. FD progression rate was determined by the change in the SBS in each patient per year. Thirty-one children had serial 99Tc-MDP scans, with a median age at first scan of 6 years (interquartile range [IQR] 4-8, range 2-10), and median follow-up 1.1 years (IQR 1.1-2.1, range 0.7-11.2). The median FD progression rate for the total group was 2.12 SBS units/year (IQR 0.81-2.94, range 0.05-7.81). FD progression rates were highest in children under age 8 years and declined with age (p = 0.03). Baseline disease severity was associated with subsequent disease progression (p = 0.009), with the highest FD progression rates in patients with moderate disease (baseline SBS 16-30), and lowest progression rates in those with severe disease (SBS ≥50). Serum levels of the bone formation marker osteocalcin were positively correlated with subsequent FD progression rate (p = 0.01, R = 0.58). There was no association between FD progression and baseline endocrinopathies, fractures, or surgery rates. FD lesions progress during childhood, particularly in younger children and those with moderate involvement. Osteocalcin may potentially serve as a biomarker for progressive disease. These findings may allow clinicians to investigate preventative therapies, and to identify children with FD who are candidates for early interventions. Published 2022. This article is a U.S. Government work and is in the public domain in the USA.
MeSH term(s)	Biomarkers ; Child ; Fibrous Dysplasia of Bone/diagnostic imaging ; Fibrous Dysplasia of Bone/pathology ; Humans ; Osteocalcin ; Radionuclide Imaging ; Technetium Tc 99m Medronate
Chemical Substances	Biomarkers ; Osteocalcin (104982-03-8) ; Technetium Tc 99m Medronate (X89XV46R07)
Language	English
Publishing date	2022-07-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Intramural
ZDB-ID	632783-7
ISSN	1523-4681 ; 0884-0431
ISSN (online)	1523-4681
ISSN	0884-0431
DOI	10.1002/jbmr.4618
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